PMID- 10028452 TI - Double therapy for IBD better than single therapy? The issue is not how but how much. PMID- 10028453 TI - [Thirteen-week intravenous repeated dose toxicity study of T-3762, a novel parenteral quinolone antimicrobial agent, and four-week recovery test in cynomolgus monkeys]. AB - A thirteen-week intravenous repeated dose toxicity study of T-3762, parenteral quinolone antimicrobial agent, and four-week recovery test was carried out in male and female cynomolgus monkeys at dosages of 26, 52 and 104 mg/kg. The following results were obtained. 1) There was no death of animals during administration period at any dose levels. In general signs, there was no abnormality at any dose levels. 2) In appetite, body weights and ophthalmological examination, there was no abnormality attributable to the treatment. 3) In urinalysis, hematological examination and biochemical examination, there was no abnormality attributable to the treatment. 4) In organ weights, macroscopic findings and histopathological findings, there was no abnormality attributable to the treatment. 5) From these results in this study, no-toxic dose level of T-3762 for cynomolgus monkeys is considered over 104 mg/kg. PMID- 10028454 TI - [Reproductive and developmental toxicity study of T-3762 in rats administered intravenously during the period of organogenesis]. AB - A teratogenicity study of T-3762, an injectable new quinolone antibacterial agent, was conducted in Sprague-Dawley rats to determine the effects on dams and next generations. T-3762 was administered intravenously to pregnant rats at the dose levels of 26, 78 and 156 mg/kg/day from day 7 to day 17 of gestation, during the organogenesis. 1. In the dams, there were no effects on general condition, food intake, water intake and body weight in the T-3762 treated groups. There were no abnormal findings on the autopsy at the end of gestation and lactation periods in the T-3762 treated groups. 2. In the fetuses, there were no effects on the number of dead and live fetuses, sex ratio and body weight in the T-3762 treated groups. No external, visceral and skeletal abnormalities attributed to T 3762 were observed. 3. In the offspring, there were no effects on birth rate, viability, differentiation of external development, body weight, sensory function, emotionality, learning ability and reproductive performance in the T 3762 treated groups. From these results, no-toxic dose levels of T-3762 are considered to be 156 mg/kg for the general toxicity and the reproductive toxicity of parents and for the development of next generation, respectively. PMID- 10028455 TI - [Significance of atrial fibrillation, left atrial thrombus and severity of stenosis for risk of systemic embolism in patients with mitral stenosis]. AB - The prognostic significance of atrial fibrillation, left atrial thrombus and the severity of mitral stenosis (MS) for systemic embolism was evaluated in 142 consecutive patients with MS (male 61, female 81; mean age 51 +/- 10 years) who were referred for cardiac catheterization. The relationships between systemic embolization, atrial fibrillation, left atrial thrombus and the size of mitral valve area obtained by the echocardiographic or Doppler method, or cardiac catheterization (Gorlin's formula) were studied. The effects of mitral regurgitation (MR) (Sellers II < or =) on systemic embolism or left atrial thrombus were also evaluated. Atrial fibrillation was observed in 117 patients (87%), 30 (28%) of whom had a history of systemic embolism. Four of 18 patients (22%) with sinus rhythm had a history of systemic embolism. Left atrial thrombus was observed in 63 patients (45%), including 17 (27%) with a history of systemic embolism. Seventeen (22%) of 76 patients without left atrial thrombus had a history of systemic embolism. Left atrial thrombus was detected in 17 of 41 (41%) patients with severe MS [mitral valve area (MVA) < or = 1.0 cm2], 8 of 25 (32%) patients with moderate MS (1.1 < MVA < or = 1.5 cm2), 2 of 14 (14%) patients with mild MS (MVA > or = 1.6 cm2), and embolization was complicated in 11% of cases of severe MS, 32% of cases of moderate MS and 21% of cases of mild MS. There was no significant difference between the 3 groups. Left atrial thrombus was more frequently observed in patients without MR than with MR (44% vs 13%, p < 0.05), but there was no significant difference in the incidence of embolism between the groups (28% vs 22%). Positive therapy intervention should be considered to prevent systemic embolism regardless of the presence or absence of sinus rhythm, MR, left atrial thrombus or severity of stenosis. PMID- 10028456 TI - [Evaluation of mitral valve lesions in patients with infective endocarditis by three-dimensional echocardiography]. AB - Recognition of the involved lesions is extremely important in mitral valve repair for infective endocarditis. Transesophageal echocardiography (TEE) is more sensitive for the detection of lesions than transthoracic echocardiography, but localization of the lesions is sometimes difficult by TEE. Three-dimensional (3D) TEE provides images of the mitral valve similar to the view from the left atrium. This study evaluated the value of 3D echocardiography for the diagnosis of involved lesions in 12 patients who underwent surgery for mitral regurgitation due to infective endocarditis. The location of the lesion in the mitral valve was classified as the medial, central and lateral portions of the anterior leaflet, and the medial, middle and lateral scallops of the posterior leaflet, respectively. In all patients, the involved sites were confirmed at operation. The sensitivities of 3D TEE for detecting the lesions at the medial, central and lateral portions of the anterior leaflet, and the medial, middle and lateral scallops of the posterior leaflet were 100%, 78% and 67%, and 100%, 100% and 100%, respectively. The specificities were 90%, 100% and 78%, and 100%, 100% and 100%, respectively. The lesions diagnosed by 3D TEE coincided with lesions confirmed at operation in 23 (92%) of 25 lesions. 3D TEE is useful for the assessment of the involved lesion of the mitral valve in patients with infective endocarditis. PMID- 10028457 TI - [Endothelial-derived nitric oxide mediates the peripheral vasodilatory effects of amrinone in humans]. AB - Amrinone, which is used for the treatment of acute congestive heart failure, has vasodilatory and positive inotropic effects through the increment of intracellular cyclic adenosine monophosphate. Recent in vitro investigations have shown that amrinone has an endothelium-dependent vasodilatory effect. The present study examined whether amrinone shows this endothelium-dependent vasodilatory effect in human peripheral vessels. Forearm blood flow during intra-arterial infusion of graded doses (12.5, 25, 50, 100, 200 micrograms/min) of amrinone was measured using plethysmography in 10 healthy subjects without organic vascular disease before and after nitric oxide synthase blocking with NG-monomethyl-L arginine (L-NMMA, 400 mumol). The graded dose of amrinone produced progressive increases in amrinone plasma concentrations, and a dose over 100 micrograms/min caused amrinone plasma concentrations of more than 1.0 microgram/ml. The increase in forearm blood flow in response to amrinone was significantly depressed after L NMMA doses of less than 100 micrograms/min, but the increase in forearm blood flow during infusion of higher doses (100, 200 micrograms/min) was not affected by L-NMMA. These results suggest that endothelial-derived nitric oxide may partially contribute to amrinone-induced vasodilation in humans. Thus, the vasodilatory effect of amrinone might be impaired in patients with endothelial dysfunction. PMID- 10028458 TI - Supraventricular tachycardia in a human immunodeficiency virus-infected man. AB - Although supraventricular tachycardias and human immunodeficiency virus infections are common diseases by themselves, a combination is not so common. Such a patient was encountered recently and described in this case report. Because misdiagnosis of tachyarrhythmias is not uncommon and may lead to inappropriate therapy-frequently resulting in acute clinical deterioration or even death, a discussion of management of supraventricular tachyarrhythmias in general was included. The recent introduction of adenosine into clinical use provides an effective agent in, and revolutionizes, the management of patients with supraventricular tachyarrhythmias. Its application, both for diagnostic and for therapeutic purposes, was discussed in some details in this report. PMID- 10028459 TI - [Survey of atrial fibrillation and thromboembolism in the elderly: a multicenter cooperative study. Research Group for Antiarrhythmic Drug Therapy]. AB - A multicenter, retrospective study was undertaken to survey the prevalence of thromboembolism complicated with atrial fibrillation and the efficacy of treatment in both elderly and younger patients. The primary prevention group consisted of 1,810 patients without prior cerebral thromboembolism, and was divided into the elderly patient group (> or = 65 years old, 588 patients) and younger patient group (< 65 years old, 1,222 patients). The elderly group had higher prevalences of chronic atrial fibrillation (65.3% vs 56.4%, p < 0.001) and ischemic heart disease and hypertension (16.8% vs 9.3% and 34.2% vs 24.4%, respectively, p < 0.001) and lower prevalence of treatment with warfarin (9.2% vs 20.1%, p < 0.001). Elderly patients with mitral valve disease and hypertension had lower prevalence of treatment with warfarin as compared with younger patients (p < 0.001). This was also true for the secondary prevention group of 147 patients with prior history of cerebral infarction (p < 0.001). During the mean follow-up period of 4.6 years, patients with underlying cardiac diseases had a higher risk of thromboembolism compared with those without cardiac diseases for both the elderly (12.1% vs 6.1%, p < 0.05) and younger (7.5% vs 3.6%, p < 0.02) groups. Treatment with antiplatelets or warfarin could reduce the risk of thromboembolism in the elderly group (p < 0.1) and the younger group (p < 0.001). The risk of major hemorrhagic complication, i.e., gastrointestinal tract or intracranial hemorrhage, was quite low in patients receiving antithrombotic drugs. The present study indicates that the attitude toward the use of warfarin for prevention of thromboembolism is conservative and the risk of thromboembolism is higher in elderly patients with atrial fibrillation in Japan. Our attitude to the use of antithrombotic drugs in elderly patients with atrial fibrillation needs to be modified. PMID- 10028460 TI - [A 55-year-old man with chronic pancreatitis complaining of inveterate abdominal pain]. PMID- 10028461 TI - [A patient with sustained ventricular tachycardia]. PMID- 10028462 TI - Podiatry folklore. PMID- 10028463 TI - Stabilization of the Chevron procedure for hallux valgus deformity with a capsuloperiostal flap. AB - This article reports on the use of a Chevron procedure in the treatment of hallux valgus for better stabilization of the osteotomy. This procedure was performed on 31 feet of 24 patients, Twenty-two of the patients were female and two were male. The average age was 41 and average follow-up time was 14 months. The average correction of the 1-2 intermetatarsal angle was 3.8 degrees and average correction of the hallux valgus angle was 15.3 degrees. On the follow-up, 93.5% of the feet were pain free and 81% did not have any discomfort with shoewear. There were two cases of superficial infection, and two patients complained of dysesthesia or hypoesthesia after the operation. Results revealed less correction loss, shorter union time, less metatarsophalangeal stiffness, and more postoperative patient tolerance. The authors attached the distally based "V" shaped medial capsuloperiostal flap to the metatarsal shaft and, because of obtained stability, used no internal fixation or postoperative cast but only night splint, allowed weightbearing on the heel as soon as the patient tolerated it, and encountered no displacement of fragments, malunion, or recurrence of the deformity. PMID- 10028464 TI - Modified lapidus arthrodesis for adolescent hallux abducto valgus. AB - The Lapidus arthrodesis was originally described for the surgical correction of hallux valgus associated with metatasus primus adductus. It was popularized on the adult patient with moderate to severe hallux valgus deformity. However, the authors present a retrospective review of 23 adolescents between the ages of 13 and 20 who underwent the procedures. Characteristics of adolescent hallux valgus include a smaller dorsal medial eminence, less valgus rotation of the hallux, and certain mechanical influences. These influences may include a generalized increase in motion at the first metatarsocuneiform joint. The modified Lapidus arthrodesis eliminates motion at the first metatarsocuneiform joint and therefore directly addresses an etiology of the deformity. Both preoperative and postoperative radiographs were evaluated for reduction in the 1-2 intermetatarsal angle. Patients were evaluated through either chart review or telephone interview for present activity level, comfortable footgear, and overall satisfaction of the procedure. Twenty-seven out of 30 feet (90%) had either a good or excellent result with only three complications and two recurrences over a mean follow-up of 61 months. PMID- 10028465 TI - Allofix freeze-dried cortical bone pins as an alternative to synthetic absorbable polymeric pins: a preliminary study in short Z bunionectomies. AB - The purpose of this study was to evaluate the effectiveness of the 2.4-mm freeze dried cortical bone pins as a secondary stabilizer in short Z bunionectomies. In addition, MRI studies were performed to evaluate the capacity of the cortical pins to incorporate into the surrounding bone tissue. A literature comparison is also made with the currently available synthetic absorbable pins. The advantages and disadvantages of these pins are discussed and compared with the results of the cortical bone pin study. Fifteen patients were included with a 6-month to 1 year postoperative follow-up. There were no obvious complications resulting from the use of the cortical pin. The pins performed well as a secondary stabilizer and incorporated with the patient's bone as proposed. The author concludes that the 2.4-mm freeze-dried cortical bone pin is a reasonable alternative to synthetic absorbable pins as applied within the parameters of the study. PMID- 10028466 TI - Surgical treatment of bi- and trimalleolar ankle fractures: should the medial collateral ligament be sutured or not? AB - In Weber type A, B, and C fractures there is no census or whether or not to suture the ruptured medial collateral ligament. From May 1990 to December 1994, operations were performed on 48 patients with such lesions. Thirty-three cases were reviewed, 29 males and four females, with an average age of 39 years (range, 15-73 years). In 22 cases there was an isolated fracture of the lateral malleolus, and in 11 cases the fracture was associated with a posterior malleolus fracture. There were tibiotalar dislocations in nine cases. Fifty-eight percent of the injuries were caused by sports activities and 27% by an ordinary fall. After a preoperative external reduction, the lateral and posterior (if necessary) fractures were anatomically and rigidly fixed (plate, pins, and wire) without any suture of the medial ligament. Medial tibiotalar and tibiofibular diastasis were totally reduced as shown during intraoperative radiographs. The follow-up at time of review was 27 months on average (range, 9 months-5 years). Functional results were excellent and good in 82.5% of cases, with a return to sports activities at a mean time of 4.3 months. X-rays were considered as normal in 73% of cases, with an anterior impingement syndrome in 15% and calcifications of the medial collateral ligament in 12%. Stress radiographs in valgus talar tilt (n = 24) were normal in all cases. The authors suggest new surgical guidelines in ankle fractures with a medial collateral rupture, based on fracture stabilization, with ligament tears left unexplored (medial, tibiofibular, and syndesmotic ligaments), and early mobilization. PMID- 10028467 TI - Critical pathway approach to diabetic pedal infections in a multidisciplinary setting. AB - The purpose of this investigation was to evaluate, utilizing clinical and financial outcomes, the critical pathway approach to diabetic foot infections in an inpatient setting. All patients admitted with a primary diagnosis of a diabetic foot infection over an 18-month period from 1995 through 1996 were included in this retrospective study. Comparison is made between the podiatry established critical pathway and nonpathway patient groups. Then comparison is made between these groups and a similar patient group from 1993 to confirm the validity of the overall results. There was a significant decrease in hospital stay and charges for pathway patients in 1995 and 1996 as compared to nonpathway patients in 1993 as well as 1995 and 1996 (p < .05). The authors also noted a significant decrease in major amputations (BKA or AKA) in pathway patients as compared to baseline values (1993 = 23%, 1995-1996 = 7%, p = .02) and as compared to patients not treated with this approach in 1995 and 1996 (pathway = 7%, nonpathway = 29%, p < .001). The data suggest that the use of a critical pathway approach allows earlier recognition, evaluation, and expedient treatment of potentially limb-threatening infections, improving patient outcomes by decreasing pedal morbidity, while encouraging judicious use of hospital resources. PMID- 10028468 TI - Staging of Charcot neuroarthropathy along the medial column of the foot in the diabetic patient. AB - Diabetes mellitus is the leading cause of Charcot neuroarthropathy. The most common location is along the medial column of the foot. Over a 2-year period, the process can result in a severely deformed foot, which is highly prone to ulcers, infection, and subsequent amputation. To help identify the early stages of the disease process, the histories, physical examinations, and radiographs of 40 patients with 51 neuropathic feet were evaluated. We were able to identify five stages of Charcot deformities. Stage 0 is a clinical stage in which the patient presents with a locally swollen, warm, and often painful foot. Radiographs are negative and technetium 99 bone scan is markedly positive. Indium and gallium scans are normal. Stage 1, in addition to the clinical findings, demonstrates periarticular cysts, erosions, localized osteopenia, and sometimes diastases. Stage 2 is marked by joint subluxations, usually starting between the second cuneiform and the base of the second metatarsal and spreading laterally. Stage 3 is identified by joint dislocation and arch collapse. Stage 4 is the healed and stable end result of the process. Clinically, there is no temperature gradient between the two feet. Radiographically, there is bony trabeculation across joint spaces indicative of mature fusion. Treatment of stage 0 consists of limited weightbearing and close observation while the diagnosis becomes clear. Stage 1 is treated with casting followed by a University of California Biomechanics Lab orthosis (UCBL), to maintain the arch while allowing limited weightbearing. In stage 2, a partial weightbearing total contact cast followed by a Charcot restraint orthotic walker (CROW) is used. Surgery may be needed at this stage, while the joints are still reducible. Arthrodesis with rigid fixation is recommended. Stage 3 is treated with casting for the acute phase, then with a patellar-tendon-bearing ankle-foot orthosis, CROW, or caliper orthosis. If ulcers are present, they are treated with weekly local debridement, antibiotics, and total contact casting. Occasionally decompressive ostectomy is required. Stage 4 may need surgical removal of the bony prominences causing the nonhealing ulcers. Extra-depth shoes and pressure-relieving orthoses are also used. Twenty-five percent of our patients diagnosed and treated in the early stages (stages 0, 1 and 2) did not develop deformity. Surgery to prevent deformity is recommended early, before the destructive stage (stage 3). Close follow-up, especially in a noncompliant population is necessary. PMID- 10028469 TI - The severe flexible flatfoot: a combined reconstructive procedure with rerouting of the tibialis anterior tendon. AB - A combined procedure is described that addresses all the components at fault in the severely flexible flatfoot deformity in children. The Evans calcaneal distraction wedge osteotomy will lengthen the lateral column, correcting the heel valgus and forefoot abduction. A naviculo--first cuneiform wedge resection (medial and plantar) and fusion will shorten and reshape the collapsed medial arch. This is augmented by reconstruction and plication of the lengthened plantar ligaments, with plantar rerouting of the tibialis anterior tendon to act as a strong plantar ligament. In addition, shifting the tibialis anterior's pull proximally acts as a sling to the talar head. Z plasty of the tight tendo Achillis is always needed. Nineteen feet in 11 patients were the subject of this study. The period of follow-up ranged from 8 to 42 months. The results were assessed according to the relief of foot strain and calf pains, improvement in shoewear, general activity, and foot shape. To evaluate foot shape, reconstruction of the medial arch and heel posture were assessed. The children and parents were satisfied with the final results in 17 feet (89.5%). Improvement of the radiological measurements was evident and was statistically significant. PMID- 10028470 TI - Pedal manifestations of disseminated intravascular coagulation. AB - Disseminated intravascular coagulation is a complex hemostatic imbalance associated with many disease states. The potentially lethal systemic consequences of this disease mandate that the podiatric physician obtain a complete detailed history in addition to proceeding with appropriate consultations from other specialties. If haste is utilized and surgical intervention is undertaken without careful consideration, a potentially fatal situation may ensue. A comprehensive case report highlighting the pedal presentation and complications, and an overview of this disease process are presented. PMID- 10028471 TI - Recurrent mycetoma of the foot. AB - Mycetoma, also known as madura foot, is a local, chronic, slowly progressive disease with the classic presentation involving tumefaction, multiple draining sinuses, and grain-filled pus. It is primarily produced by either a bacteria (actinomycetoma) or a fungal (eumycetoma) organism. Determining the causative organism is fundamental to the treatment process. All types of mycetoma infections should be treated with early surgical debridement and tissue culture. Tissue should be sent for gross, microscopic, and histopathologic evaluation. In addition to surgical management, these patients should be managed adjunctively with a prolonged course of chemotherapy. Patients with actinomycetoma are treated with an antibiotic and can expect to have a clinical cure with little chance for recurrence, whereas, patients with eumycetoma are treated with an antifungal agent and usually do poorly with a high rate of recurrence. The case presented involved an infection due to Actinomadura madurae (Nocardiaform madurae) and demonstrates successful treatment with surgical resection and prolonged doxycycline chemotherapy. PMID- 10028472 TI - Ewing's sarcoma of os calcis: case report with a review of literature. AB - A rare case of Ewing's sarcoma of os calcis is described here. Its atypical clinical and radiological features often delay the diagnosis. These features and review of literature are discussed. PMID- 10028473 TI - Bone cyst of a fishy origin: from an old catfish spine puncture wound to the foot. AB - A rare first metatarsal unicameral-type bone cyst with a deceptive radiographic appearance and size and an unusual pathological etiology was identified in a female patient. This eccentric cyst was observed only postoperatively by radiograph. Review of the patient's history documented a foot injury from a catfish spine as the etiology of this chronically inflamed cyst. PMID- 10028474 TI - Achilles tendon repair using a bone-tendon graft harvested from the knee extensor system: three cases. AB - The authors describe a new surgical technique of Achilles tendon reconstruction using bone-tendon graft from the knee extensor system. This technique is for those unusual cases of neglected or partial Achilles tendon rupture with distal tendon-substance loss at calcaneal insertion level, requiring transbone plasty fixation. Three cases are reported; the first two, followed up over a 5-year period, had excellent functional, morphological, and clinical outcomes. This new technique is compared with other available solutions: triceps plasty, other local tendon plasty, artificial plasty, and allograft. PMID- 10028475 TI - Latex allergy and the podiatric surgeon. AB - Latex allergy in recent years has become a more visible problem in the medical community. There are certain populations found to be at greater risk for this problem. Those with myelodysplasia, congenital urinary anomalies, and a history of a significant number of prior surgeries are particularly at risk, followed less commonly by health care workers and the general population. A detailed patient history is the most reliable predictor of latex sensitivity. There are various immunological and serological screening tests on the market, which are not always reliable predictors of allergy or readily available to the physician. This article reviews the current literature on latex allergy and provides insight into populations at risk, the type of allergic response seen, predictors of sensitivity, management of patients with latex allergy, and measures to prevent it. PMID- 10028476 TI - Loss of protective sensation: a practical evidence-based definition. PMID- 10028477 TI - Outcomes of preventive care in a diabetic foot specialty clinic. PMID- 10028478 TI - Further characterization of IgE-binding antigens in kiwi, with particular emphasis on glycoprotein allergens. AB - Fruit allergy is frequently associated with birch pollinosis. The aim of this study was to investigate which kiwi allergens were involved in subjects allergic to fruit alone and in patients allergic to both fruit and birch pollen. Sera of nine patients (five with both kiwi and birch pollen allergy and four with isolated kiwi allergy) were studied by immunoblot of kiwi extract. Eight of the nine sera reacted with the 30 kDa protein. Furthermore, IgE-binding proteins were seen at approximately 23 kDa (detected by five sera), 43 kDa and 80 kDa (four sera), and > 80 kDa (two sera). One serum showed no IgE binding to any kiwi allergen. The 30 kDa is the major allergen in kiwi and was purified by anion exchange chromatography and characterized by isoelectrofocusing and amino acid sequencing. The comparison of its partial amino acid sequence with data from the Swiss Protein Bank revealed that this protein is actinidine. The carbohydrate structures in kiwi and birch pollen extracts were investigated with seven lectins. On kiwi blot, Aleuria aurantia agglutinin showed strong reactivity (indicating fucose residues) to the components of 35 to 92 kDa, while concanavalin A (indicating mannose, glucose or N-acetylglucosamine residues) showed weak binding at 67 kDa. In contrast, strong binding of Galanthus nivalis agglutinin (indicating mannose residues) and concanavalin A was found on birch pollen blots. The presence of IgE against carbohydrate structures was determined by means of enzyme-linked immunosorbent assay (ELISA) after periodate treatment of kiwi extract. The IgE binding was reduced by periodate treatment of kiwi coated microtiter plates, but not by sera reacting exclusively with the 30 kDa protein. Furthermore, selected sera were treated with proteinase K-digested kiwi and birch pollen extracts as the sources of crossreactive carbohydrate determinants. In accordance with the results of sodium periodate treatment, significant levels of anti-cross-reactive carbohydrate determinant IgE were found in sera from patients allergic to both kiwi and birch pollen. Our results show that the major allergen for kiwi allergy is the 30 kDa protein and additionally that the cross-reaction between kiwi and birch pollen allergy is mainly due to carbohydrate moieties. PMID- 10028479 TI - Importance of IgG4 determination in in vitro immunotherapy follow-up of inhalant allergens. AB - Choosing the right parameters to recommend immunotherapy in allergologic diagnosis is very important. Therefore, other parameters which are independent of the improvement of clinical manifestations and which indicate the evolution of asthma are very useful. Although a decrease in skin reactions was observed in 20% to 25% of patients in previous studies, since the in vitro techniques appeared, their evolution has been observed. Total and antigen-specific IgE evolution, as well as histamine release from basophils, in immunotherapy were followed as we had presented in previous studies. In this work, we studied 151 patients with asthma and rhinosinusitis, 70 of whom were sensitive to Lolium perenne and 81 to Dermatophagoides pteronyssinus. The parameters mentioned above were used, and the patients underwent immunotherapy at three different concentrations depending on the degree of sensitization. The standard concentration was used in the first group; those patients with very high values in radioallergosorbent test (RAST) and histamine release test (HRT) were given the concentration 1:2; and lastly, the largest group of patients, who presented the highest sensitization both in vivo and in vitro, were given the concentration 1:10. As a complement to the mentioned in vitro techniques, the antigen-specific IgG4 determination (blocking antibody) was also evaluated. As we observed in previous studies, skin test, total IgE, antigen-specific IgE and HRTs showed no significant modifications in any of the three groups, in spite of the very positive clinical evolution over the 6 years. Regarding IgG4 follow-up in pollinic patients, a very significant increase was observed, reaching its highest value after 6 years, at standard concentration and with an increase of 49.4%. In conclusion, we think that antigen specific IgG4 is the only easily available and suitable parameter existing for immunotherapy follow-up. PMID- 10028480 TI - Role of substance P in increased airway hypersensitivity following induced stress in a guinea pig asthma model. AB - Stress is one of the important factors influencing bronchial asthma, but many questions still remain unanswered. To clarify this point we examined airway hypersensitivity before and after electric shock stress and the role of substance P in an animal model of asthma. We determined airway hypersensitivity to histamine and the substance P levels in serum, bronchoalveolar lavage fluid, and bronchial tissue before and after electric shock stress in biphasic asthma responsive guinea pigs which had been sensitized using ovalbumin. The cell components in bronchoalveolar lavage fluid were also examined. Airway hypersensitivity to histamine (4.9-156 micrograms/ml) was significantly increased (p < 0.01) by electric shock stress. The substance P level was also significantly increased in plasma and bronchoalveolar lavage fluid, but it was significantly decreased in bronchial tissue. The number of eosinophils in bronchoalveolar lavage fluid increased significantly after electric shock stress. These findings demonstrated that airway hypersensitivity to histamine was increased by stress and suggested that substance P, as well as eosinophils, contribute to the pathogenesis of hypersensitivity. PMID- 10028481 TI - Modulation of adhesion and chemotaxis of human neutrophils by cortisol, transforming growth factor-beta and antiinflammatory drugs. AB - Neutrophils are the first cells that accumulate in response to stimuli from the arising inflammation site. We have studied the influence of commonly used antiinflammatory (acetylsalicylic acid) and immunosuppressive (cyclosporin A, methotrexate) drugs and endogenous substances of antiinflammatory activity (cortisol, transforming growth factor-beta; TGF-beta) on the interdependent phenomena of cell motility and adhesion. Neutrophils from healthy subjects were preincubated with various concentrations of these substances and adhesion to plastic-bound monoclonal antibodies to CD11a/CD18, CD11c/ CD18 and CD44 was determined. We have found that the studied drugs significantly lowered adhesion (by 40%) of neutrophils to the ligands. Simultaneously, cell motility was investigated according to the Boyden method. We found a significant dose dependent increase in the motility of this cells in a range comparable to conventional chemoattractants for neutrophils. These data indicate that simultaneous enhancement of motility and reduction of adhesion might be a common pathway for the mechanisms of action of the most common anti-inflammatory drugs. PMID- 10028482 TI - Sensitization to Alternaria and Cladosporium in asthmatic patients and its in vitro diagnostic confirmation. AB - In order to determine the prevalence of airborne mould sensitization and the reliability of the in vitro diagnostic techniques in daily practice (antigen specific IgE and histamine release test), we performed a 3-year study in 2,200 patients diagnosed with rhinosinusitis and/or bronchial asthma. We found mould sensitization in 101 patients, 20% of whom presented monosensitization against airborne moulds, and the rest associated other sensitizations as follows: 53.7% against Dermatophagoides pteronyssinus, 45% against grass pollen and 30% against Olea europea. The most frequently involved moulds in our patients were Alternaria and Cladosporium. Seventy-six percent of the patients presented sensitization against Alternaria, 56% of whom were monosensitized, 26% presented cosensitization to Cladosporium and the remainder were sensitive to more than two moulds. Regarding Cladosporium, the percentage of patients was similar (66%), although only 23% were monosensitized and 46% presented an associated sensitization against Alternaria. We also observed a correlation between skin tests and both in vitro diagnostic techniques, with a relative sensitivity of the specific IgE determination compared to the skin test of 98% against Alternaria and 90.4% against Cladosporium, whereas the relative sensitivity of the histamine release test was 97.4% for Alternaria and 85% for Cladosporium. In conclusion, we think that in order to confirm the etiopathogenesis of the airborne moulds and before an immunotherapy treatment is indicated, the positive skin reactions should be confirmed by means of reliable laboratory diagnostic techniques, such as antigen-specific IgE determination and histamine release test. PMID- 10028483 TI - Expression of T-lineage early developmental markers by cells establishing atopic dermatitis skin infiltrates. AB - The association between the atopic dermatitis, eczema and T-cell immunodeficiency disorders are well known, thus suggesting that bone marrow T-precursors could use the micro-environment of the skin as an extrathymic site for compensatory ontogenesis. In keeping with this hypothesis, we analyzed the atopic dermatitis skin lymphocytic infiltrate phenotypes to establish their ontogenetic stage of development. Cryostatic sections (4 microns) obtained from acute lesional skin biopsies of six patients with extrinsic atopic dermatitis were processed with indirect immunoperoxidase, using a panel of first-step monoclonal antibodies (mAb) specific to CD104 (integrin beta 4 chain), CD90w (Thy 1 antigen), CD44 (phagocytic glycoprotein-1; Pgp-1), CD1a and the DNA polymerase terminal deoxynucleotidyl transferase (TdT). Within the lymphocytic dermal infiltrate different levels of immunoreactivity were observed with respect to CD104, CD90w and CD1a. A strong, spread staining was also detected for mAb specific to Pgp-1 and TdT. Together, the reported features indicate that the atopic dermatitis skin homing lymphocytes express immunophenotypes which are distinctive of the early T ontogeny. PMID- 10028484 TI - Bat feces as an indoor allergen. AB - We have demonstrated in an animal model (specific IgG) as well as in atopic patients suffering from rhinitis/asthma (specific IgE) that bat feces have antigenic properties. A single peak with high glycoprotein content was obtained by chromatography, while SDS-PAGE revealed several proteins between 29 and 116 kDa which showed immune serum blotting at 43.6 and 66 kDa. Positive specific skin tests with bat feces and IgE-RAST anti-bat feces were detected in atopic patients living in tall buildings and old houses in Buenos Aires. As bat feces did not cross-react with bat epithelium, studies evaluating rat serum and epithelium and pigeon feces in order to analyze the role of bat serum proteins, such as IgA, are encouraged. PMID- 10028485 TI - Aerobiological study of Chenopodiaceae and Amaranthaceae in the Mediterranean area of southwestern Spain. AB - The study area is characterized by a maritime Mediterranean climate, abundant presence of Chenopodiaceae in the vegetation, and a high incidence of pollinosis caused by the pollen of this family. A Hirst-type sampler was used to determine pollen concentrations in the air of the city of Huelva during 3 consecutive years (1995-1997). The total annual amount of Chenopodiaceae-Amaranthaceae pollen was between 10.59% and 6.28% of the pollen spectrum of the city, depending on the year. The annual pattern of variation in pollen concentration (5-day means) was very similar in the 3 years, and no statistically significant differences were found between years. This pattern is characterized by concentrations not exceeding 20 grains/m3 between April and the beginning of August, with an obvious seasonal variation in the second half of August and September, when the 5-day mean concentrations exceeded 40 grains/m3 and the daily maxima exceeded 100 grains/m3. This coincided with the flowering of most of the species in the group. The meteorological parameters with a statistically significant effect on daily pollen concentration during the pollen season (August 15 to September 20) included mean temperature and south wind (positive correlations) and relative humidity of the air (negative correlation). The highest intradiurnal concentrations were found between 10:00 a.m. and 5:00 p.m. PMID- 10028486 TI - International Study of Asthma and Allergies in Childhood (ISAAC) written questionnaire: validation of the asthma component among Brazilian children. AB - Written questionnaires have been widely used in epidemiological studies of asthma. However, when translated to another language, they must be validated. The International Study of Asthma and Allergies in Childhood (ISAAC) written questionnaire had been previously validated by a comprehensive study, but this had not been done in Brazil. Our objective was to validate the asthma component of the ISAAC self-applicable written questionnaire following its translation to Portuguese. A group of 10 pediatricians and 10 pediatric allergists graded the questions from 0 to 2, and established a maximum score for each question. The questionnaire was answered by parents or guardians of asthmatic children, aged 6 to 7 years old (n = 26) and of nonasthmatic control children of the same age (n = 26); and by asthmatic (n = 33) and nonasthmatic (n = 33) adolescents, aged 13 to 14 years. Half of these individuals responded to the same questionnaire after 2 to 4 weeks. This second response allowed the evaluation of the reproducibility of the ISAAC questionnaire. The maximum global score possible was 14, and cut-off levels of 5 and 6 were found for the groups of 6 to 7 and 13 to 14 year olds, respectively. There was significant agreement between the adolescents' responses to the questionnaire and those from their parents or guardians (74.3%); however, significant discordance was observed for individual questions including "wheezing with exercise." In both age periods the questionnaire was significantly reproducible (Kappa test) (6 to 7 year olds Kw = 1; 13 to 14 year olds Kw = 0.89). In conclusion, the asthma component of the ISAAC written questionnaire was proven to be reproducible, adequate and able to differentiate between asthmatics and controls. Adolescents answered the questionnaire appropriately, however the results suggest that adolescents' parents or guardians underestimate asthma symptoms which interfere little with the adolescent's daily activities. PMID- 10028487 TI - Delayed hypersensitivity to enoxaparin. AB - A 65-year-old woman experienced immediate itchy erythematous patches at the subcutaneous injection sites of sodium enoxaparin. An erythematous and infiltrated 40 x 20 mm lesion on the abdominal wall could be observed at the site of enoxaparin injection when she was referred to our clinic 48 h after injection. Lesions subsided spontaneously within 1 week. She had been on this treatment 1 and 3 years before without any adverse reaction. To clarify the nature of the reaction, epicutaneous tests with sodium enoxaparin, calcium nadroparin and calcium heparin were performed, all with negative results. Skin prick test with sodium enoxaparin was also negative. Biopsy of the cutaneous lesion showed spongiotic dermatitis, strongly suggesting a delayed hypersensitivity mechanism. We report here on a new case of delayed hypersensitivity to enoxaparin. Being female, overweight and having prolonged application of the drug were suggested risk factors present in our patient. Biopsy was essential for diagnosis. Although type IV hypersensitivity reactions to enoxaparin are rare, we should start to suspect this condition in order not to underdiagnose it. PMID- 10028488 TI - [New animal models for psychogenic impotence: an ethological approach to copulatory disorder induced by social stress]. AB - Although various experimental models of mental illness, such as anxiety and depression, have been developed, little attention has been paid to male psychogenic impotence. Since sociopsychological factors are presumed to play an important role in many cases of human impotence, an animal model of psychogenic impotence is needed to satisfy such validity. From an ethological viewpoint, we have recently developed new animal models for psychogenic impotence using sociopsychological manipulations, that is, social deprivation and social conflict. This review focused only on the methodology and the actions of drugs on such copulatory disorder induced by social stress. Possible brain mechanisms underlying stress-induced copulatory disorder were also considered. PMID- 10028489 TI - Chronic cerebral hypoperfusion-induced neuropathological changes in rats. AB - We investigated the time courses of histopathological changes in various brain regions following permanent occlusion of the bilateral common carotid arteries (2VO) in rats. 2VO rats exhibited rarefaction in the white matter, shrinkage of neurons in the cerebral cortex and hippocampus CA1-3 and dentate gyrus areas 1-3 days after the operation. These histological changes in the cortex and hippocampus were accompanied by a decrease in immunoreactivity for microtubule associated protein 2 (MAP2), a marker protein of neuronal dendrites. Immunoreactivity for glial fibrillary acid protein (GFAP) was observed at 3-7 days after the 2VO operation. A marked increase in GFAP staining of the astrocytes in the cerebral cortex and hippocampus was found 30 days after ligation. Eight-arm radial maze performance was tested from 14 days to 60 days after the operation. The 2VO rats showed fewer initial correct responses than sham-operated control rats during a repeated training period. These findings suggested that the loss in dendritic MAP2 immunoreactivity and an increase in astroglial staining and/or rarefaction of the white matter may cause neuronal death, infarction and learning impairment under conditions of chronic hypoperfusion. PMID- 10028490 TI - Central nervous system effects of the novel antiallergic agent HSR-609 and typical antiallergic agents using behavioral and electroencephalographic analyses in dogs. AB - We studied the central nervous system (CNS) effects of 3-[4-(8-fluoro-5, 11 dihydrobenz[b] oxepino[4, 3-b]pyridin-11-ylidene)piperidino]propionic acid dihydrate (HSR-609), a novel amphoteric antiallergic agent having antihistaminic activity. Its effects on gross behavior, spontaneous electroencephalograms (EEG) and some pharmacological parameters of unanesthetized, unrestrained dogs with chronic indwelling brain electrodes after oral administration were compared with typical antiallergic agents and 8-fluoro-5, 11-dihydro-11-(1-methyl-4 piperidylidene)benz[b] oxepino[4,3-b]pyridine (PY-608), a non-amphoteric basic compound having a similar chemical structure to HSR-609. HSR-609 (1, 10 and 100 mg/kg) and terfenadine (100 mg/kg) had no effect on the behavior, EEG patterns, sleep-wakefulness cycles or EEG power spectrum. Cyproheptadine (10 mg/kg), ketotifen (30 mg/kg) and PY-608 (10 mg/kg) increased slow waves with high amplitude in all EEG leads and caused dissociation between the slowing of EEG and waking behavior. Both azelastine (30 mg/kg) and oxatomide (100 mg/kg) caused generalized seizure discharges accompanied by agitation with the former and sedation with the latter. These findings suggest that observations of behavior and EEG in conscious dogs can be useful for clarifying the pharmacological characteristics of various antiallergic agents on the CNS. We were able to show that HSR-609 has no effect on the behavior and EEG of dogs because of its amphoteric chemical structure. PMID- 10028492 TI - [The act for organ and transplantation and the prospect]. AB - Organ transplantation from brain-dead state becomes possible under the act for brain death and organ transplantation after a very long incubation period of 30 years. In a year after the enforcement of the act, we have no cases of such a type of organ transplantation. There are many reasons for such difficulty, including the unfamiliarity of medical staffs to such a new type of organized medical action by teams including citizens. Here, I will discuss how to break the difficulty. PMID- 10028493 TI - [Present and future of heart transplantation in Japan and the world]. AB - During the past 31 year, cardiac transplantation has emerged as a standard mode of therapy for patients with end-stage congestive heart failure. At present, cardiac transplantation offers dramatically improved prospects for survival and rehabilitation in properly selected patients. The shortage of donor organs is the most common problem facing organ transplantation today. Despite widespread public education programs, the number of organ donors has leveled off at approximately 5,500 per year worldwide. More than 80% of patients in need of a heart, kidney, or liver allograft fail to receive the needed organ. Extensive research on the use of porcine xenografts as alternatives to allografts has been conducted since the 1980s. In this paper, the prospects for organ transplantation are reviewed. PMID- 10028494 TI - [Recent advances in living-related liver transplantation and in liver transplantation for patients with liver cirrhosis and hepatocellular carcinoma]. AB - Living-related-donor liver transplantation has been performed in more than 700 patients in Japan. This article deals with recent advances in living-related donor liver transplantation and the strategy for liver transplantation for patients with liver cirrhosis and hepatocellular carcinoma. The indication for living-related-donor liver transplantation has gradually widened to include urgent cases as well as adult patients. In living-related-donor liver transplantation for adults, limitation of graft volume has led to the use of left hepatic lobe grafts including the caudate lobe, or right hepatic lobe grafts. The results of liver transplantation for patients with hepatitis B cirrhosis, hepatitis C cirrhosis and hepatocellular carcinoma have improved, due mainly to advances in patient selection and perioperative medical Care. The widespread use of liver transplants from both living and cadaveric donors is necessary in Japan, where adult patients with viral hepatitis and hepatocellular carcinoma account for the majority of patients with end-stage liver disease. PMID- 10028495 TI - [Lung transplantation: present international status and basic approach]. AB - Lung transplantation has been established as an optional treatment for irreversible diffuse lung disease. To date, more than 8,000 patients have undergone lung transplantation, while heart-lung transplantation is confined to a very limited number of cases due to the severe shortage of donors. There are various problems in clinical lung transplantation, including limited preservation time, post-transplantation edema, acute and chronic rejection, and a shortage of donor organs. Several solutions to these problems have been found in recent experimental studies. For example, potential therapies for posttransplantation edema have been proposed, and the possibility of long-term preservation has been suggested. Research on xenotransplantation and cadaveric lung transplantation is ongoing, and this may result in options to solve the problem of the shortage of donor organs. In particular, we believe that cadaveric lung transplantation has the potential to become a clinically useful therapy in the near future. PMID- 10028496 TI - [Renal transplantation]. AB - The clinical outcome of kidney transplantation worldwide is reviewed. Total number of kidney transplantations now number 411,071, and about 26,000 have been performed annually in recent years. In Japan, the total is 11,813, and about 600 to 700 have been performed annually in recent years. Graft survival is 80% at one year and 60% at five years in cadaveric renal transplantation worldwide, and 90% at one year and 70% at 5 years, respectively, in Japan. There is no difference in the graft survival rate between Japan and Western countries. However, there have been fewer kidney transplantations in Japan than in the west. Issues which should be resolved are (1) the number of kidney transplantations, especially cadaveric transplantations, should be increased enlarged; and (2) long-term graft survival rates should be improved. To improve the long-term graft survival rates, it is necessary to evaluate the mechanisms of chronic graft failure and develop new immunosuppressive therapies to eliminate rejection crises completely. PMID- 10028497 TI - [Current status and future of pancreas transplantation]. AB - The results of pancreas transplantation have improved in the ciclosporin A era. Success rates are now similar to those in other types of organ transplantation, and the number of cases has increased concomitantly. As of December 1997, 10,283 pancreas transplantation procedures had been reported to the International Pancreas Transplant Registry. Since 1995, over 1,000 have been reported annually, 75% of which have been performed in the USA. The majority (88%) of those carried out in the USA consist of simultaneous pancreas and kidney (SPK) transplantations, followed by pancreas transplantation after kidney transplantation (10%) and pancreas transplantation alone (PTA) (2%). From 1994 to 1997, the overall one-year patient survival rate was 94%. The graft survival rate for SPK was the highest, with one- and three-year graft survival rates of 82% and nearly 80%, respectively. The administration of FK506 and mycophenolate mofetil has improved the results in patients undergoing pancreas transplantation. Althought the technical failure rate has decreased, graft thrombosis remains the most frequent cause of technical failure (5.5% for SPK with exocrine bladder drainage and 11% for SPK with enteric drainage). The standard surgical procedure has included pancreas-exocrine bladder drainage, but the current trend is to perform physiological enteric drainage. It has been reported that the portal venous and enteric exocrine drainage methods are safe, with outcomes similar to those of the standard technique. It appears that these will become the standard methods in the near future. The primary objective of improved quality of life is achieved in patients with functioning pancreas grafts, and transplantation results in modest reductions in secondary diabetes mellitus complications. However, it must still be confirmed whether the long-term quality-of-life benefits outweigh the potential risks. The secondary objective of pancreas transplantation is to prevent complications of diabetes mellitus. It is necessary to develop methods for the early detection of rejection, which will lead to significant improvements in the results of PTA. Although 15 pancreas transplantation surgeries have been carried out in Japan, they ceased after 1994. Currently, social debate to determine the rules governing such procedures is ongoing. PMID- 10028498 TI - [Organ preservation]. AB - Organ preservation is currently performed by simple cold storage or continuous hypothermic perfusion. Cold storage using University of Wisconsin (UW) solution greatly prolongs the successful preservation period for abdominal organs such as the kidney, liver, and pancreas. Thoracic organs (heart, lung), however, can be preserved for only several hours even with UW solution. As a result of improvements in organ transplantation, the number of patients on waiting lists has grown rapidly. Unfortunately, many patients die while waiting for donor organs, and expansion of the donor pool is mandatory. Possible solutions to the shortage of donor organs include the use of marginal donors and non-heart-beating donors. For this purpose, more sophisticated methods of organ preservation are needed, and therefore extensive investigations using current technologies including gene transfer should be performed. Every effort should be made to accommodate the preferences of donors. PMID- 10028499 TI - [Organ transplant network in Japan: current status and its role]. AB - The Role of Organ Transplant Network are the encouragement of the organ transplantation and fair organ sharing. Its principled are united, neutral open and nonprofit organization, so as to secure the fair and quick organ sharing based on the uniform allocation policy. Japan Kidney Transplant Network was established in 1995 nad reorganized into multi-organ sharing network, Japan Organ Transplant Network in 1997, when Japan Organ transplant Act was enacted. It consists of transplant coordinators, physicians, transplant surgeons, kidney banks, local administration, academic standings, other organization/associations and others. There are several committee, in which special subjects on organ transplantation and related matters are consulted, and review system in which each case is assessed and judged. And principal and essential items are decided by the board of members and then by the general assembly. The new computer system was introduced and registrants data are renewed every year, and recipient selection is done based on the latest registrants data. Standardized HLA examination tray was introduced and class II antigen was examined by means of DNA typing since 1997, which enabled more precise and accurate search. Hereafter, the education and encouragement of transplant coordinators to raise themselves and the more effective and extended distribution of donor cards are indispensable to promote organ donation/transplantation. PMID- 10028500 TI - [Selection criteria for aortic valve prostheses: mechanical, stented, or stentless valve or homograft?]. AB - A bioprosthesis is recommended for aortic valve replacement in patients 70 years (recently, 72 or 73 years) of age or older. The bovine pericardial valve is better suited in patients with a small aortic annulus less than 23 mm in diameter, and the porcine stented-bioprosthesis should be used in patients with an annulus larger than 25 mm. A mechanical valve is recommended in patients younger than 70 years of age with chronic atrial fibrillation or a history of thromboembolism. Moreover, a mechanical valve is selected in patients in whom it is necessary to enlarge the aortic root or annulus. When mitral valve replacement or coronary artery bypass grafting in performed concomitantly, the valve prosthesis is selected according to the age of the patient. A homograft is indicated in patients with active valve endocarditis having an abscess at the aortic annulus or root. When a patient with poor ventricular performance resulting from valvular disease is expected to undergo implantation of a ventricular assist device in the near future, a bioprosthesis is preferable. PMID- 10028501 TI - The NCCN guideline program--1998. AB - In 1995, the National Comprehensive Cancer Network (NCCN) embarked on an ambitious project to develop comprehensive diagnostic and treatment algorithms for the broad spectrum of oncologic diseases and support modalities. To date, 28 NCCN guideline panels have developed guidelines covering an estimated 93% of tumors, and an additional 9 panels have guidelines under development. This article reviews the NCCN guideline infrastructure and development process. The process relies on the expertise of the 17 NCCN member institutions and follows a formal procedure for guideline development to ensure that the recommendations offer the cancer patient the best chance for a successful outcome. PMID- 10028502 TI - Roundtable discussion. Investigational exclusion, clinical trials, and cancer. AB - Clinical trials are critical for developing and testing new treatments for cancer, but a panel of experts agreed that the state of clinical trials in the United States today is a "mess." How did we get into this situation in the first place, and how can we extricate ourselves? Should the federal government assume greater responsibility for funding and overseeing clinical trials and for establishing a standard health benefit package that defines the right to participate in clinical trials? The panel explored whether decisions to exclude patients are based on medical necessity and scientific merit or on the bottom line; whether insurance companies promise more than they can deliver; whether pharmaceutical companies are doing their share; and why lawyers are getting any share. In the end, the participants expressed hope that we, as a society, can get clinical trials back on track to serve their legitimate scientific and medical purposes. PMID- 10028503 TI - NCCN practice guidelines for the myelodysplastic syndromes. National Comprehensive Cancer Network. PMID- 10028504 TI - Incorporating new modalities into guidelines. Topotecan for myelodysplastic syndromes. AB - The National Comprehensive Cancer Network (NCCN) guidelines for patients with myelodysplastic syndromes (MDS) list myelosuppressive chemotherapy as an option for patients who have MDS with International Prognostic Scoring System (IPSS) scores of "intermediate" or "high." Myelodysplastic syndromes with these IPSS scores have an unfavorable natural history. Topotecan is a myelosuppressive drug that interacts with topoisomerase I and that has been used in the treatment of refractory AML. Its use in MDS has recently received considerable publicity. This paper reviews M. D. Anderson's results with topotecan and topotecan + ara-C in patients with MDS, focusing on comparisons of the results with ara-C and ara-C + fludarabine +/- idarubicin. While it is clear that the drug can produce complete responses, it is less clear that it differs from these other regimens. On average, complete response and survival rates are similar following administration of topotecan + ara-C or the other regimens. On the other hand, among patients with abnormalities of chromosomes 5 and/or 7, complete response rates are higher following topotecan + ara-C than for ara-C alone, or other ara-C combinations. The improvement in complete response rate among patients with abnormalities of chromosomes 5 and/or 7 has not resulted in an improvement in their survival (actuarial median about 6 months), largely reflecting a poor outcome following complete response. Indeed, the frequency of relapse in these patients suggests that any inherent increase in antileukemia activity in patients with abnormalities of chromosomes 5 and/or 7 is minimal. Given the overall results, topotecan +/- ara-C should not be regarded as standard therapy for MDS. The drug is nonetheless interesting and attempts to add to its efficacy are in progress. PMID- 10028505 TI - NCCN practice guidelines. Screening for and evaluation of suspicious breast lesions. National Comprehensive Cancer Network. AB - The intent of these guidelines is to give the health-care provider a practical and consistent framework for screening and evaluation of a spectrum of breast lesions. Clinical judgment should always be an important component of the optimal management of the patient. If the physical breast examination, radiologic imaging, and pathologic findings are not concordant, the clinician should carefully reconsider the assessment of the patient's problem. Incorporating the patient into the healthcare team's decision-making, empowers the patient to determine the level of breast cancer risk that is acceptable to her in the screening or follow-up recommendations. PMID- 10028506 TI - FDA Modernization Act: implications for oncology. AB - The Food and Drug Administration (FDA) Modernization Act, signed into law on November 21, 1997, represents a sweeping review of existing standards for the approval, labeling, and promotion of prescription medicines. Certain sections of the act will influence access that oncologists and their patients have to new treatments and to information about those treatments. Major impacts of the act include: (1) continued funding of drug reviews by the FDA to assure a continuing stream of new drugs to prevent and treat disease; (2) providing greater flexibility in drug approval by permitting approval on the basis of one clinical trial and confirmatory evidence, and by instituting "fast track" designation to certain drugs that will permit approval on the basis of surrogate end points; (3) improving the access of physicians and patients to developing treatments by instituting a clinical trials databank and by authorizing the use of investigational products in emergencies; and (4) loosening restrictions on dissemination by drug companies of health, economic, and off-label use information, while maintaining incentives to investigate new uses for developing products. PMID- 10028507 TI - NCCN Internet-based data system for the conduct of outcomes research. AB - The National Comprehensive Cancer Network (NCCN), an alliance of 17 of the world's leading cancer centers, is currently conducting its first shared outcomes project in breast cancer. City of Hope National Medical Center serves as the data coordinating center for the project. A database system has been designed and deployed which allows project staff located all over the United States to submit data to the central repository at City of Hope via the Internet. The database application consists of a series of webenabled front-end screens linked to a Microsoft SQL Server database. The NCCN system incorporates high levels of data security, confidentiality, and integrity via data encryption, password and ID protection, submission of anonymous data, and quality-control processing on several levels. The application also provides the flexibility of entering the data via the web-based screens, or transferring electronic files of data from existing database systems. Recently released SAS statistical software tools have been integrated into the system to allow for a seamless interface for analysis and web-enabled output of reports. The goals and strategies in designing the NCCN system are described and sample screens are shown. Our experience to date indicates that this system is highly effective in providing the ability to perform nationwide retrieval and analysis of outcomes data. PMID- 10028508 TI - Panel discussion. Data needs in cancer. AB - A prospective, comprehensive outcomes database was recently initiated by the National Comprehensive Cancer Network (NCCN) after a 2-year study to test data collection methods and systems. It started with data on 400 patients with newly diagnosed breast cancer at five NCCN sites, and over the next 3 years is projected to grow to include more than 12,000 patients with common cancers treated at all eligible NCCN sites. Among the goals of the database are: 1) to establish the capability to select, analyze, and report patterns of care and outcomes; 2) to allow NCCN members to assess their compliance with NCCN clinical practice guidelines and benchmark their performance against the rest of the NCCN; 3) to establish a true databased continuous quality improvement program; 4) to support clinical disease-oriented research and methodologic studies; and 5) to provide the NCCN with a vehicle for forging partnerships with others in the health-care field, such as the pharmaceutical industry, regulatory agencies, and accrediting bodies. Many of those potential partners were represented on this panel. Panelists discussed the data needs of their organizations, what they are doing to meet those needs, and how a comprehensive database will ultimately help improve patient care. PMID- 10028509 TI - Demonstrating oncology provider value: data, guidelines, and the law. AB - In the new health-care environment of value purchasing, data generated from applied clinical practice guidelines will be increasingly more important to oncology providers for both strategic and quality management reasons. This article looks at issues associated with selecting and implementing clinical practice guidelines and considers the legal issues thereof. It also offers some practical guidance for applying data in the new marketplace. PMID- 10028510 TI - Risk management and data: managed care company perspective. AB - As both public and private health plans move increasingly to managed care, a vigorous debate is occurring about how to ensure health care quality for the American public, while at the same time managing the cost of that care. Health plans generate large volumes of data related to their networks and providers, plan sponsors, member care, and medical protocols. This data can help assure quality, and at the same time help managed care organizations deal with one of the most critical tasks facing them--risk management. This paper may be helpful in providing an outline of two key areas--managed care liability for quality of patient care, and privacy and confidentiality concerns from a managed care organization perspective--followed by suggestions to avoid or minimize liability. PMID- 10028511 TI - Practice guidelines for cancer pain therapy. Issues pertinent to the revision of national guidelines. AB - The high prevalence of pain in cancer patients has been appreciated for a long time. However, despite release of cancer pain management guidelines by the Agency for Health Care Policy and Research (AHCPR) in 1994, pain is still undertreated. Recent reports in the literature have identified multiple factors that influence analgesic response and pain management, such as the ethnicity, gender, and age of the patient. Recognition of these factors, and the availability of new drugs, alternative delivery methods, and an enhanced understanding of pain mechanisms and receptor pharmacology compel a revision of the existing cancer pain management guidelines. Assessment and management of pain and other symptoms in cancer patients that influence the quality of survival are increasingly being incorporated into randomized-controlled clinical trials. Strategies should be developed by the National Comprehensive Cancer Network (NCCN) to develop and implement extant and revised pain management guidelines into clinical practice and test new hypotheses regarding pain management treatments in clinical trials. PMID- 10028512 TI - NCCN practice guidelines for upper gastrointestinal carcinomas. National Comprehensive Cancer Network. PMID- 10028513 TI - NCCN practice guidelines for occult primary tumors. National Comprehensive Cancer Network. PMID- 10028514 TI - Evaluating the quality of clinical guidelines. Linking decisions to medical evidence. AB - The validity and applicability of recommendations in clinical medicine are dependent on the design of studies upon which recommendations are based. Large prospective randomized controlled trials (RCT) generally provide the most reliable data to help guide our treatment decisions. However, analysis of decision-making in the field of hematologic malignancies indicates that only 24% of decisions can be based on randomized controlled trials. This lack of high quality data to support many decisions in the treatment of malignant disorders underscores the need to evaluate the evidence that forms the backbone of guidelines themselves. As physicians are encouraged to conform to clinical guidelines, it is important that information be made available regarding the quality of data upon which these guidelines are based. We propose the development and use of a guideline quality score based on the quality of evidence supporting each decision in a guideline. By linking the quality of evidence with specific recommendations, physicians will be in a better position to understand the strengths and weaknesses of practice guidelines. This linkage will also help physicians to streamline their efforts to obtain a new line of evidence when an existing one is not satisfactory. PMID- 10028515 TI - NCCN practice guidelines for multiple myeloma. National Comprehensive Cancer Network. PMID- 10028516 TI - Web-based resources for clinical protocol management. AB - The data monitoring regulatory procedures, and administrative tasks associated with protocol management have become increasingly complex. Relational database technology and Internet-based connectivity offer resources to improve the quality and efficiency of protocol operations. At Fox Chase Cancer Center, we have developed a suite of database applications for protocol management and tracking of patient accrual. All data transactions and reporting occur through a graphical web browser interface using standard Internet technology. Security and confidentiality have been addressed through encryption, user authentication, address restriction, and database authority. Database management has been tightly integrated with protocol operations to avoid duplication of resources and effort. Data query functions also extend to other institutional resources, such as tumor registry and the hospital clinical laboratory, to further reduce the need for redundant data storage. Newer components, such as chemotherapy orders and toxicity reporting, have been incorporated in a modular fashion. Although custom software development can be expensive and time-consuming, it offers the best opportunity for successful integration with existing resources, staff, and procedures, as well as collaboration with other institutions. PMID- 10028517 TI - Databases, websites, and the Internet. AB - By the end of the year 2000, an estimated 100 to 500 million computers may be linked to the Internet, representing an enormous level of information exchange. Even today, a broad Internet search of a term such as "breast cancer" can produce an overwhelming list of web pages, most of which will not be of interest to the typical Internet user. A more sophisticated user such as the oncology professional will more likely refine the search by adding other terms, producing a more manageable and useful list of websites. Information on cancer can be readily accessed from thousands of websites developed by the government, medical organizations, other institutions, medical journals, patient support groups, and pharmaceutical companies, as well as through medical web directories. The Cancer Information Network (CIN), an independent website geared to the oncology community, provides access to Medline, PDQ, and hundreds of cancer-related resources on the World Wide Web. CIN also offers the complete NCCN conference proceedings and practice guidelines; full text of several medical journals, textbooks, and handbooks; a daily oncology news service; a clinically oriented drug reference guide; and an extensive calendar of medical meetings and CME courses. PMID- 10028518 TI - Oncology legislative update. AB - A summary of recent and proposed legislation that may affect oncologists and their patients. The report includes information about new fraud, waste, and abuse initiatives on the part of the federal government, the outlook for research funding, Medicare reimbursement, and state negotiations and legal actions against the tobacco companies. PMID- 10028519 TI - Health-Care Financing Administration's proposed regulations to implement Stark II. AB - The Health Care Financing Administration published its proposed regulations to implement the 1993 amendments to the Stark law in the Federal Register on January 9, 1998. Several provisions are of interest to oncologists: The rental of infusion pumps to patients; how "physically present in the office" is defined; discounts on drugs; and compensation in a group practice. The details are discussed in this article. PMID- 10028520 TI - Progress toward guidelines for the management of fatigue. AB - Fatigue is a subjective state of overwhelming, sustained exhaustion and decreased capacity for physical and mental work that is not relieved by rest. Cancer related fatigue has many causes. Included in the causes are the illness itself, the side effects of virtually every treatment, depression, and other biopsychosocial factors. As a result, fatigue is the most common symptom reported by cancer patients in most descriptive studies. In addition to arising from multiple etiologies, fatigue is also multidimensional in its manifestation and impact. Its effect on the quality of life of the patient is comparable to that of pain. Experienced by most patients as an extremely frustrating state of chronic energy depletion, it leads to loss of productivity which can reduce self-esteem. As a subtle and chronic symptom, it also places people at risk for being questioned about the veracity of their complaints, particularly during the post treatment, disease-free survival period. Patients themselves are reluctant to complain of fatigue, perhaps because they believe little can be done about it, or they wish to avoid drawing attention away from treating their cancer. PMID- 10028521 TI - Incorporating new modalities into practice guidelines: platelet growth factors. AB - The outcomes of thrombocytopenia are clinically serious (hemorrhage), costly to prevent and treat (platelet transfusions and hospitalization), and may result in delay of the subsequent cycle of chemotherapy. Oprelvekin, the first commercially available platelet growth factor, has been shown to be safe and effective in reducing the need for platelet transfusions. In placebo-controlled trials of patients with solid tumors receiving dose-intensive chemotherapy, 68% of oprelvekin recipients escaped transfusion altogether, compared with only 41% of those who received a placebo. Side effects are generally mild, reversible, and related to fluid retention. Although clinical trials provide evidence about how many patients, on average, can be expected to benefit from agents such as oprelvekin, the trials provide little information about which patients in the general oncology population will benefit. Guidelines based on clinical trial data are limited by this approach. An alternative approach is to develop a clinical profile or model of patients at high risk of developing serious clinical outcomes and target platelet growth factors to these patients through the use of guidelines. Other important components of the guideline development process include a thorough evaluation of the costs of treatments and side effects as well as a careful evaluation of patient's preferences for alternative treatment strategies. Guidelines limiting growth factor use to only those patients who are most likely to benefit provide an opportunity to use expensive new agents in a cost-effective, evidence-based fashion. PMID- 10028522 TI - Roundtable discussion: Incorporating bone marrow transplantation into NCCN guidelines. AB - A newly formed National Comprehensive Cancer Network (NCCN) panel on bone marrow transplantation has the task of ensuring the incorporation of allogeneic and autologous transplantation into all disease guidelines where significant evidence exists to warrant their inclusion. The panel is further charged with ensuring that there is consistency among guidelines regarding the use of marrow transplantation. A preliminary review of existing NCCN guidelines found that marrow transplantation was appropriately included for the treatment of the common hematologic malignancies of adults, including acute myeloid leukemia, chronic myeloid leukemia, myelodysplasia, multiple myeloma, Hodgkin's disease, and the malignant lymphomas. Frequent refinements regarding lymphomas will be necessary, particularly in rapidly evolving areas, such as multiple myeloma and myelodysplasia, and conditions with changing definitions, such as malignant disease. The increasing volume of data supporting the use of autologous bone marrow transplantation in advanced primary and responding metastatic breast cancers needs to be reflected in the breast cancer guideline if it is to remain credible. Well-designed and well-conducted clinical trials are the most appropriate setting for all bone marrow transplantations and patient referral to these trials remains the standard of care in all settings. PMID- 10028523 TI - NCCN practice guidelines for kidney cancer. National Comprehensive Cancer Network. PMID- 10028524 TI - NCCN practice guidelines for testicular cancer. National Comprehensive Cancer Network. PMID- 10028525 TI - Adonia variegata (Coleoptera: Coccinellidae) bears maternally inherited flavobacteria that kill males only. AB - Inherited bacteria that parasitically distort the pattern of sex allocation of their host, biasing allocation towards female progeny, are found in many arthropods. One such manipulation is male-killing, where male progeny of infected females die during embryogenesis. We here provide evidence for a male-killing bacterium in the coccinellid beetle, Adonia variegata. We then address 3 questions. First, is this male-killing bacterium one that is found in other hosts, or does it represent a new transition to male-killing within the eubacteria? Using the sequence of the 16S rDNA of the bacterium, we found that the male-killing bacterium is a member of the Flavobacteria--Bacteroides group, most closely related to the male-killing bacterium in another ladybird beetle, Coleomegilla maculata. Secondly, is there any evidence that this bacterium affects female host physiology? In a paired test under nutritional stress, we found no evidence for a physiological benefit to infection, and weak evidence of a physiological cost, in terms of reduced fecundity. Thirdly, is there any evidence of host involvement in the transmission of the bacterium to the germ line? We found no evidence of host involvement. Rather, bacteria migrated to the ovariole independently of host cells. We conclude that the bacterium is a parasite, and discuss how 2 different species of ladybird come to be infected with 1 lineage of bacterium, and why case studies of male-killing bacteria have generally found little evidence of any symbiont contribution to host physiological functioning. PMID- 10028526 TI - The development of murine cerebral malaria does not require nitric oxide production. AB - Nitric oxide (NO) production has been suggested to be required for the development of cerebral malaria. However, the importance of this molecule for the appearance of this pathology is debated. To assess whether murine cerebral malaria is NO dependent, we investigated the course of blood-stage Plasmodium berghei ANKA (PbA) infections in inducible nitric oxide synthase (iNOS)-deficient mice. Parasitaemia, haematological alterations, survival and development of cerebral malaria were not affected by the lack of iNOS. To exclude a role of NO produced by other NOS, controls included NO suppression by oral administration of aminoguanidine (AG), a NOS inhibitor. As in iNOS-deficient mice, no difference in the parasitaemia course, survival and haematological values was observed after AG treatment. Our results indicate that NO production is not a crucial factor for the development of murine cerebral malaria. PMID- 10028527 TI - Parasite killing in murine malaria does not require nitric oxide production. AB - Nitric oxide (NO) production has been suggested to play a role as effector molecule in the control of the malarial infections. However, the roles of this molecule are debated. To assess whether blood-stage parasite killing is NO dependent, we investigated the course of blood-stage Plasmodium chabaudi chabaudi (Pcc) infections in inducible nictric oxide synthase (iNOS)-deficient mice. Parasitaemia, haematological alterations, and survival were not affected by the lack of iNOS. To exclude a role of NO produced by other NOS, controls included NO suppression by oral administration of aminoguanidine (AG), a NOS inhibitor. As in iNOS-deficient mice, no difference in the parasitaemia course, survival and haematological values was observed after AG treatment. Our results indicate that NO production is not required for protection against malaria in our murine experimental model. However, C57BL/6 mice treated with AG lost their resistance to Pcc infections, suggesting that the requirement for NO production for parasite killing in murine blood-stage malaria might be strain dependent. PMID- 10028528 TI - In vitro sensitivity of artemeter in Plasmodium falciparum-infected beta thalassaemic trait erythrocytes. AB - Using an age-fractionated RBC model, we investigated the in vitro sensitivity of artemether in beta-thalassaemic RBC infected with the K1 and FC27 strains of Plasmodium falciparum and, to study the role of oxidant stress in modulating the sensitivity pattern, pro-oxidant (riboflavin) and antioxidant (vitamin E) agents were added to cultures in the presence of artemether. With the FC27 strain, the artemether IC50 doses in thalassaemic samples (whole blood and fractions) were significantly higher compared to equivalent normal RBC samples (P < 0.05). However, with the K1 strain, such a significant difference was not demonstrable. The addition of vitamin E reduced the antimalarial effect of artemether in both the FC27 and K1 strains (P < 0.0001). In contrast, the addition of riboflavin resulted in a significant increase in antimalarial activity (P < 0.0001). This effect of the drug combinations was not influenced by the red cell type (P < 0.0001) and there was no interaction between red cell type and drug type (P < 0.0001). These findings show that reduced sensitivity to artemether occurs in whole blood and age-fractionated beta-thalassaemic trait RBC. It appears that the RBC redox status does not influence the sensitivity to artemether. PMID- 10028529 TI - In vitro encystation and excystation of Blastocystis ratti. AB - Cysts of Blastocystis ratti were produced in vitro by culturing the parasite in Iscove's modified Dulbecco's medium (IMDM) with increasing concentrations of horse serum. Yields up to 3 x 10(6) cysts/ml of culture medium were obtained after 72 h. Encystation efficiency was time, strain and inoculum size dependent. A viability of > 70% was determined by flow cytometry employing fluorescein diacetate and propidium iodide staining. The presence of chitin as a cyst wall component was demonstrated by Calcofluor White M2R staining with which cystic stages showed blue fluorescence. The changes in morphology during excystation were examined by transmission electron microscopy. The cyst enlarged in size and some vacuoles appeared within the condensed cytoplasm. The vacuoles were full of inclusions and small glycogen aggregates. Coalescence of the vacuoles led to central body formation. Glycogen deposits were prominent throughout the excystation process. Some cysts divided by binary fission before the completion of the excystation. PMID- 10028530 TI - The complexity of the sylvatic cycle of Trypanosoma cruzi in Rio de Janeiro state (Brazil) revealed by the non-transcribed spacer of the mini-exon gene. AB - American trypanosamiasis occurs in nature as a sylvatic cycle, where Trypanosoma cruzi interacts with wild triatomines and mammalian reservoirs, such as marsupials, rodents, armadillos and other animals. Due to difficulties in trying to isolate T. cruzi stocks from the sylvatic cycle, very few studies have been performed in order to understand the parasite infection in natural environments. Traditionally T. cruzi has been considered to be composed of a highly heterogeneous population of parasites. In contrast, the mini-exon and the 24S alpha rRNA gene loci have shown that T. cruzi stocks can be clustered in 2 major phylogenetic groups: lineage 1 and lineage 2. In this report, 68 recently isolated T. cruzi samples from the sylvatic cycle belonging to different geographical areas in Rio de Janeiro, Brazil, have been typed based on a variable spot in the non-transcribed spacer of the mini-exon gene. Eight isolates were from triatomines, 26 stocks were from golden-lion tamarins, 31 from opossums, 2 from rodents and 1 from a three-toed sloth. Thirty (44%-30/68) isolates were typed as lineage 1, while 36 (53%-36/68) isolates were typed as lineage 2. Two opossums presented mixed infection. Therefore, 3% (2/68) of the isolates were typed as lineage 1 + lineage 2. Using these geographical regions as models of sylvatic environments, it was observed that 96% of the Didelphis marsupialis were infected by lineage 2 isolates, while all 26 golden-lion tamarins were infected by lineage 1. The results show preferential association of the 2 lineages of T. cruzi with different hosts, composing the complexity of the sylvatic cycle. PMID- 10028531 TI - Trypanosoma cruzi does not induce apoptosis in murine fibroblasts. AB - The intracellular cycle of Trypanosoma cruzi in mammalian host cells involves the differentiation of dividing amastigote forms into flagellated trypomastigote forms. The mechanism(s) regulating the growth and differentiation of the intracellular parasites is (are) not known. The number of parasites in infected cells can be several hundred and may be enough to induce apoptosis, a suicide like death programme, generating products (e.g. nuclear proteins) that could function as signals to initiate the differentiation of amastigotes into trypomastigotes. Murine fibroblasts infected with T. cruzi were examined during a 5-day course of infection for evidence of apoptosis. However, characteristics of apoptosis, including degeneration of nuclear structure, condensation of chromatin, loss of plasma membrane integrity, or the cleavage of DNA into nucleosomal fragments, were not observed. Therefore, it is unlikely that products resulting from host cell apoptosis function to induce parasite differentiation. The possibility that T. cruzi might inhibit host cell apoptosis by increasing intracellular levels of Bcl-2, an endogenous inhibitor of apoptosis, was then investigated. Analysis of infected cells by flow cytometry did not demonstrate a significant amount of intracellular Bcl-2. This suggests that if the parasite is inhibiting host cell apoptosis, it is by a method that does not involve increasing levels of Bcl-2. PMID- 10028532 TI - Incidence from coincidence: patterns of tick infestations on rodents facilitate transmission of tick-borne encephalitis virus. AB - Tick-borne encephalitis (TBE) virus has a highly focal distribution through Eurasia. Endemic cycles appear to depend on the transmission of non-systemic infections between ticks co-feeding on the same rodent hosts. The particular features of seasonal dynamics and infestation patterns of larval and nymphal Ixodes ricinus, but not Dermacentor reticulatus, from 4 regions within TBE foci in Slovakia, are such as to promote TBE virus transmission. The distributions of larvae and nymphs on their principal rodent hosts are highly aggregated and, rather than being independent, the distributions of each stage are coincident so that the same ca. 20% of hosts feed about three-quarters of both larvae and nymphs. This results in twice the number of infectible larvae feeding alongside potentially infected nymphs compared with the null hypothesis of independent distributions. Overall, co-feeding transmission under these circumstances brings the reproductive number (R0) for TBE virus to a level that accounts quantitatively for maintained endemic cycles. Essential for coincident aggregated distributions of larvae and nymphs is their synchronous seasonal activity. Preliminary comparisons support the prediction of a greater degree of coincident seasonality within recorded TBE foci than outside. This identifies the particular climatic factors that permit such patterns of tick seasonal dynamics as the primary predictors for the focal distribution of TBE. PMID- 10028533 TI - Biomphalaria glabrata embryonic (Bge) cell line supports in vitro miracidial transformation and early larval development of the deer liver fluke, Fascioloides magna. AB - A Bge cell co-culture system, previously shown to support the in vitro production of daughter sporocysts from mother sporocysts of Schistosoma mansoni and S. japonicum, has proven capable of supporting the in vitro development of intramolluscan stages of the deer liver fluke, Fascioloides magna. Miracidia commenced transforming within 4 h of incubation with Bge cells, and had completely shed their epidermal plates within 18-24 h. Redial stages were visible inside in vitro-transformed mother sporocysts after 12-16 days of co-culture with Bge cells, and emerged as fully-developed larvae starting at 14-20 days post cultivation. Rediae survived over 60 days of in vitro culture, and reached a maximum size of 150-170 microns. Although particulate material was visible in their cecae, rediae were not observed to actively feed on Bge cells. Bge cells did not attach to or encapsulate larval stages at any time throughout the incubation period. Unlike Schistosoma spp., in which a high percentage of miracidia spontaneously shed their ciliated epidermal plates and transformed into mother sporocysts in Chernin's balanced saline solution (CBSS), transformation of F. magna was dependent on Bge cell products. Less than 5% of F. magna miracidia transformed spontaneously in either CBSS or Bge medium with 10% fetal bovine serum (complete or C-Bge). However, incubation of miracidia in either Bge cell conditioned C-Bge medium or a greater than 30 kDa fraction concentrated from conditioned CBSS increased transformation rates to 67 and 83%, respectively. This secretory Bge cell factor(s) appeared to be protein in nature since its activity was completely abrogated by heat or proteinase K treatments. Overall, these results demonstrate that Bge cells are required for stimulating in vitro miracidial transformation and supporting early larval development of a fasciolid trematode under culture conditions. This is the first report of in vitro development of rediae from miracidia for a digenetic trematode. PMID- 10028534 TI - Chemoprophylaxis of Onchocerca infections: in a controlled, prospective study ivermectin prevents calves becoming infected with O. ochengi. AB - Onchocerciasis ('River Blindness'), caused by the filarial nematode Onchocerca volvulus is of major public health importance in West Africa. Ivermectin, a drug originally developed for veterinary use, is now being incorporated in control strategies but whilst it has potent efficacy against L1 larvae (microfilariae), ivermectin is not lethal to adult (L5) O. volvulus, nor to adults of the related cattle parasite O. ochengi. We have exploited this model to determine if ivermectin has prophylactic activity against naturally transmitted, O. ochengi infections in a controlled, prospective study in northern Cameroon. Calves were treated monthly with ivermectin at either 200 micrograms/kg or 500 micrograms/kg for 21 months. None of 15 treated calves developed adult worm infection, whereas 5/6 untreated controls became infected (P < 0.001) with a total of 54 O. ochengi nodules, and all 5 developed patent microfilaridermia. These results have significant implications for the use of ivermectin in humans, and suggest that strategic chemotherapy at times of maximal transmission will confer prophylactic as well as therapeutic benefits. PMID- 10028535 TI - Influence of parasitization by Trichinella spiralis on the levels of heat shock proteins in rat liver and muscle. AB - To examine levels of heat shock proteins (HSPs) in host responses to helminth infection, rats were infected with Trichinella spiralis. The kinetics of HSP25, HSP60, HSP70 and HSP90 production in the liver and muscle of infected rats was compared with that of non-infected controls. HSPs were detected using electrophoretic analysis of fixed amounts of proteins (0.02 mg) and then blotting and incubation of membranes with polyclonal anti-HSP25 antibody, or monoclonal antibody against HSP60, or HSP70 or HSP90. Quantitation of blotted separated polypeptides reactive with the specific anti-HSP antibodies was achieved using an image analyser. Enhancement of HSP25 production was observed in the liver of infected rats, whereas muscle from the same rats exhibited enhanced production of HSP25 and HSP60 one day after infection only. These data indicate that HSPs levels can be used successfully to measure stress injury brought about by helminth infection in organs and tissues of the host. PMID- 10028536 TI - Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) for the identification of Trichinella isolates. AB - In the present study, polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis was developed to identify 5 species (Trichinella spiralis, Trichinella britovi, Trichinella nativa, Trichinella nelsoni and Trichinella pseudospiralis) and 3 phenotypes of uncertain taxonomic status (Trichinella T5, T6, and T8). Eleven restriction endonucleases were used to restrict 3 DNA fragments (1) a 2800 bp fragment of the 43 kDa excretory-secretory (E-S) protein gene, (2) a 1250 bp fragment amplified with the primer pair SB147A and (3) a 372 bp fragment amplified with the primer pair SB372A. This RFLP method allows the identification of the 8 Trichinella phenotypes as follows: T. spiralis by the HinfI or DdeI endonuclease restriction of the 2800 bp fragment; T. nativa by the RsaI restriction of the 2800 bp fragment, or by the AluI restriction of the 1250 bp fragment; T. britovi and Trichinella T8 by the AluI restriction of the 1250 bp fragments, and can be discriminated between them by the SspI restriction of the 2800 bp fragment; T. pseudospiralis by the MspI restriction of the 372 bp fragment; T. nelsoni by the HhaI or AluI restriction of the 2800 bp fragment; Trichinella T5 by the HhaI restriction of the 2800 bp fragment; Trichinella T6 by the AluI restriction of the 1250 bp fragment; and Trichinella T8 by the SspI or RsaI restriction of the 2800 bp fragment. This study reveals also an intraspecifies polymorphism in the 2800 bp and 1250 bp fragments for T. britovi, Trichinella T5 and T6. PMID- 10028537 TI - Clinical profile of 128 subjects operated for primary hyperparathyroidism. AB - From 1960 to 1990, one hundred twenty eight (128) subjects with primary hyperparathyroidism were operated in the University Hospital. The medical records were reviewed. Serum and urine chemistries were done by conventional methods, serum PTH was done by RIA's (N-, C-, and midregion) and intact by IRMA and 1,25 dihydroxycholecalciferol by a non equilibrium receptor assay from calf thymus and preceded by double Sep-Pak chromatography. The distal third of the radius (nondominant arm) was used to evaluate radial bone density (RBD), using single photon absorptiometry (Norland) and the lumbar bone density (LBD) was measured by dual energy X Ray absorptiometry (DEXA). The RBD was done in 41 females and 15 males and the LBD in 12 females and 4 males. The series comprised 95 females, age range from 15 to 79 years, and 33 males, age range from 14 to 69 years. Prominent clinical features included nephrolithiasis in 72 subjects (56%), osteitis fibrosa cystica in 2, isolated familial hyperparathyroidism in 4 subjects in one family, 7 subjects with MEN-1 in 3 families, and 4 subjects with MEN-2 in one family. Only 7 subjects were asymptomatic. Serum calcium was elevated in all, serum alkaline phosphatase was elevated in 24% and urinary hydroxiproline was increased in 48%. Serum phosphorus was low in 92%. PTH assay was either elevated or inappropriately normal for the serum calcium in all patients tested. Serum 1,25 D was elevated in 57%. The PTH level was positively correlated with the serum calcium (r = 0.70), but had no significant correlation with the serum phosphorus and the 1,25 D. The RBD expressed as the standard deviation from that of the mean for age and sex matched controls was > or = 2 SD below the mean in 39% of females and in 40% of males. In contrast to the RBD none of the subjects tested had a LBD > or = 2 SD below the age and sex adjusted mean. 103 subjects had adenomas, 20 primary hyperplasia, 2 carcinomas and in 3 surgical exploration was unsuccessful. As to the outcome of Surgery, 117 (93%) were cured. Thus, in this series, successful surgery for primary hyperparathyroidism is the rule. Primary hyperparathroidism is rarely asymptomatic and appendicular bone disease and nephrolithiasis are commonly seen. PMID- 10028538 TI - Congenital diaphragmatic hernia: mortality determinants in a Hispanic population. AB - OBJECTIVES: Determine which factors were associated with mortality in our patients, specifically whether ventilatory parameters and arterial blood gas could be used to predict outcome. The role of delaying surgery and the presence of contra lateral pneumothorax were also assessed. BACKGROUND: Mortality among babies born with congenital diaphragmatic hernia remains high. The associated pulmonary hypoplasia and hypertension account for most of the overall mortality. There is no uniform consensus as to which parameters predict outcome. METHOD: Study population consisted of thirty-two patients with CDH managed during a ten year period. Retrospective data obtained included: perinatal data, postnatal complications, ventilatory parameter data, arterial blood gas, type and age of surgery. Ventilatory index, oxygenation index and arterial to alveolar oxygen difference (A-aDO2) within the first 24 hours of life and after surgical correction were compared among the 23 patients who underwent surgical correction. Timing of surgery and frequency of pneumothorax were compared between survivors and non-survivors. Epi-Info Software Package was used for statistic analysis. RESULTS: Overall survival was 40%. Survival of surgically corrected infants was 61%. Non-survivors had significantly higher A-aDO2 than survivors (p < 0.05). No significant differences in pCO2, ventilatory index, or oxygenation index were identified between survivors and non survivors. Surgical repair performed after the first twenty-four hours of life, was associated with a higher survival rate (p < 0.05). Fourteen patients (39%) developed contralateral pneumothorax, eleven (79%) of these died. CONCLUSIONS: (1) contralateral pneumothorax was associated with higher mortality, 2) A-aDO2 was a better prognostic indicator than pCO2, ventilatory index, or oxygenation index, 3) delaying surgical repair was associated with better survival rate. PMID- 10028539 TI - Flow cytometry analysis of cell cycle in myosin II-deficient yeast. AB - OBJECTIVE: To determine whether cell cycle changes can be detected in myosin II deficient cells using flow cytometry techniques. BACKGROUND: Although the primary role of myosin II (Myo1p) in the yeast Saccharomyces cerevisiae is in cytokinesis we have reported that this conventional myosin also appears to influence the regulation of cell wall metabolism as indicated by increases in the expression of chitin metabolizing enzymes in a null mutant of the MYO1 gene. The expression of these enzymes is known to be regulated in the cell cycle suggesting that cell cycle changes may alter their expression. METHODS: Flow cytometry was employed to assess the nuclear DNA content of logarithmic yeast cell cultures as a means of determining changes in the cell cycle of Myo1p-deficient cells. RESULTS: Significant changes were observed in the Myo1p-deficient strain suggesting that these cells are arrested in G2/M-phase of the cell cycle. CONCLUSIONS: Based on the results of this preliminary study, we propose a model in which the increased activity of chitin metabolizing enzymes may be explained by a mitotic arrest in these cells. PMID- 10028540 TI - Angiogenesis: characterization of a cellular model. AB - Endothelial cell proliferation and differentiation into blood capillaries (i.e., angiogenesis) are essential for growth and development, wound healing, osetogenesis, etc. But abnormal angiogenesis during tumor progression could lead to serious consequences. Angiogenesis is a complex biochemical process, and is often difficult to study the molecular mechanism in vivo due to interference by multitude of factors. Here, I present a non-transformed capillary endothelial cell line as a model which has been extensively characterized morphologically and biochemically to study the fundamentals of the angiogenic process. Studies completed in our laboratory also evidenced that expression of Glc3Man9GlcNAc2-PP Dol is intricately connected with the balance between the cellular proliferation and apoptosis during angiogenesis. PMID- 10028541 TI - [Hydrogen peroxide in the aqueous humor: 1992-1997]. AB - Ideas prevailing in 1991 on hydrogen peroxide in the aqueous humor are outlined. They are critically examined under the light of our finding that the method used to establish aqueous humor levels of peroxide generates itself peroxide during the short time span of the analysis. This is due to the fact that the probe used, dichlorophenol indophenol (DCPIP), spontaneously auto-oxidizes in the presence of oxygen. It was concluded then that the level of hydrogen peroxide in the aqueous humor cannot be higher than about 0.3 microM, the detection limit of the DCPIP method. It was also concluded that the statement commonly made in the literature that aqueous humor hydrogen peroxide derives from the oxidation of ascorbate, an abundant component of that fluid, is based solely on the use of the DCPIP method, and so could easily be due to a methodological artifact. The same applies to the statement that the levels of hydrogen peroxide are very high in human senile cataracts. The surprising resistance to accept the results and conclusions of our 1992 publication is documented. Finally, the content is discussed of an oral presentation made at the 1997 ARVO Annual Meeting in which an important portion of our results and conclusions was confirmed, perhaps signaling a shift towards a wider acceptance of our findings. PMID- 10028542 TI - Abnormal immunological response to Mycobacterium tuberculosis antigens in a patient with chronic myelocytic leukemia and active tuberculosis. AB - The pathogenic mechanisms of immunosuppression leading to susceptibility of Mycobacterium tuberculosis (MT) infection in chronic myelocytic leukemia (CML) are not clear. To address this issue, we measured the proliferative response, variation of T cell subpopulations (CD4+, CD8+, TCR-V delta 2 and TCR-V beta 8 T cells) and the cytokine profile (IL-1 beta, IL-2, IL-4, IL-6, IL-10, TNF-alpha, IFN-gamma) after MT stimulation of peripheral blood mononuclear cells (PBMC) in a patient with concomitant CML and active pulmonary tuberculosis. The results were compared to four patients with active pulmonary tuberculosis and no other coexistent diseases. The immunologic response to phytohemagglutinin (PHA) was also evaluated. In contrast to controls, the CML PBMC failed to proliferate in response to MT antigens. Mycobacterium-reactive CD4+, V delta 2 and V beta 8 T cells did not expand after MT stimulation of the CML PBMC. In MT antigens stimulated cultures from the CML patient, IL-2 was not produced and mild reduction of IL-1 beta and INF-gamma were observed. In contrast, IL-10 was markedly elevated in these cultures. Similarly, PHA-stimulated PBMC from the CML patient showed no expansion of CD4+ and CD8+. T cells. In these cell cultures, INF-gamma concentration in supernatants was decreased and IL-10 was significantly elevated. This study suggests that patients with CML may present a profound immunosuppression of essential cellular and molecular immune effectors, a scenario which might contribute to the development of active tuberculosis. These findings further support the need of establishing immunotherapeutic modalities with potential value for myeloproliferative disorders. PMID- 10028543 TI - Early postoperative complications after coronary artery bypass grafting at the Cardiovascular Center of Puerto Rico and the Caribbean. AB - OBJECTIVES: This study describes the preoperative cardiovascular characteristics, intraoperative data, in-hospital complications and factors associated to procedural-related complications in patients undergoing coronary artery bypass grafting (CABG). BACKGROUND: There is a growing body of evidence of CABG safety and efficacy; however, limited data is available regarding the value of this surgical procedure in the Puerto Rican population. METHODS: We retrospectively reviewed the medical records of 200 consecutive patients submitted to CABG at the Cardiovascular Center of Puerto Rico and the Caribbean over a three-month period in 1997. Bivariate and multivariate analyses were performed to determine factors associated with the occurrence of complications. RESULTS: The most frequent cardiac risk factor was hypertension (77%); stable angina (60.5%) was the predominant cardiac clinical diagnosis. Three vessel disease with proximal left anterior descending coronary artery stenosis (42.1%) was the most common anatomical lesion. The rate of major complications such as death (3%), perioperative myocardial infarction (2%), reoperation to control bleeding (1.5%), pulmonary embolism (1%), and stroke (1%) was low and similar to the rate reported elsewhere. Multivariate analysis showed that non-use of LIMA graft, extended hospital stay, prolonged cardiopulmonary bypass time, and left ventricular dysfunction were significantly associated with the occurrence of complications (p < 0.05); on the other hand, there was a trend for older age to be associated with the occurrence of complications (p = 0.057). CONCLUSIONS: CABG is being performed with an acceptably low complication rate in this institution. PMID- 10028544 TI - Inhibition of xanthine oxidase by Puerto Rican plant extracts. AB - OBJECTIVES: This study was conducted to search for xanthine oxidase inhibitors in natural products obtained from plants collected in Puerto Rico and to assess the influence of these extracts in the prevention of cataractogenesis. BACKGROUND: Allopurinol is currently a xanthine oxidase inhibitor used in the treatment of gout. New alternatives with increased therapeutic activity and less side effects should be investigated. Preclusion of cataractogenesis in diabetic rats is also the focus of this investigation. Natural products in the form of plant extracts from Puerto Rico offer a rich and relatively untapped source for the discovery of new drugs that may address these kind of problems. METHODS: Nineteen collections of Myrtaceae plant extracts were screened for xanthine oxidase inhibition. A spectrophotometrical method was used employing allopurinol as positive control and a blank as negative control. A protocol of the assay with slight modifications was followed from the literature. Two extracts with the highest percentages of xanthine oxidase inhibition were evaluated for possible prevention of cataractogenesis in streptozotocin diabetic rats. The animals were given to drink these plant extracts ad libitum for three months while controls received water. The appearance of cataracts was assessed physically. RESULTS: Two of the nineteen plant extracts showed high inhibition percentages of xanthine oxidase. Eucalyptus deglupta and Syzygium malaccense displayed 51% and 64% inhibitions (IC50 44.5 micrograms/ml and IC50 51 micrograms/ml), respectively. As for the cataractogenesis inhibition, laboratory animals that drank E. deglupta for three months did not develop cataracts. CONCLUSIONS: Two plant extracts provided positive results with varying degrees of inhibition of xanthine oxidase. S. malaccense demonstrated the greatest xanthine oxidase inhibitory activity whereas E. deglupta presented the best finding for cataractogenesis prevention. The procedures used in this investigation are useful for the in vitro screening of xanthine oxidase inhibition and the in vivo evaluation of cataractogenesis prevention. PMID- 10028545 TI - Knowledge and beliefs of breast cancer among elderly Puerto Rican women: validation process of scales. AB - This paper presents the results of the validation process to determine the concepts for knowledge and beliefs about breast cancer early detection practices among Puerto Rican elderly women. An initial questionnaire was designed based on the scientific literature review and focus group experiences. To determine its reliability and validity, 50 elderly women, stratified by type of profession and place of residence, were interviewed twice. Consistency of the questionnaire was analyzed using binomial test, matched t-test, Pearson correlation coefficient, and Cronbach's coefficient effect. Factor analysis (FA) was the statistical technique used to analyze the grouping of the knowledge and beliefs statements. FA indicated that three scales for knowledge and one for beliefs can be constructed. The purpose of the scales was to identify differences among groups, according to breast cancer early detection practices. Construct validity was performed to determine the number of statistical associations between the scales and these practices. The results showed that beliefs scales was associated with practice of mammogram (p < 0.05), and visit to the gynecologist (p < 0.05) while the knowledge scale for early-detection was associated with the clinical breast examination (p < 0.05). The beliefs scale had better consistency than the knowledge scale. The Cronbach's alpha was 0.75 for the beliefs' scale and 0.30, 0.41 and 0.43 for each defined knowledge scale, respectively. PMID- 10028546 TI - Oral testimonies: the other face of the HIV story. AB - Women's needs are different from men's; the research and services related to HIV/AIDS have been focused in men's needs. The implication of this approach is that it has had very serious consequences for women who live with HIV/AIDS. It has resulted in health professionals failing to understand the emergence of the symptoms, the complications, the necessary treatments, and the complex patterns of progression of the disease. Oral testimonies are an alternative methodology for the development of theoretical and intervention models that incorporate issues pertaining to the life-styles and world-view of women with HIV and other socially alienated people. Through the testimonies of three women living with HIV the author discusses concepts such as social stigma, family, spirituality, and human solidarity and denounces the oppression, exclusion and dehumanization experiences that these brave women have experienced as a result of living with this condition. PMID- 10028547 TI - [Asbestosis]. PMID- 10028548 TI - [Mineralogical analysis and exploration of asbestos diseases]. AB - Several tools are available for the evaluation of the exposure to asbestos, particularly occupational questionnaire and mineralogical analysis of biological samples. These analysis allow quantification of the level of retention of asbestos fibres in the respiratory tract. Two groups of analysis may be used: quantification of asbestos bodies in sputum, bronchoalveolar lavage fluid or lung tissue samples using light microscopy; quantification and identification of asbestos fibres in bronchoalveolar lavage fluid or lung tissue using analytical electron microscopy. Profiles of lung retention of asbestos bodies or asbestos fibres have been described in various asbestos-related disorders, and reference values are available in control populations mainly for asbestos bodies using light microscopy. Mineralogical analysis of biological samples is not required for compensation of occupational asbestos-related diseases. However, this type of analysis may prove to be useful to the chest physician when looking for the etiology of some nonspecific respiratory diseases (interstitial pulmonary fibrosis, lung cancer), particularly when the occupational questionnaire is not contributive. As they are quite easier and less expensive, analysis using light microscopy will be performed first. PMID- 10028549 TI - [Assessment of exposure to asbestos]. AB - The aim of the study is to present the principles of assessing asbestos exposure in two different contexts: that of a patient suffering from pleuropulmonary pathology that could be attributed to asbestos and that of a group possibly exposed to asbestos. In the first case this evaluation concerns past exposure and depends typically on information obtained during the course of an interview with the patient. In the second case, the exposure is assessed by atmospheric analysis. Jobs in which occupational exposure to asbestos occurs should be examined, the tasks which entail this exposure and objects containing asbestos are discussed in the first part of the article. The accent is placed on the source of exposure, and the use of materials containing asbestos outside the asbestos industry. Some guidelines enabling the appreciation of the intensity of asbestos exposure as a function of the jobs involved and the objects handled are suggested. Regulations and the principle of quantifying asbestos in the atmosphere during direct exposure in the working environment on the one hand and during the course of passive exposure in the environment on the other are discussed in the second part of the article. PMID- 10028550 TI - [Nonmalignant asbestos-related diseases]. AB - Non malignant asbestos diseases are dominated numerically by pleural plaques. This form of circumscribed fibrosis of the parietal pleural is generally asymptomatic and its potential for evolution is weak. More rarely diffuse pleural fibrosis results from disease of the visceral pleura with a secondary fusion of the two pleural layers. Usually it follows a pleural effusion which resolves spontaneously. Its functional effects are sometimes important. The generalised practice of computerized tomographic scanning as a work up for asbestos related disease has revealed the frequent association of this diffuse pleural fibrosis with a particular form of peripheral pulmonary collapse called round atelectasis. Asbestosis or pulmonary fibrosis induced by the inhalation of asbestos has become rarer due to the improvement in working conditions in the asbestos industry. It develops following heavy exposure. The frequency of bronchopulmonary cancer is increased when asbestosis exists although it is not currently possible to say if the two disorders are independent and each is only conditioned by exposure to asbestos or if the two diseases are inextricably linked by the same physiopathological process. PMID- 10028551 TI - [Asbestos exposure and pleuropulmonary cancer]. AB - Pleuropulmonary cancers are recognized asbestos-related diseases. Mesothelioma occurs almost uniquely in individuals exposed to asbestos whereas lung cancer is strongly associated with smoking. If the asbestos exposure is sufficient however, the incidence of lung cancer is higher than would be expected from the smoking effect alone. For lung cancer in asbestos workers, asbestosis is not a prerequisite for recognition as an occupation related disease. The intensity and duration of exposure to asbestos are factors associated with higher risk of lung cancer. These factors can be estimated on the basis of the work history or, when necessary, by analyzing mineral dust from available lung tissues. PMID- 10028552 TI - [Asbestos-related occupational lung diseases. Role of the pneumology unit in screening and compensation]. AB - The application of new decrees concerning the protection of individuals against sanitary risks linked to the various possible expositions to asbestos dusts is leading to a growing involvement of pulmonologists in diagnosis procedures not only for active workers regularly examined via the occupational medicine healthcare system, but also for those who are no longer, the unemployed or retired previously exposed to asbestos fibres. The present chapter presents and comments the revised guidelines about the compensation procedures for occupational diseases, and provides useful recommendations for establishing the records leading to their medical assessment. It emphasises the importance of a close cooperation between pulmonologists and radiologists in order to avoid radiation overdosing, which could increase the risk of lung cancer, as much as possible. PMID- 10028553 TI - Noncitizens and the Supplemental Security Income program. AB - The Supplemental Security Income (SSI) program, established by the Social Security Amendments of 1972 (Public Law 92-603), was designed to provide cash assistance to needy aged, blind, and disabled citizens, and noncitizens lawfully admitted for permanent residence or permanently residing under color of law. Since then, this means-tested program has undergone many legislative changes that affect the eligibility status of noncitizens. This article, presented in three parts, discusses the legislative history of noncitizen eligibility, and details relevant laws enacted since the program's inception; provides current data on the trends and changes of the noncitizen population; and describes the larger population of foreign-born SSI recipients, of which the noncitizens are a part. Data on the number of SSI recipients born abroad but who had become citizens before applying for SSI payments were not previously available. Analytical data are from the Supplemental Security Record (SSR) matched to the Social Security Number Identification (Numident) file. PMID- 10028554 TI - Projecting immigrant earnings: the significance of country of origin. AB - This article asks whether information about immigrants beyond their age, education, and years since migration can be productively used to project their earnings. Although many factors could affect immigrant earnings, what is most useful for Social Security modelling purposes is relevant information that is readily available on a continuous basis. Country of origin is a good candidate, as it is regularly and readily available from several administrative and survey data sources. In this article, microdata samples from the 1960-90 censuses are used to examine the relationship between country of origin and the earnings of immigrants. By following cohorts of immigrants over 10-year intervals, we learn how country of origin affects the initial earnings of immigrants and how the relationship between country of origin and immigrant earnings changes as immigrants continue to live in the United States. The article also presents theoretical insights and empirical evidence about the underlying causes of the link between country of origin and immigrant earnings. PMID- 10028555 TI - [Ultrasonic diagnosis 1998. 22nd Three-country meeting of the Swiss, German and Austrian Societies for Ultrasound in Medicine. Zurich, 14-17 October 1998. Abstracts]. PMID- 10028556 TI - [Physiology of photopic and scotopic vision]. PMID- 10028557 TI - [Basilar artery insufficiency--a possible cause of sudden infant death?]. PMID- 10028558 TI - [Ultrasound ileus diagnosis]. AB - Bowel obstruction is an acute alarming situation with limited diagnostic conditions. Therapeutic decisions must be taken in time. Diagnostic differentiation between incomplete or complete bowel obstruction, intestinal obstruction and paralytic ileus is often uncertain and the underlying cause difficult to detect. Besides plain films in acute abdomen the ultrasound examination presents important additional informations: 1st Dilated intestinal loops and gas caps correlate with the characteristic x-ray finding, i.e. erected dilated intestinal loops with fluid levels. The location of the obstruction is defined in small bowel obstruction by differentiation between jejunum (with Kerckring folds) and ileum (without Kerckring folds). In large bowel obstruction the caecum is dilated and a collapse of the distal colon is detectable. 2nd Additional sonographical findings are: oedema of the intestinal walls, hyperpendulum peristalsis or absence of peristalsis, sedimentation of intestinal contents, pearlstring-like lined up gas bubbles under the ventral intestinal walls, and concomitant ascites. Duplex sonographical studies of the intestinal peristalsis may help to differentiate between mechanical obstruction and paralytic ileus. 3rd In bowel obstruction stenoses can be detected as a result of tumour, Crohn's disease diverticulitis, invagination, strangulated hernias or gall stone ileus. Intestinal adhesions cannot be found by ultrasound. Small and large bowel is dilated in paralytic ileus. Numerous causes like acute pancreatitis, ureteral colic, free gastrointestnal perforation and so on can be diagnosed. 4th In ileus of vascular disorder early diagnosis is high important, but inspite of colour flow imaging diagnostic possibilities are limited. 5th Sonographical diagnosis is of special interest when the x-ray plain films is "empty". The lack of massive fluid collection and meteorism allows an optimal ultrasound examination. In this early phase disorders of peristalsis and intestinal walls are reliably found, and it is easier to find the cause of bowel obstruction. In this way the definitive diagnosis can be arrived at earlier, because it still takes up to 6 hours to obtain the classical x-ray finding. There is a rule that the earlier ultrasound is done, the more findings one will get. PMID- 10028559 TI - [Basilar artery insufficiency--a possible cause of sudden infant death? Results of a Doppler ultrasound study of 39 children with apparent life-threatening events]. AB - AIM: Hypoperfusion of the brain stem in dependence on head and body position followed by central bradycardia and apnea may be an important cause of sudden infant death syndrome (SIDS). METHODS: 39 infants with a mean age of 10.6 +/- 10.2 weeks (6 days to 11 months) with apparent life threatening events (ALTE) were investigated by cranial Doppler sonography. Additionally 68 healthy infants aged 6 days to 5 months (m 3.7 +/- 4.1 weeks) were investigated. In all patients flow measurements were performed in one anterior cerebral artery (ACA), both internal carotid arteries (ICA), the basilar artery (BA), and both vertebral arteries (VA) in dependence on head (right/left/neutral) and body position (prone/supine). RESULTS: In healthy infants flow velocities within all intracranial arteries were independent of head and body position. In none of our infants with ALTE significant flow alterations in the ACA and both ICA in dependence on head and body position could be found. In 23 patients with ALTE no dependence of flow in the BA and both VA of head and body position could be shown. In 16 infants however pathologic flow profiles with low flow velocities could be found in the contralateral VA if the head was rotated to the other side. In 9 infants additionally pathologic flow profiles with a dramatic decrease of the flow velocities in the BA could be found. The reduction of the blood flow is caused by compression of the contralateral vertebral artery at the craniocervical junction. CONCLUSION: The reduction of blood flow in the VA and especially the BA may cause hypoperfusion of the brainstem followed by central bradycardia and apnea. Hypoperfusion of the brainstem in dependence on head and body position may be a significant cause of SIDS. By means of cerebral Dopplersonography infants at risk for SIDS may be detected. Body and head positions which should be avoided can be evaluated noninvasively. PMID- 10028560 TI - Sonography under Daylight Conditions. AB - PURPOSE: Gray scale image assessment in clinical ultrasound requires working in dim light or a dark room. Daylight conditions offer the advantage of shorter visual reaction time and enhanced visual perception. Look-up table manipulations could improve image brightness. MATERIALS AND METHODS: We investigated the possibility of brightness and contrast enhancement of coloured adaptive linear look-up tables (CALUT's) and their artifact resistance. Therefore under real-time conditions red/brown, green and blue CALUT's were calculated using the gray scale distribution (mean and standard deviation) of the actual image. The changes in contrast of several structural features (echo-poor and echogenic lesions, artifacts) were assessed by clinical investigators (n = 7). RESULTS: The CALUT's produced, independent of the original, images with constant brightness and contrast. Even under daylight conditions no artifacts appeared. Under scotopic conditions the red/brown CALUT's showed the best results compared to the unchanged image and the gray, green, and blue CALUT's. Hyper and hypoechoic differences with small contrast to the surrounding tissue are enhanced and can be detected more easily. CONCLUSION: Daylight sonography allows examination even in non-darkened rooms without loss of information. Eye adaptation to changing light conditions is no longer necessary; the offered image information is more suitable for the eye. PMID- 10028561 TI - [Ultrasound lymph node imaging in the abdomen and retroperitoneum of healthy probands]. AB - PURPOSE: Transabdominal ultrasonography is able to detect normal sized perihepatic lymph nodes. The role of transabdominal ultrasonography in detecting normal lymph nodes in other abdominal locations has not yet been examined. METHODS: 92 healthy volunteers (57 male, 35 female; age: 33 +/- 9 [19-66] years) were examined by transabdominal ultrasonography. The peripancreatic region, the location between the inferior vena cava and aorta, left paraaortal region, and the right mesenteric region next to the terminal ileum were studied with high resolution ultrasound. All transabdominal ultrasound examinations were performed with a 3.5 and 5 MHz probe using a special magnification mode without substantial loss of resolution (RES-mode, Acuson) and additionally by colour doppler imaging (Acuson XP). RESULTS: In 80/92 (87%) of the healthy subjects, all regions could be adequately visualized. In 72% of patients with adequate visualization, abdominal lymph nodes were detectable. Abdominal lymph nodes could be sonographically detected peripancreatically in 14/80 (18%), in the location between the inferior vena cava and aorta in 44/80 (55%), in the left paraaortal region in 32/80 (40%), and in the right mesenteric region next to the terminal ileum in 31/80 (39%) of the healthy subjects. CONCLUSION: High resolution ultrasonography is able to detect normal lymph nodes in different abdominal locations in 72% of healthy subjects. Sonographic detection of singular normal sized abdominal lymph nodes is not indicative of abdominal disease. PMID- 10028563 TI - [Quantitative sonography of peripheral arteriovenous malformations]. AB - Congenital vascular malformations occur in 1.5% of the general population. Depending on their localization and morphology, with dysfunction of local and central hemodynamics as well as tissue metabolism, congenital peripheral arteriovenous malformations (AVM) are of particular importance within the larger, heterogeneous group of diseases which comprise vascular malformations. AIM: The aim of this study was to evaluate our ability to quantity peripheral congenital AVM using sonographic, functional-hemodynamic, and morphological parameters. METHOD: Apart from obtaining a medical history and applying clinical and venous occlusion plethysmographic diagnostics, sonographic examinations of peripheral arteries and veins using cw-Doppler sonography and color-coded duplex sonography were performed on 8 patients with peripheral congenital AVM. For comparative purposes, the results of pre-intervention angiography examinations were also considered. RESULTS: For a sonographic quantification of AVM at the time of diagnosis, during assessments of diseases progress, and postinterventionally, both the resistance index of Pourcelot and measurement of the vascular blood flow velocities appeared to be particularly appropriate as functional-hemodynamic parameters. The sonomorphological parameters reflect the individual vascular pathology, which is determined by hemodynamic changes. CONCLUSION: Functional hemodynamic and sonomorphologic parameters allow a quantification of AVM. With knowledge of the clinical picture acquired at the time, they provide the basis for deciding upon a more extensive pre-interventional invasive radiological diagnosis. PMID- 10028562 TI - [100 MHz ultrasound of psoriasis vulgaris plaque]. AB - PURPOSE: 20 MHz sonography of inflammatory diseases has concentrated on the evaluation of the echo-poor area in the upper dermis. With regard to higher resolution, this study focuses on the alterations of the epidermis and upper dermis skin using 100 MHz sonography. METHOD: 70 fully developed psoriasis vulgaris plaques of 20 patients were examined using our 100 MHz ultrasound equipment after application of salicylic acid in petrolatum for 24 h. After informing the patient about the aims of the study, a small knife biopsy was taken from 11 plaques. RESULTS: All psoriasis plaques exhibited, in comparison with normal skin, a significant widening of the skin entry echo (p < 0.001). Focally, this echo-rich line broke up into two thinner lines. Correlating histology exhibited in these areas an orthohyperkeratosis and focal parakeratosis. The upper dermis showed an echo-poor, band-shaped area which corresponded histologically to an acanthosis, elongation of rete ridges, and widening of the stratum papillare. The mean grey level of the echo-poor area and of the dermis beneath was significantly lower (p < 0.001) than the normal adjacent dermis. The thickness of the echo-poor area correlated with the thickness of the sum of the acanthosis and the inflammatory infiltrate in the histological sections (r = 0.94). CONCLUSION: Using 100 MHz sonography changes of the skin entry echo and the upper dermis can be visualized and quantified. PMID- 10028565 TI - Date-based exports: MAFF's proposals on how the scheme will operate. PMID- 10028564 TI - [3D and color Doppler ultrasound evaluation of cystic space-occupying lesion near the head of the pancreas]. AB - AIM: Differential diagnosis of cystic lesions in the abdomen may be very difficult. We present the clinical manifestation and the diagnostic steps of a rare case of an aneurysm of the gastroduodenal artery mimicking a cystic lesion. We also discuss the imaging methods we used to verify the diagnosis such as colour Doppler sonography and 3D-sonography. METHOD AND PATIENT: A 42-year old woman with chronic pancreatitis was admitted to our hospital after an extended diagnostic program (sonography, computed tomography and laparoscopy) with the diagnosis of a pancreatic pseudocyst with vascular erosion. Using conventional sonography we found a cystic lesion of 5 x 5 cm diameter with parietal deposits between pancreas and coeliac trunk. After colour Doppler sonography we found an arterial jet in the cystic tumor; initially the source of the jet seemed to be the hepatic artery. We referred the patient to our department of radiology with the diagnosis of hepatic artery aneurysm. The aneurysm was confirmed by the angiography and was embolised with coils in the same session. However, the source of the aneurysm was not the hepatic, but the gastroduodenal artery. By postangiographical 3D-sonography we could clearly reconstruct the relation of the aneurysm to the gastroduodenal artery. CONCLUSION: Colour Doppler sonography should be the first imaging tool for clarifying cystic lesions in the abdomen. 3D sonography is a reliable and useful method to identify visceral vessels of the abdomen. Nowadays the "gold standard" angiography should preferably be used as a therapeutic procedure. PMID- 10028566 TI - FAWC's concerns about the implications of cloning. PMID- 10028567 TI - Male tortoiseshell cats in the United Kingdom. AB - A questionnaire concerning the coat colour and sex of cats being vaccinated or neutered was sent to 2585 veterinary practices; 393 (15.2 per cent) were returned and information was obtained about 9816 cats. Of 4598 males, 20 were recorded as tortoiseshell (0.43 per cent). The frequency of the orange gene was 19.7 per cent assuming that male tortoiseshell cats had two X chromosomes. The chromosome complement and/or gonadal histology of 14 male tortoiseshell cats is described. Cytogenetic analysis of 11 animals revealed six with a 38,XX/38,XY complement, two with 39,XXY, two with 38,XX, and one with a 38,XY complement. PMID- 10028568 TI - Results of non-selective adrenocorticolysis by o,p'-DDD in 129 dogs with pituitary-dependent hyperadrenocorticism. AB - One hundred and twenty-nine dogs with pituitary-dependent hyperadrenocorticism were treated according to a protocol aimed at the complete destruction of the adrenal cortices by the administration of o,p'-DDD (mitotane) at a daily dose of 50 to 75 mg/kg bodyweight for 25 days. On the third day, glucocorticoid and mineralocorticoid supplementation was begun for the induced adrenocortical insufficiency. The first followup examination after completion of the 25-day course and the subsequent twice-yearly follow-up examinations included physical examination and measurements of plasma concentrations of sodium and potassium to optimise substitution therapy. In 19 dogs the full course of 25 days treatment could not be completed. Of the 110 dogs which received the full course of treatment, the administration had to be stopped temporarily in 32 because of side effects, such as anorexia and vomiting. The actual dose of o,p'-DDD administered was not significantly different in the dogs with and without these side-effects. Clinical remission occurred in 111 dogs (86 per cent), of which 43 (39 per cent) had a relapse. The estimated one-year disease-free fraction was 77 per cent (95 per cent confidence interval [CI]: 67 to 85 per cent). The estimated one-year survival fraction was 80 per cent (95 per cent CI: 71 to 87 per cent), the two year survival was 69 per cent (95 per cent CI: 59 to 78 per cent), and the three year survival was 61 per cent (95 per cent CI: 49 to 71 per cent). The bodyweight and age of the dog, and vomiting occurring during the period of treatment, were positively correlated with the length of the disease-free period, whereas weakness during the treatment and resistance to dexamethasone suppression of the urinary corticoid/creatinine ratios at the start of the treatment were associated with a relatively short survival time. PMID- 10028569 TI - Subclinical laminitis in dairy cows: use of severity of hoof lesions to rank and evaluate herds. AB - Thirteen high-yielding Holstein herds in Ohio were ranked according to the prevalence and severity of lesions associated with subclinical laminitis (pododermatitis aseptica diffusa). One hundred and seventy-three first lactation cows, most of them in their first 100 days of lactation, and 30 pregnant heifers were assessed. The lesions evaluated were yellow waxy discoloration of the sole, haemorrhage of the sole, separation of the white line, and erosion of the heel. Each herd consisted of more than 100 lactating cows and all the herds were producing over 8500 kg of milk per cow on a rolling herd average basis. The lactating cows were housed in cubicles and maintained in concrete yards. The lesions associated with subclinical laminitis were prevalent among the 13 herds, but when each category of lesion was considered independently, significant differences in prevalence and severity were detected among the herds. These differences suggest that it may be possible to make changes in herd management which may influence the prevalence of lesions. PMID- 10028570 TI - Culture conditions required to induce capacitation and the acrosome reaction of canine sperm in vitro. PMID- 10028571 TI - Outbreak of columnaris disease in tropical aquarium fish. PMID- 10028572 TI - Aetiology of caprine contagious agalactia syndrome in Extremadura, Spain. PMID- 10028573 TI - Predation as a suspected cause of common toad (Bufo bufo) mortality incidents in Scotland. PMID- 10028574 TI - EU ban on four antibiotic feed additives. PMID- 10028575 TI - Illegal importation of medicines. PMID- 10028576 TI - Medicated feedingstuffs regulations 1998. PMID- 10028577 TI - Declining risk from beef on the bone. PMID- 10028578 TI - Streptococcal suppurative lymphadenitis in a cat. PMID- 10028579 TI - Importance of vaccination. PMID- 10028580 TI - Regulating the use of animals in research. PMID- 10028581 TI - Fluke and roundworm infestations could be 'major problems' this winter. PMID- 10028582 TI - Prevalence of disease in dogs purchased from an animal rescue shelter. AB - The prevalence of diseases suffered by dogs within two weeks of their acquisition from a rescue shelter in Northern Ireland was investigated. A postal questionnaire was completed by 556 people who had purchased a dog from the Ulster Society for the Prevention of Cruelty to Animals (USPCA) to provide information on the diseases suffered by their dog. The majority of the dogs (53.7 per cent) had an ailment the most common being coughing and diarrhoea. Of the respondents who returned their dog to the USPCA, 92 per cent did so because the animal was unhealthy. Stray dogs were more likely to have an ailment than unwanted dogs, specifically coughing, and/or skin problems. More puppies suffered from parvovirus, vomiting, and/or diarrhoea than did juveniles or adults. Adult dogs were more likely to have a cough than juveniles or puppies. There was no association between the sex of the dogs and their ailments. PMID- 10028583 TI - Spontaneous vaginal rupture in pregnant ewes. AB - Seventeen cases of spontaneous, partial or total vaginal rupture, in pregnant ewes, involving the dislocation and herniation of the intestines and uterus, were studied. Four of them also had a uterine torsion, and three of these recovered after treatment. In the remaining 13 cases the condition of the uterus was unknown. The lesion always consisted of a dorsolateral tear in the vagina with a partial or total perforation of the wall close to the uterine cervix. The affected animals were all in normal body condition. Their average age was just under five years, and most were carrying twins. Most cases occurred approximately one week before expected lambing. None of the cases was observed to have a vaginal prolapse before the vaginal rupture. Histological examination of one case revealed scar formation in the vaginal wall close to the rupture, which appeared to be due to an earlier inflammatory process or injury. The circulatory disturbance in the reproductive organs caused by the uterine torsion potentially weakens the vaginal wall. This weakness, in combination with excessive tenesmus resulting from increased tension in the uterine ligaments, and in some cases possibly with a lower vaginal resistance due to previous scarring, may be of aetiological significance in spontaneous vaginal rupture. PMID- 10028584 TI - Comparison of the effects of injections of nortestosterone phenylpropionate at single and multiple sites in cattle on the detection of its residues in plasma, urine and bile. AB - The synthetic androgen 17 beta-19-nortestosterone (beta-NT) has been used illegally as a growth promoter in cattle production in the European Union. The elimination of beta-NT and its metabolites in plasma and urine was studied in cattle which had received intramuscular injections of its phenylpropionate ester (NTPP) at either single or multiple sites at a dose rate of 1 mg/kg bodyweight. In both groups, the plasma concentrations of beta-NT, measured by enzyme immunoassay, were consistently greater than the assay's limit of quantification (0.24 ng/ml) during days 1 to 7 of the study. The mean (sd) maximum plasma concentration (Cmax) was significantly greater in the multiply injected animals (4.4 [0.48] v 2.7 [0.15] ng/ml), but other plasma pharmacokinetic parameters, AUC, CL, T1/2 beta, Tmax and MRT, were not significantly different in the two groups. The equivalent urinary concentrations exceeded the limit of quantification of the assay (4.5 ng/ml) for up to 24 days after injection. In a second study, the biliary concentrations of beta-NT and its 17 alpha-epimer (alpha-NT) were measured by gas chromatography-high resolution mass spectrometry after cattle were injected intramuscularly at either single or multiple sites with NTPP. Only alpha-NT was detected in bile for up to 62 days after injection at concentrations above the limit of quantification of the assay (0.7 ng/ml). It is concluded that in some animals, intramuscular injections of NTPP at several sites may decrease the period after injection during which free beta-NT and its metabolites are detectable in plasma and urine. After the injection of NTPP, alpha-NT was detected in bile for longer than it was detected in plasma or urine. PMID- 10028585 TI - Control of porcine proliferative enteropathy by oral administration of chlortetracycline. PMID- 10028586 TI - Seroprevalence of selected viral infections in a population of beluga whales (Delphinapterus leucas) in Canada. PMID- 10028587 TI - Calcinosis circumscripta in the salivary gland of a dog. PMID- 10028588 TI - Importation and use of medicines by farmers. PMID- 10028589 TI - Piglet tail necrosis. PMID- 10028590 TI - Updating the Veterinary Surgeons Act. PMID- 10028591 TI - Ovarian cyst in a maiden heifer. PMID- 10028592 TI - Verocytotoxin-producing Escherichia coli O157 in sheep milk. PMID- 10028593 TI - [Vaccinations and epidemiology]. AB - Diphtheria is an uncommon infectious disease in Germany. Since 1994, approximately 150,000 new cases with about 5,000 deaths have occurred in the new independent states of the former USSR. Corynebacterium diphtheriae can be imported to Germany since only 20 percent of the adult population is vaccinated against diphtheria. Compared to other European countries, Germany has one of the lowest immunization rates against measles, mumps and rubella. Despite this fact, young parents still place a high priority for immunisation of their children. One reason for failure to immunize is lack of knowledge about serious complications of vaccine-preventable diseases. Immunization rates for diphtheria and tetanus are also low among the elderly. For example, nearly 70 percent of 60- to 70 years olds are not protected against tetanus. A concerted action is necessary to improve immunization rates among adults. In particular, primary care practitioners have a special responsibility to ensure that in every patient encounter, the opportunity for booster immunization is not lost. PMID- 10028594 TI - [Immunization for adults in foreign travel]. AB - In 1997, 62.2 Mio. Germans traveled abroad according to the research society for holiday & travel--7.4 Mio. traveled outside of Europe. The journey of 26.3 Mio. Germans was associated with an increased risk related to their health. Therefore, the number of travelers is increasing who attend their family physician searching information about necessary vaccination and other options of prevention. Unfortunately, there is a lack of knowledge about health risks and their prevention when traveling abroad. The consulting physician therefore needs reliable sources of information to keep his knowledge up to date. Similar to any other medical speciality, only the continuously educated physician can offer travel medicine with high quality. PMID- 10028595 TI - [Viral hepatitis: preventable illnesses]. AB - The availability of vaccines had made on Hepatitis A as well as Hepatitis B an avoidable illnesses. However, there is a lack of knowledge referring to the epidemiological situation. This might be due to the physician's as well as the patient's underestimation of the risk of a new infection but also insufficient knowledge about indication, management of vaccination, adverse events and cost effectiveness might. Vaccination against Hepatitis A and B produce a longlasting immunisation which is indicated in every age. A combined vaccination for both infectious diseases are effective and support the compliance. The role of the family physician is decisive in the management of a sufficient vaccination strategy. PMID- 10028596 TI - [Vaccination and gene therapy with naked DNA]. AB - After injection into the organism, naked DNA causes a slight protein expression. A vaccination is possible, if the DNA encodes for viral or tumor antigens. The DNA proved to be a successful vaccine against virus as well as carcinoma in small animals and safe in humans. However, efficiency has to be increased in the latter. Therefore, combinations of different substances are currently under investigation. Naked DNA is also suitable for gene replacement or gene medicine. However, this is possible only if lowest amounts of proteins cause a biologic effect as done by cytokines, growth hormones etc. DNA is a cheap option for vaccination and treatment, it is easy to transport and therefore of interest for third world countries. PMID- 10028597 TI - [Managed care--a model also for ambulatory medical care in Germany?]. AB - Rising expenditure of health care has caused industrialized nations to change the structure of their health care systems. The goal is to achieve high quality of care at low cost. Managed care (MC)--most prevalent in the United States--plays an important role in the current discussion in Europe. This concept which provides different ways of financing and organization aims to improve the direction and control of health care delivery. Usually, a family physician takes the role of a gatekeeper by offering access to all parts of medical care. This kind of health care system seems to be associated with lower expenditure and a better state of health. Some negative developments in the USA--partly dissatisfaction of patients and physicians as well as refusal or delay of medical care--must not necessarily take place in other countries. With a critical approach to managed care, Germany may take the opportunity of adapting positive elements of MC to its health care system and avoid problems of the US system. Although the basis for testing MC-models has been created by the health care reform act in 1997, these opportunities have not been adequately taken up. PMID- 10028598 TI - [Current responsibilities of health care research and political counseling]. AB - Health systems research aims to contribute to the progressive development of medicine and health services. To bridge the gap between the two logics of scientific and the political administrative agency, politics consultancy may be applied. However, the chances of transferring scientific knowledge into rational politics vary widely. Major issues of health system research include outcome oriented health targets, outcome oriented reimbursement, health technology assessment, new forms of provision, patient information and ageing in regard to healthcare. Physicians are advised to keep in touch with these developments- although some of them are still in an embryonic stage--because they have the potential to deeply influence the physician's practice routines in the future. PMID- 10028599 TI - ["Therapy of Crohn disease" guideline. German Society of Digestive and Metabolic Diseases]. AB - During a consensus conference of the German Society for Digestive and Metabolic Diseases, seven working groups gathered in Halle (Saale) covering the topic "Therapy of Crohn's Disease". The goal of this conference was to establish standard recommendations for the conservative, dietary, surgical and psychosomatic treatment of intestinal and extraintestinal manifestations. These recommendations are based on the personal experience of the experts involved as well as the literature. In preparation of the conference, questionnaires were developed which were answered by all nearly 100 physicians specializing in internal medicine and gastroenterology. These were analysed by the chairmen of the working groups which wrote a consensus proposal in Halle. This was discussed, modified and passed by the plenary session and subsequently published in the Zeitschrift fur Gastroenterologie (German J Gastroenterology) with a comment and the relevant literature. The guideline became a standard in German gastroenterology. Unfortunately, only half of the recommendations are supported by controlled trials and other representatives of the health care system were not involved. Currently an update of this guideline is prepared via internet (www.prous.com/ts). PMID- 10028600 TI - [Systematic internal quality control in surgery 1993 to 1997]. AB - From April 1, 1993 to Dec. 31, 1997, the perioperative course of 5690 patients was recorded prospectively and postoperative morbidity and lethality was determined in the framework of a program for a systematic internal quality control. Goal of the program is the demonstration of treatment quality which possibly out quality improvement. The share of old and sicker patients was significantly increasing during the observation period. Morbidity and hospital lethality remained constant despite a rising necessity of postoperative intensive care. High risk surgery was performed on more patients in the university hospital than in non-university hospitals. The rate of postsurgical complications was lower, length of stay was equal (surgery for inguinal hernia) or lower (cholecystectomy). The rate of not indicated appendectomy could be lowered and morbidity and lethality in the treatment of esophagus carcinoma was lowered by the application of this concept. For the partial duodenopanceatectomy, the examination of the individual surgeon as a risk factor revealed a significant dependence on the experience of the surgeon. There was only a tendency of this effect demonstrable in medium or small surgery like colon resection of gastrectomy. The rate of continence preservation in rectal carcinoma was increased to 75% combined with a drop of perioperative morbidity and length of stay. The systematic internal quality control allows for the assessment of treatment quality and the fast recognition of weak spots. It is a suitable complementary tool for quality improvement in the framework of quality management in surgical patients. The extension of the concept by recording postoperative quality of life and long time results is planned. PMID- 10028601 TI - [Total quality management in laboratory medicine]. AB - The German Public Health will be continuously challenged in the future. It has to be assumed that modified managed care will not only take place sporadically. Thus, quality aspects of services gain more and more significance. Only suppliers will be successful who can offer services of highest quality at lowest prices. Quality in a comprehensive sense has to be substantiated in the near future. It is recommended to apply industry proven models also in public health service. Medical laboratories can be pioneers in this field as they have been already in the past. All previously proposed procedures can not describe quality of results comprehensively. They are based to a high degree on external control. Total quality management, however, represents a comprehensive approach. Principles are zero-defect approach, customer orientation and system management. Quality is given in the sense of TQM if the customer is permanently satisfied with the service of the supplier. In such a way, the customer defines quality of service. A customer is everyone who receives products or services. TQM overcomes the drawbacks of quality management systems, which are strongly formal and oriented by external control, as accreditation (EN 45,000) or certification (ISO 9000). Competition between hospitals is a declared goal of German health politics because usually quality is increased and cost decreased as a consequence. Competition means also comparison of services. TQM emphasizes benchmarking especially among the best suppliers. PMID- 10028602 TI - [Quality assurance of scientific information and databanks]. AB - The situation in cases of fraud and scientific misconduct--either true or false- is reviewed and its reflection in databases illustrated by examples. Exemplary quality guidelines for these cases have been published by the US National Library of Medicine, one of the major medical database producers. However, no timely and consequent application was found in some cases studied. On the whole, results in the major worldwide medical/life sciences databases are still dissatifactory. The implicite meaning of database quality (as illustrated by cases of fraud) for the decision making process, and its results for patients too--is broached and has to be discussed in the future. Some proposals for quality improvement are submitted. PMID- 10028603 TI - [Improved quality of preoperative care]. PMID- 10028604 TI - [Fetal pulse oximetry: from the first experimental studies of broad clinical use. An assessment of current status]. AB - Pulse oximetry has triggered a revolutionary change in monitoring patients in many branches of medicine. For 4 years fetal sensors with specially calibrated pulse oximeters are tested clinically. Additional examination methods are required for accurate monitoring the fetus intrapartum because of the low specificity of cardiotocographs and also to avoid unnecessary operative deliveries. Research on hand up to now has demonstrated that fetal pulse oximetry is a method easy to learn, easily applicable and well quanitifiable to improve fetal monitoring and the interpretation of the fetal heart rate patterns intrapartum. Prospective intervention studies involving management studies still have to prove the clinical value of this new technology. Only after examining a large number of hypoxic-risk fetuses we can assess whether pulse oximetry in a management can replace invasive fetal blood analysis as a continuous, non invasive method of monitoring. Various teams try to prove a context between arterial saturation values (SpO2) and biochemical changes of the fetus in connection with a crucial limiting value of 30% by correlating changes of the fetal scalp with the oxygen saturation. Guidelines for the assessment of the SpO2 values are established according to the present level of knowledge and future aspects of the method are examined. PMID- 10028605 TI - [Pulsations of the umbilical vein: pathophysiologic aspects and fetal outcome]. AB - Continuous forward flow to the fetal heart in the umbilical vein is a normal Doppler finding. Altered fetal hemodynamics can cause a pulsatile flow pattern in the umbilical vein. Pulsations in the umbilical vein were diagnosed in 14 pregnancies complicated by fetal hydrops, cardiac malformations, arrhythmia or severe intrauterine growth retardation. To document the fetal outcome, the results were analysed retrospectively. Compared with a normal Doppler group (N = 56), a significantly higher rate of perinatal death (Alpha < 1%), (64% vs 1.75%) was diagnosed, when pulsations in the umbilical vein were present. The Apgar score was significantly lower (4.5 vs 8.4) (p < 0.0002) in the group with pulsations in the umbilical vein. There was no significant difference of pH between the newborns of the two groups. Eight fetuses developed hydrops. Thirteen fetuses had increased reverse flow in the inferior vena cava. The vena cava of the acardiac fetus could not be identified. The knowledge of the poor outcome and the pathophysiologic relationships of fetal hemodynamics may be useful in clinical management. Therefore Doppler examination of the umbilical vein should be performed in high-risk pregnancies. PMID- 10028606 TI - [Acute fatty liver of pregnancy (AFLP) as a rare and severecomplication and differential diagnostic problem in the last trimester]. AB - In context of hepatic failures in pregnancy HELLP-Syndrome is defining more and more the reflections of differential diagnosis. Therefore, the inclusion of very rare complications like the AFLP with an estimated incidence of 1:13,000 becomes difficult. Since 1940 250 cases are documented in the literature. Clinical features, approaches of therapy and pathophysiological ideas of the AFLP are also proofed as her role in the spectrum of liver-involved diseases of pregnancy. PMID- 10028607 TI - [Initial results of the Erfurt Prevention of Prematurity Campaign]. AB - OBJECTIVES: Genital infection particularly bacterial vaginosis (BV) increases the relative risk of prematurity. Detection of disturbances of vaginal milieu at an early stage and the use of suitable countermeasures such as intervention with antimicrobial substances, e.g. clindamycin, can reduce the preterm birth rate, provided the diagnosis is made early enough. STUDY DESIGN: Since October 1996 pregnant women being given prenatal care in 16 of the 29 outpatient offices in Erfurt, have been informed about the Prematurity Prevention Programme and have been offered to take part and to perform self-measurements of their vaginal pH twice a week in order to screen for any disturbances in the vaginal milieu. Special CarePlan-VpH gloves (Selfcare, Oberhaching) were used to identify patients a risk (pH > 4.7). The pregnant women taking part in the programme were instructed to see their physician immediately, if abnormal values were present, in order to get them confirmed and to start lactobacillus acidophilus therapy (Gynoflor, Nourypharma, Oberschleissheim) or, in case of BV, to treat with clindamycin cream (Sobelin, Upjohn, Erlangen) i.vag. Patients being given prenatal care in the 13 outpatient offices not participating and other pregnant women in Erfurt who were not interested in the programme served as control group. RESULTS: Up to now 59 out of 314 women in the intervention group have been identified as risk cases (p > or = 4.7). 52 of them were treated with a lactobacillus preparation, and 19 additionally with clindamycin cream, 3 patients refused to have any therapy. In this ongoing study the prematurity rate was 8.3% in the self-measurement/intervention group vs. 13.0% in the control group (n = 1,842); 0.3% vs. 3.3% of the neonates belonged to the group of very early prematures with a gestational age of < 32 + 0 weeks (p < 0.01). PROM was registered in 22.3% vs. 32.1% (p < 0.001) respectively. CONCLUSION: Self measurement of vaginal pH at close intervals, as recommended by Saling, leads to the early identification of women at risk for prematurity. Earliest possible intervention by the obstetrician appears to result in reducing the rate of prematures and in particular of very early prematures (< 32 + 0 weeks). PMID- 10028608 TI - [Discordant growth of multiple fetuses in combination of HELLP syndrome and single umbilical artery in a triplet fetus]. AB - We present a case of a triplet with HELLP-Syndromin the 31st gestation week. In ultrasound one of the fetuses was to small for gestational age and one of them showed an zero-flow in Doppler ultrasound. We decided to deliver by Caesarean section in the 31st gestation week. Growth-retardiation was found in two infants. One of them had a single umbilical artery in addition. PMID- 10028609 TI - [Vulvar lesion in urogenital schistosomiasis (S. haematobium)]. AB - Genital schistosomiasis must be considered in women from endemic areas presenting with the following signs and symptoms: Vulvar papules, swelling or tumour irregular vaginal bleeding infertility, ectopic pregnancy Urinary tract schistosomiasis can affect the lower and upper female genital tract. PMID- 10028610 TI - [Bilateral renal agenesis in insulin-dependent maternal diabetes mellitus (IDDM)- a case report]. AB - We report a fetal bilateral renal agenesis in a woman suffering from insulin dependent diabetes mellitus. Early diagnosis of this lethal congenital anomaly allows well-timed termination of pregnancy. Transvaginal sonography in combination with color flow mapping render possible an accurate diagnosis of bilateral renal agenesis. Sonographic and color flow mapping features of the above described malformation as well as invasive diagnostic possibilities and causes of renal agenesis in maternal IDDM are discussed. PMID- 10028611 TI - [Premature delivery in borderline viability of the infant. A recommendations of the German Society of Gynecology and Obstetrics, the German Society of Pediatrics and Adolescent Medicine, the German Society of Perinatal Medicine and the Society of Neonatology and Pediatric Intensive Care Medicine]. PMID- 10028612 TI - Uptake of chloroform by skin on brief exposures to the neat liquid. AB - The uptake of chloroform into hairless rat's stratum corneum after application of the neat solvent directly to the skin has been studied. Tape stripping was used to determine amounts deposited within the stratum corneum and also the clearance of the compound from the skin following varied levels of exposure. Three minutes exposure to neat chloroform was adequate to achieve a limiting accumulation in the stratum corneum and thus it appears to take this long for the gradient of chloroform to be established fully across this structure. There was indication of progressively deeper penetration of chloroform as the exposure time was increased from 1 to 8 minutes. Local irritation and a loosening of the superficial layers of stratum corneum were apparent with as little as 2 minutes of exposure to the solvent and were exacerbated with further increases in exposure duration. Following exposure, clearance of the solvent from the skin surface was rapid. Interestingly, the rate of clearance, as followed by stripping, was comparable on live and freshly euthanized rats. This implies that once the exposure is terminated evaporation from the surface, and not systemic uptake by way of the local vasculature, is the predominant means of clearance at an open surface. PMID- 10028613 TI - Within-shift variability of short-term exposure to organic solvent in indoor workplaces. AB - This study examined the degree of within-shift variability of short-term exposure concentrations for workers exposed to organic solvents in indoor workplaces. For this purpose, 117 exposure data sets of 15-minute time-weighted average (15-min TWA) and those of 60-min TWA were collected from 53 workers employed in the offset printing, gravure printing, screen printing, machine control board production, fiber-reinforced plastic production, hard metal production, electrical parts production, and chemical synthesizing industries. Data analysis showed that the tenth, fiftieth, and ninetieth percentiles of the geometric standard deviations of 15-min TWA values [GSD(15m)] were 1.4, 2.3, and 4.5, respectively; and those of GSD(60m) were 1.2, 1.7, and 3.4, respectively. Based on an assumption of lognormal exposure distribution, the maximum values of 15-min TWA (the 98.4th percentile) were estimated to be 4.3, 36, and 650 times as high as the minimum one (the 1.6th percentile) for the low, middle, and high exposure variabilities, respectively; and to be 2.0, 4.3, and 8.2 times the 8-hour TWA value, respectively. Consequently, when the 8-hour TWA exceeds 0.23 times (1/4.3) the short-term exposure limit value, the high short-term exposure condition should be evaluated. The maximum values of 60-min TWA (the 93.8th percentile) were estimated to be 1.8, 5.1 and 43 times as high as the minimum one, respectively; and to be 1.3, 2.0, and 3.1 times the 8-hour TWA value, respectively. The relationship between production factors and within-shift exposure variability was also examined. The intermittent solvent use group had significantly higher median values of GSD(15m) and GSD(60m) than the continuous group. The mobile pollutant source group had a significantly higher median value of GSD(60m) than the stationary group. PMID- 10028614 TI - Thermal characteristics of clothing ensembles for use in heat stress analysis. AB - The Heat Stress Index was an early model for the assessment of heat stress. The International Organization for Standardization (ISO) standard for required sweat rate is the current generation of heat balance methods for occupational heat stress. The method assumes cotton clothing and works adequately for cotton/polyester blends. To extend the usefulness of the model, the thermal characteristics of a variety of commercially available and prototype protective clothing ensembles have been determined for application in the ISO method. The fundamental principle for assessing thermal characteristics of work clothing is establishing the critical environmental conditions in which test subjects were just able to maintain thermal equilibrium. Critical conditions were found for warm, humid conditions; hot, dry conditions; intermediate conditions of temperature and humidity; and/or moderate conditions in which metabolic rate was increased to a limiting thermal load. Typically, five subjects at each condition for each ensemble were used. Metabolic rate, average skin temperature, and the environmental conditions (air temperature and vapor pressure) were noted at the critical conditions, and the total insulation was estimated for each ensemble. From these values, the total evaporative resistance, the clothing factor for dry heat exchange (CFcl), and the clothing factor for evaporative cooling (CFpcl) were determined. When compared with reports of others on thermal characteristics the results agreed when pumping factors and clothing wetness were considered. The result was higher than expected values for CFcl and lower values for CFpcl. PMID- 10028615 TI - Measurement of benzene in the workplace and its evolution process, Part I: Overview, history, and past methods. AB - Benzene and its measurement continues to be important in the field of industrial hygiene. This two-part article reviews the history of occupational and environmental sampling and analysis of benzene from the early 1900s to the present. Part I provides an overview and details of the methods used in the past; history of the American Conference of Governmental Industrial Hygienists' threshold limit values for benzene; and reviews portable, grab, and integrated sampling methods as well as the various analytical methods. It is important to review and understand the past in order to predict future trends. PMID- 10028616 TI - Measurement of benzene in the workplace and its evolution process, Part II: Present methods and future trends. AB - This article (the second of a two-part series) provides a discussion of currently accepted methodology and possible future happenings regarding measurement of benzene in workplaces. The gap between occupational and environmental monitoring is becoming narrow. Environmental levels will always be lower than the occupational, but as the push for lower threshold limit values continues, the focus should be on the environmental aspect as the ultimate limiting factor with respect to measurement. The charcoal tube/carbon disulfide desorption procedure is slowly being stretched to its limit with respect to benzene. It may be time for serious consideration in North America regarding adoption of the proven European procedure of thermal desorption using a porous polymer tube for analysis of benzene. PMID- 10028617 TI - Studying the determinants of exposure: a review of methods. AB - To better understand where, when, and how to control occupational exposures, it is vital that hygienists understand the factors that contribute to elevated or reduced exposure levels. Over the last two decades a burgeoning literature examining the determinants of exposure has developed, yet to date the methods used in this regard have rarely been summarized in texts or elsewhere. The purpose of this article is to provide an overview of the techniques used to study the predictors of workplace exposures. Both experimental and observational studies are examined, and the advantages and limitations of each are discussed. Fundamental study design features are reviewed. These include the selection and measurement of factors potentially related to exposure, as well as the measurement of exposure itself. Decisions reached by investigators in selecting the number of sites and workers, the number of repeated observations per worker, and the duration of sampling are discussed. Also examined are issues that commonly arise in the course of data analysis of exposure determinants. These include transformation of exposure variables, correlation of predictor variables, empirical model building, and interpretation of results. Finally, methods employed to evaluate the validity of findings are summarized. PMID- 10028618 TI - Occupational exposure to chemical and biological agents in the nonproduction departments of pulp, paper, and paper product mills: an international study. AB - As part of an international epidemiological study of workers in the pulp and paper industry, previously unpublished exposure measurements were assembled in a database. This article describes 7293 measurements in nonproduction departments from 147 mills in 11 countries. The greatest variety of agents was measured in the maintenance, construction, and cleaning department, where high exposures to asbestos, chromium [VI] compounds, copper, mercury in urine, nitrogen dioxide, ozone, styrene, sulfur dioxide, trichloroethylene, and welding fumes were observed. Measurements in the storage, yard, loading, and shipping department indicated high exposures to asbestos, carbon monoxide, fungal spores, nitrogen oxides, sulfur dioxide, and total dust. The steam and power generation department had high exposures to methyl mercaptan, silica, and total dust. Measurements in process and effluent water treatment, laboratory and research, engineering, and office, administration, and cafeteria areas had few elevated exposures. Throughout the nonproduction departments, measurements of pulp-production chemicals such as chlorine and sulfur compounds tended to be low, with many below detection limits. There were some problems with the available data; in particular, detection limits were often not specified, and the data tended to be clustered in such a way that sources of exposure variability could not be distinguished. Despite these problems, the data provide new insight into the exposures of nonproduction pulp and paper industry personnel. PMID- 10028619 TI - Respirator fit factor performance while sweating. AB - The extent to which sweat accumulation inside respirators affects respirator fit has not been quantified. This study represents an attempt to measure facial sweating and to quantify its effects on fit factors of negative pressure, full facepiece respirators. Respirator fit factor (FF) data were obtained while 14 subjects completed 30 minutes of treadmill walking at an intensity of 75% of age predicted maximal heart rate in an aerosol test chamber under ambient environmental conditions. Subject facial and whole body sweat production were also measured. Statistical analysis of the treadmill FF results showed that respirator fit was significantly (p < 0.05) degraded after 14 minutes of exercise. Sweat accumulation inside the respirator facepiece averaged 30.9 +/- 15.5 g. However, no significant correlation of subject facial sweat production with overall FF values measured during exercise was found. The results of this study indicate that respirator FFs degrade significantly over time under moderate exercise and environmental conditions and suggest that facial sweat accumulation alone does not account for the reduced FF levels. PMID- 10028620 TI - Airborne microflora in Quebec dairy farms: lack of effect of bacterial hay preservatives. AB - Pediococcus pentosaceus is a lactic-acid producing bacterium inoculated in hay to prevent hay deterioration. This study sought to verify the effect of this treatment on the barn microenvironment. Air samples were obtained from 19 barns using bacterial hay treatment and from 18 control barns with six-stage Andersen samplers and all-glass impingers. Appropriate culture media were used for the recovery and identification of microorganisms. Endotoxins were measured with chromogenic Limulus amoebocyte lysate assay. Median values (respectively for treated and untreated hay barns) were: 5.28 x 10(5) and 3.84 x 10(5) colony forming units (CFU)/m3 for total bacteria; 3.18 x 10(6) and 4.5 x 10(6) CFU/m3 for molds; 1.36 x 10(3) and 1.74 x 10(3) endotoxin units/m3 for endotoxin levels; and 1.03 x 10(3) and 3.00 x 10(3) CFU/m3 for Saccharopolyspora rectivirgula. No viable P. pentosaceus were recovered. The presence of S. rectivirgula, the causative agent for farmer's lung, was not influenced by the hay treatment. Since no significant difference was observed in any of the airborne contaminants, this type of hay treatment probably does not protect farmers from the respiratory effect of ambient microbial contaminants. PMID- 10028621 TI - Effects of a novel ice-cooling technique on work in protective clothing at 28 degrees C, 23 degrees C, and 18 degrees C WBGTs. AB - This study tested a new ice cooling system that permits ice cooling system recharge without personal protective clothing removal. Six male volunteers (22.1 +/- 1.2 years) underwent tests with the new ice cooling system (COOL) and without (NOCL) at a moderate work rate (450 W) in three environments of 28, 23, and 18 +/ 1 degrees C wet bulb globe temperature. Walks at 28 degrees C were carried out first with NOCL and COOL counterbalanced, then test order and environment were counterbalanced. At 28 degrees C, mean work time in COOL significantly increased by 37.5 min (188%) over NOCL (p < 0.05). At 23 degrees C mean work time in COOL was significantly increased by 44.3 min (171%) compared with NOCL (p < 0.05). Mean work times at 18 degrees C were not significantly different, although all subjects completed the 120 minutes of work in COOL compared with a mean work time of 109 +/- 20 min for NOCL. During rest, mean reductions in rectal temperature were significantly greater in COOL than NOCL (p < 0.05) at 28 and 23 degrees C. Mean heart rate calculated for the same point in both treatments was significantly lower for COOL at 28, 23, and 18 degrees C (p < 0.05). Thermal comfort rating was significantly different at 18 and 23 degrees C (p < 0.05). This new design seemed to provide comparable cooling to conventional vests and also provides greater practicality for field use. Even in experimental form the suit demonstrated increased productivity due to extended tolerance time. PMID- 10028622 TI - Assessment of coke oven emissions exposure among coking workers. AB - Coking workers are regularly exposed to coke oven emissions, which consist primarily of polycyclic aromatic hydrocarbons and volatile organic compounds. This study measured the workers' exposure to the benzene soluble fraction of total particulates (BSF). The study population consisted of 88 coking workers as an exposure group and 59 referents. Personal breathing-zone samples of BSF and total particulates were taken from all study subjects for 3 consecutive days. The highest BSF concentrations were found among the topside oven workers (geometric mean; range) (microgram/m3): lidman (515; 72-18, 181), tar chaser (432; 51-4334), and larry car operator (185; 55-649). The lowest was 7 micrograms/m3 in the referents. Among the samples at the topside oven 84% exceeded the Occupational Safety and Health Administration standard (150 micrograms/m3 BSF). The percentage of BSF in total particulates varied across job classifications, ranging from 0.3% in wharfmen to 24% in tar chasers. Area sampling indicated that the BSF concentration at the topside area was sixtyfold higher than that at the administrative area, which was approximately 2 km from the coke oven plant. PMID- 10028623 TI - Electromagnetic radiation from VDT units: study of the effectiveness of an active shielding device. AB - Measurements of extremely low frequency electromagnetic fields and low frequency magnetic fields emitted by a set of video display terminal (VDT) units are reported. The field values measured at the position normally occupied by the user are below the safety limits. This is because the field amplitudes decrease rapidly (following a 1/R3 law) with the distance from the source, as has been verified in this work. Measurements with a commercial shielding device consisting of small plastic balls filled with a water solution of rare earth elements were also performed. The only physical mechanism that could be hypothesized to produce an active suppression of the VDT field is that rare earth atoms, which probably were chosen due to their large magnetic moment, behave as oscillating magnetic dipoles capable of emitting a secondary magnetic field that, along some particular directions, has a phase that is opposite to that of the exciting field. Unfortunately, if one analyzes this mechanism quantitatively, it is easy to show that the secondary magnetic field is absolutely negligible, as was confirmed by experimental measurements performed in this study. PMID- 10028624 TI - An evaluation of an air-supplied blouse and an air hood. AB - Fit factor studies for an air-supplied blouse (blouse) and an air hood respirator (air hood) were conducted by Lawrence Livermore National Laboratory. Nine test subjects were used to test the blouse. Three subjects were used to test the air hood. Exercises conducted in the test chamber included touching toes, raising both arms overhead, squatting, twisting at the torso while holding a rod, and running in place. Both the air hood and blouse were tested with 8 ft3/min air supply. Both respirators were worn in a test chamber. The blouse provided a fit factor of greater than 40,000. The air hood, for nearly all tests, also provided a fit factor greater than 40,000 when worn correctly. Fit factors were also measured for improperly worn air hoods. PMID- 10028625 TI - Balancing patient dose and image quality. AB - The formation of images in diagnostic radiology involves a complex interdependence of many factors. The ideal balance is to obtain an image which is adequate for the clinical purpose with the minimum radiation dose. Factors which affect radiation dose and image quality can be grouped under three headings; radiation quality, photon fluence and removal of scattered radiation. If optimal performance is to be achieved, it is necessary to understand how these factors influence image formation and affect radiation dose, and apply methodology for image quality and dose analysis at each stage in the development and use of X-ray equipment. PMID- 10028626 TI - Measurement of image quality in diagnostic radiology. AB - The aim in radiology is to obtain images which are adequate for the clinical purpose with the minimum radiation dose to the patient. If optimum performance is to be achieved, assessments of image quality must be made to balance against patient dose. The subjective nature of image interpretation makes an objective approach to such assessment difficult. Methods widely applied involve the use of test objects, which although providing a measure of imaging performance may be difficult to link to clinical image formation. The ideal method for evaluation of imaging techniques is through clinical trials and this should be used to address major questions. Scoring of quality criteria, relating to features observed in a normal clinical radiograph, provides a simple method through which image quality can be assessed in every hospital department. PMID- 10028627 TI - Use of the concept of energy imparted in diagnostic radiology. AB - The concept of energy imparted by ionizing radiation to the matter in a volume is analyzed and methods to determine the energy imparted epsilon to the patient are reviewed, in particular, determinations based on measurements of the air kerma integrated over beam area [the kerma-area-product (KAP)] and calculations needed to derive conversion factors epsilon/KAP. The energy imparted to the image receptor, epsilon rec, including the statistical aspects of the concept, and the effect of epsilon rec on image quality and patient dose are also analysed. Finally, use of the energy imparted to the patient as a risk indicator is discussed. PMID- 10028628 TI - Somatic effects in nuclear medicine and radiology. AB - Probable risks for the occurrence of somatic effects due to diagnostic radiology and nuclear medicine are summarised. The biological background of radiation carcinogenesis and epidemiological results are discussed. At the Leiden University Medical Centre the average effective dose per examination due to diagnostic radiology and nuclear medicine amount to 0.95 and 4.4 mSv, respectively. These values correspond well with the average values of 0.82 and 3.0 mSv reported for The Netherlands as a whole. Since radiological examinations are performed at a much larger frequency than nuclear medicine the relative collective dose for the first type of examinations is higher than the latter. Risk for occurency of malignancies are at least one order of magnitude lower than the hypothetical risk due to the background radiation typical of The Netherlands. PMID- 10028629 TI - Radiation dosimetry in nuclear medicine. AB - Radionuclides are used in nuclear medicine in a variety of diagnostic and therapeutic procedures. A knowledge of the radiation dose received by different organs in the body is essential to an evaluation of the risks and benefits of any procedure. In this paper, current methods for internal dosimetry are reviewed, as they are applied in nuclear medicine. Particularly, the Medical Internal Radiation Dose (MIRD) system for dosimetry is explained, and many of its published resources discussed. Available models representing individuals of different age and gender, including those representing the pregnant woman are described; current trends in establishing models for individual patients are also evaluated. The proper design of kinetic studies for establishing radiation doses for radiopharmaceuticals is discussed. An overview of how to use information obtained in a dosimetry study, including that of the effective dose equivalent (ICRP 30) and effective dose (ICRP 60), is given. Current trends and issues in internal dosimetry, including the calculation of patient-specific doses and in the use of small scale and microdosimetry techniques, are also reviewed. PMID- 10028630 TI - Exposure of critical groups to nuclear medicine patients. AB - When a radiopharmaceutical has been administered to a patient, assessment of the risk to critical groups from emitted photon radiation is by measurement of the integral dose received by an individual, or by measurements of the dose rate external to the patient coupled with appropriate occupancy factors. Estimations have been made from the available data of the dose to critical groups exposed to patients who have undergone diagnostic or therapeutic procedures. These dose estimations can be used to assess the impact of the proposed changes in statutory requirements, and to allow appropriate recommendations to be formulated. Two areas for consideration are that pregnant staff exposed to nuclear medicine patients will require an abdominal surface dose limit lower than 2 mSv to restrict their foetal dose to 1 mSv, and the current UK restrictions for the behaviour of patients who have undergone 131I treatment are either already adequate or can even be relaxed in order to restrict the exposure of members of the public to the proposed lower dose limits. Agreement is needed on the value (e.g. 95th percentile) from a study of the dose to a number of individuals which should serve as the basis for radiation protection recommendations. PMID- 10028631 TI - Patient dosimetry measurement methods. AB - This article reviews patient dosimetry measurement methods applied to diagnostic radiology examinations. Various dose quantities and their relevance to patient dose surveys are described. When contemplating a patient dose survey it is important to develop a clear measurement strategy. This involves a detailed consideration of the most applicable dose measurement method for the intended survey. Various approaches to patient dosimetry are described and reviewed. PMID- 10028632 TI - Characteristics of radiation detectors for diagnostic radiology. AB - The use of X-rays for diagnosis has been significant since its discovery. A measurement of the X-ray dose is the main determinant for risk vs benefit of these examinations. Radiation detectors are important for dose measurement. A description of these detectors, including the most frequently used ionization chamber, aids in the understanding necessary for their use. Proper and accurate use of detectors depends on an understanding of their calibration and their characteristics. Detectors such as ionization chamber, including specialized chambers, and solid detectors, including luminescent detectors, are described. This is followed by a description of the calibration process. The precision of measurements can be greatly affected by an understanding of the detector in use. PMID- 10028633 TI - Performance assessment of patient dosimetry services and X-ray quality assurance instruments used in diagnostic radiology. AB - Experiences of the Regional Radiation Physics and Protection Service (RRPPS) in performance assessment of diagnostic X-ray QA instrumentation and on-patient dosemeters are recounted. Issues relating to the provision of realistic and reproducible reference conditions for calibrated X-irradiations are considered and summary statistics from test measurements of dose and kVp meters are provided. For both dose and kVp meters it is indicated that as many as 25% of instruments used in routine use in the U.K. may require some adjustment before they can truly be said to be performing as the manufacturer intended. Results from intercomparison exercises for patient dosimetry services are also discussed. It is apparent that, for those centres participating in the exercise, dose assessments are generally being obtained to within a bias and a relative standard deviation of less then 10%. PMID- 10028634 TI - Impact of new digital X- and gamma ray imaging systems upon patient doses. PMID- 10028635 TI - Dosimetry for optimisation of patient protection in computed tomography. AB - The complex conditions of irradiation in computed tomography (CT), involving highly-collimated X-ray beams, necessitate the use of specially-defined dose descriptors such as the computed tomography dose index (CTDI). When used in a weighted form (CTDIW), this concept can describe the absorbed dose from a single slice in standard head and body phantoms. The model can easily be extended to characterise patient exposure for a complete examination by means of the reference dose quantity dose-length product (DLP). Effective dose can also be estimated from DLP, when required. PMID- 10028636 TI - Radiation dose in interventional fluoroscopic procedures. AB - Vascular interventional procedures carried out under fluoroscopic guidance often involve high radiation doses. Above certain thresholds, radiation can cause significant damage to the skin including hair loss and severe necrosis. Such damage has been reported by several investigators. Many attempts have been made to quantitate the radiation doses to the skin involved with these procedures, but dosimetry methods are often flawed. To improve the situation better monitoring of radiation doses, fluoroscopist education, and changes in technology and methods are needed. PMID- 10028637 TI - Breast dosimetry. AB - The estimation of the absorbed dose to the breast is an important part of the quality control of the mammographic examination. Knowledge of breast dose is essential for the design and performance assessment of mammographic imaging systems. This review gives a historical introduction to the measurement of breast dose. The mean glandular dose (MGD) is introduced as an appropriate measure of breast dose. MGD can be estimated from measurements of the incident air kerma at the surface of the breast and the application of an appropriate conversion factor. Methods of calculating and measuring this conversion factor are described and the results discussed. The incident air kerma itself may be measured for patients or for a test phantom simulating the breast. In each case the dose may be determined using TLD measurements, or known exposure parameters and measurements of tube output. The methodology appropriate to each case is considered and the results from sample surveys of breast dose are presented. Finally the various national protocols for breast dosimetry are compared. PMID- 10028638 TI - Estimating mean glandular dose using proprietary mammography phantoms. AB - Screening mammography programs prescribe limits on the radiation dose to the glandular tissue of a compressed breast--the Mean Glandular Dose (MGD)--which may vary between 2 and 3 mGy for a 50% adipose and 50% glandular tissue compressed breast of 4.2 to 5.0 cm thickness. Commercially available breast phantoms offer a choice of equivalent tissue thicknesses and composition ranging typically from 30% adipose and 70% glandular tissue to 50% adipose and 50% glandular tissue. A number of these phantom were compared under clinical conditions and the MGD calculated for each using the factors developed by Wu et al. [Wu, X., Barnes, G.T. and Tucker, D.M. (1991) Spectral dependence of glandular tissue dose in screen film mammography, Radiology 179, 143-148]. PMID- 10028639 TI - Radiation exposure in bone mineral density assessment. AB - Osteoporosis is a systematic skeletal disease characterized by low bone mass and microarchitectural deterioration of bone tissue which leads to diminished biomechanical competence of the skeleton and low-trauma or atraumatic fractures. Due to increased awareness of the impact of osteoporosis on the elderly population, the use of bone densitometric techniques is becoming more widespread. Considerable progress has been made in the development of non-invasive methods for the assessment of the skeleton. While DXA and QCT are commonly used techniques, the popularity of other approaches such as RA, SXA and QUS is gaining grounds. QCT has an advantage over the other techniques in its ability to measure the true volumetric density of trabecular or cortical bone. We therefore present an overview of these current techniques for bone mineral density (BMD) measurements. In the second section we discuss the radiation doses incurred in BMD measurements by patients and methods for reducing patient and staff radiation exposure are given. Studies of radiation dose to patient from DXA confirms that patient dose is small (0.08-4.6 muSv) compared to that given by many other investigations involving ionizing radiation. Fan beam technology with increased resolution has resulted in increase patient dose radiation dose (6.7-31 muSv) but this is still relatively small. Carrying vertebral morphometry using DXA also incurs less radiation dose (< 60 muSv) than standard lateral radiographs QCT has radiation dose (25-360 muSv) comparable to simple radiological examination such as chest X-ray but lower than imaging CT. Radiation dose from other techniques such as RA and SXA are in the same order of magnitude as pencil beam DXA. For pencil beam DXA and SXA systems the time average dose to staff from scatter is very low even with the operator sitting as close as 1 m from the patient during measurement. However the scatter dose from fan beam DXA systems is considerable higher and approaches limits set by regulator bodies for occupational exposure. PMID- 10028640 TI - A compliance testing program for diagnostic X-ray equipment. AB - Compliance testing is nominally that part of a quality assurance program dealing with those aspects of X-ray equipment performance that are subject to radiation control legislation. Quality assurance programs for medical X-ray equipment should be an integral part of the quality culture in health care. However while major hospitals and individual medical centers may implement such programs with some diligence, much X-ray equipment can remain unappraised unless there is a comprehensive regulatory inspection program or some form of compulsion on the equipment owner to implement a testing program. Since the late 1950s all X-ray equipment in the State of Western Australia has been inspected by authorized officers acting on behalf of the Radiological Council, the regulatory authority responsible for administration of the State's Radiation Safety Act. However, economic constraints, coupled with increasing X-ray equipment numbers and a geographically large State have significantly affected the inspection rate. Data available from inspections demonstrate that regular compliance and performance checks are essential in order to ensure proper performance and to minimize unnecessary patient and operator dose. To ensure that diagnostic X-ray equipment complies with accepted standards and performance criteria, the regulatory authority introduced a compulsory compliance testing program for all medical, dental and chiropractic diagnostic X-ray equipment effective from 1 January 1997. PMID- 10028641 TI - Patient dosimetry activities in the United States: the nationwide evaluation of X ray trends (NEXT) and tissue dose handbooks. AB - In the United States the Food and Drug Administration (FDA) in collaboration with the Conference of Radiation Control Program Directors (CRCPD) and state and local government agencies surveys clinical facilities about X-ray system air kerma and ancillary data related to patient dosimetry for a variety of diagnostic X-ray examinations. The survey program is known as the Nationwide Evaluation of X-ray Trends (NEXT). The survey utilizes reference patient-equivalent phantoms in the collection of comprehensive technical information. With knowledge of the skin entrance air kerma, specific tissue doses can be calculated. An overview of NEXT and previously published FDA tissue dose handbooks for diagnostic X-ray examinations is presented. PMID- 10028642 TI - Diagnostic medical exposures in the U.K. AB - Surveys in the U.K. have identified the patterns of patient exposure from diagnostic medical radiological procedures and have led to the development of structured advice to promote optimisation of patient protection, including diagnostic reference levels for some common conventional X-ray examinations. Trends for reductions in individual patient and collective doses from these particular procedures have been offset by increasing application of computed tomography. Practice in diagnostic nuclear medicine is conducted by authorized physicians on the basis of recommended maximum usual activities of radiopharmaceutical for specific procedures. PMID- 10028643 TI - Radiation protection and quality assurance in diagnostic radiology--an IAEA coordinated research project in Asia and eastern Europe. AB - The International Atomic Energy Agency currently has two parallel Coordinated Research Projects (CRP) running in Asia and Eastern Europe. The main objective of the CRPs is to raise the level of awareness in participating countries about the need for radiation protection for patients undergoing diagnostic radiology procedures. This is to be achieved by first assessing the status quo in a sample of hospitals and X-ray rooms in each participating country. A program of optimization of radiation protection for patients is then introduced by means of a comprehensive quality assurance program and the implementation of appropriate dose reduction methods, taking into account clinical requirements for diagnostically acceptable images. Patient dose assessment and image quality assessment are to be performed both before and after the introduction of the quality assurance program. The CRP is divided into two phases--the first is concerned with conventional radiography, while the second involves fluoroscopy and computed tomography. The CRP is still running, restricting the scope of this paper to a discussion of the approach being taken with the project. The project will be completed in 1998, with analysis to follow. PMID- 10028644 TI - Biochemical oxygen demand sensor using Serratia marcescens LSY 4. AB - A microbial biochemical oxygen demand (BOD) sensor consisting of Serratia marcescens LSY 4 and an oxygen electrode was prepared for estimation of the biochemical oxygen demand. The response of the BOD sensor was insensitive to pH in the range of pH 6.0-8.0, and the baseline drift of the signal was nearly absent even in unbuffered aqueous solution. Because heavy metal ions were precipitated from the phosphate buffer solution, unbuffered solution was used to investigate the effect of the concentration of heavy metal ions on the sensor response. Contrary to previous studies, not only Cu2+ and Ag+ but also Cd2+ and Zn2+ significantly decreased the response of the BOD sensor in unbuffered solution. Graft polymerization of sodium styrene sulfonate on the surface of the porous teflon membrane was carried out to absorb the heavy metal ions permeating through the membrane. Tolerance against Zn2+ was induced for S. marcescens LSY 4 to make the cells less sensitive to the presence of heavy metal ions. The membrane modification and the Zn2+ tolerance induction showed some positive effects in such a way that they reduced the inhibitory effects of Zn2+ and Cd2+ on the sensitivity of the BOD sensor. However, they had no effect on the protection of the cells against the interference of Cu2+ and Ag+ on the performance of the sensor. PMID- 10028645 TI - A piezoelectric biosensor as an olfactory receptor for odour detection: electronic nose. AB - Humans can detect and differentiate the presence of different odours even at trace levels of these odorous compounds. The odour quantification of any particular samples is normally based on conventional panel decisions. Other analytical instruments could be used to detect trace levels of odorous molecules. This study presents the results of a biological sensor system subject to different odorants. The system consists of a sensor in which the isolated olfactory receptor proteins (ORPs) from bullfrogs (Rana spp.) were coated onto the surface of a piezoelectric (PZ) electrode, similar to the mechanism of human olfaction. The PZ crystal served as a signal transducer. The results indicate rapid (about 400 s), reversible, and longterm (up to 3 months) stable responses to different volatile compounds such as n-caproic acid, isoamyl acetate, n-decyl alcohol, beta-ionone, linalool, and ethyl caporate. The sensitivity of the sensor ranges from 10(-6)-10(-7) g, fully correlated with the olfactory threshold values of human noses. An array of six sensors consisting of five fractionated ORPs and one referenced phospholipid probe is able to respond to different odorants and form a typical fingerprint for each odorant. PMID- 10028646 TI - Containment sensors for the determination of L-lactate and glucose. AB - This paper reports some new results on enzyme based silicon containment sensors. For the first time an L-lactate sensor in containment technology is presented. Through optimization of the buffer system the stability of the lactate sensor was enhanced and the linear response of over 10 mM was achieved. The glucose sensor has also been optimized for a large linear measurement range exceeding 30 mM. A two-enzyme chip with glucose and lactate sensor elements which were integrated on one silicon chip is presented. The response behaviour of the two-enzyme chip was very similar to the single chip behaviour. No cross-talking effects could be observed. A fabrication process for mass-production is described. PMID- 10028647 TI - A disposable biosensor for urea determination in blood based on an ammonium sensitive transducer. AB - A potentiometric urea-sensitive biosensor using a NH4(+)-sensitive disposable electrode in double matrix membrane (DMM) technology as transducer is described. The ion-sensitive polymer matrix membrane was formed in the presence of an additional electrochemical inert filter paper matrix to improve the reproducibility in sensor production. The electrodes were prepared from one-side silver-coated filter paper, which is encapsulated for insulation by a heat sealing film. A defined volume of the NH4(+)-sensitive polymer matrix membrane cocktail was deposited on this filter paper. To obtain the urea-biosensor a layer of urease was cast onto the ion-sensitive membrane. Poly (carbamoylsulfonate) hydrogel, produced from a hydrophilic polyurethane prepolymer blocked with bisulfite, served as immobilisation material. The disposable urea sensitive electrode was combined with a disposable Ag/AgCl reference electrode to obtain the disposable urea biosensor. The sensor responded rapidly and in a stable manner to changes in urea concentrations between 7.2 x 10(-5) and 2.1 x 10( 2)mol/l. The detection limit was 2 x 10(-5) mol/l urea and the slope in the linear range 52 mV/decade. By taking into consideration the influence of the interfering K(+)- and Na(+)-ions the sensor can be used for the determination of urea in human blood and serum samples (diluted or undiluted). A good correlation was found with the data obtained by the spectrophotometric routine method. PMID- 10028648 TI - Disposable DNA electrochemical sensor for hybridization detection. AB - A disposable electrochemical sensor for the detection of short DNA sequences is described. Synthetic single-stranded oligonucleotides have been immobilized onto graphite screen printed electrodes with two procedures, the first involving the binding of avidinbiotinylated oligonucleotide and the second adsorption at a controlled potential. The probes were hybridized with different concentrations of complementary sequences. The formed hybrids on the electrode surface were evaluated by differential pulse voltammetry and chronopotentiometric stripping analysis using daunomycin hydrochloride as indicator of hybridization reaction. The probe immobilization step, the hybridization event and the indicator detection, have been optimized. The DNA sensor obtained by adsorption at a controlled potential was able to detect 1 microgram/ml of target sequence in the buffer solution using chronopotentiometric stripping analysis. PMID- 10028649 TI - The Python pit organ: imaging and immunocytochemical analysis of an extremely sensitive natural infrared detector. AB - The Python infrared-sensitive pit organ is a natural infrared imager that combines high sensitivity, ambient temperature function, microscopic dimensions, and self-repair. We are investigating the spectral sensitivity and signal transduction process in snake infrared-sensitive neurons, neither of which is understood. For example, it is unknown whether infrared receptor neurons function on a thermal or a photic mechanism. We imaged pit organs in living Python molurus and Python regius using infrared-sensitive digital video cameras. Pit organs were significantly more absorptive and/or emissive than surrounding tissues in both 3 5 microns and 8-12 microns wavelength ranges. Pit organs exhibited greater absorption/emissivity in the 8-12 microns range than in the 3-5 microns range. To directly test the relationship between photoreceptors and pit organ infrared sensitive neurons, we performed immunocytochemistry using antisera directed against retinal photoreceptor opsins. Retinal photoreceptors were labeled with antisera specific for retinal opsins, but these antisera failed to label terminals of infrared-sensitive neurons in the pit organ. Infrared-receptive neurons were also distinguished from retinal photoreceptors on the basis of their calcium-binding protein content. These results indicate that the pit organ absorbs infrared radiation in two major atmospheric transmission windows, one of which (8-12 microns) matches emission of targeted prey, and that infrared receptors are biochemically distinct from retinal photoreceptors. These results also provide the first identification of prospective biochemical components of infrared signal transduction in pit organ receptor neurons. PMID- 10028650 TI - An array of Pt-tip microelectrodes for extracellular monitoring of activity of brain slices. AB - A microelectrode array (MEA) consisting of 34 silicon nitride passivated Pt-tip microelectrodes embedded on a perforated silicon substrate (porosity 35%) has been realized. The electrodes are 47 microns high, of which only the top 15 microns are exposed Pt-tips having a curvature of 0.5 micron. The MEA is intended for extracellular recordings of brain slices in vitro. Here we report the fabrication, characterization and initial electrophysiological evaluation of the first generation of Pt-tip MEAs. PMID- 10028651 TI - Determination of lysine in pharmaceutical samples containing endogenous ammonium ions by using a lysine oxidase biosensor based on an all-solid-state potentiometric ammonium electrode. AB - A new potentiometric method is proposed to determine lysine in pharmaceutical samples. This method is based on a lysine biosensor consisting of a chemically immobilized lysine oxidase membrane attached to an all-solid-state ammonium electrode. Lysine is degraded in the sensor to release ammonium, which is detected by means of the ammonium electrode. The presence of endogenous ammonium in the samples interferes with these determinations, since the response measured corresponds to the sum of the ammonium generated enzymatically and that present in the sample. This is a general drawback for all biosensors based on the detection of ammonium. Study of samples containing both lysine and ammonium showed that concentration ranges exist in which a near-logarithmic relationship between potentials measured and lysine concentrations is found. Therefore, within these ranges, lysine can be determined by using the standard addition method, with the subsequent data treatment involving an iterative linearization procedure. Results obtained with the proposed potentiometric method are consistent with those given by the standard method for amino acid analysis. PMID- 10028652 TI - Biosensor for direct determination of organophosphate nerve agents. 1. Potentiometric enzyme electrode. AB - A potentiometric enzyme electrode for the direct measurement of organophosphate (OP) nerve agents was developed. The basic element of this enzyme electrode was a pH electrode modified with an immobilized organophosphorus hydrolase (OPH) layer formed by cross-linking OPH with bovine serum albumin (BSA) and glutaradehyde. OPH catalyses the hydrolysis of organophosphorus pesticides to release protons, the concentration of which is proportional to the amount of hydrolysed substrate. The sensor signal and response time was optimized with respect to the buffer pH, ionic concentration of buffer, temperature, and units of OPH immobilized using paraoxon as substrate. The best sensitivity and response time were obtained using a sensor constructed with 500 IU of OPH and operating in pH 8.5, 1 mM HEPES buffer. Using these conditions, the biosensor was used to measure as low as 2 microM of paraoxon, ethyl parathion, methyl parathion and diazinon. The biosensor was completely stable for at least one month when stored in pH 8.5, 1 mM HEPES + 100 mM NaCl buffer at 4 degrees C. PMID- 10028653 TI - Composite films of Prussian blue and N-substituted polypyrroles: covalent immobilization of enzymes and application to near infrared optical biosensing. AB - We demonstrate the feasibility of optical biosensing using a material which, in essence, is a modified inorganic film to which various enzymes were covalently attached. Thin and transparent blue films composed of Prussian blue and incorporated into a network of N-substituted polypyrroles are sensitive to pH in the 5-9 range at 720 nm wavelength and can be modified with enzymes to result in the respective biosensors. Several methods of enzyme immobilization, using bifunctional crosslinking reagents, and various enzymes were tested. The best results were obtained using the one-step carbodiimide method which resulted in highly active, stable and transparent biosensor films for optical determination of urea and acetylcholine. The operational stability exceeded 1 month and even after 2 months of dry storage at room temperature the activity did not drop. The biosensors allow optical determination of the respective substrates in the millimolar concentration range. PMID- 10028654 TI - New immobilization method for SAW-biosensors: covalent attachment of antibodies via CNBr. AB - Surface acoustic wave devices (SAWs) based on horizontally polarized shear waves can be used as mass-sensitive immunosensors. If the standard material, aluminium, is used for the interdigital transducers (IDTs) of these devices a pretreatment with a shielding layer of polyimide is necessary to prevent corrosion processes. However, this layer also prevents an easy covalent attachment of the necessary receptive molecules. Therefore, we developed a new activation method of this inert polyimide surface by treating with cyanogenbromide using the established cyano-transfer-technique. With a subsequent covalent attachment of anti-glucose oxidase (anti-GOD) a very sensitive SAW-immunosensor for glucose oxidase (GOD) can be obtained. PMID- 10028655 TI - Recent trend of polychlorinated dibenzo-p-dioxins and their related compounds in the blood and sebum of Yusho and Yu Cheng patients. AB - We investigated the levels of polychlorinated dibenzo-p-dioxins (PCDDs) and their related compounds in blood and sebum from Yusho and Yu-Cheng patients and findings compared with those of normal subjects. Concentrations of these compounds in blood and sebum still were obviously reflected the chemical concentration in the causal rice oil ingested 17 or 26 years since the outbreak. In addition, sebum form the body surface was the most useful sample for monitoring the amount of chemicals contaminating the human body. PMID- 10028656 TI - PCDD/F concentrations in milk of nonoccupationally exposed women living in southern Catalonia, Spain. AB - Concentrations of 17 toxic 2,3,7,8-substituted polychlorinated dibenzo-p-dioxins (PCDDs) and polychlorinated dibenzofurans (PCDFs) have been determined in pooled samples of breast milk from 15 mothers living in two residential areas (Tarragona downtown and an industrial area) in the vicinity of a new hazardous waste incinerator (HWI), now under construction in Tarragona (southern Catalonia, Spain). PCDD/Fs in human milk samples ranged between 5.9 and 17.1 pg I-TEQ/g fat (162-498 pg I-TEQ/l), with a mean value of 11.8 pg I-TEQ/g fat (310.8 pg I TEQ/l). The percentages of fat ranged between 1.53 and 3.52. Although PCDD/F levels in milk from mothers living in the industrial area were found to be slightly higher than those observed in women living Tarragona downtown, most differences did not reach the level of statistical significance. In general terms, PCDD/F concentrations in human milk (pooled) samples of mothers living in the area of Tarragona are similar or lower than those previously reported for most industrialized countries. PMID- 10028657 TI - Oxidative degradation of p-toluenesulfonic acid using hydrogen peroxide. AB - The oxidative degradation of p-toluenesulfonic acid using thermally activated hydrogen peroxide was investigated. The concentrations of all aromatic and aliphatic intermediates were determined by means of HPLC. From the identification of all intermediates, a detailed reaction mechanism for the oxidative degradation of p-toluenesulfonic acid is proposed. Experiments show that the oxidation with hydrogen peroxide is an effective process for the destruction of organic pollutants. Only substoichiometric amounts of hydrogen peroxide are required to convert this refractory model compound to easily biodegradable substances. PMID- 10028658 TI - In situ (mesocosm) assessment of immunotoxicity risks to small mammals inhabiting petrochemical waste sites. AB - Oil refineries inadvertently deposit a variety of complex mixtures of organic hydrocarbons and heavy metals in the soil, many of which are thought to be potent immunotoxicants. Terrestrial ecosystems such as this have not been adequately investigated with respect to wild rodent populations. The primary objective of this study was to use mesocosms to assess the immunotoxicity risks to feral small mammal populations associated with soils contaminated with petroleum refinery wastes. A series of 4-week and 8-week exposure trials using laboratory raised cotton rats (Sigmodon hispidus) were conducted in situ on three contaminated and three reference sites on the Oklahoma Refining Company Superfund Waste Site, Cyril, Oklahoma. Cotton rats exposed to these soils showed significant alterations in selected morphological traits, in vivo humoral immune responses, complement activity, and macrophage activity. However, immune alterations were not great, suggesting that resident small mammals may be a better biomonitoring choice than using mesocosms. PMID- 10028659 TI - Degradation of 4-fluorobiphenyl in soil investigated by 19F NMR spectroscopy and 14C radiolabelling analysis. AB - The incubation of the model pollutant [U-14C]'-4-fluorobiphenyl (4FBP) in soil, in the presence and absence of biphenyl (a co-substrate), was carried out in order to study the qualitative disposition and fate of the compound using 14C HPLC and 19F NMR spectroscopy. Components accounted for using the radiolabel were volatilization, CO2 evolution, organic solvent extractable and bound residue. Quantitative analysis of these data gave a complete mass balance. After sample preparation. 14C-HPLC was used to establish the number of 4FBP related components present in the organic solvent extract. 19F NMR was also used to quantify the organic extracts and to identify the components of the extract. Both approaches showed that the composition of the solvent extractable fractions comprised only parent compound with no metabolites present. As the 14C radiolabel was found to be incorporated into the soil organic matter this indicates that metabolites were being generated, but were highly transitory as incorporation into the SOM was rapid. The inclusion of the co-substrate biphenyl was to increase the overall rate of degradation of 4FBP in soil. The kinetics of disappearance of parent from the soil using the data obtained were investigated from both techniques. This is the first report describing the degradation of a fluorinated biphenyl in soil. PMID- 10028660 TI - Interpretation of heavy metal data from mussel by use of multivariate classification techniques. AB - Different strategies of multivariate analysis of metals concentrations (Mn, Fe, Ni, V, Co, Cu, Cd, Hg, Pb, Na, K) in mussel samples from different spanish markets are used to interpret a data base and identify differences between species and origin of the samples. Principal Component Analysis and Potential curves are applied to properly classify unknown samples from representative mussels samples (Mytilus edulis and Perna canaliculus). Also, Principal Components Analysis is used as display method to visualize the relation between the variables and objects of interest. PMID- 10028661 TI - Dioxin and dibenzofuran concentrations in blood of a general population from Tarragona, Spain. AB - The concentrations of polychlorinated dibenzo-p-dioxins (PCDDs) and polychlorinated dibenzofurans (PCDFs) were determined in plasma samples of 20 nonoccupationally exposed subjects living in the vicinity of a new hazardous waste incinerator (HWI), now under construction in Tarragona (Catalonia, Spain). The mean PCDD/F value was 27.0 pg I-TEQ/g lipid with a range from 14.8 to 48.9 pg I-TEQ/g lipid. All samples showed higher PCDD than PCDF levels. Although PCDD/F concentrations were higher in women (27.7 pg I-TEQ/g lipid) than in men (25.2 pg I-TEQ/g lipid), the difference was not statistically significant. While a significant correlation (r = 0.565, p < 0.01) between the age of the subjects and the levels of PCDD/F in plasma could be observed, no significant differences were found in relation to the specific residential area. The plasma concentrations of PCDD/F obtained in the current study are discussed and compared with the results of similar investigations reported in the last two years. PMID- 10028662 TI - The toxicity and concentrations of PAHs in creosote-contaminated lake sediment. AB - Sediment samples, divided into three layers (0-10, 10-20 and 20-30 cm), were collected from 16 sites in Lake Jamsanvesi, Central Finland. The acute toxicity of pore waters and elutriates (sediment + water 1:4 v/v) were studied by bioluminescence inhibition test and by immobilisation of water fleas (Daphnia magna Straus). Concentrations of polycyclic aromatic hydrocarbons (PAHs) in sediments and elutriates were measured by gas chromatography using flame ionization detection (GC/FID). The highest total PAH concentration was 3.3 mg/g dry weight in the sediment and up to 1.7 mg/l in the elutriate of the uppermost (0-10 cm) layer, also being the most toxic to photoluminencent bacteria and water flea. When sediment and water mix, like during dredging operations, toxic compounds may spread from the sediment to the water column and can pose on environmental risk. PMID- 10028663 TI - Solar photocatalytic mineralization of commercial pesticides: methamidophos. AB - Aqueous solutions of methamidophos (O,S-dimethyl phosphoramidothioato) are mineralised in sunlight in the presence of dispersed particles of TiO2 in a pre industrial pilot plant. A commercial pesticide (Tamaron 50, 50% Methamidophos) is used as a model to demonstrate the application of the treatment. Total Organic Carbon (TOC) and PO4(3-) are analysed to confirm the mineralization of the contaminants. The concentration of organics in water was set at TOC approximately 100 mg/L, but with only illuminated TiO2, mineralization was slow. Oxidation of the organics present in the formulation is enhanced 18 times by use of an appropriate electron scavenger (peroxydisulphate) compared to TiO2 alone. PMID- 10028664 TI - Involvement of bioemulsifier in heptadecane uptake in Pseudomonas nautica. AB - A microbial surfactant was investigated for its potential to enhance the biodegradation of heptadecane. The bioemulsifier used in this study was extracted from culture supernatants of Pseudomonas nautica after growth on heptadecane. The heptadecane uptake rate-could be increased 15-fold by the addition of 1.5 mg protein of bioemulsifier per 100 mg of heptadecane. Scanning electron microscopy showed that bioemulsification was the main mode allowing the transfer of hydrocarbon in the presence of the isolated compound. PMID- 10028665 TI - Aerobic biodegradation of dichloroethylenes in surface and subsurface soils. AB - Laboratory studies were conducted to examine the aerobic biodegradation of dichloroethylenes (cis-1,2-DCE, trans-1,2-DCE and 1,1-DCE) in soil and groundwater. Authentic surface and subsurface materials with no reported DCE exposure history were used. All DCE isomers were observed to biodegrade to varying degrees in the soils examined. Use of radiolabeled [14C] test chemicals allowed correlation of DCE disappearance with mineralization to 14CO2. Study results indicate that naturally occurring microorganisms in soil and groundwater are capable of degrading cis-1,2-, trans-1,2- and 1,1-DCE without laboratory supplementation of exogenous organic nutrients, or previous exposure history. The data further suggest that degradative potential may vary with soil type, DCE isomer structure, and concentration. PMID- 10028666 TI - Identification and semiquantitative estimation of antibiotics added to complete feeds, premixes, and concentrates. AB - Classical microbiological methods for determining antimicrobial compounds in feeds are nonspecific. Thus, there is a need to identify biological activity, and bioautography is used for this purpose. A routine method for detecting the following antimicrobial substances in feeds is described: avilamycin, avoparcin, Zn-bacitracin, erythromycin, flavomycin, furazolidone, lasalocid, monensin, narasin, penicillin, salinomycin, spiramycin, tetracyclines, tylosin, and virginiamycin. Carbadox can be detected by UV light examination of the plates prior to bioautography. Semiquantitative estimations of antibiotic content are compared with quantitative determinations of the above mentioned substances in feeds, except erythromycin, penicillin, and tetracyclines. Detection limits range from 0.1 mg/kg (chlortetracycline) to 20 mg/kg (lasalocid). The method involves agar diffusion of buffered samples, a neutral extraction of polyether antibiotics followed by thin-layer chromatography (TLC), and an acid extraction for other antibiotics followed by TLC. Five test bacteria were used for the main detection by agar diffusion: Micrococcus luteus ATCC 9341, Staphylococcus aureus ATCC 6538P, Corynebacterium xerosis NCTC 9755, Bacillus cereus ATCC 11778, and B. subtilis ATCC 6633. Identification after TLC was achieved by bioautography with the most sensitive microorganism(s). This method allows one laboratory technician to analyze up to 30 feed samples within 2.5 working days, provided that feeds of the same category are analyzed in the same run, and that labels of additives are available. Qualitative and semiquantitative information are valuable when performing a quantitative antibiotic determination and it provides proof that the activity determined is due to the tested substance. This last feature is essential from the perspective of quality assurance of results. PMID- 10028667 TI - Screening nitrate in forages with a test strip: collaborative study. AB - A collaborative study was conducted for screening nitrate in forages with a commercially available test strip. The method involves extracting a finely ground sample with deionized water. The test strip is dipped in the sample extract. The color of the reaction zone on the test strip changes from white to pink or purple depending on the nitrate concentration in sample extract. The nitrate present in the extract is determined by comparing the color of the test strip to the color scale on the test strip container. Six blind quintuplicates of forage samples were analyzed by 20 collaborators. Nitrate concentrations in forage samples tested ranged from < 1000 ppm nitrate to > 10,000 ppm nitrate on dry matter basis. Each collaborator was asked to assign each sample to one of the 4 following nitrate concentration ranges: (1) < 1000 ppm, (2) 1000 to 5000 ppm, (3) > 5000 ppm to 10,000 ppm, and (4) > 10,000 ppm. Nineteen of 20 collaborators reported results. Results from 2 laboratories were rejected as outliers by inspection and chi 2 test. Sensitivity rates (p+) ranged from 0.965 to 0.998, with standard errors of 0.006 to 0.16. Specificity rates (p-) ranged from 0.991 to 0.997 for the 4 ranges, with standard errors of 0.003 to 0.006. False-positive rates (pf+) ranged from 0.006 to 0.046, with standard errors of 0.006 to 0.025. False-negative rates (pf-) ranged from 0.003 to 0.007, with standard errors of 0.003 to 0.006. Screening nitrate in forages with a test strip has been adopted first action by AOAC INTERNATIONAL. PMID- 10028668 TI - Thin-layer chromatographic determination of catecholamines, 5-hydroxytryptamine, and their metabolites in biological samples: a review. AB - A review of methodology for separation, detection, and quantitative determination of catecholamines, 5-hydroxytryptamine, and their acidic metabolites in biological tissue and fluids by thin-layer chromatography is presented. Selected procedures, including fluorometric scanning densitometry for catecholamine acetyl derivatives and color scanning densitometry for acids, are described. PMID- 10028669 TI - Reversed-phase thin-layer chromatography with different stationary phases in studies of quantitative structure-biological activity relationship of new antimycotic compounds. AB - Reversed-phase thin-layer chromatography with RP-8, RP-18, and RP-18W stationary phases was used in quantitative structure-activity relationship (QSAR) studies of new antimycotic compounds. The retention behavior of 10 dihydroxythiobenzanilides was examined for acquisition of log k' data. With water-acetone mixtures as the mobile phases, the concentration range for which the correlation between log k' and acetone concentration is linear was established for each stationary phase and used to determine hydrophobicity parameters log k'w by linear extrapolation. The effect of substituents on retention constants was quantitated by using the group contribution parameters tau W. On the basis of QSAR equations obtained from these studies, log k'w data can be used to predict antifungal activities of dihydroxythiobenzanilides with satisfactory accuracy. PMID- 10028670 TI - Determination of oxytetracycline, tetracycline, and chlortetracycline in milk by liquid chromatography with postcolumn derivatization and fluorescence detection. AB - A multiresidue method for isolation and liquid chromatographic determination of oxytetracycline (OTC), tetracycline (TC), and chlortetracycline (CTC) in milk is presented. The sensitivity of the method is adequate to meet the needs of regulatory agencies. The European Community established 100 micrograms/kg as the maximum residue limit (MRL) in milk for TC, CTC, and OTC. Recoveries exceeded 80% for all tetracyclines at all levels, with good precision. Correlation coefficients of standards curves for individual tetracyclines isolated from fortified samples ranged from 0.991 for CTC to 0.998 for OTC. Other antibiotics that might interfere with analysis did not interfere with elution times of OTC, TC, and CTC. The procedure is rapid, precise, and quantitative and requires minimal preparation and minimal use of organic solvents. It can be applied to routine surveillance programs. We can prepare 10 samples for analysis in about 1.45 h. PMID- 10028671 TI - Determination of neomycin in animal tissues by liquid chromatography. AB - Tissue samples are digested under hot alkaline conditions after initial conditioning at room temperature with phosphate-buffered saline. The cooled digest is deproteinated with concentrated perchloric acid. After centrifugation and pH adjustment, the clear supernatant is applied to an ion-exchange cartridge, and after the cartridge is washed, the neomycin is eluted with dilute perchloric acid. This eluate is derivatized with 9-fluorenylmethyl chloroformate prior to liquid chromatography using a wide-pore spherical silica C4 column and fluorescence detection. Recovery and repeatability are calculated from tissue extract standard calibration curves produced from the same assay. Recoveries ranged from 80 to 120% for fortifications of 0.25-1.00 mg/kg for muscle tissue and from 80 to 100% for fortifications of 0.50-10.0 mg/kg for kidney tissue. Limits of quantitation were 0.25 and 0.50 mg/kg, respectively, for muscle and kidney tissues. Limits of detection were 0.125 and 0.20 mg/kg, respectively, for muscle and kidney tissues. PMID- 10028672 TI - Liquid chromatographic determination of carotenoids and vitamins A and E in multivitamin tablets. AB - Carotenoids and vitamins A and E in multivitamin tablets can be determined simultaneously by reversed-phased liquid chromatography (LC) with a programmable UV detector. Samples were dissolved in dimethyl sulfoxide and then extracted with hexane. A portion was injected onto a Symmetry C18, 150 x 4.6 mm id, 5 microns column and chromatographed with a mobile phase of acetonitrile--0.25% ammonium acetate in methanol and 0.05% triethylamine in dichloromethane. A step gradient was used. The system was operated at 25 degrees C with a flow rate of 1.5 mL/min. UV detection was at 325 nm for retinols, 285 nm for tocopherols, and 450 nm for carotenoids. Detection limits were less than 0.3 ng for retinol and retinyl acetate; 2 ng for alpha-tocopherol acid succinate; 10 ng for alpha-tocopherol, gamma-tocopherol, and alpha-tocopherol acetate; and 0.4 ng for alpha-carotene and beta-carotene. Intraday and interday coefficients of variation ranged from 1.40 to 5.20%. The sample preparation method and LC assay are practical for quality control and routine analysis of multivitamin tablets. PMID- 10028673 TI - Dry rehydratable film method for enumerating confirmed Escherichia coli in poultry, meats, and seafood: collaborative study. AB - A rehydratable dry-film plating method for Escherichia coli, the Petrifilm E. coli/Coliform (EC) Count Plate in foods, has been compared with the AOAC INTERNATIONAL most probable number (MPN) method. Eleven laboratories participated in the collaborative study. Three E. coli levels in 8 samples each of frozen raw ground turkey, frozen raw ground beef, and frozen cooked fish were tested in duplicate. Mean log counts for the Petrifilm plate procedure were not significantly different from those for the MPN procedure for cooked fish samples inoculated with low or high inocula levels, for samples of raw turkey inoculated at medium level, and for beef inoculated at low, medium, and high levels. Repeatability and reproducibility variances of the Petrifilm EC Plate method recorded at 24 h were as good as or better than those of the MPN method. The dry rehydratable film method for enumerating confirmed E. coli in poultry, meats, and seafood has been adopted first action by AOAC INTERNATIONAL. PMID- 10028674 TI - Validation of the LacTek test applied to spiked extracts of tissue samples: determination of performance characteristics. AB - LacTek tests are competitive enzyme-linked immunosorbent assays intended for rapid detection of antimicrobial residues in bovine milk. In this study, the LacTek test protocol was modified for use with extracts of bovine tissue to detect beta-lactam, tetracycline, and sulfamethazine residues. Test performance characteristics--precision, accuracy, ruggedness, practicability, and analytical specificity and sensitivity--were investigated. Results suggest that LacTek tests can be easily adapted to detect antimicrobial residues in extracts of lean ground beef. However, positive samples may not contain residues at violative concentrations (i.e., Canadian maximum residue limits), and therefore, additional analysis would be required for final confirmation and quantitation (e.g., chromatography). PMID- 10028675 TI - Determination and survey of ochratoxin A in wheat, barley, and coffee--1997. AB - Ochratoxin A (OA) is a nephrotoxic and nephrocarcinogenic mycotoxin produced by Aspergillus and Penicillium species. It has been found mainly in cereal grains and coffee beans. The purpose of this study was to investigate the occurrence of OA in cereal grains and in coffee imported to the United States. A modified liquid chromatographic (LC) method for determining OA in green coffee was applied to wheat, barley, green coffee, and roasted coffee. The test sample was extracted with methanol-1% NaHCO3 (7 + 3), and the extract was filtered. The filtrate was diluted with phosphate-buffered saline (PBS), filtered, and passed through an immunoaffinity column. After the column was washed with PBS and then with water, OA was eluted with methanol. The eluate was evaporated to dryness, and the residue was dissolved in acetonitrile-water (1 + 1). OA was separated on a reversed-phase C18 LC column with acetonitrile-water-acetic acid (55 + 45 + 1) as eluant and quantitated with a fluorescence detector. Recoveries of OA from the 4 commodities spiked over the range 1-4 ng/g were 71-96%. The limit of detection was about 0.03 ng/g. OA contamination at > 0.03 ng/g was found in 56 of 383 wheat samples, 11 of 103 barley samples, 9 of 19 green coffee samples, and 9 of 13 roasted coffee samples. None of the coffee samples contained OA at > 5 ng/g; only 4 samples of wheat and 1 sample of barley were contaminated above this level. PMID- 10028676 TI - Preparative method for isolating alpha-zearalenol and zearalenone using extracting disk. AB - A liquid chromatographic method is described for the determination of zearalenol and zearalenone in corn. Zearalenol and zearalenone are extracted from corn with methanol-water (1 + 1) and cleaned up using a solid-phase extraction (SPE) disk, separated on a reversed-phase analytical column, and detected with a fluorescence detector. The SPE disk concentrated and cleanly separated zearalenol and zearalenone from sample interferences. Standard calibration curves for zearalenol and zearalenone for the concentration range 25-500 ng/mL were linear. The small extract disk had a column capacity equivalent to 1 g extracted corn. Zearalenol and zearalenone were added at levels ranging from 10 to 2000 ng/g to a control sample that contained no detectable levels of zearalenol and zearalenone. Both toxins were recovered from spiked samples at 106.3 and 103.8%, with coefficients of variation of 7.6 and 13.0%, respectively. The method has an estimated reliable limit of detection and limit of quantitation around 10 and 40 ng/g for each toxin, respectively. PMID- 10028677 TI - Analytical monitoring of citrus juices by using capillary electrophoresis. AB - A capillary electrophoretic method was developed to analyze simultaneously most citrus juice components in a single procedure. After filtration, sample components are separated with an uncoated capillary tubing and a 35 mM sodium borate buffer (pH 9.3) containing 5% (v/v) acetonitrile. Analyses were run at 21 kV and 23 degrees C. Compounds monitored regularly were the biogenic amine synephrine, some flavonoids (didymin, hesperidin, narirutin, neohesperidin, and naringin), the polyphenol phlorin, 3 UV-absorbing amino acids (tryptophan, phenylalanine, and tyrosine), ascorbic acid, an unidentified peak generated by heat and storage, and the preservatives sorbate and benzoate that can be added to citrus products. Separation can be achieved in 20 min, and each compound can be subsequently quantitated. Didymin, narirutin, and phlorin peaks were used with an artificial neural network to assess the volume of added pulp wash, a by-product of juice preparation. This method allows rapid monitoring of citrus juices, giving information on quality, freshness, and possible adulteration of the product. Similar procedures could be used to monitor other fruit juices and quantitate diverse juice blends. PMID- 10028678 TI - A liquid chromatographic method for analysis of all-rac-alpha-tocopheryl acetate and retinyl palmitate in medical food using matrix solid-phase dispersion in conjunction with a zero reference material as a method development tool. AB - A liquid chromatographic method is described for analysis of all-rac-alpha tocopheryl acetate and retinyl palmitate in medical food. The vitamins are extracted from medical food without saponification by matrix solid-phase dispersion and chromatographed by normal-phase chromatography with fluorescence detection. Retinyl palmitate and all-rac-alpha-tocopheryl acetate are quantitated isocratically with a mobile phase of 0.125% (v/v) and 0.5% (v/v) isopropyl alcohol in hexane, respectively. Results compared favorably with label declarations on retail medical foods. Recoveries determined on an analyte fortified zero reference material for a milk-based medical food averaged 98.3% (n = 25) for retinyl palmitate spikes and 95.7% (n = 25) for all-rac-alpha tocopheryl acetate spikes. Five concentrations were examined for each analyte, and results were linear (r2 = 0.995 for retinyl palmitate and 0.9998 for all-rac alpha-tocopheryl acetate) over the concentration range examined, with coefficients of variation in the range 0.81-4.22%. The method provides a rapid, specific, and easily controlled assay for analysis of retinyl palmitate and all rac-alpha-tocopheryl acetate in fortified medical foods. PMID- 10028679 TI - Determination of neutral lactase activity in industrial enzyme preparations by a colorimetric enzymatic method: collaborative study. AB - Thirteen laboratories participated in a collaborative study to validate a colorimetric assay for determining neutral lactase activity in industrial enzyme preparations. Each laboratory received 5 duplicate samples with activity levels of 2000 and 5000 neutral lactase units provided by 4 commercial suppliers. Two laboratories did not return results. Method performance was calculated according to AOAC guidelines. From the 11 remaining laboratories, 3 were excluded from statistical analysis because of invalid data determined during initial review by Youden pair, value versus laboratory. Repeatability relative standard deviation (RSDr) values ranged from 3.20 to 8.62%, and reproducibility relative standard deviation (RSDR) values ranged from 8.77 to 16.35%. With outliers excluded, RSDr values ranged from 2.94 to 5.01%, and RSDR values ranged from 7.50 to 13.84%. The colorimetric enzymatic method for determining neutral lactase activity in industrial enzyme preparations has been adopted first action by AOAC INTERNATIONAL. PMID- 10028680 TI - A validated liquid chromatographic method for determining folates in vegetables, milk powder, liver, and flour. AB - A liquid chromatographic (LC) method was elaborated for determining folates in foods. Folates were extracted by homogenizing in buffer and heat treatment. A portion was incubated with an enzyme preparation containing conjugase, amylase, and protease. After purification by affinity chromatography, folate monoglutamates were determined by reversed-phase LC with fluorescence and diode array detection. Gradient elution with phosphate buffer and acetonitrile was used to separate vitamers. The most abundant folate forms naturally present in foods were detected, including tetrahydrofolic acid, 5-methyltetrahydrofolic acid, and 5-formyltetrahydrofolic acid. 10-Formylfolic acid could be detected by applying a second fluorescence detector. Folic acid, used for fortification, might also be quantitated with this system. The difference between folate concentrations in sample extracts, with and without treatment of conjugase, is a measure of the quantity of polyglutamates in the food matrixes. An additional treatment with conjugase, amylase, and protease reflects the amount of matrix-bound folates. The LC system gave a linear response over the range 0-100 ng/mL. Detection limit for these compounds were 7 pg/mL for tetrahydrofolic acid and 5-methyltetrahydrofolic acid and 59 pg/mL for 10-formylfolic acid (signal-to-noise ratio > or = 3) when 100 microL was injected. Detection limits for 5-formyltetrahydrofolic acid and folic acid were 1 ng/mL. Repeatability relative standard deviation values for separate folates in 3 candidate Certified Reference Materials (CRMs)--mixed vegetables (CRM 485), pig liver (CRM 487), and whole-meal flour (CRM 121)--and a Certified Reference Material milk powder (CRM 421) varied from 3.3 to 21.0% for the concentration range 1.8-1440 micrograms/100 g. Recoveries ranged from 73 to 109%. Use of amylase and protease was advantageous. Use of a commercially available folate-binding protein for cleanup saved time and money and was effective. Results for 5-methyltetrahydrofolic acid were in good agreement with results obtained with other LC methods. Results for total folates were lower than results obtained with microbiological methods. PMID- 10028681 TI - Determination of niacin in infant formula and wheat flour by anion-exchange liquid chromatography with solid-phase extraction cleanup. AB - Niacin content must be included on food labels of infant formula products and bakery products containing enriched flour. Liquid chromatographic (LC) determination of niacin in complex food matrixes is complicated by the presence of endogenous compounds that absorb at the commonly used wave-length of 260 nm. Also, the presence of particulate matter in the standard sulfuric acid extraction procedure results in reduced life of LC columns and precolumns. A simple, rapid, solid-phase extraction (SPE) procedure for separation and cleanup of niacin from a complex food matrix digest has been developed. By using a vacuum manifold with the SPE column system, multiple samples can be processed quickly and efficiently for LC analysis, compared with gravimetric column cleanup. Sulfuric acid sample digest is passed over an aromatic sulfonic acid cation-exchange (ArSCX-SPE) or a sulfonated Florisil SPE column. Niacin is eluted with 0.25M sodium acetate-acetic acid, pH 5.6 buffer in vacuo. LC chromatograms of the resulting eluate are free of interference from other components absorbing at 260 nm at the retention time of niacin. Validation of the method was obtained from agreement of analytical results on available reference materials. For both SPE methods, values for niacin in SRM 1846 Infant Formula (milk-based powder) were within uncertainty ranges of the certified value. Use of several calibration procedures (the LC computer program, a peak area response graphic standard curve, or the method of standard additions) with both SPE procedures resulted in niacin values for 3 RM-Wheat Flours (not certified for niacin) in agreement (90-105%) with their respective values reported in the literature. Several commercial wheat flours showed a broad 260 nm interference, resulting in high niacin values. Niacin recoveries from spiked soy-based liquid infant formulas ranged from 95-107% with the ArSCX-SPE column. Calibration curves of niacin were linear up to 400 micrograms/mL, with a detection limit of 0.2 microgram/mL. PMID- 10028682 TI - Liquid chromatographic determination of sugar alcohols in beverages and foods after nitrobenzoylation. AB - Use of p-nitrobenzoyl chloride (PNBC) to form an ultraviolet-absorbing derivative was attempted to determine the sugar alcohols meso-erythritol, xylitol, D sorbitol, and D-mannitol by liquid chromatography (LC). LC determination of derivatives was performed on an ODS column with acetonitrile-water (65 + 35) as mobile phase. Calibration curves were linear in the concentration range 0.01-100 micrograms/mL. Method sensitivity is 10 to 1000 times higher than that of LC with refractive index detection and gas chromatography with flame ionization detection. Recoveries of sugars added to various foods at 0.1 and 1% ranged from 91 to 102% for meso-erythritol, 75 to 115% for xylitol, 81 to 105% for D sorbitol, and 81 to 108% for D-mannitol. PMID- 10028683 TI - Fat contents of cereal foods: comparison of classical with recently developed extraction techniques. AB - Eight cereal products ranging from a fat-free ready-to-eat (RTE) cereal (frosted flakes) to a full-fat high-ratio cake mix were subjected to analyte separation by anhydrous diethyl ether extraction (EE), acid hydrolysis/mixed ether extraction (AH), solid-phase extraction (SPE), and supercritical fluid extraction (SFE) with CO2 and with CO2 modified with 15% ethanol (SFEmod). Gravimetric analyses of extracts indicated higher (P < or = 0.05) crude fat values by AH than by EE, SFE, or SFEmod. Extractions followed by fatty acid methyl ester analysis also produced higher (P < or = 0.05) triglyceride means by AH than by other methods used for heat-treated RTE cereals and for ready-to-cook (RTC) cream of wheat. Therefore, for labeling purposes, AH seems most appropriate because in most cases it achieves higher triglyceride values than extraction with solvent(s) alone. SFE and SPE, on the other hand, yield fat values similar to those obtained by EE and offer the advantages of reduced solvent volume, short extraction times, and ease of laboratory automation. PMID- 10028684 TI - Sporicidal testing of commercial germicides using a chemical standard and a calibrated bioindicator. AB - The AOAC sporicidal method uses as a standard the resistance of spores on carriers to 2.5N HCl. This resistance is variable at exposure times ranging from 2 to 20 min. The method described in this paper uses a glutaraldehyde standard and distinguishes various levels of sporicidal activity in the presence of 1-5% glutaraldehyde by using appropriate spore strains, spore preparations, and spore levels. The resistances of 2 Bacillus subtilis 19659 spore preparations cultured in 10% Columbia broth plus manganese and nutrient agar plus minerals, as well as that of B. subtilis var. niger cultured on Lab-Lemco agar, were tested. T-soy broth was a better recovery medium than fluid thioglycollate or modified fluid thioglycollate for B. subtilis 19659 spores exposed to HCl. Sporicidal tests were done on B. subtilis 19659 spores with 2 types of spore preparations. A commercial glutaraldehyde germicide was used for comparison of the sporicidal activity of the glutaraldehyde standard. Two strains of B. subtilis spores and 4 levels of spores (20,000-80,000, 100,000-400,000, 500,000-800,000, and 1,000,000 and up) were removed from check penicylinders from the same batches used for sporicidal tests. B. subtilis var. niger spores were the most resistant to HCl, while B. subtilis 19659 spores were more resistant to glutaraldehyde. Sporicidal activities of a commercial germicide containing 2.5% glutaraldehyde with additives and another containing 5% glutaraldehyde in phosphate buffer were similar. Both totally destroyed high levels of B. subtilis 19659 spores cultured in 10% Columbia broth plus manganese. Results indicate that use of a glutaraldehyde standard, calibrated numbers of spores on penicylinders (bioindicators), and appropriate spore strains and preparations can reduce the variability of sporicidal testing of commercial germicides. PMID- 10028685 TI - Determination of submicrogram-per-liter concentrations of caffeine in surface water and groundwater samples by solid-phase extraction and liquid chromatography. AB - A method for determining submicrogram-per-liter concentrations of caffeine in surface water and groundwater samples has been developed. Caffeine is extracted from a 1 L water sample with a 0.5 g graphitized carbon-based solid-phase cartridge, eluted with methylene chloride-methanol (80 + 20, v/v), and analyzed by liquid chromatography with photodiode-array detection. The single-operator method detection limit for organic-free water samples was 0.02 microgram/L. Mean recoveries and relative standard deviations were 93 +/- 13% for organic-free water samples fortified at 0.04 microgram/L and 84 +/- 4% for laboratory reagent spikes fortified at 0.5 microgram/L. Environmental concentrations of caffeine ranged from 0.003 to 1.44 micrograms/L in surface water samples and from 0.01 to 0.08 microgram/L in groundwater samples. PMID- 10028686 TI - Analysis of a mixture of polychlorinated biphenyls and chlorinated pesticides in human serum by column fractionation and dual-column capillary gas chromatography with electron capture detection. AB - An analytical method is presented for precise identification and quantitation of 29 specific polychlorinated biphenyl (PCB) congeners and 15 chlorinated pesticides in human serum. Analyte surrogates PCB 30, PCB 204, 2,2',4,4',5,5' hexabromo-biphenyl, perthane, alpha-hexachlorocyclohexane, and dichlorobenzophenone were added to each sample. The serum was extracted with an organic solvent and separated by adsorption chromatography into 3 elution fractions for high-resolution gas chromatographic analysis. Each fraction was analyzed by dual-column capillary chromatography followed by electron capture detection. Two capillary columns, DB-5 and DB-1701, with different polarities were used to increase selectivity for each analyte. Quantitation was performed by selecting 2 sets of calibration standard mixtures and 1,2-dichloronaphthalene as an internal standard. Mean recoveries ranged from 39 to 126% for selected analytes and from 31 to 88% for surrogates. Detection limits for specific congeners and pesticides are reported. Typical chromatographic profiles of calibration standard mixtures, as well as a human sample, are illustrated. Verification of each analyte is assessed, and results of analyses of selected human samples and quality control criteria used to ensure data validity also are presented. PMID- 10028687 TI - Multiresidue gas chromatographic method for determining synthetic pyrethroid pesticides in agricultural products: collaborative study. AB - Fourteen laboratories from 6 countries and regions participated in an international collaborative study to evaluate a multiresidue gas chromatographic (GC) method for determining 8 synthetic pyrethroid pesticides in grains, fruits, and vegetables. The study design was based on Youden's matched-pairs principle for collaborative tests of analytical methods. Each laboratory analyzed 12 collaborative samples of wheat, oranges, and tomatoes as blind samples. Wheat samples were extracted with acetonitrile-water (2 + 1), while orange and tomato samples were extracted with acetone. Residues were partitioned into hexane, evaporated to dryness with a rotary evaporator, and then dissolved in hexane. The hexane extract was partitioned with acetonitrile and cleaned up on a 5% water deactivated Florisil column with 6% ethyl ether in hexane as eluant. Residue concentrations were determined by GC with electron capture detection with splitless injection by comparison with single-point calibration standards. The appropriate standard concentration was determined by screening sample extracts before analysis. The multiresidue method was tested over the concentration range of 0.095-1.909 mg/kg depending on the 8 different of pesticides and agricultural products analyzed in the collaborative study. Statistical analysis of data from 13 laboratories showed weighted average recoveries for 8 pyrethroids in wheat, oranges, and tomatoes at 0.105-1.909, 0.095-1.909, and 0.105-0.954 mg/kg, respectively, ranging from 91.8 to 100.2%, from 88.1 to 100.6%, and from 88.2 to 101.5%, respectively. Reproducibility relative standard deviation values ranged from 6.46 to 17.74%, from 5.94 to 18.13%, and from 5.59 to 10.48%, respectively. Repeatability relative standard deviation values ranged from 6.34 to 10.84%, from 5.19 to 11.72%, and from 3.20 to 8.09%, respectively. The multiresidue GC method for determining synthetic pyrethroid pesticides in agricultural products has been adopted first action by AOAC INTERNATIONAL. PMID- 10028688 TI - High-sensitivity analysis and sequencing of peptides and proteins by quadrupole ion trap mass spectrometry. AB - This paper describes experience with the commercially available LCQ quadrupole ion trap mass spectrometer applied to the off-line analysis of peptides and proteins. The standard front end of the electrospray probe was replaced with a micromanipulator which, with the aid of a magnifying device, allowed the use of a variety of miniaturized spraying interfaces. The low sample consumption and extended analysis times of these devices were ideally suitable to obtain improved results in terms of sensitivity and mass accuracy. This needed a careful optimization of the number of ions stored inside the trap (ion target parameter) and required spectrum averaging of many scans. A method is presented for the mathematical fitting of ZoomScan spectra to theoretical isotopic distributions, which allowed the mass determination of large peptides with more accuracy than that achieved by conventional deconvolution algorithms. A very simple on-line desalting configuration is also described which needed no external micro-high performance liquid chromatographic pumps, and can be easily mounted using the built-in syringe delivery system of the LCQ. This set-up allowed extended analysis times of 'in-gel' protein digests in subpicomole amounts. Finally, the multiple fragmentation capabilities of the ion trap were found to be extremely useful for the analysis of peptide modifications such as phosphorylation and for sequencing individual peptides from highly complex MHC-bound peptide pools. PMID- 10028689 TI - Isolation from pig liver microsomes, identification by electrospray tandem mass spectrometry and in vitro immunosuppressive activity of a rapamycin tris-epoxide metabolite. AB - It was demonstrated that rapamycin is metabolized in vitro by pig liver microsomes under the influence of the cytochrome P450-dependent mixed function oxygenase system to a rapamycin tris-epoxide metabolite, as demonstrated by electrospray tandem mass spectrometry. The in vitro immunosuppressive activity of this metabolite was found to be lower than that of rapamycin, probably because the rapamycin effector sector was structurally modified. The effector region of rapamycin was recognized to include the conjugated double bonds of this compound and metabolic reactions affecting this region may change the binding affinity of the rapamycin-FKBP binary complex towards another pharmacological receptor bound to the binary complex. Moreover, metabolic modifications in the effector region are probably able to induce a change in the binding affinities of the rapamycin FKBP binary complex, including the pipecolic acid moiety and the lactone function of the parent drug. PMID- 10028690 TI - Low-energy collisionally activated decomposition and structural characterization of cyclic heptapeptide microcystins by electrospray ionization mass spectrometry. AB - Characteristics of electrospray ionization mass spectrometry/collision-induced dissociation (ESIMS/CID) mass spectra of microcystins, cyanobacterial cyclic heptapeptide hepatoxins, were examined. The collision conditions showed remarkable effects on the quality of the CID mass spectra, which were divided into three patterns according to the number of Arg residues. A characteristic cleavage reaction and neutral losses of MeOH, NH3 and guanidine group(s) from the (2S,3S,8S,9S)-3-amino-9-methoxy-2,6,8-trimethyl-10-phenyldeca-4 E,6E-dienoic acid (Adda) and Arg residues were observed in the ESI and ESIMS/CID mass spectra, suggesting the most probable protonation sites in [M + H]+ and [M + 2H]2+ ions of microcystins. Microcystins with no Arg residue showed only [M + H]+ ions with a proton reacting at the methoxyl group in the Adda residue, and the ESIMS/CID/MS data revealed their structures unambiguously. The protonation site in [M + H]+ ions of microcystins with Arg residue(s) was the guanidine group. The [M + 2H]2+ ions of microcystins possessing one Arg residue had one proton on the Arg residue and probably another proton on the Adda residue, while the [M + 2H]2+ ions of microcystins having two Arg residues showed protonation at both Arg residues and the ESIMS/CID/MS data assigned their sequences. Structures of microcystins possessing one Arg residue can be assigned by ESIMS/CID/MS of [M + H]+ ions combined with those of [M + 2H]2+ ions. PMID- 10028691 TI - Extinction of responding maintained by timeout from avoidance. AB - The resistance to extinction of lever pressing maintained by timeout from avoidance was examined. Rats were trained under a concurrent schedule in which responses on one lever postponed shock on a free-operant avoidance (Sidman) schedule (response-shock interval = 30 s) and responses on another lever produced 2 min of signaled timeout from avoidance on a variable-ratio 15 schedule. Following extended training (106 to 363 2-hr sessions), two experiments were conducted. In Experiment 1 two different methods of extinction were compared. In one session, all shocks were omitted, and there was some weakening of avoidance but little change in timeout responding. In another session, responding on the timeout lever was ineffective, and under these conditions timeout responding showed rapid extinction. The within-session patterns produced by extinction manipulations were different than the effects of drugs such as morphine, which also reduces timeout responding. In Experiment 2 shock was omitted for many consecutive sessions. Response rates on the avoidance lever declined relatively rapidly, with noticeable reductions within 5 to 10 sessions. Extinction of the timeout lever response was much slower than extinction of avoidance in all 4 rats, and 2 rats continued responding at baseline levels for more than 20 extinction sessions. These results show that lever pressing maintained by negative reinforcement can be highly resistant to extinction. The persistence of responding on the timeout lever after avoidance extinction is not readily explained by current theories. PMID- 10028692 TI - Blocking a selective association in pigeons. AB - Experiment 1 demonstrated for the first time a stimulus-reinforcer interaction in pigeons trained with free-operant multiple schedules of reinforcement. Pigeons that treadle pressed in the presence of a tone-light (TL) compound for food exhibited primarily visual stimulus control on a stimulus-element test, whereas pigeons that avoided shock in TL exhibited auditory control. In Experiment 2, this selective association was blocked in pigeons pretrained with the biologically contingency-disadvantage element of the compound (i.e., tone-food or light-shock) before TL training. When this pretraining preceded compound-stimulus training, control was now auditory in pigeons that treadle pressed for food and was visual in pigeons that avoided shock. Previous attempts at blocking this selective association were unsuccessful in pigeons (LoLordo, Jacobs, & Foree, 1982) but were successful in rats (Schindler & Weiss, 1985). Experiment 2 established that selective associations can be blocked in pigeons when the procedures that were effective with rats were systematically replicated. These results further demonstrate the cross-species generality of an associative attentional mechanism involving a biological constraint on learning in species with different dominant sensory systems. PMID- 10028693 TI - Psychophysics of remembering. AB - We present a new model of remembering in the context of conditional discrimination. For procedures such as delayed matching to sample, the effect of the sample stimuli at the time of remembering is represented by a pair of Thurstonian (normal) distributions of effective stimulus values. The critical assumption of the model is that, based on prior experience, each effective stimulus value is associated with a ratio of reinforcers obtained for previous correct choices of the comparison stimuli. That ratio determines the choice that is made on the basis of the matching law. The standard deviations of the distributions are assumed to increase with increasing retention-interval duration, and the distance between their means is assumed to be a function of other factors that influence overall difficulty of the discrimination. It is a behavioral model in that choice is determined by its reinforcement history. The model predicts that the biasing effects of the reinforcer differential increase with decreasing discriminability and with increasing retention-interval duration. Data from several conditions using a delayed matching-to-sample procedure with pigeons support the predictions. PMID- 10028694 TI - Invertase activity associated with the walls of Solanum tuberosum tubers. AB - Three fractions with invertase activity (beta-D-fructofuranoside fructohydrolase, EC 3.2.1.26) were isolated from mature Solanum tuberosum tubers: acid soluble invertase, invertase I and invertase II. The first two invertases were purified until electrophoretic homogeneity. They are made by two subunits with an apparent M(r) value of 35,000 and their optimal pH is 4.5. Invertase I was eluted from cell walls with ionic strength while invertase II remained tightly bound to cell walls after this treatment. This invertase was solubilized by enzymatic cell wall degradation (solubilized invertase II). Their K(m)s are 28, 20, 133 and 128 mM for acid soluble invertase, invertase I, invertase II and solubilized invertase II, respectively. Glucose is a non-competitive inhibitor of invertase activities and fructose produces a two site competitive inhibition with interaction between the sites. Bovine serum albumin produces activation of the acid soluble invertase and invertase I while a similar inhibition by lectins and endogenous proteinaceous inhibitor from mature S. tuberosum tubers was found. Invertase II (tightly bound to the cell walls) shows a different inhibition pattern. The test for reassociation of the acid soluble invertase or invertase I on cell wall, free of invertase activity, caused the reappearance of all invertase forms with their respective solubilization characteristics and molecular and kinetic properties. The invertase elution pattern, the recovery of cell wall firmly bound invertase and the coincidence in the immunological recognition, suggest that all three invertases may be originated from the same enzyme. The difference in some properties of invertase II and solubilized invertase II from the other two enzymes would be a consequence of the enzyme microenvironment in the cell wall or the result of its wall binding. PMID- 10028695 TI - Vacuolar H(+)-pyrophosphatase purified from pear fruit. AB - A vacuolar H(+)-translocating inorganic pyrophosphatase was purified from pear fruit through selective detergent treatments, Superose 6 and Mono Q column chromatography. The specific activity of the purified enzyme was 850 mumol h-1 mg protein-1. The Mr of V-PPase was 66 kDa by SDS-PAGE and the polypeptide cross reacted with the antiserum against V-PPase of mung bean. The purified V-PPase was stimulated by potassium and inhibited by calcium and N, N' dicyclohexylcarbodiimide. PMID- 10028698 TI - Quassinoids from the twigs and thorns of Castela polyandra. AB - The structures of six new C20 quassinoids and one new C19 quassinoid, all isolated from the twigs and thorns of Castela polyandra, were established by a combination of spectroscopic and single-crystal X-ray analysis. Five known quassinoids and one known sterol were also identified. PMID- 10028699 TI - A strategy for assessing the effects of xenobiotics on fish reproduction. AB - Environmental pollutants, such as industrial and agricultural chemicals, heavy metals, drugs and products with hormonal activity may disrupt reproduction of aquatic wildlife such as fish. Such xenobiotics may cause disruption of the reproductive endocrine system, or they may directly affect gamete development and viability as a result either of their cytotoxicity or by altering the hormonal environment during gamete development. The various possible sites of action are reviewed, and it is suggested that tests for toxicity should isolate the specific component of the reproductive system that is most sensitive to such disruption and that this may be at levels well below that which causes mortality or visible signs of stress. Fish are proposed as the most suitable aquatic organism for such tests. PMID- 10028700 TI - An ELISA for brown trout (Salmo trutta) vitellogenin and its use in bioassays for environmental estrogens. AB - An enzyme linked immunosorbent assay (ELISA) was developed for the detection of the egg yolk precursor vitellogenin (Vg) in plasma of brown trout (Salmo trutta). Purified Vg from a 17 beta-estradiol-induced trout was used as the competing antigen in the ELISA which is based on polyclonal antibodies. The ELISA's performance was optimized and characterized. The assay's working range was (25 500 ng ml-1), its sensitivity was (10.5 ng ml-1), and it had an intra-assay coefficient of variation of less than 10% between 30 and 1000 ng ml-1. The ELISA was used in bioassays for the detection of environmental estrogens, including estrogen mimics, in whole and fractionated industrial waste waters. Those bioassays were based on intraperitoneal (i.p.) injection-, static renewal-, and flow through exposure systems. The response threshold of both bioassays is limited to 1-2 micrograms ml-1 Vg by a low level plasma interference that was regularly detected in plasma from non-induced male fish. The responsiveness of the bioassays was characterized using progressive doses of 17 beta-estradiol. The i.p.-based assay, which was responsive to at least 100 micrograms kg-1 of 17 beta estradiol, was used to screen extracts of pulp mill effluent and black liquor for estrogenic effects. Neither extract induced Vg in our assay. The i.p. assay was also used to test 4-tert-octylphenol (OP) and the PAH derivative, retene, for estrogenic activity. OP induced Vg in the i.p.-exposed fish; no Vg induction was detected in the retene-exposed fish. The static renewal bioassay, which was responsive to at least 0.1 microgram ml-1 of 17 beta-estradiol over a 15-day exposure period, was used to screen whole pulp mill effluents for estrogenic effects. No Vg induction was detected in the effluent-treated fish. PMID- 10028701 TI - Development of a sensitive E-screen assay for quantitative analysis of estrogenic activity in municipal sewage plant effluents. AB - A simplified proliferation test with human estrogen receptor-positive MCF-7 breast cancer cells (E-screen assay) was optimized and validated for the sensitive quantitative determination of total estrogenic activity in effluent samples from municipal sewage plants. After solid phase extraction of 1 l sewage on either 0.2 g polystyrene copolymer (ENV+) or 1 g RP-C18 material and removal of the solvent, analysis of the extracts in the E-screen assay could be performed without any clean-up step. This was even possible with untreated sewage. Parallel extraction of four sewage samples on both different solid phase materials gave comparable quantitative results in the E-screen. A blank sample did not induce cell proliferation. As additive behaviour of the estrogenic response of single compounds was proven for two different mixtures each containing three xenoestrogens, total estrogenic activity in the sewage samples, expressed as 17 beta-estradiol equivalent concentration (EEQ), could be calculated comparing the EC50 values of the samples with those of the positive control 17 beta-estradiol. The detection limit of the E-screen method was 0.05 pmol EEQ/l (0.014 ng EEQ/l), the limit of quantification 0.25-0.5 pmol EEQ/l (0.07-0.14 ng EEQ/l). In total, extracts of nine effluent and one influent sample from five different municipal sewage plants in South Germany were analyzed in the E-screen. All samples strongly induced cell proliferation in a dose-dependent manner which was completely inhibited by coincubation with 5 nM of the estrogen receptor antagonist ICI 182,780. The proliferative effect relative to the positive control 17 beta-estradiol (RPE) was between 30 and 101%. 17 beta-Estradiol equivalent concentrations were between 2.5 and 25 ng/l indicating a significant input of estrogenic substances via sewage treatment plants into rivers. PMID- 10028702 TI - Amphibians as a model to study endocrine disruptors: I. Environmental pollution and estrogen receptor binding. AB - Many chemicals released into the environment without toxicological risks have the capacities to disrupt the function of endocrine systems. These endocrine disruptors disturb normal endocrine mechanisms and have been observed in nearly all classes of vertebrates. The aim of this research is to develop a comprehensive model to study endocrine disruption using the amphibian Xenopus laevis. The assessment of estrogenic potencies of endocrine disruptors includes several levels of investigation: (I) binding to liver estrogen receptor, (II) estrogenic activity in vitro by inducing vitellogenin synthesis in primary cultured hepatocytes, and (III) in vivo effects on sexual development caused by exposure of larvae. The present paper is focused on the first part by establishing a radioreceptorassay for [3H]17 beta-estradiol ([3H]E2) binding using liver cytosol fraction. In order to get optimum binding conditions we performed kinetic, saturation, and competitive displacement experiments. Association of [3H]E2 to estrogen receptor revealed that maximum specific binding is achieved between 18 and 48 h of incubation. Scatchard analyses of saturation experiments resulted in a homogenous saturable population of estrogen receptors having no significant differences of binding parameters between both sexes. The values of Kd (dissociation constant) in males and females were 22.4 +/- 6.0 and 15.0 +/- 2.8 nM (mean +/- S.E.M.; n = 5), respectively, while corresponding Bmax (maximum binding capacity) revealed 89 +/- 46 and 136 +/- 46 fmol [3H]E2/mg protein. The specificity of estrogen receptors as shown by competitive displacement experiments demonstrated receptors being highly specific just for estrogens, but not for other endogenous steroids having the following ranking of binding affinities: E2 > estrone > dehydroepiandrosterone > aldosterone > or = testosterone > or = corticosterone > or = progesterone. The affinity ranking of environmental chemicals compared to E2 was: E2 > tetrachlorbiphenyl > diethylphthalate > 2,2-bis-(4-hydroxyphenyl)-propan (bisphenol A) > or = 4 nonylphenol > or = 3-t-butyl-4-hydroxyanisole > or = 4-octylphenol > dichlor diphenyl-trichlor-ethan (4,4'-DDT). Analyses of five sewage effluents for displacement of [3H]E2 binding resulted in three samples displacing more than 50% of specific binding at their original concentration. Taken together the established radioreceptorassay for [3H]E2 binding in Xenopus laevis liver cytosol is useful to screen estrogen receptor binding of pure compounds or complex mixtures of them, which is the prerequisite for causing either estrogenic or antiestrogenic effects. PMID- 10028703 TI - Amphibians as a model to study endocrine disruptors: II. Estrogenic activity of environmental chemicals in vitro and in vivo. AB - Several environmental chemicals are known to have estrogenic activity by interacting with development and functions of endocrine systems in nearly all classes of vertebrates. In order to get a better insight of potential estrogenic effects on amphibians caused by environmental pollution this study aims to develop a model for investigating endocrine disruptors using the amphibian Xenopus laevis. In that model the potential estrogenic activity of endocrine disruptors is determined at several levels of investigation: (I) binding to liver estrogen receptor; (II) estrogenicity in vitro by inducing vitellogenin synthesis in primary cultured hepatocytes; and (III) in vivo effects on sexual development. Here we deal with establishing methods to assay estrogenic activity of environmental chemicals in vitro and in vivo. In vitro we used a semiquantitative reverse transcriptase-polymerase chain reaction (RT-PCR) technique to determine mRNA-induction of the estrogenic biomarker vitellogenin in primary cultured hepatocytes of male Xenopus laevis. Time courses of vitellogenin-mRNA in the presence and absence of 10(-6) M 17 beta-estradiol (E2) resulted in a marked loss of mRNA from controls after 2 days while E2 treatment kept vitellogenin-mRNA at a relatively stable level. After 36 h of incubation estrogenic activities of E2, 4 nonylphenol (NP), and 2,2-bis-(4-hydroxyphenyl)-propan (bisphenol A) at concentrations ranging from 10(-10) to 10(-5) M were assayed by RT-PCR of vitellogenin-mRNA and showed the following ranking of dose-dependent potency: E2 > NP > bisphenol A. These in vitro results were confirmed further by in vivo experiments determining sexual differentiation of Xenopus laevis after exposure to E2 and environmental chemicals during larval development. Concentrations of 10(-7) and 10(-8) M E2 as well as 10(-7) M of NP or bisphenol A caused a significant higher number of female phenotypes compared to controls indicating a similar ranking of estrogenic potencies in vivo as in vitro. In addition, butylhydroxyanisol and octylphenol, both showed feminization at 10(-7) M while octylphenol was also effective at 10(-8) M. In summary these results demonstrate for the first time the use of a semiquantitative RT-PCR technique for screening estrogenicity by assaying mRNA induction of the estrogenic biomarker vitellogenin in vitro. The combination of this newly developed method with classical exposure experiments is necessary for determination of the biological significance of estrogenic chemicals. PMID- 10028704 TI - Monitoring of estrogen mimics by a recombinant yeast assay: synergy between natural and synthetic compounds? AB - Properties of mixtures of compounds exhibiting estrogenic potential have been questioned in the past. Synergistic effects of endocrine disrupters have been proposed, but could never be confirmed. In this study, the transactivational potential of xenoestrogens and phytoestrogens has been evaluated in a yeast test system. Pesticides such as endosulfan, dieldrin, atrazine, and the main metabolites, desethylatrazine and desisopropylatrazine, have been tested and their behavior as mixtures is compared to the behavior of the single compounds. Our results are in contrast to a report (Tran et al., 1996) on the inhibitive effects of xenoestrogens on 17 beta-estradiol-dependent transactivation. Phytoestrogens have been investigated in a similar manner. A synergistic effect could not be confirmed for both, xenoestrogens and phytoestrogens. These compounds are either weak estrogens or completely lack estrogenic potential. Their endocrine disrupting potential in more complex systems must be therefore attributed to other molecular mechanisms such as to metabolic modification or interference with steroidogenesis. This study shows that yeast systems are useful tools for monitoring pure estrogenic properties. PMID- 10028705 TI - Behavior and occurrence of estrogens in municipal sewage treatment plants--I. Investigations in Germany, Canada and Brazil. AB - The developed method enables the quantification of estrogens in sewage samples down to 1 ng/l and in river water down to 0.5 ng/l. Mean recoveries of the analytes in ground water after SPE extraction, clean-up and derivatization generally exceeded 75%. The determined R.S.D. varied from 0 to 14% at a spiking level of 0.05 microgram/l. Even in the raw influent and the final effluent from municipal STPs the mean recoveries of estrogens were mostly above 70%. Using this method the behavior and occurrence of natural estrogens and synthetic contraceptives in municipal sewage treatment plants (STP) were investigated in German and Canadian facilities. In the sewage of a German municipal STP close to Frankfurt/Main 17 beta-estradiol and estrone were determined, with mean concentrations of 0.015 microgram/l and 0.027 microgram/l, respectively. In two investigated municipal STPs, 17 beta-estradiol and 16 alpha-hydroxyestrone were eliminated with a higher efficiency than 17 alpha-ethinylestradiol and estrone. In Canadian and German STP discharges estrone, 17 beta-estradiol, 17 alpha ethinylestradiol and 16 alpha-hydroxyestrone were frequently detected within the lower ng/l-range. A maximum concentration was found for estrone with 70 ng/l. In 15 investigated German rivers and streams only estrone was present with a maximum concentration of 1.6 ng/l. PMID- 10028706 TI - Behaviour and occurrence of estrogens in municipal sewage treatment plants--II. Aerobic batch experiments with activated sludge. AB - Aerobic batch experiments containing a diluted slurry of activated sludge from a real sewage treatment plant (STP) near Frankfurt/Main were undertaken, in order to investigate the persistence of natural estrogens and contraceptives under aerobic conditions. The batch experiments showed that while in contact with activated sludge the natural estrogen 17 beta-estradiol was oxidized to estrone, which was further eliminated in the batch experiments in an approximate linear time dependence. Further degradation products of estrone were not observed. 16 alpha-hydroxyestrone was rapidly eliminated, again without detection of further degradation products. The contraceptive 17 alpha-ethinylestradiol was principally persistent under the selected aerobic conditions, whereas mestranol was rapidly eliminated and small portions of 17 alpha-ethinylestradiol were formed by demethylation. Additionally, two glucuronides of 17 beta-estradiol (17 beta estradiol-17-glucuronide and 17 beta-estradiol-3-glucuronide) were cleaved in contact with the diluted activated sludge solution and thus 17 beta-estradiol was released. The glucuronidase activity of the activated sludge was further confirmed by the cleavage of 4-methylumbelliferyl-beta-D-glucuronide (MUF-beta glucuronide) in a solution of a activated sludge slurry and Milli-Q-water (1:100, v/v). The turnover rate obtained was approximately steady state, with a turnover rate of 0.1 mumol/l for the released MUF. Hence, it is very likely that the glucuronic acid moiety of 17 beta-estradiol glucuronides and other estrogen glucuronides become cleaved in a real municipal STP, so that the concentrations of the free estrogens increase. PMID- 10028707 TI - Analysis and occurrence of estrogenic hormones and their glucuronides in surface water and waste water in The Netherlands. AB - An analytical procedure was developed that enables routine analysis of four estrogenic hormones in concentrations below 1 ng/l in surface water and waste water. The recovery was 88-98% with a limit of detection of 0.1-2.4 ng/l depending on the compound and the matrix measured. This method was used to determine the occurrence of 17 beta-estradiol, 17 alpha-estradiol, estrone and 17 alpha-ethinylestradiol in the aquatic environment in The Netherlands. The data show that estrogenic hormones can be detected at low concentrations (up to 6 ng/l) at some locations in surface water. In selected effluents of waste water treatment plants estrone and 17 beta-estradiol were detected in concentrations in the ng/l range. Concentrations of 17 alpha-estradiol and the contraceptive 17 alpha-ethinylestradiol were in most of these samples below the limit of detection. Hormone glucuronides were not detected in most surface water and effluents. PMID- 10028708 TI - Occurrence of antibiotics in the aquatic environment. AB - The recent monitoring of drug residues in the aquatic environment has gained much interest as many pharmaceutical compounds can frequently be found in sewage treatment plant (STP) effluents and river water at concentrations up to several microgram/l. This article describes the analysis of various water samples for 18 antibiotic substances, from the classes of macrolid antibiotics, sulfonamides, penicillins and tetracyclines. Samples were preconcentrated via lyophilization and quantified using HPLC-electrospray-tandem-mass spectrometry. The investigated STP effluents and surface water samples showed frequent appearance of an erythromycin degradation product, roxithromycin and sulfamethoxazole with concentrations up to 6 micrograms/l. Neither tetracyclines nor penicillins could be detected at concentration levels above 50 and 20 ng/l, respectively. From the large number of ground water samples that were taken from agricultural areas in Germany, no contamination by antibiotics was detected except for two sites. This indicates that intake from veterinary applications to the aquatic environment is of minor importance. PMID- 10028709 TI - The exposure assessment for veterinary medicinal products. AB - The proposed methodology for the assessment of the environmental risks of the use of veterinary medicinal products is the hazard quotient approach. This article will elaborate on the exposure assessment with exposure models adapted to the Dutch agricultural situation. Based on the exposure assessment, decisions are made on the acceptability of the environmental risk of a product. Therefore, regulatory authorities have to be careful in choosing exposure scenarios. It will be shown that simple alterations of general models with an eye for common agricultural practice change predicted exposure concentrations by a factor of 2 40. In addition, the current proposals for effect assessment are too diverse, and the triggers that lead to further extensive testing are either useless, or at the least inconsistent with each other. An interdisciplinary approach using knowledge of veterinary and agricultural practice, risk management, and environmental toxicology and chemistry, is needed to determine relevant exposure scenarios. PMID- 10028710 TI - Polar drug residues in sewage and natural waters in the state of Rio de Janeiro, Brazil. AB - The drug residues of lipid regulators, anti-inflammatories and some drug metabolites have been detected in raw sewage, treated waste water and river water in the state of Rio de Janeiro, Brazil. These residues are mainly derived from humans via excretion. The median concentrations in the effluents of sewage treatment plants (STPs) of most drugs investigated in this study ranged from 0.1 to 1 microgram/l. The removal rates of individual drugs during passage through a Brazilian STP varied from 12 to 90%. As a consequence of the incomplete removal of these residues during passage through a STP, rivers were also found to be contaminated. Median concentrations ranged from between 0.02 and 0.04 microgram/l in river water, whereas the maximum values were observed to be up to 0.5 microgram/l. PMID- 10028711 TI - Biodegradation of the iodinated X-ray contrast media diatrizoate and iopromide. AB - The degradation of the iodinated contrast media diatrizoate and iopromide was investigated in laboratory tests. With regard to the expected behaviour of the contrast media in the environment, test systems with activated sludge, river water and river water plus sediment were established. In some of the experiments 14C-labelled contrast media were used to study degradation at low concentrations and to detect the transformation products. Degradation by as well as binding to aerobic-activated sludge of diatrizoate was poor, suggesting that this substance is hardly retained in sewage treatment plants. In systems with river water and sediment deacetylation of diatrizoate started after a lag period of 3 weeks and followed first order kinetics with rate constants of approximately 0.15 day-1. Two metabolites were formed that were stable until day 200 of aerobic incubation. Finally, further transformation of the aerobic metabolites was observed under anoxic conditions. In activated sludge, approximately 85% of iopromide were transformed into two metabolites. Like the parent compound they were highly hydrophilic and less than 16% were bound to sludge solids. In water/sediment systems, disappearance of iopromide started spontaneously with a first order constant of 0.04 day-1. One metabolite that was stable throughout the incubation period was formed with a delay of 20 days. In river water the concentration dependent disappearance of iopromide was studied. The shortest half-life was 3.1 days at a concentration of 16.0 mumol l-1 and increased at concentrations below and above this value. The metabolites of iopromide were not identified, but partial deiodination of iopromide was shown. Mineralisation of the two contrast media or their metabolites to carbon dioxide was not observed. PMID- 10028713 TI - Determination of carboplatinum and cisplatinum by interfacing HPLC with ICP-MS using ultrasonic nebulisation. AB - A novel HPLC technique has been developed for the determination of carboplatinum(II) and cisplatinum(II) which are used for chemotherapy. The compounds were separated by a HPLC column. The eluent was on-line nebulized into the nebuliser gas flow using ultrasonic nebulisation. The resulting aerosol was driven by the nebuliser gas stream through a 30-cm heating path, a 60-cm cooling path for desolvatisation and into the plasma of the ICP-MS. The detection was carried out on platinum mass 195Pt. Different RP C18 techniques were tested to obtain the best separation and detection results of the two platinum compounds. The solvent-generated anion exchanger method was selected as the method with the best handling and sensitivity. This technique allows a good separation of the two compounds within 3 min. The detection limits for carboplatinum and cisplatinum were 130 and 80 pg, respectively. The newly developed system has been applied to study the behaviour of the platinum species under different anion influences in aqueous solutions. These investigations are necessary for the future development of an extraction from environmental samples for the two compounds. In further experiments the distribution of the two platinum species, Na2Pt(II)Cl4 and the palladium species. Na2Pd(II)Cl4 between water/sediment, water/charcoal, sewage sludge/water and the distribution in the solution after iron flocculation were investigated to plan an extraction method for the platinum species from environmental matrices. PMID- 10028712 TI - European hospitals as a source for platinum in the environment in comparison with other sources. AB - The concentration of platinum in the sewage of five European hospitals originating from excreted antineoplastic drugs, cisplatin and carboplatin, was analyzed in a short term study to provide an order of magnitude of Pt emissions from hospitals into aquatic environments. These emissions were compared with a rough estimation of emissions by cars. The average daily concentrations in the hospital effluents were approximately < 10-601 ng l-1 Pt (20-3580 ng l-1 in 2-h mixed samples). As expected from consumption data, the daily average concentrations should range from < 10-710 ng l-1 Pt. Platinum emitted by hospitals is 3.3-12.3% (1.3-14.3 kg per year) the estimated amount emitted by cars equipped with catalytic converters in the different European countries. Compared to platinum emissions from other sources, the effluents of hospitals are a minor source of platinum in municipal sewage, but they should not to be disregarded. Other possible sources for the emission of platinum into the environment should be considered in further investigations. PMID- 10028714 TI - [Relationship of allergen structure and allergic reaction]. PMID- 10028715 TI - [Japanese cedar pollen allergen standardization: analysis of major allergens]. PMID- 10028716 TI - [A cross-reactivity of Candida albicans at the serum IgE level to the other yeast species]. PMID- 10028717 TI - [Serum eosinophil cationic protein, urinary eosinophil protein X and urinary N methylhistamine during acute asthma in children]. AB - Serum eosinophil cationic protein (ECP), urinary eosinophil protein X (EPX) and urinary N-methylhistamine were investigated in 24 asthmatic children during acute asthma to determine the sequential variation in the parameters. Serum ECP levels and urinary EPX levels were high during acute asthma, and decreased gradually with improvement of acute asthma, however, these levels of eosinophil drived proteins were significantly higher than those in non-atopic children. There was no significant variation of urinary NMH levels. Significant inverse correlation was found between lung function and urinary EPX level. The present study suggests that serum ECP and urinary EPX may be useful for monitoring airway inflammation during acute asthma, and activation of eosinophils may persist after improvement of acute asthma. PMID- 10028718 TI - [Circadian rhythm of parasympathetic nervous function in asthmatic children]. AB - We examined the circadian rhythm of parasympathetic nervous function in asthmatic children. The subjects were 80 patients with asthma (mild 54 patients, moderate 15 patients and severe 11 patients) and 90 individuals in healthy children. All the patients underwent 24-electrocardiography in normal condition. We measured the %RR50 for hour and analyzed the rhythm using the single cosine fitting method, comparing the values of the Amplitude, the MESOR and the Acrophase in terms of the therapy and also the severity of asthma. Circadian rhythm disappeared in 9 of the 80 asthmatic children and was observed in all the individuals in the healthy children. The value of MESOR was lower in the asthmatic children than in the healthy children. There was no significant difference between the different severity or therapies in each group. In some asthmatic children, the circadian rhythm of parasympathetic nervous function disappeared, the parasympathetic nervous function was low in remission. It is suggested that the disorder of biologic rhythm is related to the pathogenesis of asthma. PMID- 10028719 TI - [Evaluation of theophylline in children hospitalized with asthma attack]. AB - The purpose of this study is to determine whether theophylline provides clinical benefits in the hospitalized children with asthma attack. Aminophylline was intravenously given to the 50 patients (Group A) who were admitted 1994. A small dose of aminophylline compared to that of Group A was given to the 44 patients (Group B1) who were admitted 1998. On the other hand, aminophylline was not given to the 12 patients (Group B2) who were admitted 1998. However, there were no differences among those groups in the duration of admission, in the total dose of intravenously given methylprednisolone, and in the improvement of clinical score of asthma. These results suggested that there was no clinical benefit in using theophylline for treatment to hospitalized children with asthma attack combined high fever. PMID- 10028720 TI - [Irreversible airflow limitation in asthmatics]. AB - To evaluate irreversible airflow limitation in asthmatics, we studied 168 patients admitted to our hospital with acute exacerbation of asthma. All patients were given intravenous methylprednisolone for at least 7 days to maximum 14 days and the best of PEF (% of predicted) was evaluated. In all subjects, the best of PEF showed significant correlations with both the patients' age (r = -0.411, p < 0.0001) and the duration of asthma (r = -0.494, p < 0.0001). A significant correlations between the best of PEF and the duration of asthma were also observed in both patients over 60 years old (r = -0.157, p < 0.0001) and non smokers (r = -0.568, p < 0.0001). We conclude that asthma may develop irreversible airflow limitation in itself and the degree of impairment of lung function correlated with the duration of the disease. PMID- 10028721 TI - [A study of clinical significance of leucocyte migration test in drug eruption]. AB - In 202 patients suspected of drug eruption, the identification of the allergenic drugs were performed by leucocyte migration test (LMT). Leucocyte migration activating factor (LMAF) was detected in 94 cases (46.5%) and Leucocyte migration inhibitory factor (LMIF) in 93 cases (46.0%) for tests either without patients' serum or with patient's serum. Either LMAF or LMIF was detected in 158 cases (78.2%). LMAF was detected in 46 cases (22.8%) for tests only without patient's serum, and in 68 cases (33.7%) for tests only with patient's serum. Accordingly, LMAF was found significantly more frequently with patient's serum than without patient's serum (p < 0.01, chi 2-test). The drugs showing either LMAF-positive or LMIF-positive were detected in 193 of all 647 suspected drugs, in which 53 drugs (27.5%) were beta-lactam antibiotics and 36 (28.0%) were non-steroidal antiinflammatory drugs. LMAF was detected significantly higher than LMIF in beta lactam antibiotics-induced eruptions (p < 0.01, chi 2-test), which LMIF was detected significantly higher than LMAF in non-steroidal antiinflammatory drugs induced eruptions (p < 0.01, chi 2-test). Our finding indicate that both LMAF and LMIF may be involved in the pathogenesis of drug eruptions, that the detection of either LMAF or LMIF may be valuable to identify the allergenic drugs in drug eruption by means of LMT and that the production of LMAF may be enhanced in the presence of patients' sera. Furthermore, the pathogenic mechanism of beta-lactam antibiotics-induced eruption may be different from that of non-steroidal antiinflammatory drugs-induced eruption. PMID- 10028722 TI - [A fundamental study on clinical significance of measuring eosinophil protein X in spot urine in asthmatics]. AB - To define the clinical significance of measuring eosinophil protein X (EPX) in spot urine in asthmatics, we undertook the fundamental study in 32 stable asthmatics having anti-asthmatic agents and 10 normal healthy controls, and obtained the following results. 1) Peripheral eosinophil counts, urinary EPX (u EPX), urinary leukotriene E4 (u-LTE4), and serum eosinophil cationic protein (s ECP) values were significantly higher in asthmatics than those in the controls. 2) U-EPX values were not associated with the type of asthma and severity of the disease. 3) A significant correlation was observed between u-EPX values and peripheral eosinophil counts, but not between s-ECP values and peripheral eosinophil counts. Furthermore, no correlation was observed between u-EPX and s ECP values. 4) U-EPX values did not correlate with either u-LTE4, %FEV1, or histamine PC20 values. Accordingly, EPX value in spot urine may be a useful maker to assess the activation of eosinophils in asthmatics. PMID- 10028723 TI - The association between first DHI milk-test parameters and subsequent displaced abomasum diagnosis in dairy cows. AB - First Dairy Herd Improvement Corporation (DHI) test milk that was sampled prior to displaced abomasum (DA) diagnosis was used to examine the association between milk yield (kg), fat (%), protein (%), or fat/protein ratio and DA in dairy cows. 27 DA cases were matched to 3 controls per case by herd and calving date. Logistic regression was used to examine the effect of each milk parameter on the odds of DA, adjusting for lactation number and days in milk (DIM) at test. Higher odds of DA diagnosis was found with lower milk yield, higher milk fat percentage, lower milk protein percentage and higher fat/protein ratio. We conclude that milk yield, fat percentage, protein percentage and fat/protein ratio may be used to detect cows at risk for DA. Our findings also indicate that cows diagnosed with DA were energy deficient prior to DA diagnosis. PMID- 10028724 TI - [Multiplex PCR for the diagnostic detection of Coxiella burnetii in cow's milk]. AB - A multiplex PCR based assay was developed for the highly sensitive and specific detection of Coxiella (C.) burnetii in cow's milk. The assay simultaneously amplifies a diagnostic target within the C. burnetii IS1111 sequence and a control target within the bovine CD18 gene. The internal PCR amplification control allows the discrimination of false negative results (single tube reaction failures) from negative results due to true absence of target sequences. In order to maximize the sensitivity of the assay, a sample preparation method including a centrifugation step to concentrate the bacterium was developed. In milk samples artificially contaminated with serial dilutions of C. burnetii, about four particles per ml could reproducibly be detected. The sensitivities of both assays, multiplex PCR and PCR with only a single pair of primers ('simplex' PCR), were observed to be similar. PMID- 10028725 TI - [Detection of equine arteritis virus (EAV) in stallions--a contribution to the improvement of EAV diagnosis]. AB - Serum samples from 72 stallions were examined for the occurrence of antibodies against equine arteritis virus, of which 41 animals (57%) were found to be positive. 32 of the seropositive stallions were then screened for persistent EAV infection, before and after the breeding season. Semen samples were investigated by RT-PCR followed by dot blot hybridization and nested PCR, and by virus isolation on cell cultures as well. The carrier state was virologically confirmed in 11 of 32 stallions (34%) during the first and in 9 of 20 (45%) during the second investigation. RT-PCR followed by confirmatory methods was more sensitive when compared to virus isolation on cell cultures. It is suggested to implement the national and EU directives by recommending RT-PCR as a routine diagnosis of EAV in semen samples. PMID- 10028726 TI - [Experimental investigations into the effect of Escherichia coli and Clostridium perfringens on the steroid estrone]. AB - Together with the faecal and the urinary discharge of animals and humans natural and synthetic estrogenes are excreted into the environment. About their degradation in the environment only few facts are known. Their reduction is probably of microbial enzymatical nature. For looking into that question it was investigated by in-vitro-attempts whether Escherichia coli or Clostridium perfringens influence the estrone. Therefore estrone was incubated together with the microorganisms tested (experimental groups) and without those (control groups) in nutrient medium for these bacteria over 48 hours with 37 degrees C (aerobic) or 42 degrees C (anaerobic). For the executed procedure an enzyme immunoassay was used. It could be seen that E. coli does not show a provable effect on the estrone concentration under this conditions. Whereas C. perfringens might have a potency for the degradation of the hormone tested. The experiments shows that there exists obviously a difference between estrone and 4-pregnene-20 beta-o1-3-one in the same system of test. PMID- 10028727 TI - [Serologic and virologic investigations on the presence of BLV infection in a dairy herd in Syria]. AB - 237 cattle of a dairy herd in Syria were tested for anti-BLV antibody by the ELISA. 194 animals were additionally examined by the agar gel immunodiffusions test (AGID) on BLV antibodies and 100 by polymerase chain reaction (PCR) for BLV provirus. BLV specific antibodies were determined by means of AGID and ELISA at 62.9% and 69.2% of the examined animals, respectively. Using the PCR method the BLV provirus was detected in 89% of the investigated cattle. Only one ELISA seropositive animal was negative for BLV provirus. The results show the high BLV contamination of this herd and lead to the presumption of wide spread enzootic bovine leukosis in Syria. In the case of the diagnosis of BLV-infection, the PCR technique compared to the serological tests proved to be much more sensitive. By the detection of BLV antibody, the ELISA showed a higher sensitivity than the AGID and in this way, is advisable as a method of choice for screening investigations. Restriction enzyme and sequence analysis of PCR-amplificates demonstrate that different BLV provirus variants (A, B and C) in the examined herd occur, where the variant C which a high similarity to an Australian BLV provirus isolates showed, occurred most frequently at 92.5%. PMID- 10028728 TI - [Application and possibilities of digital radiography demonstrated on a skull radiograph]. AB - The application of digital radiography has not been used widely in veterinary medicine. This paper gives an overview of the possibilities in post processing of digital radiographs for imaging a nasal fracture on a right lateral skull radiograph of a two years old German Shepherd. The following algorithms of the digital ADC (Agfa Diagnostic Center)--system were used: edge-contrast, latitude reduction, noise reduction, window-levelling and MUSI-contrast (MUlti Scale Image Contrast). MUSI-contrast is a recently developed algorithm by Agfa, which improves the recognition of fine details in all scales. These parameters will be explained individually and the use is demonstrated with the skull radiographs. It shows that only a coordinate parameter setting will lead to an optimal image. The option of filtering diagnostic information in using digital post processing represents a clear step forward and reduces the number of repeat shots. PMID- 10028729 TI - One year on. PMID- 10028730 TI - Oral health promotion--opportunity knocks! AB - The soon to be published White Paper Our Healthier Nation will set out the Government's new public health agenda for the NHS. To improve oral health and reduce inequalities it is vitally important that the dental profession becomes an active player in the implementation of this policy. Each member of the dental team has an important role to play in oral health promotion. PMID- 10028731 TI - Anaesthesia referral. PMID- 10028732 TI - Inadequate sedation experience. PMID- 10028733 TI - Amendments to maintaining standards. PMID- 10028734 TI - Hastily reached decision? PMID- 10028735 TI - Justification in dental radiology. PMID- 10028736 TI - Oral cancer biopsy in general practice. PMID- 10028737 TI - Water, water everywhere but not a drop to drink? AB - Biofilms are emerging as an increasing problem as medical technology advances. Dental practice is no exception and interest in the role of biofilms within dental units as a possible source of cross-infection is intensifying. It is difficult to quantitate the risks associated with aerosolised bacteria for the majority of patients seen in general practice. However, it seems prudent to eliminate this source of infection during treatment of compromised patients. This article attempts to provide a brief overview of current concepts and problems in this area of infection control. PMID- 10028738 TI - How to overcome failed local anaesthesia. AB - Local anaesthetic failure is an unavoidable aspect of dental practice. A number of factors contribute to this, which may be related to either the patient or the operator. Patient-dependent factors may be anatomical, pathological or psychological. This paper considers the reasons for unsuccessful dental local anaesthetic injections and describes techniques which may be useful in overcoming failure. PMID- 10028739 TI - Double gloving and a glove perforation indication system during the dental treatment of HIV-positive patients: are they necessary? AB - AIM: The aim of this study was to compare the incidence of glove perforation when double gloved or single gloved during the routine treatment of HIV-positive patients. In addition, a glove perforation indication system based on a double gloving technique was assessed. DESIGN: Prospective, randomised and open study of glove perforation. METHODS: 138 consecutive HIV-positive patients underwent routine dental treatment by senior dental staff and dental hygienists in a teaching hospital. Staff wore either single gloves (Regent Biogel D or standard surgical gloves) or double gloves (Regent 'Reveal' perforation indication system or standard surgical gloves). A subjective assessment of glove comfort, sensitivity and ease of donning was made using a visual analogue scale. RESULTS: The incidence of glove perforation/procedure was low, 2.9%. There were no skin penetrating injuries, visible exposure to body fluids or unnoticed perforations. Double gloving was subjectively less comfortable and sensitive than single gloving (P < 0.0001). The glove perforation indication system did not increase the detection of intra-operative perforations. CONCLUSIONS: There is unlikely to be any significant benefit from the use of a double gloving technique or perforation indication system during the routine dental treatment of HIV-positive patients. PMID- 10028740 TI - Young dentists--work, wealth, health and happiness. AB - OBJECTIVE: To determine the relationships between working conditions for new dental graduates and their mental and physical health. DESIGN: A cross-sectional postal survey. SUBJECTS: Graduates from the years 1991 and 1994 were selected to provide cohorts before and after the introduction of mandatory vocational training. A total of 232 graduates were sent questionnaires and 183 replied (77%): 90 men (49%) and 93 women (51%). SETTING: The cohorts came from all Scottish dental schools. When surveyed in 1996/1997, 66% were working in Scotland and 28% were in England. The rest were elsewhere in the UK or abroad. MEASURES: Measures included a wide range of conditions at work: number of patients seen, pace of work, hours worked, attitudes to work, financial arrangements, alcohol consumption, sickness-absence, physical and mental health. RESULTS: There were significant differences between those working in general practice and those in hospital in terms of the hours, numbers of patients seen, feelings of competence and senior support. Methods of payment for treatment in general practice also revealed differences in perception of work: most pressure at work was associated with part NHS and part private funding. Mental health and alcohol consumption were equivalent to age-matched junior doctors, but increased psychological symptoms in female dentists were significantly associated with the number of units of alcohol consumed. CONCLUSION: Selected working conditions are associated with reported competence, stress and health among young dentists. PMID- 10028741 TI - The identification of agreed criteria for referral following the dental inspection of children in the school setting. AB - AIM: To clarify the function of the school based dental inspection. OBJECTIVE: For representatives of the Community Dental Service, General Dental Service and Hospital Dental Service to identify an agreed set of criteria for the referral of children following school dental inspection. DESIGN: Qualitative research methodology used to establish a consensus for the inclusion of referral criteria following dental screening. SETTING: Ellesmere Port, Cheshire, England. MATERIALS: A Delphi technique was used to establish a consensus amongst the study participants on the inclusion of nine possible criteria for referral following dental screening. All participants scored each criterion in the range 1-9, with a score of 1 indicating that referral of individuals with the condition should definitely not take place, and a score of 9 indicating referral should definitely take place. Referral criteria were accepted only if they achieved a group median score of 7 or more, with an interquartile range of three scale points, with the lower value being no less than 7. RESULTS: Four of the nine possible criteria met the agreed group standard for inclusion: 'Sepsis', 'Caries in the secondary dentition', 'Overjet > 10 mm', and 'Registered & caries in the permanent dentition'. CONCLUSION: It is possible to agree clear criteria for the referral of children following the school dental inspection. PMID- 10028742 TI - Impact of a Menninger training experience. AB - In light of her experience working with victims of severe physical and psychological trauma, the author comments on the benefits of her training in psychodynamic psychology. She highlights in particular the value of understanding the complexity of diagnosis and the importance of psychodynamically informed thinking in all treatment approaches. PMID- 10028743 TI - A noble profession. AB - Organized psychoanalysis has now achieved an era of openness to new ideas and change, and the result has been an exciting ferment in both theory and technique. Most recently, the field has focused on "intersubjectivity," the study of how the therapist's personality acts and reacts with that of the patient. Despite the subjectivities inherent in the process of treatment, there is good justification for viewing the field as an empirical discipline, indeed a science, because the multiple inputs by practitioners contributing to the literature, debating on panels, and critically assessing new contributions result in a gradual approach to truth and validity. This hermeneutic approach is not sufficient in itself and in no way contradicts the need for other, more controlled, research approaches. PMID- 10028744 TI - The role of the psychiatrist in organ transplantation. AB - The psychiatrist has multiple roles on the transplant team, beginning with the transplantation psychiatry consultation (TPC). It addresses such issues as risks of exacerbation or recurrence of a psychiatric illness, pharmacokinetic and pharmacodynamic considerations due to organ failure, potential drug interactions involving psychotropic and immunosuppressant medications, adequacy of support system, history of medical compliance, emotional and cognitive preparedness for transplantation, mental status findings supplemented by standardized cognitive testing and psychosocial rating instruments, and decision-making capacity. The consultation concludes with an overall assessment of the patient's psychosocial strengths and limitations, and recommended interventions to optimize his or her candidacy for transplantation. The consultation findings aid the psychiatrist and the transplant team in striving for fairness and the ideal of "neutrality" in an effort to serve the needs of the patient, other transplant candidates, and society with regard to optimal organ stewardship. PMID- 10028745 TI - Something old and something new: love, creativity, and the enduring relationship. AB - In the initial phase of a romantic relationship, excitement often reflects the reawakening of early narcissistic fantasy. For most couples, when the passionate intensity that is derived from primitive narcissism fades, the expansiveness of a developing sense of self that is a by-product of the creative process can, in turn, revitalize the partnership. Arieti's work on creativity is applied to understanding how some passionate intensity can be retained over the lifetime of a marriage. PMID- 10028746 TI - A daughter of a depressed mother: a case report. AB - Stern notes that infants attempt to enliven their depressed mothers. The reconstructed childhood of a patient who was the daughter of a depressed mother is discussed. The treatment of this 31-year-old single woman whose talk was rapid, whose comments were studded with high-powered names, and whose checks bounced is described. The intensity of this patient's attempts to connect with the therapist illustrated her need to enliven the therapist. This adult charmer is reminiscent of the infants that Stern observed in interaction with their depressed mothers. PMID- 10028747 TI - The contribution of life events to pseudoseizure occurrence in adults. AB - Life events associated with pseudoseizures were studied in 58 adults. Recent precipitants were diverse and triggered affect that was usually related to current life problems or remote trauma. Four patterns of remote and recent events were found, two related to trauma and two to inadequate emotional expression. When evaluating pseudoseizure precipitants, clinicians should consider the meaning of recent events in light of remote trauma, current life context, and dysfunctional familial patterns of handling affect. PMID- 10028748 TI - Mohawks and combat boots: the schizoid dilemma of punks. AB - The author explores how clinicians may use the construct of the schizoid dilemma as a means to understand young adult punk rockers. The basic dilemma, in Fairbairn's formulation, is whether to withdraw from relational attachments because of a history of disappointments by others. The punk phenomenon may be understood as an object-relational stance resulting from a particular resolution of the schizoid dilemma. The author describes characteristics of punk individuals in terms of this construct, and discusses their relation to such possible pathology as depression and substance abuse. Finally, an explanation is offered for the phenomena that both drive an individual to treatment and lead to premature termination of it. PMID- 10028749 TI - Self psychology interpretation of the Thematic Apperception Test. AB - Self psychology theory of personality has gained recognition as an important contribution to the psychoanalytic understanding of personality. The authors present guidelines for the interpretation of Thematic Apperception Test (TAT) material in accordance with self psychology, and provide as a case example a detailed interpretation of the TAT material of one patient. Material from the therapist's summary of the treatment is provided in support of the self psychology interpretation proposed. The authors encourage further efforts to expand the application of self psychology to the understanding of psychological testing material. PMID- 10028750 TI - Training psychiatric residents for Part II of the American Board of Psychiatry and Neurology Examination. AB - Of the physicians who took the American Board of Psychiatry and Neurology (ABPN) Examination, Part II, in 1995, 41% failed. The Accreditation Council for Graduate Medical Education (ACGME) requires that residency psychiatry programs conduct an organized evaluation of residents' clinical skills at least twice during the 4 years of training. At the University of Oklahoma Health Science Center-Tulsa, the residents attend formal didactic instruction on conducting a psychiatric interview. Having gained this didactic foundation, they then participate in actual patient interviews. First- and 3rd-year residents are mock examiners, paired with an experienced board-certified psychiatrist. Second- and 4th-year residents examine an actual patient. A survey evaluating this curriculum was rated as very good to excellent by the participants. PMID- 10028751 TI - [Body condition and dislocated abomasum: comparative investigations into back fat thickness and additional criteria in cattle]. AB - The body condition, the kind of parturition, the milk yield and diseases during early lactation were investigated in 228 cows including heifers. Overconditioning (back fat thickness > 30 mm) before parturition resulted in cows falling ill with mastitis and abomasal displacement (DA). These cows mobilised the most fat in comparison with healthy cows and cows suffering from different diseases after parturition. Especially heifers (83%) which gave birth to heavier male calves fell ill with DA, therefore needed assistance during labour because of dystocia. Besides DA additional disturbances occurred in those heifers, e.g. 50% mastitis, and 30% retentio secundinarum in this investigation. The daily milk yield amounted to 13.1 kg in cows with DA and to 23 kg in healthy cows. The presented results support the classification of DA into the fat mobilisation syndrome. Consequently overconditioning and stress during parturition need to be avoided to prevent DA. PMID- 10028752 TI - [Effect of antibody-containing egg powder on development of active immunity in calves]. AB - Investigations on the influence of an egg powder containing antibodies was conducted on 15 young calves to measure the development of an active immune response. The product investigated, Globigen 88 (Lohmann Animal Health GmbH & Co. KG), was mixed with a milk replacer and administered to a group of 5 calves over 8 days twice a day. In addition, two control groups were established each consisting of 5 calves. The first group received the corresponding amount of egg powder without antibodies and the second group received exclusively milk replacer. In all groups serum antibody content was measured over 22 days. The average antibody content was decreased in the serum of the test groups. Avian immunoglobulins were not detectable. The development of active immunity in calves was not hindered. Furthermore a significant daily increase in weight was observed in test groups. PMID- 10028753 TI - [Effect of ad lib and restricted milk feeding on the course of illness and body weight in young calves with diarrhea]. AB - Two different feeding regimens for calves (age up to 21 days) suffering from acute diarrhea were evaluated with respect to course of illness and change in body weight. The patients of the experimental group were given whole milk ad libitum three times a day. The patients of the control group were offered whole milk at a rate of 13% their body mass per day divided into three meals. In addition, both groups were offered an oral rehydration solution at a rate 9.5% of body mass per day, also divided into three portions. Data from 60 calves (30 in both groups) were available for statistical analysis. The duration of illness in the experimental group was 10.9 +/- 6.0 days vs. 10.0 +/- 5.2 days in the control group. The daily increase of body mass in the experimental group averaged 0.607 +/- 0.452 kg, the one in the control group 0.230 +/- 0.231 kg (p = 0.0002). The calves of the experimental group required 13.16 +/- 11.18 I milk per kg weight gain, the calves of the control group 21.39 +/- 12.80 I. Six calves of the experimental group and two calves of the control group subsequently had a relapse. On the basis of the results obtained, a feeding regimen for calves suffering from acute diarrhea is suggested. PMID- 10028754 TI - [Investigations on renal excretion of sodium in dairy cattle]. AB - Serum and urine were taken from healthy dairy cattle from 22 different farms. 214 animals belonged to the Swiss Brown breed and 210 were crossbreds of Simmental Red Holstein. The animals were given at least 70 g of sodium chloride with their daily feed ration. On 6 farms sodium chloride was offered ad libitum in form of licks, which was presumed to be sufficient for covering their needs. Concentrations of sodium (UR Na), potassium (UR K) and creatinine were analyzed from serum and urine and fractional excretion of Na and K was calculated. Concentrations of sodium and potassium in urine from all cows (mean +/- sd) was 60.9 +/- 44.7 mmol/l and 370.7 +/- 66.9 mmol/l respectively. The FE values were 0.954 +/- 0.939% for sodium and 173.1 +/- 54% for potassium. In 5.5% of the animals values for UR Na < 10 mmol/l were found. There were no significant differences, however, were found in sodium and potassium excretion among farms. Urine samples of at least 10 animals should be analyzed in order to have a reliable estimation of the supply with sodium chloride within a herd. Our results do not support the hypothesis that low sodium excretion would be a predisposing factor for Bovine Dilative Cardiomyopathy in Simmental-Red Holstein cattle. PMID- 10028755 TI - [Investigations on the treatment of cerebrospinal nematode infections in goats]. AB - In 17 goats the therapeutical outcome of cerebrospinal nematodiasis, a parasitic infection in the central nervous system with the nematode Elaphostrongylus cervi, is described. The diagnosis was made on the basis of physical findings and cerebrospinal fluid eosinophilia. The therapy was based on the administration of a non-steroidal antiinflammatory drug (flunixin meglumine) and two anthelmintics (fenbendazol, ivermectin) for five days. The response to therapy was documented immediately and 30 days after therapy and by owners report up to 30 months. Eleven goats (64.7%) showed an improvement of the neurological signs directly after therapy. Three had a complete recovery. Signs of a light and middle ataxie were still present in 6 and 2 goats, respectively. Six recumbent goats (35.3%) had to be euthanasied because of a non-therapeutical response. This study has shown a clinical impression of successful use of flunixin meglumine, fenbendazole and ivermectin in goats with light to middle neurological signs. The goats could accommodate the remaining ataxia without showing a reduced production. Goats with high neurological deficits could not be successful treated based on the high degree of the neurological damage. PMID- 10028756 TI - [Borna disease in cattle (consensus report)]. AB - Short survey on definition, occurrence, cause, importance, pathogenesis, clinical findings, course, postmortal lesions, treatment, prevention and eradication of Borna disease in cattle. PMID- 10028757 TI - Total serum bile acid concentrations in dairy cows with fatty liver and liver failure. AB - In forty-five Holstein Frisian dairy cows (1-6 weeks post partum; mean age: 5.1 +/- 1.2 years) the serum total bile acid concentrations (SBA) were measured enzymatically. In all cows a left sided abomasal displacement was corrected surgically by right side laparotomy and omentopexy three days before investigation. The liver fat content was determined in all cows histologically. Liver failure was assumed if typical clinical signs (ataxia, general depression, recumbency or coma), an increased venous plasma ammonia level (> 35 mumol/l) and a decreased plasma amino acid index (< 4.0) were found. Cows without liver failure (N = 29) were grouped according to the liver fat content as cows with mild (N = 5), moderate (N = 19) or severe hepatosteatosis (N = 5). Histological examination of liver biopsies in cows with liver failure (N = 16) revealed in twelve cases a severe fatty liver and in four cases a hydropic degeneration of the liver tissue. Although in cows without liver failure mean SBA concentrations were higher in the group with moderate (47.3 +/- 30.9 mumol/l) or severe fatty liver (32.9 +/- 21.7 mumol/l) than in that with mild lipidosis (18.0 (16.8 mumol/l), differences were not significant. The mean SBA concentration in cows with liver failure (70.5 +/- 49.5 mumol/l) was only significantly (p < 0.05) increased compared to cows with uncomplicated mild hepatic lipidosis. In conclusion, the determination of SBA concentrations is of little value in the recognition of fatty liver or even liver failure due to the considerable variance of SBA concentrations in dairy cows. PMID- 10028758 TI - [Evaluation of the California mastitis test (CMT) reaction in goat milk and its interpretation]. AB - For evaluation of different factors regarding CMT results 65 goats were used. Age, milking hygiene and technique of the animals were recorded and the CMT results were evaluated in relation to those parameters. Correlations between CMT results and age as well milking hygiene and -technique respectively were found. Furtheron the CMT was evaluated as indicator for mastitis diagnosis. Therefore clinical examination of the udder, bacteriological examination of milk samples (aseptically collected) and the determination of the somatic cell count were carried out. The results showed that CMT is not specific for infected udder halves. As important udder pathogens staphylococci were found, S. aureus and CNS at the same level. This investigation has shown that CMT can be used as additional diagnostic tool concerning goat mastitis, but it should not be overestimated because of different factors which influence the cell count. For the control of udder health additional diagnostic measures are of utmost necessity. PMID- 10028759 TI - [Bile acid concentrations in serum, bile and feces of healthy calves and calves with diarrhea]. AB - On 32 calves (age 3 to 14 days) with spontaneously occurring diarrhoea, the following investigations were carried out: Regular examination of serum bile acid concentrations, collection of the entire faeces with determination of bile acid concentrations, as well as microbiological examinations. Six clinically healthy calves served as control group. In addition, bile acids in bile were determined in 16 other calves of the same age group and in 6 beef bulls. There was no significant influence of daytime or feed intake on serum bile acid concentration in diarrhoeic or healthy calves. Possibly due to the low concentrations of bile acids in the bile of young calves (4.8 +/- 3.7 mmol/l, compared to 57 +/- 13 mmol/l in the bulls), the concentrations in faeces were also rather low (control group 623 +/- 92, calves with diarrhoea 318 +/- 277, after diarrhoea. 794 +/- 935 mumol/kg). Most of it was cholic acid, whereas only traces of desoxycholic acid were found. In spite of the comparatively low concentrations of fecal bile acids, the diarrhoeic calves excreted larger amounts of bile acids than the healthy calves (12.7 +/- 13.5 vs. 1.4 +/- 0.8 mumol/kg), but this was independent of the type of enteropathogen or pathogen combinations which were detected. There were no indications for a direct influence of the diarrhoea by bile acids. However, through enteral bile acid losses, profuse diarrhoea lasting several days can cause a reduction in the total bile acid pool. PMID- 10028760 TI - [Milk substitutes with high ash and macro mineral contents--of importance in loose feces of young calves?]. AB - In 3 feeding experiments with 23 calves (age: 5-18 days at trials' start) the effects of high ash and mineral contents in the diet on feces composition (dry matter, pH, concentrations of lactic and volatile fatty acids, mineral contents) and digestibility rates of organic matter, nutrients and minerals as well as on some parenteral parameters (electrolytes in serum, renal excretion) were tested. In all feeding experiments a change-over-design was used, during 10 days each of all calves was fed the control and experimental diet, respectively. In the first trial (8 calves) high ash and mineral contents in the milk replacer were caused by use of a special whey product (25% in the diet), in the second experiment (n = 7) comparable ash and macromineral concentrations were achieved by adding minerals to the basic diet, in the third trial (n = 8) the whey product was used in a lower proportion (15% of the diet). Ash concentrations in diet (g/kg dry matter): 68 versus 138 (trial 1), 75 versus 135 (trial 2), 75 versus 93 (trial 3). The differences in the ash contents were based mainly on differences in the sodium and potassium concentrations. PMID- 10028761 TI - Clinical experiences with rabies in cattle in Hungary. AB - Over the past years, bovine rabies has become a significant problem in Hungary. Not only do foxes play and important role in the transmission of the virus to cattle, but also cats have recently been recognized as an important source of infection in cattle. In the investigated regions, seasonal peaks of transmission could be observed. The first cases of the year occurred in June, but the most cases were diagnosed in autumn and early winter. The average clinical course of rabies in infected animals extended over a period of 2-6 days, occasionally shorter and longer courses were presented. A short clinical course was usually related to an early onset of prominent nervous symptoms, while prolonged cases expressed fewer nervous signs. Prevention and control of the disease can be best achieved by regional oral vaccination of foxes as the positive results demonstrate in the Transdanubian region of Hungary. PMID- 10028762 TI - [Analysis of secretion into the saliva of cefoxitin (Mefoxin), imipenem (Tienam) and meropenem (Meronem)]. AB - The salivary excretion of cefoxitin (Mefoxin), a second-generation beta-lactam antibiotic of the cefalosporin group, which shows enhanced anti-anaerobic effect was investigated in oral surgery patients. In animal experiments the saliva levels of imipenem (Tienam) and meropenem (Meronem), which also belong to the betalactam carbapenem group were studied. The antibiotics were administered parenterally in single therapeutic doses, then blood samples were taken first after half an hour then hourly, and mixed saliva was collected for 6 hours. Cefoxitin was found to reach top level in the 1st hour, then this level decreased rapidly, and in the 4th hour it was no longer measurable. Out of the carbapenems imipenem showed highest level in the 2nd hour and in the 4th hour its concentration in the saliva was minimal. Meropenem reached a higher level in the saliva (1,5-2 times higher than the serum level) in the 2nd hour after administration, which persisted even in the 6th hour. The experimental results justify the administration of these antibiotics in dentistry and oral surgery. PMID- 10028763 TI - [The role of plastic shock absorbers in dental implantation]. AB - The mechanical behaviour of different plastics (PE, PP, PI, PA, ABS, POM) was examined by static and dynamic loading. Detection of microdeformations and photoelastic stress analysis served as the examination method. According to the results, polyethylene is unsuitable, however the other plastics, with clauses, are suitable as shock absorbers. Apart from the mechanical investigation photoelastic stress analysis also revealed the benefit of osseointegration in force transmission to the bone. PMID- 10028764 TI - [Surgical management of a pleiomorphic adenoma of unusual location]. AB - The authors describe the occurrence of a parotid pleiomorphic adenoma in an unusual location, beginning in the small salivary gland of the lower lip. The location of the pleiomorph adenoma is rare as mentioned in the bibliography, however, not demonstrated with many actual cases. PMID- 10028765 TI - [Risk patients in dentistry]. AB - Authors study the risk diseases in dental practice. They analyze the possible complications and the methods of their prevention in each risk group. They take deal with the importance of antibiotic prophylaxis, the problems of local anaesthesia and the management of patients who suffer from coagulation disturbances. They present the management of risk patients in two cases. They emphasize the importance of anamnestic history in every case before dental treatment. PMID- 10028766 TI - Aging and homelessness. AB - Aging homeless persons have been largely neglected in the gerontological and homeless literature. This article presents an overview of homelessness and aging within the context of a testable, provisional model for explaining homelessness in this population. The author proposes 16 individual and 5 structural and programmatic variables that contribute to the etiology and sustenance of homelessness among aging persons. PMID- 10028767 TI - Long-term admissions to home health agencies: a life table analysis. AB - This article uses the first national survey of home health agencies and their patients to characterize the complete length-of-use distribution for an elderly admissions cohort. Of the 26 million older Americans admitted to home health agencies in 1992, 36% received care for at least three months, 22% for at least six months, and 15% for at least one year. Analyses suggest that one-year limits on Medicare's home health benefit would have affected a relatively small percentage of new admissions (less than 13%) but would have amounted to 300,000 or so beneficiaries in 1992. In contrast, proposals to limit Medicaid would have affected a more substantial proportion of home health agency admissions (about one fourth) but only a relatively small number of older Americans (30,000 in 1992). Such length of use limits would also disproportionately affect those at highest risk for nursing home admission: very old, unmarried, minority women with relatively unstable chronic conditions. PMID- 10028768 TI - Conceptualization and measurement of quality of life in dementia: the dementia quality of life instrument (DQoL). AB - Direct assessment of quality of life (QoL) of persons with dementia has largely been ignored due to logistical, conceptual and practical issues. This article presents a disease-specific conceptual framework of QoL for dementia. Based on this conceptualization, a 29-item instrument designed to assess QoL by direct interview with dementia patients was developed and tested on 99 participants. The data show that the instrument is reliable and shows evidence of validity. Nearly all participants (96%) were able to respond to questions appropriately. Thus, persons with mild to moderate dementia can be considered good informants of their own subjective states, paving the way to consider patient responses rather than proxy measures as the gold standard for assessing QoL for persons with dementia. PMID- 10028769 TI - Retirement patterns and employee benefits: do benefits matter? AB - This article investigates the impact of postretirement employee benefits on the likelihood that workers expect to retire before age 62 and age 65. Using data from the 1992 Health and Retirement Study, probit regression models were estimated to explore the effect of pension plans and retiree health insurance on the expectation of early retirement. With respect to pension plans, the effects of both the type of pension plan and the expected benefits from those plans are explored. Similar effects were explored for retiree health benefits. The results indicate that postretirement pension benefits and the availability of retiree health benefits have a significant influence on workers' retirement age expectations. PMID- 10028770 TI - Social relationships of Latino grandparent caregivers: a role theory perspective. AB - This article uses a role theory perspective to examine the social relationships of 74 Latinos, mostly middle-aged and older Puerto Rican and Dominican women, rearing their grandchildren in New York City. Fully 81% of households were below poverty level. Most grandparents had large families and were socially connected, but two thirds of households were skipped-generational and many grandparents lacked reliable help with child rearing. Most relied on a focal secondary caregiver, usually an adult daughter, and extrafamilial supports. These and other sources of strain and support for the grandparent caregiver role in Latino families are discussed, as is the impact of this role on their social relationships. PMID- 10028771 TI - Age at migration and family dependency among older Mexican immigrants: recent evidence from the Mexican American EPESE. AB - This study employs new data on Mexican-origin individuals aged 65 and older in the Southwestern United States to examine the impact of the age at which an individual immigrated to the United States on his or her sources of income and living arrangements. The data reveal that, in general, those who immigrated after the age of 50 are more dependent on their families than the native born or those who immigrated earlier in life. Although our findings must be interpreted cautiously because of small cell sizes, those who immigrated later in life are found to be less likely than the native born or those who immigrated earlier to have private pensions and Social Security income. They are also more likely to be living with their children and to be receiving money from them. We discuss the implications of recent restrictions on the eligibility of even legal immigrants for Supplemental Security Income on intergenerational relations and on the potential burden placed on the older immigrant's family, many of which may be seriously strained in hard economic times. PMID- 10028772 TI - Children-in-law in caregiving families. AB - Data were collected from 252 coresident caregiving daughters and daughters-in-law and their husbands. We hypothesized that biological children would give more care than children-in-law and that children-in-law would have very different caregiving experiences and resultant appraisals than biological children. Contrary to our hypotheses, we found that the experiences are very similar for biological children and children-in-law in caregiving families. We suggested that the important factor is not the relationship to the elder that has the impact--it is the quality of the relationship with the elder that is consistently significant. PMID- 10028773 TI - The impact of new demands for assistance on caregiver depression: tests using an inception cohort. AB - Family caregivers of patients facing high numbers of new demands for assistance following hospital discharge were more likely to experience increased levels of depression in the following six months compared with caregivers facing similar overall demands but few new demands for assistance following hospital discharge. New demands for assistance had a significant independent effect upon the levels of depression and were independent of family relationship (spouse vs nonspouse) and caregiver gender. These findings provide insight into theories of caregiver stress, begin to specify the interaction of time following the onset of a stressful event and caregivers' subsequent reactions, and suggest which caregivers may require some assistance following discharge of their patients. PMID- 10028774 TI - Policy choices for Medicaid and Medicare waivers. AB - This article reviews the authority and processes for issuing Medicare and Medicaid waivers, highlights waiver-based differences in states' home- and community-based (HCB) service systems, and critiques emerging efforts to capitate, integrate, and privatize the long-term care system. Potential pitfalls relate to payment rates, risk, service substitution, accountability, and drains on HCB infrastructure. Before merging HCB services into larger prepaid systems, policy makers are advised to examine implementation challenges, resist ad hoc fixes, clarify HCB entitlements, and strengthen current infrastructure. PMID- 10028775 TI - Perceived social control as a mediator of the relationships among social support, psychological well-being, and perceived health. AB - The purpose of the present study was to delineate the process by which social support facilitates better health outcomes in older adulthood. In order to best understand the process behind the support-outcome relationship, an aspect of perceived control specific to the social domain was hypothesized to mediate the said relationship. Measures of social support included quantity of support from family and friends and the perceived satisfaction with that support. Outcome measures included depression, life satisfaction, and self-reported perceived physical health. Based on previous research, the hypothesized model of control serving as a mediator was tested against two alternative hypotheses including an examination of control as a moderator of the support-outcome relationship as well as support as a mediator of the control-outcome relationship. Results indicated that perceived control mediates the support-outcome relationship in two independent samples, each comprised of approximately 250 adults older than 65, primarily Caucasian and functioning independently, illustrating the strong replicative nature of the findings. This examination begins to illuminate the process by which social support may facilitate well-being in older adulthood by focusing on the internal structures that may play a crucial role in the utilization of the social support. PMID- 10028776 TI - A multidisciplinary ethics teaching conference on a geropsychiatric service. AB - This article describes an ethics case conference on a multidisciplinary geropsychiatric service, and its unique clinical, training, and research benefits. We describe the structure of the conference, the major topics addressed, the perceived advantages, and the research implications. We conclude that the care of older patients, the education of students and trainees interested in aging issues, and cutting-edge geriatric research are all advanced by such a conference. PMID- 10028777 TI - Practical measurement. PMID- 10028778 TI - Psychometric assessment of four fatigue scales with a sample of rural cancer patients. AB - There are differences between rural and urban persons experiencing cancer that may make the experience of fatigue more difficult for rural cancer patients. There were no scale to measure fatigue that had been validated with rural cancer patients. The purpose of the present research was to study the psychometric properties of four fatigue scales for use with rural cancer patients. The four scales were the Multidimensional Assessment of Fatigue Scale, the Fatigue Severity Scale, the Visual Analogue Scale for Fatigue, and the Rhoten Fatigue Scale. The four scales were mailed to 270 rural cancer patients, with 131 usable scales returned (48% return rate). Interitem correlations, Cronbach's alpha reliability, and factor analyses were performed on the four scales. Based on these analyses, the Multidimensional Assessment of Fatigue Scale, the Fatigue Severity Scale, and the Visual Analogue Scale for Fatigue were judged to be adequate for use with rural cancer patients. PMID- 10028779 TI - A comparison of newborns' NBAS reflex responses using total and individual scores. Neonatal Behavioral Assessment Scale. AB - The purpose of this study was to compare results found using a total summative score of abnormal reflex responses with the results found using individual reflex scores. The 20 reflexes included as part of the Brazelton Neonatal Behavioral Assessment Scale (NBAS) were assessed on 196 neonates on the 1st and 2nd days postnatally. Differences due to of type of delivery, birth weight, whether their mothers were insulin-dependent diabetics or nondiabetics, and day of testing were assessed by using analysis of variance. The key results were that all effects found using the total reflex score were replicated with individual reflex scores and that individual reflex scores also revealed effects not shown using the total score. It was concluded that the individual reflex scores, rather than the total score, should be used when evaluating newborn reflex performance. PMID- 10028780 TI - Development of a scale to measure information needs in cancer care. AB - Developing approaches to improve the use of scarce health care resources is of increasing importance in cancer care. Being able to target the provision of information to the primary needs of consumers ensures more productive use of expensive teaching time by health care professionals. Researchers and clinicians have used a variety of measurement techniques to assess the information needs of individuals with cancer at various points in their illness trajectory. The two most common types of scaling techniques used by researchers to measure information needs have been summative and differential. The advantages and disadvantages of using these types of measurements are evaluated. This article describes the development and pilot testing of a measure of the information needs in cancer patients that uses one type of differential scaling technique, Thurstone scaling. This measure was subsequently converted into a patient friendly computerized program capable of helping consumers identify their information priorities before their medical visits. Individualized teaching may be guided by this new measurement technique in the future. PMID- 10028781 TI - Methodologic issues in the measurement of oxytocin in human neonates. AB - Oxytocin's (OT) role in the onset and maintenance of labor and in the letdown reflex is well known. OT also has been recognized as a neurotransmitter having functions in the central nervous system, including an influence on behavior (e.g., initiation of maternal behavior). This research was conducted to (1) evaluate whether human tactile contact in the human newborn would increase urine OT levels and alter infant behavioral state, and (2) determine the reliability of measuring OT in human infant urine. Although the data did not support the hypotheses, it was noted that OT levels significantly decreased in infants who cried during the study period and that there was no correlation between infant's chronologic age and OT levels. The findings illustrate several methodologic and measurement problems in the study of OT in human infants and that urine sampling in the neonate is not the most reliable method to evaluate change in OT levels. Some general issues concerning research with human infants also are discussed. Further research is recommended to document baseline levels of OT in neonates and to explore the use of salivary OT to measure short-term responses to interventions. PMID- 10028782 TI - Development and psychometric evaluation of the Demands of Immigration Scale. AB - The Demands of Immigration Scale (DI) measures demands associated with immigration, including loss, novelty, occupational adjustment, language accommodation, discrimination, and not feeling at home in the resettlement country. The DI scale was evaluated in a sample of 1,647 immigrants from the former Soviet Union who had resided in the United States from a few months to 20 years. Confirmatory factor analysis supported the proposed factor model. The DI subscales were internally consistent and had good test-retest reliability. Support for concurrent validity was demonstrated by correlations in the expected direction between the DI total and subscale scores and measures of depression and somatization. Support for discriminant validity was demonstrated by mean group differences in some or all of the DI dimensions according to age and years in the United States. PMID- 10028783 TI - Self-care agency: the concept and how it is measured. AB - Self-care agency (SCA) is a phenomenon of great interest. Nevertheless, difficulty comes when attempting to compare results of studies. This difficulty is caused by the multiple conceptual definitions and instruments used across disciplines. Based on the literature, a historical view of the conceptual development of SCA, a description of the extant instruments, and a discussion of the fit between these definitions and instruments are presented. Researchers need to determine if they plan to measure personal abilities for self-care or the actions taken by an individual for self-care and choose their instruments appropriately. PMID- 10028784 TI - Short-term and long-term results after early treatment with the Castillo Morales stimulating plate. A longitudinal study. AB - The present study is divided into 2 parts: The first explains the concept of stimulating plate therapy at the Muenster Clinic and the second presents a longitudinal study of mouth and tongue posture in trisomy 21 children treated with this concept. 47 children underwent a pre-treatment examination (Rec1), and 38 attended a first follow-up examination (Rec2) after an average of 4 months of stimulating plate treatment. The second follow-up examination (Rec3) was on average 53 months after the end of treatment and covered 18 patients. Data acquisition was based on standardized parent questionnaires and standardized clinical examination records. Rec2 showed in part a highly significant improvement in orofacial appearance. These results were confirmed by the parent interview, according to which the mouth and tongue posture improved in 76.3% of the children during the time they were wearing the plate. Even when the plate was not in place, the result remained stable in 65.8% of the patients. Up to Rec3, further improvement was recorded in some results. The symptoms: "mouth mostly wide open" and "tongue mostly protruding way over lips" were reduced. The number of children whose tongue was "mostly in the oral cavity" increased correspondingly. At Rec3, the parents also rated the mouth posture in 88.9% and the tongue posture in 77.7% of the children as stable or further improved. PMID- 10028785 TI - Electromyography of the perioral and masticatory muscles in orthodontic patients with atypical swallowing. AB - Subjects with an open bite and an atypical swallowing pattern before (n = 20) and after (n = 10) orthodontic treatment and subjects with a normal swallowing pattern (n = 15) were examined. The electromyographic (EMG) activity of the upper and lower lips in the region of the modiolus and of the mentalis, masseter and temporal muscles was evaluated during the swallowing of saliva and of water and after the chewing of peanuts as well as during maximal biting in intercuspal position. During swallowing the atypical swallowers exhibited larger EMG activities of the perioral muscles and smaller EMG activities of the masticatory muscles than the control subjects. During maximal biting in intercuspal position, major EMG activity of the masseter and temporal muscles and minor EMG activity of the perioral muscles were recorded in both groups. No normalization of the electromyographic swallowing pattern could be observed during orthodontic treatment (closure of the open bite). PMID- 10028786 TI - Condylar restoration after early TMJ fractures and functional appliance therapy. Part II: Muscle evaluation. AB - The aim of this study was to analyze and to describe the condition of the lateral pterygoid muscle during and after functional appliance therapy in children who had sustained condylar fractures. The treatment group consisted of 19 patients with an average age of 13.4 years, who had sustained a unilateral fracture at an average age of 8.4 years and had been treated functionally for 6 to 8 months. Muscle condition was assessed through axial soft tissue description. The volume and density of the lateral pterygoid muscle were measured in both groups and were compared on the basis of sex, age and fracture type. 74% of the patients in the follow-up group showed muscle differences of more than 10% between the 2 sides. In 2/3 of these patients the lateral pterygoid of the fracture side was 13 to 69% smaller. The volumes of the contralateral pterygoid muscles in the 2 patient groups differed by 10% on the basis of sex. Both in the treatment group and in the follow-up group the volume difference between the healthy and fractured side was as high as 70% depending on localization and type of fracture. Deep fractures and fractures with complete dislocation of the condyle evoked the most serious reduction in muscle volume. PMID- 10028787 TI - Extraction therapy in patients with Class II/2 malocclusion. AB - The aim of this study was to analyze the dynamic development of Class II, Division 2 malocclusion with reference to the untreated patients from the Belfast Growth Study. As a second step, the influences of premolar extraction in all 4 quadrants and of maxillary second molar extraction in the upper jaw in Class II/2 patients were examined, focusing on the cephalometric variables in comparison to those of the untreated patients from the Belfast study. The longitudinal cephalometric values of 20 patients in each group were compared. In addition, the possibility of third molar eruption was evaluated in the extraction patients from the panoramic radiographs. The overbite based on study models at the beginning and end of treatment was calculated. Furthermore, renewed spacing after premolar extraction was assessed. The results derived from cephalometric analysis demonstrated that profile flattening was also observed in untreated Class II/2 patients during the growth period. Comparison of these data with those obtained from the extraction groups revealed a significantly marked recession of the upper lip after premolar extraction. In contrast, only slightly increased flattening after maxillary second molar extraction was observed compared with the untreated patients of the control group. Whereas the interincisal angle was reduced to a value approximating that of untreated Class I patients after maxillary second molar extraction, only a small decrease was recorded after premolar extraction. From our point of view, the claim that premolar extraction facilitates third molar eruption should be seen in an extremely critical light and should not contribute to the decision in favor of extraction. In addition, there is a problem of renewed spacing in the extraction area after premolar extraction. PMID- 10028788 TI - Bond strength of a fluoride-releasing bracket adhesive. Experimental study. AB - The aim of the study was to examine a new fluoride-releasing light-cured filling composite for its bonding and debonding qualities when used as a bracket adhesive. The material investigated was a hybrid composite containing a chemically modified fluoride apatite, which is claimed to provide the enamel with phosphate, calcium, and fluoride ions in the presence of an acid pH, recharging its resources of these ions through fluoride-containing toothpastes used in daily oral hygiene. Concurrently suitability as an enamel conditioner was tested in a new self-etching primer, which does not require water rinsing but is gently air dried instead. For comparison a conventional light-cure single-component adhesive was used together with 37% orthophosphoric acid. After application of the respective conditioners, mesh-backed metal brackets were bonded to 20 human premolars in each of the 2 adhesive groups and subjected to a shear test. Bond failure location was evaluated using the Adhesive Remnant Index (ARI). Average bond strength of the experimental bracket adhesive and the conventional etchant was 8.96 MPa. Conditioning with the self-etching primer led to a decrease of mean shear bond strength values to 6.55 MPa. Highest bond strength was determined in the control group (12.19 MPa). The bond strength results obtained in the shear test recommend the new material as a bracket adhesive to be used with orthophosphoric acid for etching. PMID- 10028789 TI - The eleventh hour or where are our orthodontic limits? Case report. AB - It is illustrated in a patient with periodontal attachment loss up to the apical root third that a combined periodontal/orthodontic approach may be beneficial even in seemingly hopeless cases. The problems of orthodontic limits and the positive effects of guided tissue regeneration are discussed. PMID- 10028790 TI - Report on the 10th Interdisciplinary Symposium of the Cleft Lip and Palate Study Group, October 17/18th 1997. PMID- 10028791 TI - Spinal cord lesions--pathologist point of view. PMID- 10028792 TI - Development of an indigenous screening instrument in Pakistan: the Aga Khan University Anxiety and Depression Scale. AB - The use of translations of instruments for detecting anxiety and depression continues to be debated. An indigenous screening instrument has been developed in Urdu for anxiety-depression syndromes at the Aga Khan University. It has been developed from the complaints of 150 anxious and depressed patients presenting to a non-speciality clinic and has been validated in 53 patients in a psychiatry clinic. The questionnaire has 25 items, 13 psychlogical and 12 somatic. At a score of 20 it has a sensitivity of 66%, a specificity of 79%, a positive predictive value of 83 and a negative predictive value of 60. In comparison with available instruments in Urdu, comprising of either psychological or somatic items, this scale includes both, which increases its reliability for use as a screening instrument by Community Health Workers in a primary health care setting, in epidemiologic work in Pakistan and in transcultural psychiatric research. PMID- 10028793 TI - Spinal cord compression: histologic spectrum of lesions. AB - Histologic diagnosis ultimately determines the prognosis and treatment of lesions causing spinal cord compression. Modern imaging techniques have revolutionized the procedure of localizing lesions presenting with signs and symptoms of spinal cord compression. As a result, these lesions are more accessible for fine needle aspiration and biopsy. A quick diagnosis is possible if cytologic preparation is made. Similarly, intraoperative frozen section facility not only provides rapid diagnosis, but also offers opportunity of appropriate management decision there and then. Histology in many cases needs help of special stains and immunocytochemistry. This study looks at the histologic spectrum of these lesions, gender distribution and age range in Pakistani population. PMID- 10028794 TI - Iron deficiency anaemia: continuous versus intermittent treatment in anaemic children. AB - Iron deficiency anaemia is a common disorder among paediatric population. Traditionally, oral iron is given for treatment on daily basis. We undertook this study to compare the results of intermittent with continuous oral iron therapy in children. The study was conducted at Combined Military Hospital (CMH), Lahore. Children (aged 1 to 6) with iron deficiency anaemia (Hb 11 g/dl) were allocated at random into two groups, A (n = 27) and B (n = 28). The mean Hb of group A, before treatment, was 8.56 (+/- 1.51) g/dl and that of group B was 8.32 (+/- 1.68) g/dl. Group A was given daily oral dosage of 6 mg/kg of elementAL iron whereas group B was given the same dosage of iron but only 3 days a week. After 2 months of treatment the Hb of group A rose to a mean of 11.06 (+/- 0.72) g/dl and that of group B was increased to 11.3 (+/- 0.90) g/dl, respectively. The difference, in the rise of Hb of two groups, was not statistically significant. It was concluded that in our sample of population, the results of intermittent and continuous oral iron therapy, for iron deficiency anaemia in children aged 1 to 6 years, were identical. PMID- 10028795 TI - Soft tissue sarcomas: pattern diagnosis or entity? AB - Soft tissue sarcomas (STS) are a diverse and heterogeneous group of tumours. The sub-classification of these tumours is of importance for both prognosis and treatment. Classically, sub-categorization is based purely on histomorphological grounds, but as new techniques evolve, a more conclusive and accurate diagnosis can be made. This study describes the prevalence of soft tissue sarcomas in adults diagnosed at The Aga Khan University Hospital (AKUH) and the impact of immunohistochemistry (IHC) on the precise sub-categorization of these tumours. The study included 364 adults (age 16+) who were diagnosed as soft tissue sarcoma in the past six years (May 1991-July 1997) at the Histopathology lab of the AKUH. Where indicated, tumours were stained with a panel of antibodies using the PAP technique. Of these, 237 (65%) were male and 127 (35%) were female. The median age at which all sarcomas were diagnosed was 39.5 years. The most common site was the lower extremity (29%). The most frequently diagnosed sarcoma was leiomyosarcoma (13%), followed by malignant nerve sheath tumour (12%), rhabdomyosarcoma (10%) and liposarcoma (10%). Cases were further analyzed by dividing them into two groups, each group comprised of all sarcomas diagnosed during the specified period. In the period 1991-1994, only 16% of cases were further analyzed using IHC, while in the period 1995-1997, IHC was performed on 59% of cases. In the 1991-1994 group, a conclusive diagnosis was made in 57% of the cases and in the 1995-1997 group in 78%. A Chi-square test was performed, which proved that these results were statistically significant. Soft tissue sarcoma is one of the key areas in surgical pathology where immunohistochemistry plays an important role in both precise diagnosis and sub-categorization. PMID- 10028796 TI - Febrile seizures: clinical course and diagnostic evaluation. AB - A study was done on 111 children admitted in a university hospital in Tehran with fever and seizures to document the pattern of illness and to define indications for performing a lumbar puncture in children with fever and convulsions. Bacterial meningitis was diagnosed in 4 patients, aseptic meningitis in 2 and 105 children had febrile seizures. The cause of fever was gastro-enteritis in 39 patients and upper respiratory tract infection with or without Otitis media in 40. Although most patients were drowsy on admission (n = 93), none had any signs of meningeal irritation, except one child with slight nuchal rigidity. Out of the 4 children with bacterial meningitis, 3 had meningeal signs, but in one 10 month old baby with no signs, the diagnosis was made on the cerebro-spinal fluid findings after a lumbar puncture. These results support the view that a lumbar puncture should be performed on all infants under 12 months who present with fever and convulsions and strongly considered between 12 and 18 months. After 18 months a lumbar puncture is mandatory in the presence of signs of meningeal irritation. PMID- 10028797 TI - Prevalence of rhesus phenotypes among local population in Karachi. PMID- 10028798 TI - Graft versus host disease following blood transfusion during coronary artery bypass grafting. PMID- 10028799 TI - Cervical epidural anesthesia for sub-total thyroidectomy in a patient with aortic incompetence. PMID- 10028800 TI - Acantholytic squamous cell carcinoma of skin--a case report. PMID- 10028801 TI - Management of hyperlipidaemia in general practice. PMID- 10028802 TI - Bacterial isolates from neutropenic febrile pediatric patients and their sensitivity patterns to antibiotics. AB - Patients on cytotoxic therapy often develop neutropenia and fever. Our interest was to identify the common pathogens isolated from such patients and to study the sensitivity patterns of these organisms to the antibiotics used in their treatment. Thus, guidelines can be established by hospitals to identify which antibiotics can be used in the treatment of these patients when the results of cultures and sensitivities are not available. We conducted a retrospective study of neutropenic pediatrics presenting to AKUH from July, 1990 to June, 1996. A total of 153 isolates in 35 different patients were studied. Samples for culture were taken from the sites at risk. The majority of samples consisted of blood, stool, pus and urine. Twenty stool samples were also sent for microscopy. Malignancies were both hematological and non-hematological. Gram negatives were isolated in 52.9%, gram positives in 33.9% and parasites in 13.2%. Salmonella paratyphi B was the most commonly isolated organism, followed by Pseudomonas aeroginosa, Giardia lamblia was the most common parasite. Sensitivity patterns of these organisms to antibiotics studied showed that Escheria coli had the lowest sensitivity rate being only 40% sensitive to Aztreonam and 64% sensitive to Ofloxacillin. A comparison was made between our findings and those reported in literature, as well as the risk factors for developing neutropenia. A guide to management is also discussed. PMID- 10028803 TI - [The first-three year report of the Tuberculosis Control Project, Lumbini, Rupandehi]. AB - The Tuberculosis Control Project, Lumbini, Rupandehi (TCPLR) is a bilateral cooperative venture between two NGO's, the Nepal Anti-Tuberculosis Association (NATA) and the Japan Anti-Tuberculosis Association (JATA), which consists of planning and implementing pilot tuberculosis control activities in Lumbini, Rupandehi district in Nepal, aiming at achieving high cure rate of newly detected smear-positive pulmonary tuberculosis patients before introducing DOTS strategies. Between December 1993 and July 1996, 349 tuberculosis (TB) cases were enrolled in the TCPLR. The categories of cases were as follows: 138 cases (40%) of new smear-positive pulmonary TB [new Sm(+) PTB], and 54 cases (15%) of smear positive pulmonary TB other than new Sm(+) PTB [other Sm(+) PTB] including such cases as continued treatment and relapse, 106 cases (30%) of new smear-negative TB [new Sm(-) TB], and 51 cases (15%) of other smear-negative TB other than New Sm(-) PTB [other Sm(-) TB]. The number and proportion of new Sm(+) PTB cases enrolled in the project have been increasing [6 cases (23%) for the first year, 102 cases (54%) for the third year] although the proportion is still low (40% overall). The regimens of chemotherapy in the initial intensive and the continuation phases of treatment according to the categories of TB were as follows: New Sm(+) PTB; 2HRZE(S)/6HE, other Sm(+) PTB; 2HRZES/1HRZE/5HRE, and Sm( ) TB; 2HRZ/6HE. The proportion of cases treated by the appropriate regimen of chemotherapy has increased. The cohort analysis of the treatment outcome of the cases enrolled in the project showed the following. The proportion of cured cases plus smear-unconfirmed cases completing treatment among new Sm(+) PTB was 74% overall, however, the proportion of defaulters increased in the third year. The proportion of cured cases plus smear-unconfirmed cases completing treatment among other Sm(+) PTB cases was 66% overall, which is slightly lower than that of new Sm(+) PTB cases, however, the difference was not so marked. The proportion of treatment completed cases among smear-negative pulmonary TB cases was 77% overall, however, proportion of defaulters increased in the third year. The treatment outcome in this report was obtained before the adoption of DOTS strategies: However, it showed that cure and treatment completion rates were comparable to those obtained in the SEARO countries which adopt DOTS strategies. The treatment outcome could be improved after the introduction of DOTS strategies in 1997. PMID- 10028804 TI - [Clinical analysis of foreign patients with tuberculosis found in Chugoku-Shikoku area]. AB - In this study, we investigated 45 foreign patients who had been diagnosed as having tuberculosis in Chugoku-Shikoku area during the past 12 years. Regarding regional characteristics, in Hiroshima prefecture an epidemic of tuberculosis was experienced among patients coming from South America, but antituberculous therapy was performed for 87% of the patients because of the high coverage of the health insurance scheme. But in Okayama prefecture, most of the patients were female and came from Asian countries, such as, the Philippines. Antituberculous therapy was not performed for nine patients because of no coverage of the health insurance scheme. In the other prefectures, only a few cases of tuberculosis were experienced, but in Yamaguchi prefecture two of three foreign patients were multidrug-resistant tuberculosis. PMID- 10028805 TI - [A tuberculosis epidemic among four relatives who live in the neighborhood of index case]. AB - A tuberculosis epidemic occurred among 4 relatives who live in the neighborhood of the index case. A thirty-three year old female was admitted to a hospital in July 1994 with high fever and cervical lymphoadenopathy. Culture examination of her sputum was positive for acid-fast bacilli and her chest X-ray showed diffuse small nodules. During the following sixteen months, five new patients with pulmonary tuberculosis were found among the relatives who lived in the neighborhood of the index case. The contact examination was first limited in her own family members, however, after detection of the second case, the examination was extended to other relatives living nearby, and another four patients were found. The results of PPD skin test of ten contact children showed strongly positive reaction, and chemoprophylaxis was indicated. Contacts examination is very important especially for patients with highly infectious tuberculosis. PMID- 10028806 TI - [A case of bronchiectasis with abundant expectoration of Mycobacterium gordonae]. AB - A 68 year old woman consulted our hospital because of 6 month history of dry cough. Her chest X-ray revealed bronchiectasis in the left lung. Three sputum specimens were culture positive for acid fast bacilli (AFB) 200 colonies. The bacilli were scotochromogenic, niacin test was negative and hydrolysis of tween 80 was positive, and they were identified as M. gordonae. M. gordonae is rarely implicated as a pathogen but a few reports suggest it may be pathogenic. Though our patient had clinical symptom and expected abundant M. gordonae, her chest X ray revealed no progression. Thus, it was hardly possible to consider this case as a case caused by the infection with M. gordonae. In previous reports of M. gordonae pulmonary disease, chest X-ray findings showed cavity, infiltration and consolidation, however, no case with bronchiectasis was reported and chest X-ray findings of this case are interesting. PMID- 10028807 TI - [Evaluation on the clinical background on early death in patients with pulmonary tuberculosis during the past five years]. AB - We evaluated the clinical background of early death (within 3 months after admission to our hospital) in patients with active pulmonary tuberculosis during the past five years (1992-1996). Among 65 active pulmonary tuberculosis patients who died during the past five years, 32 (49%) died directly of tuberculosis. Thirteen (41%) of those 32 patients died of acute respiratory failure and 9 patients (28%) died in emacitation state. Twenty two patients (69%) died within 3 months after admission to our hospital (the early death group) and 10 patients (31%) died after 3 months (the late death group). Thirteen patients (59%) in the early death group died of acute respiratory failure. On the other hand, none in the late death group died of acute respiratory failure but 4 patients died of chronic heart and/or respiratory failure and 4 patients died in emarciation state. Compared to the patients in the late death group, more patients in the early death group had long total delays (patient's and doctor's delays), had coexisiting diseases, had fallen into acute respiratory failure, and were under malnutrition. We evaluated the nutritional condition of patients using the Onodera's PNI (Prognostic Nutritional Index; 10 x serum almumin concentration + 0.005 x peripheral lymphocyte count) and the PNI value was lower among the patients in the early death group than among those in the late death group. To prevent death due to tuberculosis, we emphasize that it is important to start anti-tuberculosis therapy before patients fall into acute respiratory failure and/or malnutrition. PMID- 10028808 TI - [A clinical study of causes of death from active pulmonary tuberculosis with chemotherapy]. AB - We evaluated retrospectively the causes of death from active pulmonary tuberculosis by the review of records and chest radiograohs of 364 patients (male 282, female 82) with active pulmonary tuberculosis, who were admitted to our hospital during 1995 to 1998. 43 patients (male 33, female 10) were died under anti-tuberculous chemotherapy. 20 cases were tuberculous death; death from acute progression of tuberculosis without response to chemotherapy (acute progression group) in eight cases and death from debility in spite of partial response to chemotherapy (debility group) in eight cases. 23 cases were died from underlying diseases; death from malignant neoplasmas (malignant group) in nine cases and death from complication of bacterial pneumonia (pneumonia group) in seven cases. In acute progression group, the age (mean +/- SE) was 64.8 +/- 5.2 years old and the survival period from admission was 11.8 +/- 4.2 days. Five cases were laborer or unemployed. This group was characterized with far advanced diseases presenting extensive lung lesions complicated with DIC or hepatic dysfunction, low performance status (PS), severe malnutrition and lymphocytepenia. In debility group, the age was 70.8 +/- 3.9 years old and the survival period from admission was 254.6 +/- 90.7 days. Five cases were laborer or unemployed. This group was characterized with multiple underlying diseases, low PS, previous anti tuberculous chemotherapy and resistance to INH and/or RFP. In malignant group, the age was 69.3 +/- 3.2 years old and the survival period from admission was 99.9 +/- 21.2 days. This group was characterized with relatively well nourished, relatively good PS in comparison with other groups, and lymphocytepenia. In pneumonia group, the age was 82.8 +/- 1.7 years old and the survival period from admission was 153.3 +/- 54.5 days. This group was characterized with remarkably advanced age, low PS related to underlying disorders of central nervous system. In the causes of death with active pulmonary tuberculosis under chemotherapy, inhomogenous groups were included. Extensive disease, low PS, malnutrition, lymphocytopenia, previous chemotherapy, resistance to INH and/or RFP, and poorer social circumstances seemed to be risk factors for tuberculous death. In contrast, underlying malignant nepolasma, lower PS, and far advanced age were seemed to be the risk factors for non-tuberculous death. PMID- 10028810 TI - [Evaluation of home-oxygen-therapy for old tuberculosis cases, especially emphasis on the medical support for more comfortable life]. AB - We investigated the home-oxygen-therapy (HOT) for old tuberculosis patients. Tuberculosis cases are 100 of 296 all home-oxygen-therapy during the period from Aug. 1986 to Dec. 1997. 36 dead cases of these 100 were evaluated. Average period for HOT was 988 days (32.9 months). The mean rate of home stay was 78.9%. HOT is very useful for supporting comfortable home stay life. Our Medical respiratory Care (MRC) system is consist of primary education on HOT start, respiratory rehabilitation, mass education, annual rehabilitation trip and home nursing. Our MRC team is consist of 2 doctors, 12 nurses, 3 physical therapists, a dietician, a pharmacist and a medical clerk. We consider that it's important to support more comfortable life of the patients with chronic respiratory distress syndrome due to old tuberculosis. PMID- 10028809 TI - [Report of national survey on death due to tuberculosis in 1994 in national hospitals and the treatment and prognosis of tuberculous patients with mechanical ventilation]. AB - 1. National survey on died patients with active tuberculosis (tbc) or tbc sequelae had been held in national hospitals every five year from 1959 (3433 cases) to 1994 (688 cases). In 1994, 330 patients died due to pulmonary tbc. Recent study revealed the decreased rate of death due to operation, or far advanced cavitary cases, and the increased rate of nontuberculous death, aged people (> 60 yrs), and nontuberculous complications. Main causes of death in pulmonary tbc were lung insufficiency (about half) and general weakness (almost one fifth) in any survey. Rapid progression of pulmonary tbc had been increased cause of death (20.9% in 1994). Main attributable factors of death in 1994 in pulmonary tbc cases were severe condition on admission (38.4%), disturbed lung function (31.2%) and old age (33.2%). Delayed treatment (13.9%) and complications (12.1%) were increasing factors. Early death within 3 months from onset in 1994 was seen in patients < 60 yrs as well as in patients > 80 yrs. Severity due to delayed treatment and rapid progression were supposed to the causes of early death. 2. During 1994 to 1997, mechanical ventilation (MV; > 24 hours) was applied to 18 patients with active pulmonary tuberculosis; 10 acute respiratory failure (ARF), 5 chronic respiratory failure (CRF), 2 central nervous system tbc and 1 hemoptysis. Only one ARF case and three CRF ones survived. ARF cases had low PaO2/FIO2 (about 100), low albuminemia, short MV period (7 cases: < 7 days) and steroid therapy (9 cases). CRF cases had higher PaO2/FIO2 (294), longer MV period (4 cases: > 30 days) and all CO2 narcosis. 3. Noninvasive positive pressure ventilation (NIPPV) was applied to 23 patients with pulmonary tbc sequelae. In 13 patients with stable chronic respiratory failure (mean PaO2 91 mmHg, PaCO2 82 mmHg) 10 continued NIPPV and started home mechanical ventilation (HMV). In 10 patients with acute on chronic respiratory failure (mean PaO2 61 mmHg, PaCO2 92 mmHg) 2 patients fell into tracheal intermittent positive pressure ventilation (TIPPV). Eight patients recovered with NIPPV and 5 started HMV. NIPPV is supposed to be very effective to treat severe chronic hypercapmic respiratory failure. PMID- 10028811 TI - [The causes of death of pulmonary tuberculosis: late sequelae of pulmonary tuberculosis]. AB - We investigated the causes of death of late sequelae of pulmonary tuberculosis. Chronic respiratory failure is one of the most frequent cause of death in the patients of late sequelae of pulmonary tuberculosis. We compared the long term prognosis of chronic respiratory failure in case of emphysema and pulmonary tuberculosis. In the patients with chronic respiratory failure by pulmonary emphysema, the prognosis was poor in those with pulmonary hypertension. But in case of late sequelae of pulmonary tuberculosis, prognosis was not affected by presence or absence of pulmonary hypertension. The determinants of prognosis of late sequelae of pulmonary tuberculosis are the indication of home oxygen therapy, malnutrition, and hypoxemia. Fungal infection, especially aspergilloma, is a common secondary infection of late sequelae of pulmonary tuberculosis. We investigated forty-two cases of aspergilloma as late sequelae of pulmonary tuberculosis, and of those 15 patients died. The causes of death were pneumonia and respiratory failure. Measurement of galactomannan antigen of aspergillus in serum using ELISA or PCR, it was apparent that the outcome was poor in the patients positive for antigen. It suggested that the prognosis of the patients with aspergilloma related with some degree of invasion of Aspergillus in parenchyma. It was reported that neoplasm is closely related to chronic tuberculous empyema. Lymphoma is most frequently complicated with chronic tuberculous empyema, and squamous cell carcinoma, adenocarcinoma, sarcoma and carcinoid were reported as complication of chronic empyema. We reported the case of angiosarcoma, originated from chronic empyema in left thoracic cavity formed after being treated for tuberculosis with artificial pneumothorax. Recently, the number of patients with late sequelae of pulmonary tuberculosis have been decreased, but some severe cases of patients of pulmonary tuberculosis will suffer from late sequelae of pulmonary tuberculosis, and that is still a great problem of the clinical course of pulmonary tuberculosis. PMID- 10028812 TI - [Materials chemistry of advanced bioceramic coatings]. PMID- 10028813 TI - [A longitudinal cohort study on the relation between physical condition and masticatory ability in the elderly]. AB - The present study was conducted to determine the relation between physical condition and masticatory ability. The subjects were residents over 65 years old living in three different areas in Sagae City. The physical conditions assessed were height, weight, rate of body fat, grip strength, and bone mineral density. Masticatory ability was evaluated by the test jelly method. The results were as follows: 1) There was a difference in physical condition among subjects from the three residential areas. 2) For males, the group who maintained their masticatory ability exhibited better physical condition than those who did not. As for females, however, the physical condition was more strongly affected by age than masticatory ability. PMID- 10028814 TI - [Diagnosis for dental implant using computed tomography and precise implantation using modified stent]. AB - The diagnosis of jaw bones using X-ray computerized tomography is effective to decide the method of implantation, the position of the implant, and the direction for the insertion of the implant. However, it is difficult to apply anatomical information to the superstructures of implants, as well as to prepare implant sockets at the proper site by using an ordinary surgical stent. This would affect the effectiveness of the X-ray computerized tomography considerably. The X-ray computerized tomography with a diagnostic stent has been used in our clinic. CT multiplaner reconstruction images with radiopaque markers are useful to examine the adaptability of implant and to determine an appropriate site of implantation for an ideal prosthesis. Moreover, the diagnostic stent is modified to the surgical stent by drilling guide holes to reproduce a precise direction for inserting implant. By applying this stent, it is possible to reproduce the optimal site and direction for the placement of implant. In this report, two cases, which were treated with diagnosis and the placement of implants by using this technique, were studied. One was a case of overdenture and the other was that of upper anterior prostheses. In both cases, precise implantation was achieved by using this technique. PMID- 10028815 TI - Quality of health care for people with developmental disabilities: the challenge of managed care. AB - Health care quality issues for people with developmental disabilities under managed care were explored. Health-related quality was defined in terms of four domains: structure, process, outcome, and satisfaction. Three general problems in the assessment of health care quality were identified: lack of quality measures, patient response problems, and lack of system elements. Selected current measurement systems were described in relation to their use for people with developmental disabilities. An approach to developing quality measures was outlined using Healthy People 2000, Health Plan Employer Data Information Set, and clinical practice issues. The movement toward quality improvement was examined and recommendations presented for steps in developing and measuring health care quality. PMID- 10028816 TI - Twelve years later: adjustment in families who adopted children with developmental disabilities. AB - In most studies positive outcomes for families who have adopted children with developmental disabilities have been described. In this previous research, however, investigators have examined primarily short-term adjustment. In contrast, in the current longitudinal investigation 9 years after an initial interview, we assessed the adjustment and functioning of families who have adopted children with developmental disabilities. Results indicate that nearly 12 years after their adoptions, families remaining in the study reported generally positive outcomes and good adjustment to their adopted children. Whereas there were changes in these families, especially as the children approached adolescence and early adulthood, these changes were perceived as potential sources of reward as well as sources of stress. PMID- 10028817 TI - Social disclosure among coworkers without disabilities in supported employment settings. AB - The depth and breadth of reported self-disclosure by workers without disabilities (respondents) for three types of coworkers (i.e., work acquaintances, work friends, and social friends) were assessed. Reported self-disclosure of coworkers to supported employees was also compared, and the extent to which self-disclosure by respondents to job coaches correlated with intimacy of relationships between supported employees and respondents was analyzed. Results indicated that depth of self-disclosure can contribute to friendship formation, but coworkers did little self-disclosing to supported employees. Self-disclosure to job coaches did not correlate significantly with the development of relationships between the coworkers and supported employees. There is a need to teach supported employees to self-disclose to their coworkers and to prompt coworkers to talk about themselves in depth. PMID- 10028818 TI - Staff recruitment challenges and interventions in agencies supporting people with developmental disabilities. AB - Recruitment challenges and costs were identified by administrators from 129 randomly selected agencies that provide residential, vocational, and other services to persons with developmental disabilities in Minnesota. Finding qualified applicants was the most difficult staffing problem reported. Common recruitment incentives included providing competitive benefits, allowing time off without pay, and offering paid leave time. Relatively few agencies used innovative strategies (e.g., bonuses for employees who recruit new workers). The average agency had vacancy rates of 6% in direct-support positions and 4% in first-line supervisor positions. On the basis of these findings, one could determine that the cost of advertising and overtime for vacant positions in Minnesota could approach $6.7 million per year. PMID- 10028819 TI - Eighteen fractures in a man with profound mental retardation. AB - A 39-year-old man with generalized tonic clonic epilepsy and profound mental retardation sustained 18 fractures (15 in appendicular and 3 in axial bones) during 19 years. Both femoral necks were fractured, requiring surgical repair. Although he had been on antiepileptic drugs for 35 years, he had no radiographic or biochemical sign of osteomalacia. He had a very low bone mineral density, suggesting osteoporosis. This case illustrates an important medical problem affecting people with developmental disability and a management challenge for their caretakers. PMID- 10028820 TI - Word from Washington. PMID- 10028821 TI - Pitfalls in the pursuit of life, liberty, and happiness. PMID- 10028822 TI - General learning disorder: a new designation for mental retardation. PMID- 10028823 TI - Ideology, politics, and science in understanding developmental disabilities. PMID- 10028824 TI - Colleen McCullough's Tim: a literary representation of mental retardation. PMID- 10028825 TI - [Nurses' knowledge of alcohol-related problems and their treatment: a comparison of nurses in general hospital and alcoholism treatment units]. AB - Nurses have the most contact with patients in the clinical settings, and they play an important role in the guidance and education of patients. Nurses' basic knowledge of alcohol-related problems greatly influences early discovery of and early intervention against alcohol-related problems in general units (GU). In a study undertaken mainly to understand the status of nurses' knowledge in GU, a survey was performed to compare the knowledge and attitude of nurses working in GU and those with working in units specializing in the treatment of alcoholism (AU). For reference, we used the results of separate surveys performed previously on the general population. The results showed that, compared with nurses in AU, nurses in GU (1) were more tolerant of drinking, but (2) were more stigmatic concerning alcoholism, and (3) had little knowledge concerning alcohol-related problems. Nurses in GU tended to have less knowledge about alcohol-related problems than the general population. Moreover, the knowledge of nurses in AU could not be considered sufficient. This study suggested the need for basic education concerning alcohol-related problems and their treatment aimed at nurses. PMID- 10028826 TI - Study on Parkinson's disease and alcohol drinking. AB - To clarify alcohol drinking habits of patients with Parkinson's disease (PD) in Japanese, we compared mean values of alcohol consumption of PD patients and controls with special references to genetic polymorphism of ALDH2. Ninety-three Japanese outpatients with PD (39 males, 54 females) diagnosed by three skilled neurologists from 4 hospitals in Kanto area were analyzed for ALDH2 genotypes and alcohol consumption. A total of 297 healthy controls (156 males, 141 females) in the same area were also analyzed. PCR- SSCP (polymerase chain reaction-single strand conformational change polymorphism) analysis was used to determine ALDH2 genotypes. Mean values of alcohol consumption (ethanol g/month/person) from patients with PD were estimated by direct interview, and those from controls were obtained by questionnaire. Distributions of three genotypes and allele frequencies of ALDH2 were not different between patients and controls, however mean values of alcohol consumption of PD group were significantly lower than those of control group when compared between the same ALDH2 genotype. Our data suggested that the lower values of alcohol consumption in patients with PD for every ALDH2 genotypes may be caused by other factors such as premorbid personality rather than ALDH2 variant. PMID- 10028827 TI - [The inhibitory effect and the mechanism of ethanol absorption by L-carnosine zinc complex in mouse gastrointestinal tract]. AB - The effect of L-carnosine-zinc complex(Car-Zn) on ethanol absorption was investigated after oral administration(adm) to mice. One hour after oral adm of Car-Zn, and 14C-ethanol was given orally or intraperitoneally(i.p.). After passage of time, the blood was drawn from the tail vein, and 14C-radioactivities determined. The Car-Zn showed a dose-dependent inhibition of the appearance of 14C-radioactivities in blood following oral 14C-ethanol loading, while Zn acetate did not induce any alteration as compared with control. Car-Zn pretreatment did not induce any change in the blood 14C-radioactivity when ethanol was given i.p. The 14C-radioactivity and zinc in gastrointestinal tract after oral adm of Car-Zn and 14C-ethanol showed significantly higher levels than those of control for 7 hr. Distribution of 14C-radioactivities in other organs of Car-Zn treated mice were lower than those of control 3 hr after adm, while it was similar or higher than those of control 7 hr after adm. The excretions of 14C-radioactivity through expiration in Car-Zn group was a lower than that of control. Also, the urinary and fecal excretions of 14C-radioactivity were low values at 5.0% and 0.5% of the administered dose 72 hr after adm, respectively. Also, the 14C-radioactivities remaining in the organs did not detect or were very low values. In vitro study, Car-Zn stimulated the metabolism of ethanol to acetaldehyde and acetic acid in 9,000 g supernatant of small intestine. The major route of excretions of 14C radioactivity may be excreted into the expired air. The results suggest that Car Zn shows a long-term adhesive and permeable action on gastrointestinal tract in the mouse; as a result, this may inhibited ethanol absorption. PMID- 10028828 TI - [Effects of long-term ethanol administration on the kidneys, bones and muscles of mice]. AB - Reports on effects of ethanol intake on the kidneys and bones are few. Circulation of blood through the kidneys is large in amount; kidney takes water soluble exogenous substances and their metabolites in from the blood and accumulates them in the cells and interstitial tissues; in addition kidney plays important roles in producing substances that activate a living body and associating with their functions. The author let male and female ICR mice take 16% ethanol (Sake) ad lib for 472 days beginning at the age of 38 days. Observations were carried out on renal tissues and other organs which have some connection with the renal function. These included bones (femur, knee joint, tibia), muscle (gastrocnemius), 1 alpha, 25(OH)2D3 and erythropoietin (EPO). The results were as follows: Renal tissue observations: Significantly more cases of appearances of basophilic renal tubular, swelling of tubular epithelial cells and urinary casts in tubular lumens, PAS positive deposits in glomerulus, and atrophy of glomerulus were seen in the ethanol groups than in a group used as the control. These occurrences were significantly clear and intensive relative to those in the control. Findings in gastrocnemius: Significantly large number of muscle atrophy, random variation of fiber size and multinucleated fibers were seen. Observations on bones based upon soft X-ray pictures: Bone atrophy, thinning of bone trabeculae, thinning of bone cortex, and porosity of bone cortex were disclosed significantly more than the control. Values of 1 alpha, 25(OH)2D3 and EPO were significantly high increased in the ethanol groups relative to the control. Through the above-mentioned results, it has been supposed that ethanol intake affects kidney tissues and consequently affects bones and muscles. PMID- 10028829 TI - [Alcoholic problem among homeless people around Shibuya Station]. AB - It has been reported that the general public has the impression that many of the homeless people have alcoholic problems, and that these problems make their life problems worse. While there has been some research on this subject, most of them focus on the people who use public or private services. So, this study was conducted to investigate the alcoholic problems focused on the homeless people who were around Shibuya station. An investigation covering the questions about their job, company, sleeping style, amount of alcohol taken per day, CAGE and blood examination was compiled using questionnaires. The results were compared with people who are not homeless people and among homeless people. There were forty-nine homeless people who responded to the questionnaire and 34 homeless people who responded to the blood examination. The mean age of the homeless people was 53.1 years and no significant difference was seen between the homeless and the control. About 46% of the homeless reported that they do not drink. Sixteen per cent of the homeless respondents answered positively to the CAGE, No difference was found in having past history of liver dysfunction and in blood examination between them. There was a tendency that the amount of alcohol increases when the homeless have company. The level of gamma GTP increased significantly according to the amount of alcohol (p < 0.05). This study can be valued because of the attempt to focus not on the homeless who use services but on the homeless who stayed in the city. But the number of the targeted homeless people was small and there was selection bias that is not easy to be excluded in this type of research. Further studies on the impact of alcohol etc. should be developed to improve their lives. PMID- 10028830 TI - [Detection mode of leprosy and its disability grading in Khulna City, Bangladesh]. AB - The early case detection followed by WHO/MDT is the most important in leprosy control program not only for the destruction of linkage of infection but also the prevention of disability in leprosy. PIME Sisters leprosy program has been carrying out active case detection for leprosy since 1986 in Khulna, the third biggest metropolitan city in Bangladesh. The relation between several detection modes and their associated disability grading was analyzed in order to see the contribution of each detection mode to disability grading. The disability grading of new registered patients from 1995 to 1997, 1,115 cases in total was analyzed according to its detection mode. Voluntary reporting patients from "out of control area" had both high disability grading of G = 2 (38.0%) and high MB rate (39.3%). On the other hand voluntary reporting patients in control area had less disability grading of G = 2 (12.2%) and less MB rate (25.3%). The number of patients referred by local doctors was still small and had both high disability grading of G = 2 (27.0%) and high MB rate (51.4%). Children detected under school surveillance did not have any marked disability of G = 2 (0%) and were almost PB patients (88.6%). (Prevalence rate of school surveillance was low.) Patients detected under general surveillance had low disability grading of G = 2 (2.6%). The disability grading (G = 2) of voluntary patients from control area (12.2%) was three times as much as that of patients from general surveillance (2.6%). Lastly patients of family contacts who were aware of the first symptoms had relatively less disability grading (5.9%). The small number of patients referred by local doctors (3.3% of total number) with high disability grading meant that there would be still great need of information programs on leprosy for local medical professions to think about leprosy. The high disability grading of patients from "out of control area" meant that the more effective leprosy control program should be done in "out of control area". PMID- 10028831 TI - [Present situation of leprosy in highly endemic area of tropical Asia--a seroepidemiological study of Mycobacterium leprae infection in general inhabitants]. AB - One of the most important unsolved problems in epidemiology of leprosy is the heterogeneous geographic distribution of the disease. There are highly endemic area called "Pocket" in the endemic countries. Little is known why leprosy is so endemic in the area. We conducted, therefore, an epidemiological study on M. leprae infection and distribution of leprosy bacilli in the environment by using serological and molecular biological techniques. It was found that considerable number of general inhabitants in the pocket are infected with leprosy bacilli and more than 20% of the villagers are carrying M. leprae on the surface of the nasal cavity; suggesting that leprosy bacilli in the residential environment play an important role in high prevalence of leprosy in the endemic area. New preventive measures such as chemoprophylaxis, in addition to MDT, will be needed for global elimination of the disease. PMID- 10028832 TI - [2D-FASE MRCP for pediatrics with congenital biliary dilatation: usefulness of non-breath-hold one-shot MRCP]. AB - The usefulness of magnetic resonance cholangiopancreatography (MRCP) using the non-breath-hold one-shot technique was evaluated. Ten children suffering from congenital biliary dilatation (CBD) were included. Four of them were preoperative cases, and the remaining six postoperative. All MR images taken were compared with endoscopic retrograde cholangiopancreatography or intraoperative cholangiography. MR images using the non-breath-hold one-shot technique clearly showed the confluence of the common bile duct and the main pancreatic duct in seven of the cases. The confluence of the common bile duct and main pancreatic duct was obscure in the other three cases, mainly due to motion artifact. These results show that this non-breath-hold one-shot technique is useful for diagnosis and postoperative follow-up of congenital biliary dilatation in children. PMID- 10028833 TI - [Activation of the complement system and cytokine production by radiographic contrast media in vascular endothelial cells in vitro]. AB - The direct effect of four different radiographic contrast media (RCM) on the release of C3a and C5a and the production of IL-1 alpha and TNF-alpha from vascular endothelial cells was examined in vitro. The test RCM were as follows: diatrizoate (ionic monomer), iopamidol (nonionic monomer), ioxaglate (ionic dimer), and iotrolan (nonionic dimer). These were added to serum-free medium and adjusted to a final concentration of 1% (2.8 mg Iodine/ml). Human microvascular endothelial cells were stimulated by serum-free medium containing the test RCM for eight hours. After incubation, the media were aspirated and assayed for the concentrations of C3a, C5a, IL-1 alpha and TNF-alpha. Finally, the cells were harvested by trypsin, and their viability was determined by the dye-exclusion method. Diatrizoate and iotrolan had higher C3a release than the control (p < 0.05). No increase in C5a, IL-1 alpha or TNF-alpha levels was observed with any of the tested RCM, and there was no significant difference in cell viability with any of the tested RCM. The results of this study suggest that diatrizoate and iotrolan activated the complement system through the alternative pathway by directly stimulating vascular endothelial cells. These observations suggest that a direct effect of RCM on vascular endothelium might play a role in the pathogenesis of local drug eruptions due to RCM. PMID- 10028834 TI - [Effect of the skull on brain perfusion SPECT imaging]. AB - Because attenuation gradually decreases reconstructed counts from the periphery to the center portion of the object, the deep region far from the detector is not clearly observed if attenuation is not compensated. In brain perfusion SPECT, diagnosis is sometimes made using filtered back projection images without attenuation compensation (FBP). Brain perfusion SPECT has the unique characteristic that the radiopharmaceutical accumulates only within the brain and is never taken up by the surrounding skull. This study investigated the effect of skull on brain perfusion SPECT reconstructed with FBP. We theoretically derived the relation between the counts of brain and the linear attenuation coefficient of skull. It was found that the difference in reconstructed counts between the deep gray matter and peripheral gray matter decreased due to the existence of the skull. This result indicated that the deep gray matter was inclined to be visible if the FBP images were displayed according to relative counts normalized to the maximum count of each image. In order to confirm this, we made a numerical phantom with realistic human brain and skull contours on the basis of MR images from a normal volunteer. The linear attenuation coefficient of brain was assumed to be 0.15 cm-1, while that of skull was assumed to be 0.26 cm-1 (denoted as BONE+) or 0 cm-1 (BONE-). In accordance with the theoretical results, the deep gray matter of BONE+ images was more clearly observed than that of BONE- images, if these were displayed using the relative counts of each images. The physical phantom experiments also supported the theoretical and numerical phantom studies. PMID- 10028835 TI - [Computer-aided diagnosis in the detection of temporal changes in sequential chest radiographs]. AB - To aid radiologists in the diagnosis of screening chest radiographs, a temporal subtraction technique using digital image processing was developed. The accurate image registration of two sequential images enables us to detect even subtle changes in the "difference image" between them. In this report, a new method based on matching "lung markings" is introduced. Twenty-nine pairs of sequential posteroanterior chest radiographs with and without temporal changes were selected from cases examined with the computed radiography system. Image registration was employed, with the local matching of "lung markings" in previous and current radiographs. Observer performance tests were carried out by eight radiologists, with and without the "difference image." Observer performance tests with the temporal subtraction image showed that six of eight observers diagnosed them with higher sensitivity (mean, 43.9% vs. 55.3%) and a comparable false positive response. Mean area under the AFROC (alternative free-response receiver operating characteristics) curve also improved from 0.596 to 0.647, a statistically significant difference. The subtraction image using this registration technique improved diagnostic accuracy for subtle temporal changes. PMID- 10028836 TI - [Severe late effects of esophageal cancer treated by simultaneous intraluminal hyperthermo-brachytherapy: a case report]. AB - Severe late effects occurred after the treatment of esophageal cancer by external irradiation and simultaneous intraluminal hyperthermo-brachytherapy. This is the first case report on late side effects. A 73-year-old man was treated with radiotherapy alone according to his decision. The stage was T2N0M0 according to the 1987 UICC. External irradiation of 40 Gy/20 fr was delivered followed by simultaneous intraluminal hyperthermo-brachytherapy once weekly for four weeks (16 Gy/4 fr). Complete response was achieved. Eight months later, local recurrence and ulcer were found, and surgery was performed. The specimen showed healing of an ulcer acknowledged before surgery and another deep ulcer next to the tumor that penetrated the adventitia, which was close to perforation. The histopathologic specimen showed severe stenosis of muscular arteries in the adventitia, which was caused by fibrosis of the endothelium. The findings suggested that enhancement might be occurred with this combined therapy. PMID- 10028837 TI - [Sick lungs despite better air quality?]. PMID- 10028838 TI - [Limits of beryllium detection with laser microprobe mass spectrometry (LAMMS)]. AB - Search for beryllium (Be) in tissues or urine in suspected beryllium disease is often disappointing due to inferior sensitivity of the methods employed. We evaluated the clinical use of laser microprobe mass spectrometry (LAMMS) for measurement of Be and detected the metal to a minimum concentration of 1 microM. We then investigated the biological relevance of this concentration. We looked at the alveolar macrophages in 7 patients subsequent to an incubation period of 24 h as well as peripheral blood mononuclear cells (PBMNC) and various cell lines with and without addition of beryllium sulfate (BeSO4). We also investigated skin biopsies of two patients 28 days after intracutaneous injections of BeSO4 (beryllium skin testing) and alveolar macrophages of A/J mice at various time intervals after a beryllium sensitisation protocol and a single intratracheal injection of BeSO4 (maximum interval: 15 weeks). Be was not defectable in native patient alveolar macrophages (AM), but in 6 of 7 cases after coincubation with BeSO4. There was no significant Be signal in any analysed PBMNC sample or cell line--even after coincubation with Be--or in the skin probes. Murine AM, however, had incorporated significant amounts of Be, which were detectable until the end of the experiments 15 weeks later. We conclude that concentrations of Be in acute disease (here, inoculation of Be in mice) exceed 1 microM and are thus detectable by LAMMS. On the other hand, concentrations in chronic processes (in this cosar, skin testing) are below the detection limits of LAMMS. Further results suggest compartmentalisation of the immune processes induced by Be because the alveolar macrophages were able to incorporate Be while PBMNC were not and because AM--at least in the animal experiments--seem to store Be intracellularly. PMID- 10028839 TI - [The physician in the dilemma between confidentiality and mandatory reporting of occupational diseases]. AB - If a physician may reasonably suspect an occupational disease after examining his or her patient he is liable by German law to report this directly to the statutory accident insurance body or the Government institution responsible for the medical safety of working places, in accordance with section 202 of the Federal German social legislation code VII. This legal obligation to officially report an occupational disease is based on weighing the pros and cons in respect of balancing out an individual's right to privacy on the one hand and the (in this case predominant) public safety interests on the other. Legislation does not provide for the individual to effectively object to such reporting and hence the physician is obliged to report even if the patient objects. When doing so the physician does not violate his legal obligation to observe medical professional secrecy as defined according to section 203 German Penal Code by section 4 of the German professional medical code. PMID- 10028840 TI - [Information on a new occupational disease: "Lung cancer caused by polycyclic aromatic hydrocarbons with evidence of the effect of a cumulative dose of at least 100 benzo(a)pyrene years ([microgram/m3] * years)]. PMID- 10028841 TI - [Results and complications of fiber bronchoscopy in HIV positive patients]. AB - Fibreoptic bronchoscopy is an established diagnostic procedure for HIV-associated pulmonary infections. We retrospectively evaluated the diagnostic effectivity and safety of fibreoptic bronchoscopy with bronchoalveolar lavage (BAL) and transbronchial biopsy (TBB) in 153 patients with late-stage HIV infection and clinical signs of pulmonary infection or abnormal chest radiograph. Bronchoscopy leads to diagnosis in 82.4% and changed therapy in 54%. 45 patients (30%) were found to have pneumocystis carinii pneumonia (PCP), the most common bronchoscopic finding, followed by bacterial lung disease (29.3%). BAL had a sensitivity of 78% for PCP. Diagnostic yield of BAL for PCP was higher in patients without previous treatment (positive results in 82%) with regard to PCP independend of the prior treatment. Serious complication occurred in 22 cases (pneumothorax: 6 (3.9%), bleeding: 12 (7.8%), hypoxaemia: 4 (2.6%)). High serum levels of lactate dehydrogenase (LDH) correlated with pulmonary complications like pneumothorax. Age, sex and kind of pulmonary infection did not influence complication rates. 6 (3.9%) episodes of spontaneous pneumothorax occurred in the further course, 3 of them concurrently with PCP or prior history of PCP. We conclude that fibreoptic bronchoscopy is of great value for diagnosing pulmonary infection in HIV seropositive patients. TBB provides incremental diagnostic information not available from BAL, especially in patients pretreated with cotrimoxazol or pentamidin. For that reason we believe that TBB should be performed in these patients. PMID- 10028842 TI - [Pathologic-anatomic findings in surgical lung volume reduction of advanced emphysema]. AB - Surgical lung volume reduction is a method for treatment of advanced pulmonary emphysema after all other therapeutic approaches have failed. 280 atypical lung resection specimen of 81 patients were examined pathologico-anatomically using routine stains. In all cases combinations of various forms of emphysema were found; in 65.8% there were also bullous changes (with > or = 1 cm diameter) focally. Acute bronchiolitis was seen in 41.8% of the specimens, an only slight (if at all) chronic bronchiolitis in 26.7% and bronchioloectasia in 45.4% of the cases. Focal intraalveolar aggregates of granulocytes were identified in 16.1%, and the process of permanent scarring resulting in "organised pneumonia" in 20.6% of the specimens. Occult neoplasms were found in 9.9% of the patients and specific changes in 27.2%. Bronchiolitis is relevant for postoperative prognosis and an indication for intensifying antibiotical and antiinflammatory therapy. Preoperative diagnostical procedures should be intensified to find out these patients. Inflammatory changes must be investigated in respect of etiology and pathogenesis. PMID- 10028843 TI - [Immunohistologic study of the localization of ICAM-1 (intercellular cell adhesion molecule 1) in alveolar epithelium in the human lung]. AB - The intercellular cell adhesion molecule 1 (ICAM-1) is expressed in the endothelium of pulmonary blood vessels, in the alveolar epithelium and in the bronchial epithelium. Because of conflicting reports in the literature on the question whether ICAM-1 is exclusively expressed in pneumocytes Type I or also in pneumocytes Type II, the present study aimed at characterising the cell types in normal human alveolar epithelium which show immunoreactivity for ICAM-1. Immunohistochemistry for ICAM-1 was performed on a series of 19 specimens of normal human lung. In addition, double staining procedures of ICAM-1 together with cell type specific antigens were performed. To detect pneumocytes Type II an antibody to cytokeratin 18 (CK 18) was used. Alveolar macrophages were marked by an antibody to the monocyte macrophage-specific leukocyte antigen CD 68. Vascular endothelium was stained by common endothelial markers (Ulex europaeus agglutinin Type I, anti-von Willebrand factor). The alveolar septa showed intense surface staining for ICAM-1 that could be localised predominantly to pneumocytes Type I. There were also single ICAM-1 positive cells having the characteristics of pneumocytes Type II in respect of their morphological appearance and their cytokeratin pattern. For the interpretation of these results the fact had to be considered that pneumocytes Type I can partly cover up pneumocytes Type II. This was confirmed by ultrastructural observations. Our findings suggest that ICAM-1 plays a part in the interaction between intraalveolar leukocytes and the alveolar epithelium. PMID- 10028845 TI - [Dosage of DNCG (Intal, Aarane)]. PMID- 10028846 TI - [Induction of Ph-negative normal clone and long-term survival by combined treatment with G-CSF plus middle dose cytosine arabinoside for patients with chronic myeloid leukemia in blastic transformation]. AB - Three patients with chronic myeloid leukemia (CML) in blastic transformation were treated with G-CSF plus middle dose cytosine arabinoside (Ara-C). G-CSF was administered (150 mg, s.c. or 300 mg, d.i.v./day) 24 hr prior to Ara-C (2-3 g/body, 6 hour d.i.v. for 2-5 days) and continued until the peripheral neutrophil count rose above 1,000/microlitre. As a supplement, VP-16 (80 mg/m2, for 2 days) was administered as warranted to control the growth of blastic cells. All 3 patients survived for more than 12 months with a favorable performance status. Normal karyotypes were detected in 2 of the patients after chemotherapy. One of those patients in paticular demonstrated normal bone marrow findings with the almost complete disappearance of the Ph-positive clone. In vitro cultures of peroxidase-negative CML blastic cells revealed that G-CSF stimulated the induction of blastic cells into the cell cycle and that blastic cell apoptosis was more pronounced in cells cultured with G-CSF plus Ara-C than with G-CSF or Ara-C alone. G-CSF plus middle dose Ara-C therapy appears to be a strong candidate for the treatment of CML in blastic transformation with a poor prognosis. PMID- 10028847 TI - [Multifocal nodular AL amyloidosis in primary Sjogren's syndrome]. AB - Primary Sjogren's syndrome (primary SS) is characterized by lymphocytic and plasma cell infiltration of the lacrimal and salivary glands, sometimes extending to extraglandular sites. An increased incidence of B-cell lymphoproliferative disorders has been observed in patients with primary SS. We recently studied an unusual case of primary SS associated with multifocal nodular AL amyloidosis (amyloidomas), located in the lower respiratory tract and oral mucosa. A 66-year old woman with primary Sjogren's syndrome since 1966 was hospitalized in 1996 because of multifocal nodular shadows on a chest radiograph. An open lung biopsy specimen was obtained, revealing a large mass of amorphous eosinophilic material with green birefringence when stained with Congo red. Numerous plasma cells surrounded the amyloid deposits, aggregated in nodules and around blood vessels. The cytoplasm of these cells stained monotypically with anti-lambda light chain, using a peroxidase technique. Amyloid material did not stain with antibodies directed against kappa and lambda light chains, or against IgG, IgA and IgM heavy chains. Immunofixation of the serum and concentrated urine did not demonstrate monoclonal immunoglobulins. AL-amyloidomas might be a manifestation of local immunoglobulin production and amyloid formation within extramedullary plasmacytoma. This plasmacytoma might be burned out, namely, overcome by the deposits and no longer recognizable. PMID- 10028848 TI - [Therapy-related MDS/leukemia carrying dup(11) (q21q23) with MLL gene tandem duplication]. AB - A 42-year-old woman had been given a diagnosis of malignant lymphoma, follicular, small cleaved cell. She had undergone chemotherapy including etoposide (1,500 mg/total) and was in her second complete remission. Four years and 4 months later, refractory anemia with excess of blasts (RAEB) with dup(11) (q21q23) x 2 developed in the patient and progressed to acute myeloid leukemia (AML-M5b). Despite regression of the AML to RAEB, a clone with the additional abnormality of del(20) (q11q13.1) appeared and transformed the RAEB into AML-M6. Rearrangement of the MLL gene was observed, and FISH analysis demonstrated that the signal sequences from the gene's 5' and 3'-terminal regions had detached. RT-PCR techniques detected a tandem duplication of MLL gene exons 2 through 8. This was considered to be one of the mechanisms behind the formation of the 11q23 abnormality observed in this patient. PMID- 10028849 TI - [Acute promyelocytic leukemia accompanied by scrotal Fournier's gangrene during ATRA treatment and relapsed as external ear tumor]. AB - A 43-year-old man was admitted because of gingival bleeding. A diagnosis of acute promyelocytic leukemia (APL) was made. He was given combination chemotherapy including all-trans retinoic acid (ATRA). During the myelosuppression stage, the patient developed Fournier's gangrene of the scrotum. He achieved complete remission and underwent a hemicastration procedure. Seven months later, bilateral external ear tumors developed. Biopsy specimens of the tumors revealed infiltration of APL cells. A second remission was obtained by chemotherapy including ATRA. However, bilateral ear tumors developed again 5 months later despite indications of normal marrow without proliferation of leukemic blasts. Irradiation successfully reduced the ear tumors, but the patient died of cerebral hemorrhage from a left frontal extramedullary tumor. This was a rare case of APL accompanied by Fournier's gangrene of the scrotum during ATRA treatment, and by extramedullary tumors of the external ear and brain during leukemic relapse. PMID- 10028850 TI - [Lymphoma associated hemophagocytic syndrome with plasmacytosis in the bone marrow and hypergammaglobulinemia]. AB - A 72-year-old woman was admitted to our hospital because of fever, anemia and thrombocytopenia in March 1997. Laboratory findings showed elevated serum LDH levels and polyclonal gammopathy. Bone marrow aspiration samples revealed hemophagocytosis and plasmacytosis. Although serum interleukin-6 was elevated, serum interferon-lambda and tumor necrosis factor-alpha were below detectable limits. Magnetic resonance images disclosed a tumor in the patient's pelvic cavity. The tumor was resected and diagnosed as non-Hodgkin's lymphoma. The patient was treated with combination chemotherapy and has remained in complete remission. Also, histiocyte and plasma cell counts in the bone marrow fell significantly and the serum interleukin-6 level returned to the normal range. We reasoned that lymphoma cells may have induced plasmacytosis in the bone marrow and polyclonal gammopathy accompanied by hemophagocytic syndrome. PMID- 10028851 TI - [Extranodal non-Hodgkin's lymphoma associated with systemic bone metastasis and secondary myelofibrosis]. AB - A 68-year-old woman was admitted in March 1997 because of lumbago, fever, vomiting, and general malaise. Laboratory data disclosed anemia and severe hypercalcemia (7.7 mEq/l). Multiple osteolytic lesions were detected in the patient's vertebra, pelvis, and bilateral tibia by x-ray films and 99mTc bone scintigrams. Bone marrow aspiration sample was not obtained due to dry tap. Marked myelofibrosis and proliferation of lymphoid cells were revealed by a bone marrow biopsy specimen. Immunohistochemical analysis showed that cells in the biopsy specimen were positive for L-26 and LCA, but not for UCHL-1. Gastrointestinal endoscopic examination found multiple polypoid lesions in the stomach; biopsy specimens of the lesion tissue disclosed invasion by B lymphoid cells. A diagnosis of diffuse large B cell lymphoma was thus made. THP-COP chemotherapy was performed, but only minimal response was obtained. Lymphoma cells subsequently invaded the brain stem, and the patient eventually died of respiratory failure. PMID- 10028852 TI - [Chemotherapy-resistant CD7-positive stem cell lymphoma presenting with intra abdominal mass]. AB - We report a case of CD7+ stem cell lymphoma. A 47-year-old man presented with general malaise and lumbago in April 1997. The patient exhibited swollen left cervical lymph-nodes and an intra-abdominal bulky mass. He was referred to us because lymph-node biopsy specimens indicated a diagnosis of diffuse type malignant lymphoma. An abdominal CT scan disclosed large retroperitoneal, para aortic, and mesenteric root masses. Bone marrow involvement was shown by bone marrow biopsy specimens, though no circulating blasts were detected at presentation. The patient was treated with high-dose CHOP therapy without any benefit. Though ESHAP therapy was performed as salvage chemotherapy, the abdominal masses did not shrink at all. The patient died of tumor progression in November 1997. In the terminal stage, the lymphoma cells emerged in the peripheral blood and thus became available for analysis. The cells expressed CD5, 7, 34, 38, 71, but were negative for CD1, 2, 3, 4, 8, 10, 13, 14, 16, 19, 20, 21, 25, HLA-DR, and EMA. An immunoglobulin heavy chain gene rearrangement band was detected by Southern blot analysis. However, no T cell receptor lambda or beta chain gene rearrangement bands were detected. PMID- 10028853 TI - [Sick sinus syndrome after chemotherapy for malignant lymphoma with right atrial tumor at initial presentation]. AB - A 56-year-old man was admitted complaining of throat discomfort and dyspnea. He was given a diagnosis of diffuse large B-cell lymphoma on the basis of findings from tumor biopsy specimens of his left pharynx. MRI tomograms and ultrasonic cardiograms revealed a right atrial tumor causing tricuspid stenosis. Although chemotherapy rendered the cardiac tumor indistinct on MRI and UCG images, gallium 67 scintigraphy still demonstrated abnormal cardiac uptake. After 6 courses of CHOP therapy, sick sinus syndrome with syncope suddenly developed in the patient. A cardiac pacemaker was immediately implanted, and radiotherapy was started. The patient's sinus rhythm returned to normal shortly afterward, and the gallium-67 uptake eventually disappeared. In this case gallium-67 scintigraphy was the only diagnostic procedure capable of detecting evidence of residual disease. PMID- 10028854 TI - [Partial splenic embolization as a preoperative treatment for refractory idiopathic thrombocytopenic purpura]. AB - A 53-year-old woman presented with idiopathic thrombocytopenic purpura (ITP) that was refractory to corticosteroid therapy. Her bleeding had worsened gradually due to prolonged thrombocytopenia, but her low platelet count after high-dose intravenous gamma globulin therapy contraindicated a splenectomy. We therefore decided to perform a partial splenic embolization (PSE). The patient's platelet count increased gradually thereafter, allowing us to safely perform a splenectomy. We concluded that PSE is a useful preoperative procedure, especially for patients with ITP that is refractory to high-dose intravenous gamma-globulin therapy. Moreover, it is possible to predict the effects of a splenectomy preoperatively if the PSE procedure is used. PMID- 10028855 TI - Neuronal migration disorders. Part I: Terminology, classification, pathophysiology, EEG and epilepsy. AB - Intractable epilepsies and partial epilepsies, which make up a great majority of epileptic disorders, are not better recognized and their etiologies unveiled with the help of the new imaging techniques. The development of magnetic resonance imaging (MRI) permits the accurate diagnosis while the patients are alive of the neuronal migration disorders (NMD), which constitute an important group of intractable epilepsies. Previously, NMD cases were described by neuropathologists from autopsy materials, and many of these developmental disorders were not considered compatible with prolonged survival. Cerebral malformations due to neuronal migration anomalies are described in association with motor and mental retardation, learning disabilities, microcephaly, dysmorphic features and epilepsy. Neuronal migration takes place in all parts of the central nervous system (CNS) during the shaping process of the CNS; it actually includes both the central and peripheral nervous systems. However, in common usage the meaning of "neuronal migration disorders" is restricted to the neocortex. PMID- 10028856 TI - Neuronal migration disorders. Part II: Magnetic resonance imaging. AB - With the widespread use of magnetic resonance imaging (MRI), neuronal migration disorders (NMD), including lissencephaly, pachygyria, polymicrogyria, schizencephaly, unilateral hemimegalencephaly and gray matter heterotopia, are more frequently and easily diagnosed. When NMD is a diagnostic consideration, MRI should be the imaging method of choice with the high contrast between gray and white matter it provides and its high resolution multiplanar display of anatomy. Magnetic resonance imaging displays the size, configuration and distribution of cortical gyri and cortical thickness for the evaluation of possible lissencephaly, pachygyri and polymicrogyri. It will successfully demonstrate deposits of gray matter in abnormal locations when gray matter heterotopias are present. With its multiplanar imaging capability, MRI will demonstrate the cleft extending from the pial surface to the ventricular ependyma whether the lips of the cleft are fused or separate, thus providing the diagnosis of schizencephaly. PMID- 10028857 TI - Turkish experience with rhabdomyosarcoma: an analysis of 255 patients for 20 years. AB - Two hundred and fifty-five previously untreated patients (pts) with rhabdomyosarcoma (RMS) (age range 15 days to 17 years, median 5 years) were evaluated and treated in our institution. Head and neck primaries were seen in 125 patients (49%), abdominopelvic in 73 (29%), trunk and lung in 20 (5%) and extremity lesions in 37 (15%). The histology was: embryonal 137; alveolar 42; botryoid 18; pleomorphic 14. Forty-four patients could not be subclassified. The stage of the patients were as follows: 15 in state I, 74 in stage II, 139 in stage III and 27 in stage IV, according to the IRS grouping system. Patients were treated with a combination of surgery and radiation to doses of 35-55 Gy according to the patient's age and stage. All the patients received chemotherapy according to VAC or pulse-VAC (before 1988) and modified AVAC (after 1988) protocol. Survival curves were calculated by the Kaplan-Meier method. The statistical significance of each variable was tested by the log-rank test. Overall survival was 42 percent at 10 years. Three important predictors for survival time were clinical group (p < 0.001), age (p < 0.001) and primary site (p = 0.005). The best results involved clinical group I-II, age one to five years and orbital and genitourinary primary sites. An important predictor of survival time was also detected between those treated during the first ten years (1972-82) and last 10 years (1982-92), p < 0.005. Of the 96 deaths, 37 were from progressive disease, 24 from infection, 4 during postoperative period (first 7 days), 18 from unknown causes and 13 from other causes. PMID- 10028858 TI - Recombinant interferon-alpha-2A with or without steroid pretreatment in children with chronic hepatitis B. AB - Interferon is the most promising therapeutic agent for the treatment of chronic viral hepatitis. The results of studies suggest that corticosteroid pretreatment may improve the response rate. Twenty-nine children with chronic hepatitis B (CHB) were randomly assigned to receive recombinant interferon alpha (rIFN-alpha) alone (Group 1.5 million units/m2 body surface, 3 times a week for 24 weeks) or to receive oral prednisone (Group 2.2 mg/kg/day for 3 weeks, discontinued by tapering the dose within 1 week) followed by rIFN-alpha (same dose as above). Tests for liver function and hepatitis B virus (HBV) markers including HBV-DNA were done periodically. Overall, 10 patients (34.5%) cleared hepatitis Be antigen and 13 (44.8%) HBV-DNA. Anti-HBe seroconversion was observed in nine patients (31%). Only three patients (10.3%) cleared hepatitis B surface antigen and seroconverted to anti-HBs. No response was obtained in 11 patients (37.9%). There was no statistically significant difference between the two treatment groups regarding response rate. Baseline transaminases levels and HBV-DNA concentrations were predictive parameters for HBeAg clearance. It is concluded that prednisone pretreatment does not have a beneficial effect in children with CHB. PMID- 10028859 TI - A multicenter child maltreatment study: twenty-eight cases followed-up on a multidisciplinary basis. AB - Twenty-eight maltreated cases were presented in this multicenter study. Hospital distribution was as follows: Dr. Behcet Uz Children's Hospital, 54 percent; Dokuz Eylul University Hospital, 21 percent; Ege University Hospital, 14 percent; Tepecik Social Security Hospital, 7 percent; Ataturk State Hospital, 4 percent. Age and sex distribution was two months to 25 years and 43 percent male, 57 percent female. The offender was the father in 71 percent, the mother in 32 percent and multiple in 25 percent of the cases. More than three child maltreatment risk factors were present in 93 percent. Nineteen patients (68%), nine of which were effectively followed-up were reported to the Social Affairs Bureau. Sixty-four percent gained acceptable health with the support of our team, 14 percent died, and 21 percent failed to comply with follow-up. A multidisciplinary group may interfere both medically and socially with these cases to interrupt the course of maltreatment. Every children's hospital needs such a team to increase diagnosis establishment necessary to initiate social support. PMID- 10028860 TI - Rh blood group system in Turkey. AB - Because of the absence of original data concerning the Rh blood group system in Turkey, for the benefit of researchers interested in the human blood groups field, serological results obtained in Hacettepe University Hospitals' Blood Center between 1980 and 1996 have been evaluated for the first time in this paper. During the study, 581,606 people were evaluated for Rho (D) positivity and negativity. In addition, 5,600 people from different parts of Turkey were screened for the five major antigens (D, C, E, c, e) of the Rh blood group system and, according to the results, various gene frequencies and most likely genotypes were calculated. Results clearly show that the Rh blood group system in Turkey is completely, in line with that of the Caucasians. PMID- 10028861 TI - Fc gamma receptor allotypes in children with bacterial meningitis. A preliminary study. AB - IgG2 antibody is the essential subclass to protect against encapsulated bacteria Fc gamma RIIa is the only Fc gamma receptor that interacts with human IgG2. The two genetically determined allotypes of human Fc gamma RIIa, Fc gamma RIIa-R131 and Fc gamma RIIa-H131 alleles have functionally different reactivities with IgG2 in vitro, and H/H-131 cells have markedly higher binding affinity for human IgG2. Homozygous Fc gamma RIIIb-NA1/NA1 PMNLs show higher phagocytic capacity than Fc gamma RIIIb-NA2/NA2 PMNLs. To evaluate in vivo significance of Fc gamma RIIa and Fc gamma RIIIb allotypes, we analyzed Fc gamma R allotypes in children with bacterial meningitis due to Haemophilus influenzae type b, Streptococcus pneumoniae and Neisseria meningitidis. Fc gamma RII and Fc gamma RIIIb polymorphisms were determined by using quantitative flow cytometry. Fc gamma RIIa were studied in 23 children with bacterial meningitis and 50 healthy Turkish controls, and Fc gamma IIIb in 18 and 43 such individuals, respectively. The distribution of Fc gamma RIIa in the healthy Turkish control group was found to be significantly different from that in the Chinese and Japanese population (p < 0.05), but similar to that of the white population in the USA and the Netherlands. No case (0%) had the Fc gamma RII-H/H-131 Fc gamma RIIIb-NA1/NA1 the corresponding figure in the controls was 4 (9.3%). Homozygous Fc gamma RIIa-H/H 131 phenotype was underrepresented with borderline significance (p: 0.057) in patients below two years of age in comparison with the healthy subjects and with patients with meningitis over two years of age (p: 0.059). Although the study needs to be conducted in a large series of patients in order to draw a firm conclusion, Fc gamma RIIa polymorphism may be a contributing factor to the increased susceptibility to meningitis with encapsulated bacteria in children below two years of age. PMID- 10028862 TI - Attention deficit hyperactivity disorder (ADHD): a practical scale for pediatricians. AB - Attention deficit hyperactivity disorder (ADHD) is a common disturbance causing school failure and social problems. Early diagnosis and intervention allow ADHD children to adjust and succeed at school and in daily life. To identify these patients, we designed a practical questionnaire for parents. When tested on children with ADHD (n = 100), children with psychiatric problems (n = 35), and on age- and sex-mached control children (n = 100), this scale was found to be highly useful in distinguishing these three groups from each other, especially after the identification and elimination of items with lower specificity. The use of the Hacettepe ADHD scale is recommended for pediatricians, general practitioners and teachers to allow earlier diagnosis of this condition. PMID- 10028863 TI - The clinical predictors of intrauterine fetal death. AB - Five hundred and thirteen (513) patients with intrauterine fetal death managed between 1983 and 1990 at Hacettepe University Hospital were analyzed retrospectively. Fetal death rate was 20.5/1,000 deliveries during the study period. The mean age of the mothers at diagnosis was 27.6 years. Of the 326 multigravida patients, 113 (34.6%) had a history of abortion and 113 had a history of previous intrauterine fetal death. The leading causes of intrauterine fetal death in this series were maternal hypertension in 167 patients (32.5%) followed by abruptio placentae in 38, Rh incompatibility in 30 and congenital anomalies in 30 patients. However, in 175 patients (34.1%), the cause of intrauterine fetal death could be explained. Three mothers were lost: one from pulmonary embolism complicating deep venous thrombosis, one from heart failure due to rheumatic disease, and one from cerebral injury following a traffic accident. The patients with a history of fetal demise should be managed under high risk category with close antepartum surveillance, especially in the last trimester, so as to reduce intrauterine fetal deaths which are mostly attributable to preventable causes. PMID- 10028864 TI - Use of localized proton nuclear magnetic resonance spectroscopy in Canavan's disease. AB - Canavan's disease is characterized by megalencephaly, leukodystrophy and early motor and mental retardation. On computerized tomography and magnetic resonance imaging, severe changes compatible with white matter disease due to demyelination is observed. It has been demonstrated that urinary N-acetylaspartate levels are increased because of a deficiency of aspartoacylase (N-acyl-L-aspartate aminohydrolase) in these patients. In this study, with the use of proton nuclear magnetic resonance spectroscopy, we were able to demonstrate elevated levels of N acetylaspartate compared to choline and creatine in the frontal region white matter of three patients. The in vivo measurement of N-acetylaspartate, choline and creatine in the brain by magnetic resonance spectroscopy offers an additional noninvasive diagnostic test for establishing the diagnosis of Canavan's disease. PMID- 10028865 TI - Herpes encephalitis in children. MRI assessment. AB - The magnetic resonance imaging (MRI) findings in 14 patients with biopsy or polymerase chain reaction proven herpes simplex encephalitis were retrospectively reviewed to evaluate the diagnostic value of MRI in the early diagnosis of herpes simplex encephalitis in children. In addition to the early findings, follow-up MRI scans were obtained in four patients. Typical limbic system involvement was seen in 78 percent of the cases. Contrast-enhanced MRI was found to be superior to routine MRI sequences and computerized tomography (CT) in the early detection of inflammation. Follow-up MR images in four patients demonstrated the volume loss and late petechial hemorrhage in the involved regions. Magnetic resonance imaging is the method of choice in the diagnosis and follow-up of herpes simplex encephalitis. PMID- 10028866 TI - Alpha-2-macroglobulin levels in early respiratory distress syndrome. AB - The vasoactive products of uncontrolled protease activity can play an important role in the pathogenesis of respiratory distress syndrome in newborn infants. In this study alpha-2-macroglobulin, which has antiproteolytic activity, was studied in the first few hours of life in preterm infants with and without respiratory distress syndrome. Mean plasma alpha-2-macroglobulin levels were found to be similar in both groups. These findings implicated that alpha-2-macroglobulin has no significant role in the pathogenesis of respiratory distress syndrome. PMID- 10028867 TI - Noninvasive cardiac evaluation of young patient with cystic fibrosis. AB - Cardiac involvement was evaluated by echocardiography in 26 young cystic fibrosis patients. The mean age was 48.4 months (range 3 months to 15 years). The findings were compared with 26 age- and sex-matched children without a history of cardiopulmonary complaints. All patients had normal values of left ventricular ejection fraction and fractional shortening. Interventricular septal and posterior left ventricular wall thicknesses were similar to control group but right ventricular free wall thickness was found greater than in the control group. Abnormal septal motion was documented in six patients. Right ventricular pre-ejection period to ventricular ejection time ratio was found over the upper limit of normal in two patients and there was a negative correlation with clinical Shwachman scores (r: -0.55). Left ventricular pre-ejection period to ventricular ejection time ratio was found over the upper limit of normal in five patients. For both mitral and tricuspid valves, the mean ratios of peak velocity during passive filling (E) phase of diastole to peak velocity during atrial contraction (A) phase were found significantly lower than in the control group (p < 0.05). Early diastolic peak velocity was similar to that in the control group but late atrial peak velocity was higher in the patient group (p < 0.05). Isovolumic relaxation time was found the same as in the control group. We conclude that cardiac changes in diastolic and systolic functions begin at very young ages in cystic fibrosis patients. PMID- 10028868 TI - Extrapontine myelinolysis in a nine-year-old child. AB - Extrapontine myelinolysis in the pediatric age group is very rare. We report a nine-year-old girl with the classical clinical syndrome of pontine and extrapontine myelinolysis following liver trauma due to a traffic accident. She was referred to our hospital for further investigation of convulsions due to severe postoperative hyponatremia. She had no hypoxic event or other identifiable cause for the neurological symptoms. Neurological deterioration began about two days after correction of hyponatremia and followed a period of temporary improvement in hyponatremic encephalopathy. Diagnosis of extrapontine myelinolysis was confirmed with the identification of typical features on magnetic resonance imaging. The rapid correction of hyponatremia seemed the most likely cause since other biochemical tests including liver function tests were all within normal ranges. The long term clinical outcome was good. It is important to carefully monitor the rate of correction in electrolyte disturbances, and to consider the individual variation in response to therapy. PMID- 10028869 TI - Acute rheumatic fever with three major criteria: polyarthritis, carditis and chorea. A case report. AB - An eight-year-old girl is presented with three major criteria of acute rheumatic fever: polyarthritis, carditis and chorea. The diagnosis was confirmed with a history of pharyngitis 15 days prior to admission and with the findings of positive acute phase reactants such as elevated erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP), elevated anti-streptolysin-O (ASO) titration, and clinical findings of polyarthritis, carditis and chorea. Patient responded well to salicylate and phenobarbital treatment. The rare association of these three major criteria in acute rheumatic fever is emphasized. PMID- 10028870 TI - Toxic methemoglobinemia after injection of prilocaine in a newborn. A case report. AB - The acute onset of cyanosis in an infant is an alarming development. We report an infant who became cyanotic after injection of prilocaine. Prilocaine is a local anesthetic that is widely used in clinical practice, but usage in infancy easily causes methemoglobinemia. Acquired methemoglobinemia occurs in individuals exposed to an increased amount of agents that oxidize hemoglobin iron. PMID- 10028871 TI - A family presenting Goltz syndrome (focal dermal hypoplasia) in three generations. AB - In this report we present three affected females of the same family in three generations. The cases have features of focal dermal hypoplasia (Goltz syndrome). One of the three affected females is the index case and the others are her mother and her grandmother. We performed skin biopsies on them. According to histopathological examinations skin lesions were compatible with Goltz syndrome. These cases exhibited focal dermal hypoplasia (FDH) manifestations including skin, dental and skeletal abnormalities. The affected females were seen in three generations of the same family which pointed to its X-linked dominance. PMID- 10028872 TI - Early assessment of pulmonary involvement in limited scleroderma. A case report. AB - Limited scleroderma is typified by insidious progression of skin involvement. The onset of internal organ involvement is delayed until the second decade, the lungs being the most important from the prognostic point of view. Early detection of pulmonary lesions is of paramount importance. This paper presents a 16-year-old male patient with a history of Raynaud's phenomenon followed by progressive tightening of skin over the fingers, hands and face. He had early pulmonary involvement detected by high resolution computed tomography (HRCT) and proven by histopathologic examination as usual interstitial pneumonia; even the chest x-ray and pulmonary function tests were normal. A combination of prednisolone and D penicillamine was planned for treatment because of his having both pulmonary and gastrointestinal system involvement. 99 m technetium diethylenetriamine pentaacetate (99 m Tc-DTPA) test is very sensitive for pulmonary lesions and it has shown a rapid clearance in the early stage. This method is also useful for following up the therapeutic trial. PMID- 10028873 TI - X-linked agammaglobulinemia and isolated growth hormone deficiency. AB - X-linked agammaglobulinemia and isolated growth hormone deficiency was first described in 1980 and then classified as a different primary immune deficiency. Delayed puberty in patients with X-linked agammaglobulinemia may result in delayed secretion of growth hormone (GH). To determine true isolated growth hormone deficiency. GH stimulation tests and other hypophyseal hormone evaluations must be performed. In this paper, we report a 15-year-old boy with X linked agammaglobulinemia and isolated growth hormone deficiency, and review related literature. PMID- 10028874 TI - Variable clinical expression of Holt-Oram syndrome in three generations. AB - Holt-Oram syndrome is a distinct autosomal dominant entity presenting with upper limb defects and cardiac abnormality. No correlation between the severity of the heart and the limb defects has been established. Here we report variable clinical expression of Holt-Oram syndrome in three generations. The grandfather presented with typical upper limb defects: phocomelia of arms with three digits on each hand, congenital heart defect and narrow shoulders. His son manifested cardiac conduction disturbance with no congenital heart or skeletal defect. The granddaughter showed ventricular septal defect and moderate radial deviations of both hands with no obvious hypoplasia of the extremities. Clinical data of the presented family suggests lack of penetrance with respect to skeletal and structural cardiac abnormalities in the Holt-Oram syndrome. PMID- 10028875 TI - A case of truncus arteriosus type II. AB - A case of truncus arteriosus type II is reported. Truncus arterious is an uncommon congenital cardiac defect where a single great vessel exits the heart. Truncus arteriosus is usually fatal, if untreated. This defect occurs when the conus arteriosus and the truncus divide erroneously in the embryo. Palliative surgery in truncus arteriosus has been unsuccessful. Pulmonary banding has been tried and was ineffective and usually fatal. We operated on a nine-month-old (6200 g) male infant with a type II (Edwards-Collett) defect and a large ventricular septal defect. The pulmonary artery average pressure was 51 mmHg. We performed a cardiopulmonary bypass in the usual manner. Pulmonary arteries were resected from the truncal root, and primary end-to-end anastomosis of the truncal root to the ascending aorta was performed. Right ventricle to pulmonary artery continuity was provided using a valveless Gore-Tex graft. We lost our patient due to intractable pulmonary hypertension on the first postoperative day. PMID- 10028876 TI - Congenital tricuspid insufficiency due to a cleft in tricuspid anterior leaflet associated with perimembranous VSD. An unusual case report. PMID- 10028877 TI - [Biological and chemical warfare]. PMID- 10028878 TI - [Space medicine]. PMID- 10028879 TI - [Viruses, bacteria and toxins as biological warfare]. AB - Biological weapons are an important part of the level of international threat. Technological development has made biological weapon production relatively simple and cheap, and although a UN convention from 1972 bans biological weapons, governments as well as non-governmental organisations or individuals have developed biological weapons for offensive use in war or terrorism. This article reviews the publically available literature, and clinical and therapeutic possibilities are described. The possibilities for protection of military and civilian groups are discussed and the need for a national contingency plan is emphasized. PMID- 10028880 TI - [An observation department for children with acute disease]. PMID- 10028881 TI - [Causes of need for reoperation following surgery for varicose veins in Denmark]. AB - In a surgical varicose vein practice 509 patients who had suffered recurrent varicose veins following surgery in other institutions were traced. The causes of recurrences were identified in a retrospective analysis and related to the source of primary treatment: in hospital treatment (n = 290), surgical practice (n = 56) or another varicose vein specialist (n = 104). A significant difference was noted between the three institutions in the use of saphenofemoral resection (78%, 63% and 97%) as well as greater saphenous vein stripping (44%, 14% and 0%). Lack of or insufficiently performed saphenofemoral surgery were identified as contributing to saphenofemoral insufficiency in 40% and 43% of patients primarily treated in hospital and in surgical practice, respectively, but only in 14% of those treated by a varicose vein specialist (p < 0.001). Primary sapheno popliteal resection had been used equally infrequently (11%, 13% and 16%, respectively) and was equally frequently insufficiently performed (66%, 57% and 41%). This retrospective investigation concludes that insufficient varicose vein surgery is a major contributor to recurrences, particularly when primary surgery is performed in hospital or in surgical practice, as opposed to in a varicose vein practice. These results warrant a reorganisation of varicose vein surgery in Denmark. PMID- 10028882 TI - [Eosinophilic cystitis. A survey]. AB - The purpose of this study was to evaluate the incidence, diagnostic criteria and treatment of eosinophilic cystitis in the period 1989-94 in Denmark. A questionnaire was sent to all Danish surgical, urological and pathological anatomical departments. Fifty-six patients were diagnosed as having eosinophilic cystitis at the surgical departments and 135 patients were diagnosed at the pathological-anatomical departments. The treatment was most often instillation of steroids in the bladder or oral antihistamine. Success of treatment was generally acceptable. The questionnaire confirmed that eosinophilic cystitis is a rare disease. We recommend the pathological-anatomical departments to use certain diagnostic criteria for eosinophilic cystitis. The treatment is symptomatic. A diagnostic number from the Danish Health Board is needed. PMID- 10028883 TI - [A screening test for depression in general practice. The COOP/WONCA chart]. AB - Depressed patients in general practice may be difficult to identify. Questionnaires may be used for screening but some of the existing instruments are difficult to use and have only to a limited degree been introduced in general practice. In this study 798 patients' answers to the COOP/WONCA chart "Feelings" were compared to GPs' diagnosis according to ICD-10 criteria for depressive single episode (F32). At cut-off2/3 (slight/moderate problems) the chart had a sensitivity of 89% (76-100%) and specificity of 75% (72-78%). The predictive value of a positive test was not higher than 33% for any cut-off point and the predictive value of a negative test never less than 98%. A two-phased diagnostic strategy with the COOP/WONCA chart as step one is suggested as a possible and relatively simple way to optimize recognition of depressive patients in general practice. PMID- 10028884 TI - [Birth weight as a predictor of young men's intelligence. A historical cohort study]. AB - The objective was to examine the relation between birth weight and cognitive function in young adult life. The study includes 4300 Danish conscripts born between 1973 and 1975, and the main outcome measure was the mean score in the Borge Prien IQ test at drafting. The score is the number of correct answers to 78 questions and it correlates with full scale intelligence quotient (IQ). Data on birth weight were collected from the birth registry. The mean score in the Borge Prien test increased from 39.9 at a birth weight of < or = 2500 g to 44.6 at a birth weight of 4200 g after adjustment for gestational age and length at birth, maternal age and parity, and other variables. Above a birth weight of 4200 the test score decreased slightly. Birth weight is associated with cognitive performance in young adult life and factors that interference with foetal growth may influence adult cognitive performance. PMID- 10028885 TI - [Misuse of emergency ambulance services]. AB - The aim of the study was to investigate the incidence of misuse of ambulance emergency services for minor injuries in a defined area and population. Case records concerning all patients (2708) treated in the period 19.02-13.06.96 at the A&E departments at Holstebro and Herning Central Hospitals were reviewed. The following factors were predictive of use of ambulance for transportation to the A&E department in minor injuries: Traffic accident, age 18-25 years and injuries to head and back. Approximately 50% of all patients transported by ambulance emergency were estimated to have been able to be treated by general practitioners instead. In conclusion, although a certain amount of misuse of ambulance emergency services among patients treated for minor injuries were identified, the incidence of misuse was not more than 1.5/day in a population of appr. 200.000. PMID- 10028886 TI - [Comorbidity of infantile autism and blindness]. AB - A three year-old girl with Leber's amaurosis was found to fulfil the criteria for autism, as will as being mentally retarded. Despite her blindness she displayed unusually by early motor development and was able to move around in her surroundings without difficulty. This case suggests that this ability was due to her relevant use of a minor visual remnant and, as is often seen in blindness, a capability of reflecting the surroundings--a "bat sense". The pervasive development a disorder influenced her abilities more strongly than her sensory handicap. PMID- 10028887 TI - [Intracoronary brachytherapy against restenosis after percutaneous transluminal coronary angioplasty]. PMID- 10028888 TI - [Quality assurance of chromosome examinations in the samples of amniotic fluid and placenta. A 6-year follow-up: no sign of analytic errors in 6384 samples]. PMID- 10028889 TI - [Chemical warfare poisoning in time of peace]. PMID- 10028890 TI - 1998 and beyond--Legge's legacy to modern occupational health. AB - Thomas Legge achieved much in his professional lifetime. The purpose of this lecture is to highlight some of these achievements in the light of what we have achieved since then. In other words, if Legge was in the audience today, how would he feel we have performed? On 'industrial maladies', progress has been made in reducing poisoning by heavy metals but our success with chrome ulceration and lead depends on surveillance and control. Room for improvements remain. For asbestos related diseases, Legge would be disappointed with our progress. Two areas of particular concern to Legge were upper limb disorders and 'occupational neurosis'. Much remains to be done. As a member of the 1st Committee on Compensatable Diseases, a review of the Scheme to date will focus on the common diseases now being prescribed and on the threats to the Scheme from the Benefits review. For the future, there are many challenges in the newer workplaces and the changing workforces. The HSE initiatives for a new occupational strategy and the Government Green Paper on Public Health provide great opportunities for the occupational health professional to influence the nature and shape of future public health strategy. Above all we must have some of Legge's characteristics to achieve this-vision, passion and commitment. PMID- 10028891 TI - Mechanisms and mediators in coal dust induced toxicity: a review. AB - Chronic inhalation of coal dust can cause several lung disorders, including simple coal workers pneumoconiosis (CWP), progressive massive fibrosis (PMF), chronic bronchitis, lung function loss, and emphysema. This review focuses on the cellular actions and interactions of key inflammatory cells and target cells in coal dust toxicity and related lung disorders, i.e. macrophages and neutrophils, epithelial cells, and fibroblasts. Factors released from or affecting these cells are outlined in separate sections, i.e. (1) reactive oxygen species (ROS) and related antioxidant protection mechanisms, and (2) cytokines, growth factors and related proteins. Furthermore, (3) components of the extracellular matrix (ECM), including the modifying role of ROS, cytokines, proteases and antiproteases are discussed in relation to tissue damage and remodelling in the respiratory tract. It is recognised that inhaled coal dust particles are important non-cellular and cellular sources of ROS in the lung, and may be significantly involved in the damage of lung target cells as well as important macromolecules including alpha-1 antitrypsin and DNA. In vitro and in vivo studies with coal dusts showed the up regulation of important leukocyte recruiting factors, e.g. Leukotriene-B4 (LTB4), Platelet Derived Growth Factor (PDGF), Monocyte Chemotactic Protein-1 (MCP-1), and Tumor Necrosis Factor-alpha (TNF alpha), as well as the neutrophil adhesion factor Intercellular Adhesion Molecule-1 (ICAM-1). Coal dust particles are also known to stimulate the (macrophage) production of various factors with potential capacity to modulate lung cells and/or extracellular matrix, including O2-., H2O2, and NO, fibroblast chemoattractants (e.g. Transforming Growth Factor-beta (TGF beta), PDGF, and fibronectin) and a number of factors that have been shown to stimulate and/or inhibit fibroblast growth or collagen production such as (TNF alpha, TGF beta, PDGF, Insulin Like Growth Factor, and Prostaglandin-E2). Further studies are needed to clarify the in vivo kinetics and relative impact of these factors. PMID- 10028892 TI - Personal exposure to dust, endotoxin and crystalline silica in California agriculture. AB - AIMS: The aim of this study was to measure personal exposure to dust, endotoxin and crystalline silica during various agricultural operations in California over a period of one year. METHODS: Ten farms were randomly selected in Yolo and Solano counties and workers were invited to wear personal sampling equipment to measure inhalable and respirable dust levels during various operations. The samples were analysed for endotoxin using the Limulus Amebocyte Lysate assay and crystalline silica content using X-ray diffraction. In total 142 inhalable samples and 144 respirable samples were collected. RESULTS: The measurements showed considerable difference in exposure levels between various operations, in particular for the inhalable fraction of the dust and the endotoxin. Machine harvesting of tree crops (Geometric mean (GM) = 45.1 mg/m3) and vegetables (GM = 7.9 mg/m3), and cleaning of poultry houses (GM = 6.7 mg/m3) showed the highest inhalable dust levels. Cleaning of poultry houses also showed the highest inhalable endotoxin levels (GM = 1861 EU/m3). Respirable dust levels were generally low, except for machine harvesting of tree crops (GM = 2.8 mg/m3) and vegetables (GM = 0.9 mg/m3). Respirable endotoxin levels were also low. For the inhalable dust fraction, levels were reduced considerably when an enclosed cabin was present. The percentage of crystalline silica was overall higher in the respirable dust samples than the inhalable dust samples. CONCLUSIONS: Considerable differences exist in personal exposure levels to dust, endotoxin and crystalline silica during various agricultural operations in California agriculture with some operations showing very high levels. PMID- 10028893 TI - Hierarchical cluster analysis applied to workers' exposures in fiberglass insulation manufacturing. AB - The objectives of this study were to explore the application of cluster analysis to the characterization of multiple exposures in industrial hygiene practice and to compare exposure groupings based on the result from cluster analysis with that based on non-measurement-based approaches commonly used in epidemiology. Cluster analysis was performed for 37 workers simultaneously exposed to three agents (endotoxin, phenolic compounds and formaldehyde) in fiberglass insulation manufacturing. Different clustering algorithms, including complete-linkage (or farthest-neighbor), single-linkage (or nearest-neighbor), group-average and model based clustering approaches, were used to construct the tree structures from which clusters can be formed. Differences were observed between the exposure clusters constructed by these different clustering algorithms. When contrasting the exposure classification based on tree structures with that based on non measurement-based information, the results indicate that the exposure clusters identified from the tree structures had little in common with the classification results from either the traditional exposure zone or the work group classification approach. In terms of the defining homogeneous exposure groups or from the standpoint of health risk, some toxicological normalization in the components of the exposure vector appears to be required in order to form meaningful exposure groupings from cluster analysis. Finally, it remains important to see if the lack of correspondence between exposure groups based on epidemiological classification and measurement data is a peculiarity of the data or a more general problem in multivariate exposure analysis. PMID- 10028894 TI - An expert system for the evaluation of historical asbestos exposure as diagnostic criterion in asbestos-related diseases. AB - Compensation schemes for asbestos-related diseases have developed different strategies for attributing a specific disease to occupational exposure to asbestos in the past. In the absence of quantitative exposure information that allows a valid estimate of an individual's historical exposure, general guidelines are required to retrospectively evaluate asbestos exposure. A risk matrix has been developed that contains qualitative information on the proportion of workers exposed and the level of exposure in particular industries over time. Based on this risk matrix, stepwise decision trees were formulated for decisions regarding the decisive role of historical asbestos exposure in case ascertainment of asbestosis and mesothelioma. Application of decision schemes will serve to speed up the process of verifying compensation claims and also contribute to a uniform decision-making process in legal procedures. PMID- 10028895 TI - Modeling breathing-zone concentrations of airborne contaminants generated during compressed air spray painting. AB - This paper presents a mathematical model to predict breathing-zone concentrations of airborne contaminants generated during compressed air spray painting in cross flow ventilated booths. The model focuses on characterizing the generation and transport of overspray mist. It extends previous work on conventional spray guns to include exposures generated by HVLP guns. Dimensional analysis and scale model wind-tunnel studies are employed using non-volatile oils, instead of paint, to produce empirical equations for estimating exposure to total mass. Results indicate that a dimensionless breathing zone concentration is a nonlinear function of the ratio of momentum flux of air from the spray gun to the momentum flux of air passing through the projected area of the worker's body. The orientation of the spraying operation within the booth is also very significant. The exposure model requires an estimate of the contaminant generation rate, which is approximated by a simple impactor model. The results represent an initial step in the construction of more realistic models capable of predicting exposure as a mathematical function of the governing parameters. PMID- 10028896 TI - When joggers die. PMID- 10028897 TI - Preventing strokes with surgery: experience counts. PMID- 10028898 TI - Lowering cholesterol reduces mortality for heart patients with "normal" lipids. PMID- 10028899 TI - Hazards for patients with cardiac pacemakers and defibrillators. PMID- 10028900 TI - I have heart failure and it is getting worse. Now I have trouble doing even simple things around the house. I am 67 years-old, and my doctor tells me I am too old for a heart transplant. I have heard of an operation in which they cut out a piece of heart muscle and that makes the heart work better. Is this something I should consider? PMID- 10028901 TI - I am 48 years-old and recently learned that I have diabetes. I know that my risk of heart attacks is high, and I want to know what I can do to prevent heart disease. Should I be injecting insulin two or three times a day in an attempt to get very "tight" control of my blood sugar? PMID- 10028902 TI - My fingers get very white and even painful when I am outside in the cold. My physician says this is a circulation problem. Does this put me at higher risk for heart disease? PMID- 10028903 TI - I have had a diagnosis of heart failure for many years, but I recently had an echocardiogram, and the doctor told me it showed my heart was not weakened at all. What is causing my shortness of breath? PMID- 10028904 TI - Brain tumors. New technology helps diagnosis, treatment. PMID- 10028905 TI - Health tips. Tired eyes. PMID- 10028906 TI - Cholesterol-lowering margarine expected out this year. PMID- 10028907 TI - New pill helps fight advanced gum disease. PMID- 10028908 TI - Irritable bowel syndrome. Gaining control of your symptoms. PMID- 10028909 TI - Easy bruising. Should you be worried if you bruise easily? PMID- 10028910 TI - Carbohydrates. What role do they play in your diet? PMID- 10028911 TI - My daughter-in-law has been diagnosed with Raynaud's. Can you tell me more about this condition? PMID- 10028912 TI - I've been trying to get rid of excess facial hair ever since I can remember. Is there any effective medication for this problem? PMID- 10028913 TI - Arthritis. New treatments and daily decisions are keys to an active lifestyle. PMID- 10028914 TI - Excitotoxic brain damage in the rat induces interleukin-1beta protein in microglia and astrocytes: correlation with the progression of cell death. AB - Interleukin-1 beta (IL-1beta) has been proposed as a mediator of several forms of brain damage, including that induced by excitotoxins. In vitro studies suggest that glial cells are the effector cells of IL-1beta-mediated neurodegeneration. We have investigated the expression of IL-1beta protein by glial cells in vivo in response to NMDA receptor-mediated excitotoxicity in the rat parietal cortex and striatum. Expression of IL-1beta by glial cells was investigated using immunocytochemistry 30 min to 7 days after infusion of the NMDA agonist cis-2,4 methanoglutamate (MGlu; 10 nmol) into the cortex. Early expression (1-4 h) of IL 1beta by microglia was directly related to lesion development. Later expression by microglia (up to 24 h), and by astrocytes (2-7 days), was widespread compared to the area involved in excitotoxic cell death and co-localised with areas of reactive gliosis. Infusion of MGlu into the striatum induced a similar temporal pattern of IL-1beta expression by microglia and astrocytes. However, IL-1beta expressing glial cells were localised strictly to the area of striatal cell death. Infusion of PBS or a subtoxic dose of MGlu into the cortex or striatum induced only limited neuronal death and negligible glial IL-1beta expression. These studies reveal that IL-1beta is expressed specifically by microglia during the early response to excitotoxicity in the adult rat cortex and striatum. However, the widespread and delayed IL-1beta expression by astrocytes suggests diverse roles for IL-1beta in response to excitotoxicity. PMID- 10028915 TI - Occurrence of the diffuse amyloid beta-protein (Abeta) deposits with numerous Abeta-containing glial cells in the cerebral cortex of patients with Alzheimer's disease. AB - Diffuse amyloid beta-protein (Abeta) deposits with numerous glial cells containing C-terminal Abeta fragments occur in the cerebral cortex of patients with Alzheimer's disease. By using a panel of antibodies specific for various epitopes in the Abeta peptide, we have investigated the immunohistochemical nature of the diffuse Abeta deposits. The extracellular material contains Abeta with a C-terminus at residue valine40 (Abeta40) as well as residues alanine42/threonine43 (Abeta42). The N-termini include aspartate1, pyroglutamate3, and pyroglutamate11, with pyroglutamate3 being dominant. Microglia and astrocytes in and around these deposits contain intensely staining granules. Most of these granules are negative for antibodies to the N-terminally located sequences of Abeta. These include 6E10 (Abeta1-17), 6F/3D (Abeta8-17), and the N-terminal antibodies specific to aspartate1, pyroglutamate3, and pyroglutamate11. The C-termini of intraglial Abeta are comparable with those of the extracellular deposits. The microglia and astrocytes have quiescent morphology compared with those associated with senile plaques and other lesions such as ischemia. Complement activation in these deposits is not prominent and often below the sensitivity of immunohistochemical detection. Although factors which may cause this type of deposit remain unclear, lack of strong tissue responses suggests that these deposits are a very early stage of Abeta deposition. They were found only inconsistently and were absent in a number of cases examined in this study. Further analysis of these deposits might provide important clues regarding the accumulation and clearance of Abeta in Alzheimer's disease brain. PMID- 10028916 TI - TGF-beta1-dependent differential expression of a rat homolog for latent TGF-beta binding protein in astrocytes and C6 glioma cells. AB - Transforming growth factor-beta1 (TGF-beta1) is widely recognized for its multiple roles in development, cellular maintenance, and protection against injury. In the brain, TGF-beta1 upregulation in microglia/macrophages is a predominant response to lesion and during pathology. However, the precise functions of TGF-beta1 in this context are still enigmatic. The present study investigates changes in astroglial gene expression as a major target of TGF-beta1 signaling in the brain. Differential display reverse transcription-polymerase chain reaction (DDRT-PCR) was used to identify several gene fragments differentially regulated by TGF-beta1 in rat astrocytes and C6 glioma cells. Among the cDNAs regulated by TGF-beta1 in C6 cells two cDNAs showed homology to alpha-tropomyosin and glycerol-3-phosphate dehydrogenase, respectively. Cloning of a full length cDNA corresponding to a differentially regulated gene fragment revealed close homology to latent TGF-beta binding protein (LTBP)-2. Data using antisense LTBP-2 oligonucleotides to decrease LTBP-2 expression suggest that LTBP 2 functions to activate TGF-beta. Therefore, it is likely that upregulation of the rat LTBP-2 homolog mRNA in C6 cells and cortical astrocytes by TGF-1 might lead to self-activation and exaggeration of TGF-beta signaling. These data will extend our current understanding of TGF-beta1 functioning on lesion-related features of glial cells. PMID- 10028917 TI - Strongly compromised inflammatory response to brain injury in interleukin-6 deficient mice. AB - Injury to the central nervous system (CNS) elicits an inflammatory response involving activation of microglia, brain macrophages, and astrocytes, processes likely mediated by the release of proinflammatory cytokines. In order to determine the role of interleukin-6 (IL-6) during the inflammatory response in the brain following disruption of the blood-brain barrier (BBB), we examined the effects of a focal cryo injury to the fronto-parietal cortex in interleukin-6 deficient (IL-6-/-) and normal (IL-6+/+) mice. In IL-6+/+ mice, brain injury resulted in the appearance of brain macrophages and reactive astrocytes surrounding the lesion site. In addition, expression of granulocyte-macrophage colony-stimulating factor (GM-CSF) and metallothionein-I+II (MT-I+II) were increased in these cells, while the brain-specific MT-III was only moderately upregulated. In IL-6-/- mice, however, the response of brain macrophages and reactive astrocytes was markedly depressed and the number of NSE positive neurons was reduced. Brain damage-induced GM-CSF and MT-I+II expression were also markedly depressed compared to IL-6+/+ mice. In contrast, MT-III immunoreactivity was markedly increased in brain macrophages and astrocytes. In situ hybridization analysis indicates that MT-I+II but not MT-III immunoreactivity reflect changes in the messenger levels. The number of cell divisions was similar in IL-6+/+ and IL-6-/- mice. The present results demonstrate that IL-6 is crucial for the recruitment of myelo-monocytes and activation of glial cells following brain injury with disrupted BBB. Furthermore, our results suggest IL-6 is important for neuroprotection and the induction of GM-CSF and MT expression. The opposing effect of IL-6 on MT-I+II and MT-III levels in the damaged brain suggests MT isoform-specific functions. PMID- 10028918 TI - Temporal expression pattern of peripheral myelin protein 22 during in vivo and in vitro myelination. AB - Peripheral myelin protein 22 (PMP22) was initially described as a minor component of peripheral myelin. Mutations affecting the PMP22 gene cause demyelinating neuropathies, supporting a role for the protein in PNS myelination. Furthermore, PMP22 carries the L2/HNK-1 carbohydrate epitope suggesting an adhesion/recognition function. Despite advances in characterizing the PMP22 gene, the specific role(s) of the protein in myelin remains unknown. In this study we determined the temporal expression pattern of PMP22 in comparison to galactocerebroside (GalC) and myelin associated glycoprotein (MAG), early constituents of PNS myelin, and to protein zero (P0) and myelin basic protein (MBP), late components of myelin. In sciatic nerve lysates, PMP22 was detected at postnatal day 3, after MAG, but before MBP expression. The same results were obtained in cocultures of dorsal root ganglion neurons and Schwann cells (SCs). Low levels of PMP22 were found in early, anti-MAG and anti-GalC immunoreactive, myelinating cocultures. However, PMP22 could only be detected in the SC plasma membrane after basal lamina formation. In long-term myelinating cocultures PMP22 levels continued to increase and the protein was found in anti-P0 and anti-MBP immunoreactive myelin segments. Furthermore, PMP22, MBP, and P0 protein levels were greatly enhanced by progesterone treatment of the cocultures. The highest levels of PMP22 expression were associated with late stages of myelination; however the presence of the protein in nonmyelinating SCs and in SCs commencing myelination supports multiple roles for PMP22 in peripheral nerve biology. PMID- 10028919 TI - Delta-opioid receptor immunoreactivity on astrocytes is upregulated during mitosis. AB - Endogenous opioid peptides and opioid receptors are expressed by brain cells early during normal development, and exogenous opiate exposure in this period is known to affect brain cell proliferation and maturation. Despite the abundant evidence that opioids affect brain development, little is known about the mechanisms involved. In this study cortical astrocytes in primary culture were examined immunohistochemically by using antibodies against the opioid receptors. The immunoreactivity for delta-opioid receptors was strongly upregulated during mitosis with an increase in immunostaining that started in early prophase and lasted through the M-phase to cytokinesis. Similar effects could not be observed when antibodies against the mu- or kappa-opioid receptor subtypes were used. Cultured neurons and microglia presented a strong and homogenous immunostaining for the delta-opioid receptor and no further upregulation of immunoreactivity could be detected in these cells. The presence of functional delta-opioid receptors on the mitotic astrocytes was verified by using microspectrofluorometry for detection of delta-opioid agonist induced changes in intracellular free calcium concentrations ([Ca2+]i). In these experiments fluo-3/AM incubated cells showed a rapidly induced delta-opioid agonist (DPDPE, 10(-6) M) evoked increase in [Ca2+]i. These results suggest an upregulation of the delta-opioid receptors that could represent a mechanism involved in the response to opioids in the developing brain. PMID- 10028920 TI - Muller cell swelling, glutamate uptake, and excitotoxic neurodegeneration in the isolated rat retina. AB - We characterized morphological effects of the endogenous excitotoxin, glutamate in ex vivo retinal segments prepared from 30-day-old rats. Initial changes induced by glutamate consisted of reversible, sodium-dependent Muller cell swelling. This glial swelling was mimicked by glutamate transport substrates but not by ionotropic glutamate receptor agonists. Only very high concentrations of exogenous glutamate (3,000 microM) produced excitotoxic neuronal damage. The neuronal damage was accompanied by severe glial swelling and was blocked by an antagonist of non-N-methyl-D-aspartate (NMDA) receptors but not by an NMDA receptor antagonist. Because glutamate uptake can be influenced by changes in cellular energy levels, we studied the effects of oxidative and glycolytic energy depletion on glutamate-mediated Muller cell swelling. Oxygen deprivation produced little morphological change and did not alter either glutamate-mediated Muller cell swelling or glutamate-induced excitotoxicity. In contrast, inhibition of glycolysis by iodoacetate produced severe neuronal damage without Muller cell swelling. In the presence of iodoacetate, exogenous glutamate failed to cause glial swelling. The neuronal damage produced by iodoacetate was inhibited by pyruvate, a substrate that sustains oxidative energy pathways. In the presence of iodoacetate plus pyruvate, glutamate failed to cause Muller cell swelling but became neurotoxic at low concentrations through activation of non-NMDA receptors. These results indicate that glycolytic energy metabolism plays a critical role in sustaining ionic balances required for Muller cell glutamate uptake and glial uptake helps to prevent glutamate-mediated excitotoxicity. PMID- 10028921 TI - Glial fibrillary acidic protein is necessary for mature astrocytes to react to beta-amyloid. AB - Upregulation of the glial fibrillary acidic protein (GFAP) in astrocytes is a hallmark of the phenomenon known as reactive gliosis and, yet, the function of GFAP in this process is largely unknown. Our previous studies have shown that mature astrocytes react vigorously to substrate bound beta-amyloid protein (BAP) in a variety of ways (i.e., increased GFAP, enhanced motility, unusual aggregation patterns, inhibitory ECM production). In order to uncover which, if any, of these phenomena are causally related to the function of GFAP, primary cortical astrocytes from transgenic mice lacking GFAP were cultured on BAP substrates at low or high density and at various lengths of time following in vitro maturation. Differences between mutant and control cells became progressively more obvious when cells were matured in vitro for two weeks or longer and especially in cultures that were at high density. Mature control astrocytes show a dramatic response to BAP by aggregating into a meshwork of rope like structures that completely bridge over the peptide surface. In marked contrast, mature GFAP-null astrocytes initiate the response much more slowly and had a much reduced ability to aggregate tightly. Furthermore, we prepared hippocampal slice cultures from GFAP-/- and GFAP+/+ mice and compared their astrocytic responses to injected BAP. GFAP-/- astrocytes of hippocampal slice cultures failed to form a barrier-like structure around the edge of the BAP deposit as did GFAP+/+ astrocytes. Our data suggest that GFAP may be essential for mature astrocytes to constrain certain types of highly inflammatory lesions in the brain. PMID- 10028922 TI - GABA inhibits endozepine release from cultured rat astrocytes. AB - In the mammalian brain, the endogenous ligands for benzodiazepine receptors (also called endozepines) are predominantly synthesized by glial cells. It has recently been reported that rat astrocytes in primary culture release substantial amounts of endozepines. The aim of the present study was to investigate the possible involvement of GABA in the control of endozepine release. Exposure of cultured rat astrocytes to GABA (10(-7) to 10(-5) M) induced a dose-related inhibition of endozepine secretion. At higher doses (3 x 10(-5) to 10(-3) M), the effect of GABA gradually diminished. The inhibitory effect of GABA (10(-5) M) was mimicked by the GABA(B) receptor agonist baclofen (10(-5) M). In contrast, the GABA(A) receptor agonists 3APS and isoguvacine (10(-5) M each) did not modify endozepine release. The inhibition of endozepine secretion evoked by GABA and baclofen (10( 5) M each) was totally abrogated by the specific GABA(B) receptor antagonist phaclofen (10(-4) M). GABA and baclofen caused a significant inhibition of forskolin-evoked production of cAMP in astrocytes and this effect was abolished in the presence of phaclofen. In contrast, isoguvacine had no effect on cAMP production. Exposure of astrocytes to dbcAMP induced a time- and dose-dependent stimulation of endozepine release. These data indicate that GABA, acting through GABA(B) receptors negatively coupled to adenylyl cyclase, inhibits endozepine release from cultured rat astrocytes. The secretion of endozepines thus appears to be a valuable marker to monitor astrocyte activity. PMID- 10028923 TI - Cardiovascular responses produced by microinjection of serotonin-receptor agonists into the paraventricular nucleus in conscious rats. AB - Activation of serotonin (5-hydroxytryptamine, 5-HT) receptors in the brain produces cardiovascular responses by altering autonomic outflow. The paraventricular nucleus (PVN) contains a modest density of 5-HT receptors and has connections to autonomic centers. Experiments were designed to determine whether cardiovascular responses were produced by the administration of 5-HT2- and 5-HT1A receptor agonists into the PVN of conscious rats. The microinjection of the 5-HT2 receptor agonist DOI [(+/-)-1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane HCl] into the PVN produced dose-dependent (1-10 nmol) increases in heart rate and blood pressure; the peak responses were +39 +/- 10 beats/min and +6 +/- 2 mm Hg, respectively. Both responses were blocked by the concomitant administration of the selective 5-HT2-receptor antagonist LY53857 into the PVN. By contrast, the microinjection of the selective 5-HT1A-receptor agonist R(+)-8-OH-DPAT [R(+)8 hydroxy-2-(di-n-propylamino) tetralin HBr; 1-10 nmol] into the PVN did not affect blood pressure or heart rate. These data suggest that 5-HT neurons projecting from the raphe nuclei to or near the PVN can participate in the central control of the cardiovascular system by way of 5-HT2 receptors. Apparently 5-HT neurons terminating in the PVN can increase blood pressure and heart rate and produce sympathoadrenal activation, metabolic and hormonal responses consistent with those observed in several different stress paradigms. PMID- 10028924 TI - Modulation of HERG potassium channels by extracellular magnesium and quinidine. AB - Torsades de pointes is a polymorphic ventricular arrhythmia resulting from congenital or drug-induced (acquired) QT prolongation. Pharmacologic suppression of repolarizing potassium currents is one mechanism causing the acquired long QT (LQT) syndrome. Recent studies have linked mutations in a gene encoding a potassium channel subunit (HERG) to the LQT syndrome. Clinical experience indicates that intravenous magnesium sulfate is effective in reversing torsades de pointes, but the molecular basis of this effect is not understood. This study was designed to investigate the effects of extracellular magnesium (Mg2+) on HERG potassium currents. HERG potassium channels were expressed in Xenopus oocytes and in a human cell line and were examined by voltage-clamp methods. Extracellular Mg2+ (0.3-10 mM) caused a concentration-dependent shift in the membrane-potential dependence of HERG channel opening, causing a reduction in K+ current. This effect was much greater than that observed in another human delayed rectifier K+ channel, hKv1.5, suggesting a specific interaction with the HERG channel. Quinidine is an antiarrhythmic drug that also causes torsades de pointes under certain conditions. Quinidine (3 microM) inhibited HERG currents expressed in oocytes by 32.1 +/- 3.2% (n = 5), whereas 1 microM quinidine inhibited HERG currents in tsA201 cells by 75.8 +/- 2.4% (n = 12). Increasing extracellular Mg2+ did not relieve the inhibition by quinidine, but caused additional suppression. These results indicate that extracellular Mg2+ exerts a direct action on HERG potassium channels, resulting in suppression of outward repolarizing potassium current. It is concluded that modulation of this important K+ current is not the mechanism by which intravenous magnesium terminates drug-induced LQT and torsades de pointes. Potent suppression of HERG channel current by quinidine, compared with that of I(Ks) and I(Na), is a likely contributor to torsades de pointes arrhythmias. PMID- 10028925 TI - A new Ca-antagonist, azelnidipine, reduced blood pressure during exercise without augmentation of sympathetic nervous system in essential hypertension: a randomized, double-blind, placebo-controlled trial. AB - This study was carried out to evaluate the effect of a new long-acting calcium channel antagonist, azelnidipine, on hemodynamic and neural responses to exercise. Ten patients (age, 36-69 years) with mild essential hypertension were enrolled in this study. A randomized, double-blind, crossover treatment of azelnidipine at a dose of 8.0 mg once daily for 4 weeks was performed. After a 4 week placebo period, the patients exercised in a submaximal test by using an ergometer with azelnidipine or placebo treatment. The changes caused by exercise in arterial blood pressure (BP), heart rate, cardiac output (CO), and systemic vascular resistance were evaluated. In addition, the plasma norepinephrine (NE), epinephrine (E), plasma renin activity, and plasma aldosterone concentration were determined at rest, at peak exercise, and at the recovery period. Both the SBP and diastolic (D) BP were decreased at rest by azelnidipine treatment (from 158 +/- 10/97 +/- 7 to 145 +/- 14/90 +/- 9 mm Hg). Azelnidipine significantly decreased both SBP and DBP during exercise (SBP, F = 6.09, p < 0.05, Fi = 0.612, NS; DBP, F = 17.78, p < 0.001, Fi = 0.298, NS). No significant changes in the resting heart rate and CO were observed, and the exercise-induced increase of these parameters was also not affected by azelnidipine. Azelnidipine produced no significant change of the resting plasma NE and E levels and an exercise-induced increase of plasma NE. In conclusion, these results indicate that azelnidipine, different from another dihydropyridine-type calcium channel antagonists, does not produce any changes in the hemodynamic and neurohumoral response to exercise, and it may be beneficial for patients with mild essential hypertension. PMID- 10028926 TI - Different effects of the beta-adrenoceptor antagonists celiprolol and metoprolol on vascular structure and function in long-term type I diabetic rats. AB - An intriguing problem of diabetes mellitus is the development of generalized angiopathy and concomitant hypertension. However, there is still a controversy whether beta-adrenoceptor antagonists can be used as antihypertensive agents in diabetes. Four groups of rats were investigated: nondiabetic controls, diabetes mellitus, diabetes + celiprolol (250 mg/kg body weight/day), diabetes + metoprolol (125 mg/kg body weight/day) after 6 months. Diabetes was induced by i.v. streptozotocin injection. We examined vascular structure and function histologically and by an in vitro microvideoangiometry of isolated perfused mesenterium. Additionally, we investigated the effects of hyperglycemia and celiprolol on NO release in cultivated aortic endothelial cells and the effect of celiprolol on transendothelial paracellular permeability. Diabetes resulted in endothelial dysfunction, characterized by a reduced response to acetylcholine and L-N(G)-nitro-arginine and an unchanged response to sodium nitroprusside (SNP). These effects were significantly antagonized by celiprolol but were not influenced by metoprolol treatment. This was supported by the finding of typical vascular changes associated with diabetes like media thickening, reduced cardiac capillary/muscle fiber ratio, and glomerulosclerosis, which were significantly reduced by celiprolol but not influenced by metoprolol treatment. Ketonuria improved after celiprolol treatment, whereas blood glucose, lipids, and body weight were not different between the diabetic groups. In cultured cells, celiprolol did not induce direct NO release but reversed the impairment of stimulated NO release caused by hyperglycemia. Furthermore, celiprolol reduced endothelial paracellular permeability. We conclude that celiprolol can exert antiangiopathic effects in diabetic rats and that both beta-adrenoceptor antagonists did not aggravate diabetic angiopathy and metabolic derangement. PMID- 10028927 TI - Inhibition of intracellular Ca2+ mobilisation by low antiproliferative concentrations of thapsigargin in human vascular smooth-muscle cells. AB - Low nanomolar concentrations of thapsigargin, a modulator of intracellular Ca2+ ([Ca2+]i) pools, inhibit vascular smooth-muscle cell (VSMC) proliferation. Because the mechanisms underlying this effect have not been defined, the effect of antiproliferative concentrations of thapsigargin on [Ca2+]i in fura-2-loaded VSMCs was studied by using dynamic video imaging of [Ca2+]i. After seeding on coverslips, human VSMCs were incubated for 1-48 h with thapsigargin before loading with fura-2 or during imaging. Mobilisation of [Ca2+]i was stimulated with 1 microM ionomycin in Ca2+-free medium and the increase in [Ca2+]i detected by using Ca2+ imaging techniques. Continuous exposure of cells to low concentrations of thapsigargin (which failed measurably to increase in [Ca2+]i) reduced the ionomycin response in a time- and dose-dependent manner (100% inhibition at 10 nM thapsigargin after 1 h exposure). After exposure of cells to 10 nM thapsigargin for 1 h followed by washing and further incubation for < or = 72 h, there was a time-dependent recovery of the ionomycin response. Because the concentrations of thapsigargin and exposure times are identical to those that inhibit replication in VSMCs, it is proposed that depletion of [Ca2+]i pools mediates the inhibitory effect of thapsigargin on VSMC proliferation. PMID- 10028928 TI - Evaluation of the acute electrophysiologic effects of intravenous dronedarone, an amiodarone-like agent, with special emphasis on ventricular repolarization and acquired torsade de pointes arrhythmias. AB - In the anesthetized dog with complete chronic AV block (CAVB), we evaluated and compared the acute electrophysiologic effects of dronedarone i.v. (Dron, 2 times 2.5 mg/kg/10 min) and amiodarone i.v. (Amio, 2 times 5 mg/kg/10 min). This canine model with a high sensitivity for acquired torsade de pointes (TdP) provides an ideal substrate to evaluate ventricular repolarization abnormalities. Six ECG leads and two endocardial monophasic action potential (MAP) recordings in the left and right ventricle (LV and RV) were simultaneously recorded to measure QT time, action-potential duration (APD), interventricular dispersion (deltaAPD = LV(APD) - RV(APD)), early afterdepolarizations (EADs), ectopic beats (EBs), and TdP. Measurements were made at the spontaneous idioventricular rhythm (IVR) and 1,000-ms steady-state pacing. To investigate its short-term, antiarrhythmic properties, Dron was given after almokalant (0.12 mg/kg)-induced TdP. Furthermore, in another set of experiments, oral Dron (20 mg/kg, b.i.d) was given for 3 weeks to conscious CAVB dogs. Dron, i.v., shortened ventricular repolarization (QT, 435 +/- 60 to 360 +/- 55; LV(APD) 395 +/- 75 to 335 +/- 60 ms; p < 0.05), whereas IVR and ventricular effective refractory period (VERP, 225 +/- 30 to 230 +/- 30 ms) remained similar. Therefore the VERP/QT ratio increased (0.55 +/- 0.04 to 0.61 +/- 0.03; p < 0.05). Similar results were obtained with Amio, i.v.. Almokalant-induced TdP was characterized by an increased repolarization duration, deltaAPD, and EADs. Dron, i.v., suppressed the EADs, EBs, and TdP by a reduction and homogenization of repolarization (LV(APD), 505 +/ 110 to 455 +/- 80 ms, and deltaAPD, 110 +/- 55 to 65 +/- 40 ms). Long-term oral Dron increased the PP interval, CL-IVR, and QT(c) time. In contrast to oral treatment, Dron i.v. shortens ventricular repolarization parameters, resulting in suppression of EAD-dependent acquired TdP. The increased VERP/QT ratio after Dron i.v. may indicate an important second antiarrhythmic property. PMID- 10028929 TI - Platelet-derived growth factor-induced vasodilatation in mesenteric resistance arteries by nitric oxide: blunted response in spontaneous hypertension. AB - Platelet-derived growth factor (PDGF) is a potent mitogen for vascular smooth muscle cells, but its effects on vasomotion remain controversial. Both vasoconstriction and vasodilatation of isolated rat aortic rings have been reported. The effects of PDGF on responses of perfused mesenteric resistance arteries from normotensive Wistar-Kyoto and spontaneously hypertensive rats were studied by using a video dimension analyzer. PDGF receptor messenger RNA (mRNA) expression in endothelial cells isolated from mesenteric arteries of both normotensive and hypertensive rats was studied by reverse transcriptase polymerase chain reaction (RT-PCR) analysis. In both normotensive and hypertensive rats, PDGF-BB concentration-dependently induced vasodilatation (maximal response, 25 +/- 4% and 13 +/- 4% at 10(-8) M, respectively; p < 0.05, normotensive vs. hypertensive rats). Endothelium removal or preincubation with N(omega)-nitro-L-arginine methyl ester, but not indomethacin, inhibited these relaxations, indicating that these vasodilatations are endothelium dependent and mediated by nitric oxide. RT-PCR analysis showed that both PDGF-alpha and -beta receptor mRNAs were present in endothelial cells of the mesenteric arteries of normotensive as well as hypertensive rats. In addition, relaxations induced by both PDGF-AA and -AB were significantly less than those induced by PDGF-BB in both strains, suggesting that vasodilatation is mediated mainly by the PDGF-beta receptor subtype. No vasoconstriction was observed after application of PDGF-BB to both normotensive and hypertensive mesenteric arteries with or without endothelium. In rat mesenteric resistance arteries, PDGF induces endothelium dependent vasodilatation mediated by nitric oxide. At sites where PDGF is released or locally produced, therefore, the growth factor may participate in regulating vascular tone, and this endothelium-dependent regulation is attenuated in spontaneous hypertension. PMID- 10028930 TI - Bioactivity of natriuretic peptide coinfusions; no evidence for unique effects of BNP in conscious sheep. AB - Few studies have addressed the possibility that brain natriuretic peptide (BNP) possesses a profile of bioactivity that is distinct from that of atrial natriuretic peptide (ANP). Accordingly, we assessed the biologic actions of BNP in the setting of maximal or near-maximal ANP-induced biologic activity. Background ANP infusions (7.5 pmol/kg/min) administered on all study days, increased plasma ANP (approximately 120 pM) and cyclic guanosine monophosphate (GMP) levels (approximately 40 nM), and induced significant decreases in arterial pressure and cardiac output associated with increased heart rate, hematocrit, diuresis, and natriuresis. Increasing the dose twofold after 1 h (experiment 1, n = 5) showed no enhancement of these actions despite a further twofold increase in plasma ANP and cyclic GMP (both p values <0.001). Addition of low-dose BNP (2 pmol/kg/min) after 1 h background infusion (experiment 2, n = 8), increased plasma BNP levels (30 pM, p < 0.001) but caused no significant effects on the hemodynamic, renal, or hormonal indices measured. In conclusion, in the setting of maximal hemodynamic, renal, and endocrine responses to high-dose background infusions of ANP, coinfusion of BNP exhibits no enhancement of, or additional, biologic activity. This study provides no evidence for unique short-term biologic actions of ANP and BNP. PMID- 10028931 TI - Calcium sensitivity and the effect of the calcium sensitizing drug pimobendan in the alcoholic isolated rat atrium. AB - We compared the effect of inotropic interventions (isoproterenol and pimobendan) and the relation between Ca2+ and isometric twitch force in atrial muscle from control rats and rats that had consumed alcohol for 2 months. At extracellular Ca2+ concentrations of 1-4 mM, alcohol atria developed less force than the controls. The median effective concentration (EC50) for extracellular Ca2+ was 3.2 +/- 0.01 mM for the alcohol group and 2.8 +/- 0.001 mM for the control group, whereas at maximal Ca2+, developed force was the same in both groups. To test whether the myofilament response to Ca2+ is altered with chronic alcohol consumption, we measured the relation between Ca2+ and force of atrial fiber bundle preparations extracted with Triton X-100. The Ca2+-force relation of alcohol atria (EC50 = 2.4 +/- 0.001 microM) was significantly shifted to the right of that of the control atria (EC50 = 1.94 +/- 0.001 microM Ca2+). Compared with controls, the alcohol atria demonstrated a significant depression in the inotropic effect of the beta-adrenergic agonist isoproterenol over a broad concentration range (10(-9)-10(-6) M). We also tested the effect of pimobendan, an inotropic agent with both phosphodiesterase-inhibiting and myofilament Ca2+ sensitizing actions. Developed force at concentrations of pimobendan <75 microM was similar between groups. However, at concentrations of pimobendan >75 microM, the developed force in alcohol atria was significantly less than control. Our results indicate that 2 months of alcohol consumption is associated with decreases in myofilament Ca2+ sensitivity and altered responsiveness to different inotropic agents. PMID- 10028932 TI - Renal afferent and efferent arteriolar dilation by nilvadipine: studies in the isolated perfused hydronephrotic kidney. AB - Although calcium antagonists are believed to exert preferential vasodilator action on the renal preglomerular afferent arteriole, we recently demonstrated that efonidipine, a novel calcium antagonist, vasodilates both afferent and efferent arterioles. Nilvadipine also is reported to increase renal blood flow and reduce filtration fraction, suggesting indirectly afferent and efferent arteriolar vasodilation. No direct investigation, however, has been conducted examining the renal microvascular action of nilvadipine. We therefore characterized the renal microvascular reactivity to nilvadipine, by using the isolated perfused rat hydronephrotic kidney. The administration of angiotensin II (0.3 nM) caused marked vasoconstriction of afferent (from 13.5 +/- 0.6 to 9.2 +/- 0.6 microm, p < 0.01, n = 6) and efferent arterioles (from 11.5 +/- 1.0 to 7.4 +/ 0.7 microm, p < 0.01; n = 5). The subsequent addition of nilvadipine (10 nM, 100 nM, and 1 microM) caused 37 +/- 5%, 91 +/- 4%, and 95 +/- 8% reversal of afferent arteriolar constriction, respectively. Similarly, efferent arterioles manifested 59 +/- 12% reversal by 1 microM nilvadipine. Thus unlike nifedipine, which we previously reported to cause modest efferent arteriolar dilation (21 +/- 1% reversal at 1 microM), nilvadipine possesses the greater ability to dilate efferent arterioles (p < 0.01 vs. nifedipine), although both antagonists cause similar magnitudes of afferent arteriolar vasodilation. Variable effects on the efferent arteriole suggest the heterogeneity in the calcium antagonist with regard to the renal microvascular action of this agent. PMID- 10028933 TI - Mechanism of endothelial nitric oxide-dependent vasorelaxation induced by wine polyphenols in rat thoracic aorta. AB - The mechanisms by which red wine polyphenolic compounds (RWPCs) induced endothelium-dependent relaxation were investigated in rat thoracic aorta rings with endothelium. RWPCs produced relaxation that was prevented by the nitric oxide (NO) synthase inhibitor, N(omega)-nitro-L-arginine-methyl-ester. This relaxation was abolished in the absence of extracellular calcium in the medium or in the presence of the Ca2+ entry blocker, La3+, but it was not affected by the nonselective K+ channels blocker, tetrabutylammonium. N-Ethyl-maleimide (NEM), a sulfhydryl alkylating agent, abolished vasorelaxation produced by RWPCs and acetylcholine but not that produced either by the sarcoendoplasmic reticulum Ca2+ adenosine triphosphatase (ATPase) pump inhibitor, cyclopyazonic acid (CPA) or the calcium ionophore, ionomycin. Neither pertussis toxin (PTX) nor cholera toxin (CTX) inhibited the vasorelaxant effect of RWPC. The effect of RWPC was not affected by the phospholipase C (PLC) blocker, L-alpha-glycerophospho-D-myo inositol 4-monophosphate (Gro-pip), and the phospholipase A2 pathway blockers, quinacrine and ONO-RS-082. Finally, the protein kinase C (PKC) inhibitor, GF 109203X, and tyrosine kinase inhibitors, tyrphostin A-23 and genistein, did not impair the response to RWPCs. These results suggest that RWPCs produce endothelium-NO-derived vasorelaxation through an extracellular Ca2+-dependent mechanism via an NEM-sensitive pathway. They also show that PTX- or CTX-sensitive G proteins, activation of PLC or PLA2 pathways, PKC, or tyrosine kinase may not be involved. PMID- 10028934 TI - Effects of bimakalim on human cardiac action potentials: comparison with guinea pig and nicorandil and use-dependent study. AB - Electrophysiologic effects of K(ATP) channel openers (KCOs) are rarely studied for tissue and species specificity, and use-dependent investigations in human tissues are lacking. We therefore investigated in vitro the concentration dependent effects of the KCO bimakalim [from 10 nM to 10 microM, at 1,000 ms of cycle length (CL) and 37 degrees C] on human (atrium, n = 4, and ventricle, n = 6) and guinea pig (atrium, n = 7, and ventricle, n = 6) transmembrane action potential (AP). The frequency relation (from CL 1,600 to 300 ms, 31 degrees C) of human atrial AP duration 90% (APD90) shortening (10 microM vs. baseline, n = 7) also was determined. A parallel study was performed with the KCO nicorandil (from 10 nM to 1 mM, n = 3) in human atrial APs, at 31 degrees C. Resting membrane potential and maximal upstroke velocity of AP were not modified by bimakalim at maximal concentration, whereas AP amplitude was decreased in both guinea pig preparations (p < 0.05); APD90 was shortened in all tissues (p < 0.01). Median effective concentration (EC50) for APD90 shortening at 37 degrees C was 0.54 and 2.74 microM in atrial and ventricular human tissue, respectively, and 8.55 and 0.89 microM in atrial and ventricular guinea pig tissue, respectively. In human atrial tissue at 31 degrees C, EC50 with bimakalim was 0.39 microM; a much higher value was seen with nicorandil (210 microM). Bimakalim (10 microM)-induced APD90 shortening as a function of stimulation rate was greatest at longest CL. Evidence is provided for (a) species (human vs. guinea pig) and tissue (atrium vs. ventricle) differential AP sensitivity to bimakalim; (b) an approximately 500 fold higher efficacy of bimakalim versus nicorandil to shorten human atrial APD90; and (c) normal use-dependence of human atrial APD90 shortening with bimakalim at 10 microM. PMID- 10028935 TI - Effects of antiaggregant and antiinflammatory doses of aspirin on coronary hemodynamics and myocardial reactive hyperemia in conscious dogs. AB - Clinical studies have shown that low doses of aspirin (<300 mg/day) inhibit thromboxane A2 production and platelet aggregation but preserve prostacyclin synthesis. In contrast, high doses of aspirin (>1,000 mg/day) suppress the synthesis of both eicosanoids. Because the consequences of aspirin administration have never been investigated on coronary vasomotor tone in vivo, we investigated the effects of low and high doses of aspirin on systemic and coronary hemodynamics under basal conditions and after myocardial reactive hyperemia in conscious dogs. Dogs were instrumented with a Doppler flow probe and a hydraulic occluder. Coronary blood flow was measured in the conscious state at baseline and during myocardial reactive hyperemia after 10, 20, and 30 s of coronary occlusion. Thromboxane B2 serum concentrations, an index of platelet aggregation, decreased by >90% after long-term i.v. administration of aspirin, 100 mg/day for 7 days (low dose). Neither systemic and coronary hemodynamics nor reactive hyperemia were affected by the drug. After combined administration of this low dose of aspirin and of the nitric oxide synthase (NOS) inhibitor, N(omega)-nitro L-arginine (L-NNA, 30 mg/kg/day/7 days), reactive hyperemia decreased to the same extent as when L-NNA was administered alone. After administration of a unique high-dose aspirin (1,000 mg, i.v.), myocardial reactive hyperemia was markedly reduced, and this effect was still observed after previous blockade of NOS and cyclooxygenase by L-NNA and diclofenac, respectively. Thus long-term treatment with a low antiaggregant dose of aspirin does not alter the ability of coronary vessels to dilate during myocardial reactive hyperemia in conscious dogs. In contrast, short-term administration of a high antiinflammatory dose of aspirin severely blunts myocardial reactive hyperemia through a mechanism that is independent of both cyclooxygenase and nitric oxide metabolic pathways. PMID- 10028936 TI - Total arterial compliance in ambulatory hypertension during selective beta1 adrenergic receptor blockade and angiotensin-converting enzyme inhibition. AB - Aortic root flow and pressure estimates were obtained noninvasively with Doppler echocardiography and calibrated subclavian artery pulse tracing in 30 subjects with ambulatory hypertension in a randomized, crossover study with 4 weeks' treatment and washout periods. Total arterial compliance, assessed by use of a three-element Windkessel model of the arterial tree, increased 42% with atenolol (50-100 mg once daily), and 7% (p = NS) with captopril (25-50 mg twice daily). Atenolol reduced mean arterial pressure by 15%, heart rate by 22%, and cardiac output by 14%, and increased acceleration time of aortic root flow by 17% and stroke volume and ejection time each by 11%. Captopril reduced mean arterial pressure and total peripheral resistance each by 7%. Acceleration time of aortic root flow, ejection time, heart rate, stroke volume, and cardiac output were not significantly changed by captopril. We conclude that total arterial compliance, at the operational blood pressure, increases during selective beta1-adrenergic receptor blockade in subjects with ambulatory hypertension. Although the main mechanism may be a reduction in mean arterial pressure, it should be considered whether reduced heart rate may play an additional role. The nonsignificant increase in total arterial compliance during angiotensin-converting enzyme inhibition may primarily be a consequence of a modest reduction of the mean arterial pressure. PMID- 10028937 TI - Vasodepressor responses to [D-Ala2]-endomorphin 2 (TAPP) are mediated by an L NAME-sensitive mechanism in the rat. AB - Endomorphin 1 and 2 are newly discovered endogenous ligands for the mu-opioid receptor. We recently showed that endomorphin 1 and 2 have vasodepressor activity, and in this study, responses to a novel endomorphin analog [D-Ala2] endomorphin 2 (TAPP) were investigated in the systemic vascular bed of the rat. Intravenous injections of TAPP, endomorphin 1, and endomorphin 2 decreased systemic arterial pressure in a dose-related manner. Decreases in systemic arterial pressure in response to TAPP were similar to vasodepressor responses to endomorphin 1 and 2 and were not altered by passage of time. Decreases in systemic arterial pressure in response to TAPP, endomorphin 1, and endomorphin 2 were attenuated by the opioid receptor antagonist naloxone (2 mg/kg, i.v.) when the vasodepressor response to the ORL1-receptor agonist nociceptin (orphanin FQ) was not altered. Decreases in systemic arterial pressure in response to TAPP, endomorphin 1 and 2, and acetylcholine were attenuated by the nitric oxide synthase inhibitor N(omega)-nitro-L-arginine methyl ester (L-NAME; 50 mg/kg, i.v.) when decreases in systemic arterial pressure in response to nociceptin and calcitonin gene-related peptide (CGRP) were not altered. These results indicate that TAPP, endomorphin 1, and endomorphin 2 decrease systemic arterial pressure by a naloxone-sensitive mechanism and suggest that the vasodepressor response to TAPP, endomorphin 1 and 2, but not nociceptin, is mediated by the release of nitric oxide. PMID- 10028938 TI - The time course of cardioprotection induced by GR79236, a selective adenosine A1 receptor agonist, in myocardial ischaemia-reperfusion injury in the pig. AB - The cardioprotective effects of the selective adenosine A1-receptor agonist, GR79236 (N-[(1S, trans)-2-hydroxycyclopentyl]adenosine), were examined in a porcine model of myocardial ischaemia-reperfusion injury. When pigs were subjected to a 50-min coronary artery occlusion followed by 3-h reperfusion, GR79236 (10 nmol/kg, i.v.) significantly reduced infarct size whether given 10 min before the onset of ischaemia or reperfusion. This effect was independent of the bradycardia induced by GR79236, as it was also observed in animals in which heart rate was maintained by electrical pacing. However, GR79236 administered 10 min after reperfusion did not reduce infarct size. GR79236 had no effect on the incidence or outcome of ventricular dysrhythmias in this pig model of infarction. Similarly, ischaemic preconditioning (IPC, 2 x 10-min ischaemia and 10-min reperfusion) significantly reduced infarct size. The selective adenosine A1 receptor antagonist, 8-cyclopentyl-1,3-dipropylxanthine (DPCPX; 3.3 micromol/kg, i.v.), abolished the haemodynamic and cardioprotective effects of GR79236 and the cardioprotective effects of IPC in anaesthetised pigs. In conclusion, GR79236 exerted a marked cardioprotective effect in a porcine model of myocardial ischaemia-reperfusion injury, provided that it was administered before reperfusion. This suggests that GR79236 may have clinical utility in the treatment of various aspects of ischaemic heart disease. PMID- 10028939 TI - Antihypertensive properties of KRN4884, a novel long-lasting potassium channel opener. AB - The antihypertensive action of KRN4884 (5-amino-N-[2-(2-chlorophenyl)ethyl]-N' cyano-3-pyridinecarboxamidine ), a newly synthesized 3-pyridine derivative was examined in conscious spontaneously hypertensive rats (SHRs). A single administration of KRN4884 (0.5, 1.5 mg/kg, p.o.) produced a dose-dependent and long-lasting antihypertensive effect. The 7-day repeated administration of KRN4884 (0.5, 1.5 mg/kg, p.o.) did not diminish antihypertensive activity during the treatment period or induce rebound hypertension after the discontinuation of treatment. To examine the mechanism of the antihypertensive effect of KRN4884, we studied its vasorelaxing effects in rat isolated aortae precontracted with 25 mM KCl. Single application of KRN4884 showed a slower onset of inhibitory action than that of levcromakalim. KRN4884 was approximately 26-fold more potent than levcromakalim and 10-fold less potent than nilvadipine. KRN4884- and levcromakalim-induced vasorelaxation were antagonized by glibenclamide. Furthermore, we observed the recovery of the contraction inhibited by these drugs after repeated washing. The inhibitory effect of KRN4884 was restored only after four washes, whereas that of levcromakalim was completely restored after one wash. The nilvadipine-induced inhibitory effect was the most resistant to washing among these drugs. These results suggest that KRN4884 shows a long-lasting antihypertensive effect based on its potent potassium channel-opening action. The long-lasting action may be due to a slow association/dissociation with/from the binding sites on vascular smooth muscle. PMID- 10028941 TI - Effects of the calcium sensitizer [+]-EMD 60263 and its enantiomer [-]-EMD 60264 on cardiac ionic currents of guinea pig and rat ventricular myocytes. AB - The thiadiazinone enantiomers [+]-EMD 60263 and [-]-EMD 60264 ((+)-5-(1-(alpha ethylimino-3,4-dimethoxybenzyl)-1,2,3,4-tetrah ydroquinoline-6-yl)-6-methyl-3,6 dihydro-2H-1,3,4-thiadiazine-2 -on) exhibit distinct stereoselectivity for Ca2+ sensitizing action ([+]-enantiomer) and phosphodiesterase inhibition ([-] enantiomer). However, in isolated guinea pig papillary muscle, both compounds cause an action-potential prolongation that has been related to a nonselective depression of the delayed rectifier potassium current. Because [-]-EMD 60264 did not increase force of contraction despite phosphodiesterase inhibition, we postulated that one or several additional actions may oppose the anticipated positive inotropic effect. Therefore we investigated whether other membrane currents were also affected in voltage-clamped ventricular cardiomyocytes. Both [+]-EMD 60263 and [-]-EMD 60264 reduced sodium current as well as L-type calcium current in guinea pig ventricular myocytes, but steady-state inactivation or conductance curves of I(Na) and I(Ca) were not shifted along the voltage axis. Inward rectifier and transient outward current were studied in rat myocytes, but neither current was affected. We conclude that the positive inotropic action of [+]-EMD 60263 can be explained by prevalence of the Ca2+-sensitizing effect over its inhibitory actions on Na+ and Ca2+ current, whereas the negative inotropic effect of [-]-EMD 60264 may be caused by inhibition of I(Ca) predominating over PDE inhibition. PMID- 10028940 TI - SIN-1-induced cytotoxicity in cultured endothelial cells involves reactive oxygen species and nitric oxide: protective effect of sepiapterin. AB - The purpose of this study was to examine whether tetrahydrobiopterin (BH4), one of the cofactors of nitric oxide (NO) synthase, attenuates endothelial cell death induced by 3-morpholinosydnonimine-N-ethylcarbamide (SIN-1), which is known to produce both superoxide and NO. Endothelial cell death was assessed by the release of intracellular lactate dehydrogenase (LDH). Addition of SIN-1 (500, 1,000 microM) to endothelial cells induced cell death from 6 h after its addition. The SIN-1-induced endothelial cell death was strongly reduced by treatment with carboxy-PTIO, a NO scavenger, or superoxide dismutase (SOD). Iron chelators and hydroxyl radical scavengers also reduced the SIN-1-induced endothelial cell death. Interestingly, the SIN-1-induced endothelial cell death was also reduced by treatment with catalase. Thus NO, superoxide, hydroxyl radical, and hydrogen peroxide are likely to be implicated in SIN-1-induced endothelial cell death. Moreover, pretreatment with sepiapterin, a precursor of BH4 synthesis, reduced the SIN-1-induced endothelial cell death and increased the intracellular BH4 content. Both the protective effect of sepiapterin and the increase in intracellular BH4 content were prevented by co-pretreatment with N acetylserotonin (NAS), an inhibitor of BH4 synthesis. The protective effect of sepiapterin also was observed when up-take of trypan blue was used as another marker of cell death. These findings suggest that BH4 has a protective effect against endothelial cell death caused by the presence of NO and superoxide. The protective effect of BH4 may at least partly involve scavenging of superoxide or hydrogen peroxide or both, because we and other groups previously found that BH4 has a scavenging activity for reactive oxygen species. PMID- 10028942 TI - Presynaptic antisympathetic action of amiodarone and its metabolite desethylamiodarone. AB - Amiodarone has a "reserpine-like" sympatholytic action in the heart. The aims of this study were to test whether desethylamiodarone (DEA), the in vivo bioactive metabolite of amiodarone, has this action and whether this action could be demonstrated in a neuronal preparation. Experiments were performed in intact rats, perfused hearts, or brain synaptosomes treated with DEA and amiodarone, and concentrations of norepinephrine (NE) and dihydroxyphenylglycol (DHPG), the intraneuronal metabolite of NE, were assayed in plasma, coronary effluent, and synaptosomes. In perfused hearts, DEA at 1, 3, and 10 microM increased DHPG overflow by threefold, sixfold, and ninefold, respectively (all p < 0.01 vs. control). DEA at 1 microM was more potent than amiodarone in increasing DHPG overflow. DEA at 1 and 3 microM also inhibited NE release evoked by sympathetic nerve stimulation (p < 0.05). In intact rats, intravenous DEA at 15 mg/kg elicited onefold increase in plasma DHPG level, and oral pretreatment with amiodarone did not interfere with the sympatholytic action of intravenous amiodarone. In synaptosomes, 40-min incubation with amiodarone, DEA (both 10 microM), and reserpine reduced synaptosomal NE content by 42, 45, and 60%, respectively. Thus similar to its parent drug, DEA exerts a presynaptic sympatholytic action in rat hearts in vivo and in vitro. This action of amiodarone and DEA also was observed in synaptosomes. PMID- 10028943 TI - Vasoconstrictor effects of various melatonin analogs on the rat tail artery in the presence of phenylephrine. AB - We performed a pharmacologic analysis of the increase in perfusion pressure induced by melatonin and related analogues in the perfused rat tail artery precontracted by 1 microM phenylephrine. Melatonin, 2-iodomelatonin, 6 chloromelatonin, and S20098 (N-[2-(7-methoxy-1-naphthyl)ethyl]acetamide) produced a concentration-dependent enhancement of the vasoconstrictor response evoked by 1 microM phenylephrine with a rank order of potency compatible with the pharmacologic profile defined for high-affinity melatonin receptors. Melatonin had no effect on electrically induced [3H]noradrenaline release, but the neurogenic vasoconstriction was increased at melatonin concentrations of 100 and 300 nM. Increasing concentrations of the naphthalenic-based antagonist S20928 (N [2-(1-naphthyl)ethyl]cyclobutanecarboxamide) caused a parallel rightward shift in the melatonin concentration-response curve without depressing the maximal response. The pA2 value of S20928 was 7.01 +/- 0.08. Luzindole, 1 microM, an antagonist of Mel1b melatonin receptors, was without effect on melatonin-induced responses. By using reverse transcription-polymerase chain reaction (RT-PCR), we found that messenger RNA (mRNA) encoding for Mel1a is transcribed in the rat tail artery. In conclusion, the results show that melatonin produced an enhancement of the contractile response elicited by phenylephrine in the perfused rat tail artery. This vasoconstrictor response appears to be mediated through activation of Mel1a receptors located on smooth-muscle cells. No evidence for an action of melatonin on either the endothelium or sympathetic nerve endings was found. PMID- 10028944 TI - Relevance of inter- and intraventricular electrical dispersion to arrhythmogenesis in normal and ischaemic rabbit myocardium: a study with cromakalim, 5-hydroxydecanoate and glibenclamide. AB - This study aimed to investigate the role of electrical dispersion in arrhythmogenesis by using K(ATP) channel modulating agents. Monophasic action potential duration (MAPD90), effective refractory period (ERP), and conduction delay were measured at three ventricular sites in isolated working rabbit hearts. Cromakalim (10 microM), glibenclamide (3 microM), or 5-hydroxydecanoate (100 microM) were administered before and throughout 30 min of regional ischaemia and 15 min of reperfusion. Before ischaemia, cromakalim reduced MAPD90 and ERP in all areas and facilitated induction of ventricular fibrillation in five of 12 hearts. In these hearts, cromakalim increased interventricular ERP dispersion from 17 +/- 5 to 38 +/- 5 ms. During ischaemia, cromakalim decreased MAPD90 dispersion within the left ventricle from 84 +/- 5 to 44 +/- 4 ms, but did not affect ERP dispersion and arrhythmogenesis. 5-Hydroxydecanoate had no effect on MAPD90 and ERP shortening or dispersion during ischaemia and reperfusion and was not antiarrhythmic. Glibenclamide reduced forward flow to zero, preventing further electrophysiologic studies. In conclusion, in this model, an increase in interventricular ERP dispersion predisposes to ventricular fibrillation in normoxic conditions after cromakalim administration. However, a decrease in ischaemia-induced MAPD90 dispersion by cromakalim does not affect arrhythmogenesis. A lack of effect of 5-hydroxydecanoate on electrical dispersion during ischaemia is accompanied by a lack of antiarrhythmic activity. PMID- 10028945 TI - The role of angiotensin II AT1 receptor in the maintenance of hemodynamics in a canine model of coronary microembolization-induced heart failure. AB - The purpose of this study was to determine whether Angiotensin II (Ang II) contributes to the regulation of resting hemodynamics via Ang II type 1 (AT1) receptors in awake dogs with coronary microembolization-induced heart failure. Six dogs were surgically instrumented for measurement of systemic hemodynamics and for coronary microembolization. The acute hemodynamic effects of a selective AT1-receptor antagonist, GR138950 (1 mg/kg, i.v.), were determined before and after congestive heart failure (CHF). GR138950 had no effects on hemodynamics before CHF Daily coronary microembolizations (through the previously implanted coronary catheter) resulted in CHF, as documented by hemodynamic measurements, a slight but significant increased Ang II plasma level (17.4 +/- 1.6 vs. 23 +/- 1.0 pg/ml; p < 0.05), and characteristic clinical signs of CHF. After CHF, GR138950 significantly increased left ventricular dP/dt(max) (LVdP/dt(max)) from 1,754 +/- 68 to 2,347 +/- 114 mm Hg/s and decreased LV systolic pressure (LVSP) from 118 +/ 5 to 101 +/- 7 mm Hg; meanwhile, heart rate (from 132 +/- 4 to 102 +/- 6 beats/min) and LV end-diastolic pressure (LVEDP; from 17 +/- 3 to 9 +/- 1.5 mm Hg) were significantly decreased. Mean arterial pressure (MAP) was not affected. The peak effects occurred 90 min after administration. Thus Ang II contributes significantly to resting hemodynamics via AT1 receptors in this CHF model; that is, the specific AT1 blocker inhibits the negative inotropic actions of Ang II in the CHF state. PMID- 10028946 TI - Cardiovascular disease and the kidney: an epidemiologic overview. AB - Essential hypertension and congestive heart failure (CHF) are examples of cardiovascular disorders that may cause renal failure, although sometimes a primary kidney defect may lead to hypertension. Renal damage in malignant and severe hypertension is dramatic, extensive, and rapidly progressive, although nephrosclerotic damage, which develops slowly and appears late in hypertension, is a rare cause of morbidity because mild to moderate hypertension is now the most common form. However, the incidence of end-stage renal failure associated with hypertension is markedly increasing, perhaps because of underdiagnosis of renal damage in hypertension, insufficient lowering of blood pressure in clinical practice, or inability of antihypertensive drugs to lower blood pressure sufficiently to preserve the kidney, a goal that may need specific drugs that act, for example, on the renin-angiotensin system (RAS). Renal vasoconstriction and reduction of renal blood flow are early companions of cardiac insufficiency and may be involved in the development of sodium and water retention. Profound reduction of cardiac output and arterial hypotension in severe CHF may lead to acute renal failure. Chronic renal insufficiency is associated with elevated cardiovascular morbidity and mortality. Renal impairment is often caused by a disease process, such as diabetes mellitus, that involves both the cardiovascular system and the kidney. When the primary disease is renal, possible reasons for an association include renal-dependent increase in blood pressure, activation of the RAS, overproduction of other vasoactive substances of renal origin, and electrolyte imbalances leading to fatal arrhythmias. PMID- 10028947 TI - The kidney as part of the cardiovascular system. AB - Renal vascular damage caused by arterial hypertension brings about changes in the systemic vascular function and structure. Nephrosclerosis appears to run in parallel with systemic atherosclerosis, accounting for the increased cardiovascular morbidity and mortality in hypertensive patients. Parameters indicating a change in renal function (increased serum creatinine concentration, proteinuria, and microalbuminuria) are independent predictors of increased cardiovascular morbidity and mortality and must therefore be considered in the classification of cardiovascular risk in hypertensive patients. PMID- 10028948 TI - Microalbuminuria as a predictive factor for cardiovascular events. AB - We tested the hypothesis that microalbuminuria screening in a general practice setting would identify high-risk nondiabetic hypertensive patients, and we measured microalbuminuria response to drug treatment. General practitioners were enrolled who had collected medical histories and performed physical examinations and routine laboratory tests in more than 11,000 untreated hypertensive, nondiabetic patients. Microalbuminuria was measured with an albumin-sensitive immunoassay test strip. The patients' mean age was 57 years, 51% were men, and mean duration of hypertension was 69 months. Twenty-five percent of patients had coronary artery disease (CAD), 17% had left ventricular hypertrophy (LVH), 5% had had a stroke, and 6% had peripheral vascular disease (PVD). Microalbuminuria was present in 32% of men and 28% of women. In patients with microalbuminuria, 31% had CAD, 24% had LVH, 6% had had a stroke, and 7% had PVD. In patients without microalbuminuria, all of these rates were significantly lower: 22%, 14%, 4%, and 5%, respectively (p < 0.001). Furthermore, in patients with CAD, LVH, stroke, or PVD, microalbuminuria was significantly greater than in patients who did not have these complications (p < 0.001). A multiple stepwise regression analysis with microalbuminuria as the dependent variable showed microalbuminuria depended on the following factors, in order of importance: systolic blood pressure, retinopathy, CAD, diastolic blood pressure, and LVH (all p < 0.0001). A multiple stepwise regression analysis with each of the concomitant diseases as the dependent variable showed that microalbuminuria was an independent and significant variable for each of the conditions. The patients were assigned to monotherapy with either angiotensin-converting enzyme (ACE) inhibitors, beta blockers, calcium antagonists, or diuretics. All of the drugs reduced microalbuminuria, although the beta-blocker carvedilol was superior (p < 0.05). We concluded microalbuminuria is an important risk factor that can be influenced by treatment. PMID- 10028949 TI - Angiotensin-converting enzyme inhibitors and kidney protection: the AIPRI trial. The ACE Inhibition in Progressive Renal Insufficiency (AIPRI) Study Group. AB - A protective effect of angiotensin-converting enzyme (ACE) inhibitors has been shown in patients with diabetic nephropathy but has not been clearly established in nondiabetic renal disease. A multicenter European study was designed to determine whether the ACE inhibitor benazepril was safe and effective in protecting residual renal function in patients with various renal diseases and mild to moderate renal failure. The trial involved 583 patients from 49 centers in Italy, France, and Germany. The patients were randomized to receive benazepril or placebo plus other antihypertensive agents, the target being a diastolic blood pressure of less than 90 mm Hg. Thirty-one patients in the benazepril group and 57 patients in the placebo group reached the end point [the time elapsed from entry to (a) doubling of serum creatinine (SCr) concentrations and (b) start of renal replacement therapy; p < 0.001 at 3 years]. The associated reduction in the relative risk of reaching the end point was 53% in benazepril-treated patients, with actuarial renal survival probability significantly better at 3 years. The best survival of renal function was observed in patients with chronic glomerular diseases and proteinuria greater than 1.0 g/24 h. Benazepril is effective in slowing the rate of progression and improving the survival of renal function in patients with renal diseases of various origins. This protective effect is associated with a clinically relevant decrease in both blood pressure and proteinuria. PMID- 10028950 TI - The renin-angiotensin system and its receptors. AB - The renin-angiotensin system (RAS) plays an important role in blood pressure control and in water and salt homeostasis. It is involved in the pathophysiology of hypertension and structural alterations of the vasculature, kidney, and heart, including neointima formation, nephrosclerosis, postinfarction remodeling, and cardiac left ventricular hypertrophy (LVH). Recently, an increased knowledge of the effector peptides of the RAS, their receptors, and their respective functions has led to a new principle of treatment for hypertension: the inhibition of angiotensin (Ang) II via angiotensin-converting enzyme inhibitors or Ang II receptor antagonists. In this review, the Ang receptors AT1 and AT2 and the potential roles of shorter angiotensin fragments, including Ang III(2-8), Ang IV(3-8), and Ang(1-7), are discussed. PMID- 10028951 TI - Angiotensin II antagonism in clinical practice: experience with valsartan. AB - Angiotensin (Ang) II antagonists provide specific and selective blockade of Ang II at the AT1 receptor, regardless of the enzymatic pathway of production. Valsartan has an affinity for the AT1 receptor 30,000 times that of the AT2 receptor. Valsartan is not a prodrug and undergoes little metabolism. It has a half-life of approximately 9 h, but duration of antihypertensive action at the usual dose of 80 or 160 mg daily is 24 h. The trough to peak ratio is 0.66. Valsartan has antihypertensive efficacy at least equivalent to that of established antihypertensive drugs and has additive effects in combination. The efficacy of valsartan appears to be independent of age, sex, and race. Valsartan is effective in hypertensive patients with renal insufficiency and is associated with maintenance of renal function. It is well tolerated, with a side-effect profile indistinguishable from that of placebo, and does not cause cough. Ang II antagonists are a promising class of cardiovascular drugs with considerable potential in clinical practice. PMID- 10028952 TI - Angiotensin II antagonism and the heart: valsartan in left ventricular hypertrophy. AB - Left ventricular hypertrophy (LVH) represents an independent risk factor for cardiovascular morbidity and mortality, and normalization of left ventricular mass has become a desirable goal of antihypertensive treatment. In a randomized, double-blind study, the angiotensin II (AT1-receptor) antagonist valsartan (Diovan ; 80-160 mg q.d.) was compared with the beta-blocker atenolol (50-100 mg q.d.) over 8 months in previously untreated patients with essential hypertension and LVH. Sixty-nine patients were randomized, of whom 58 were evaluated by echocardiography. After 8 months of treatment in the atenolol group [n = 8 with additional hydrochlorothiazide (HCTZ)], initial blood pressure was reduced from 160/103 to 147/92 mm Hg (p < 0.0001). In the valsartan group (n = 9 with HCTZ), blood pressure decreased from 163/101 to 146/90 mm Hg (p < 0.0001). Left ventricular mass index decreased from 127 to 117 g/m2 in the atenolol group and from 127 to 106 g/m2 in the valsartan group. Long-term treatment with valsartan resulted in a significant reduction of LVH in patients with essential hypertension. PMID- 10028953 TI - Valsartan and the kidney: present and future. AB - Angiotensin (Ang) II type 1 (AT1) receptor antagonists are orally active drugs that specifically block the subtype 1 of Ang receptors. In contrast to AT1 receptor antagonists, angiotensin-converting enzyme (ACE) inhibitors block the actions of Ang II incompletely. Furthermore, the bradykinin-potentiating effects of ACE inhibitors may contribute to the mechanism of action of ACE inhibitors. Data in experimental animals suggest that AT1 receptor antagonists decrease the glomerular filtration rate (GFR) to a lesser degree than ACE inhibitors. The greater effect of ACE inhibitors in decreasing glomerular pressure was attenuated with a bradykinin antagonist. In rat models of renal damage with proteinuria, acute reduction of proteinuria was seen with ACE inhibitors but not with AT1 receptor antagonists, whereas long-term reductions of proteinuria were of similar magnitude with both agents. Renal histology after several months revealed that AT1 receptor antagonists and ACE inhibitors were equally renoprotective in various renal damage models. AT1 receptor antagonists, like ACE inhibitors, exhibit a natriuretic effect equal to moderate doses of a thiazide diuretic. In patients with severe volume depletion, use of AT1 receptor antagonists may lead to acute renal failure. Valsartan was tested in a double-blind trial in patients with moderate to severe renal failure and led to a substantial decrease in diastolic and systolic blood pressure, whereas there was no difference from placebo for changes in GFR. Urine protein increased with placebo and decreased with valsartan. The data indicate that valsartan in renal failure patients is effective in lowering blood pressure while leaving renal excretory function unaltered. Whether there is a renoprotective effect can only be shown in long term trials, which are under way. PMID- 10028954 TI - Ill-advised 'freedom' of scientific information. PMID- 10028956 TI - UK panel formed to rebuild trust in government science advice. PMID- 10028955 TI - German call to invest more in technology. PMID- 10028957 TI - Scientists fight for right to withhold data. PMID- 10028959 TI - German science fights animal rights bill. PMID- 10028958 TI - Roche and Promega back in court for Taq. PMID- 10028960 TI - Japanese university approves genetic tests on in vitro embryos. PMID- 10028961 TI - Language bias discredits the peer-review system. PMID- 10028962 TI - A transformed view of cyclosporine. PMID- 10028963 TI - Colour vision. A patchwork of cones. PMID- 10028964 TI - New way to activate caspases. PMID- 10028965 TI - Electronic motion in DNA. PMID- 10028966 TI - Auditory distance perception in rooms. AB - The perceived distance of a sound source in a room has been shown to depend on the ratio of the energies of direct and reflected sound. Although this relationship was verified in later studies, the research has never led to a quantitative model. The advent of techniques for the generation of virtual sound sources has made it possible to study distance perception using controlled, deterministic stimuli. Here we present two experiments that make use of such stimuli and we show that a simple model, based on a modified direct-to reverberant energy ratio, can accurately predict the results and also provide an explanation for the 'auditory horizon' in distance perception. The modification of the ratio consists of the use of an integration time of 6 milliseconds in the calculation of the energy of the direct sound. This time constant seems to be important in spatial hearing-the precedence effect is also based on a similar integration window. PMID- 10028967 TI - The arrangement of the three cone classes in the living human eye. AB - Human colour vision depends on three classes of receptor, the short- (S), medium- (M), and long- (L) wavelength-sensitive cones. These cone classes are interleaved in a single mosaic so that, at each point in the retina, only a single class of cone samples the retinal image. As a consequence, observers with normal trichromatic colour vision are necessarily colour blind on a local spatial scale. The limits this places on vision depend on the relative numbers and arrangement of cones. Although the topography of human S cones is known, the human L- and M cone submosaics have resisted analysis. Adaptive optics, a technique used to overcome blur in ground-based telescopes, can also overcome blur in the eye, allowing the sharpest images ever taken of the living retina. Here we combine adaptive optics and retinal densitometry to obtain what are, to our knowledge, the first images of the arrangement of S, M and L cones in the living human eye. The proportion of L to M cones is strikingly different in two male subjects, each of whom has normal colour vision. The mosaics of both subjects have large patches in which either M or L cones are missing. This arrangement reduces the eye's ability to recover colour variations of high spatial frequency in the environment but may improve the recovery of luminance variations of high spatial frequency. PMID- 10028968 TI - Asymmetric Notch activation specifies photoreceptors R3 and R4 and planar polarity in the Drosophila eye. AB - Planar polarity is seen in epidermally derived structures throughout the animal kingdom. In the Drosophila eye, planar polarity is reflected in the mirror symmetric arrangement of ommatidia (eye units) across the dorsoventral midline or equator; ommatidia on the dorsal and ventral sides of the equator exhibit opposite chirality. Photoreceptors R3 and R4 are essential in the establishment of the polarity of ommatidia. The R3 cell is thought to receive the polarizing signal, through the receptor Frizzled (Fz), before or at higher levels then the R4 cell, generating a difference between neighbouring R3 and R4 cells. Both loss of-function and overexpression of Fz in the R3/R4 pair result in polarity defects and loss of mirror-image symmetry. Here we identify Notch and Delta (Dl) as dominant enhancers of the phenotypes produced by overexpression of fz and dishevelled (dsh), which encodes a signalling component downstream of Fz, and we show that D1-mediated activation of Notch is required for establishment of ommatidial polarity. Whereas fz signalling is required to specify R3, Notch signalling induces the R4 fate. Our data indicate that Dl is a transcriptional target of Fz/Dsh signalling in R3, and activates Notch in the neighbouring R4 precursor. This two-tiered mechanism explains how small differences in the level and/or timing of Fz activation reliably generate a binary cell-fate decision, leading to specification of R3 and R4 and ommatidial chirality. PMID- 10028969 TI - Frizzled regulation of Notch signalling polarizes cell fate in the Drosophila eye. AB - The Drosophila eye, a paradigm for epithelial organization, is highly polarized with mirror-image symmetry about the equator. The R3 and R4 photoreceptors in each ommatidium are vital in this polarity; they adopt asymmetrical positions in adult ommatidia and are the site of action for several essential genes. Two such genes are frizzled (fz) and dishevelled (dsh), the products of which are components of a signalling pathway required in R3, and which are thought to be activated by a diffusible signal. Here we show that the transmembrane receptor Notch is required downstream of dsh in R3/R4 for them to adopt distinct fates. By using an enhancer for the Notch target gene Enhancer of split mdelta, we show that Notch becomes activated specifically in R4. We propose that Fz/Dsh promotes activity of the Notch ligand Delta and inhibits Notch receptor activity in R3, creating a difference in Notch signalling capacity between R3 and R4. Subsequent feedback in the Notch pathway ensures that this difference becomes amplified. This interplay between Fz/Dsh and Notch indicates that polarity is established through local comparisons between two cells and explains how a signal from one position (for example, the equator in the eye) could be interpreted by all ommatidia in the field. PMID- 10028970 TI - Cyclosporine induces cancer progression by a cell-autonomous mechanism. AB - Malignancy is a common and dreaded complication following organ transplantation. The high incidence of neoplasm and its aggressive progression, which are associated with immunosuppressive therapy, are thought to be due to the resulting impairment of the organ recipient's immune-surveillance system. Here we report a mechanism for the heightened malignancy that is independent of host immunity. We show that cyclosporine (cyclosporin A), an immunosuppressant that has had a major impact on improving patient outcome following organ transplantation, induces phenotypic changes, including invasiveness of non-transformed cells, by a cell autonomous mechanism. Our studies show that cyclosporine treatment of adenocarcinoma cells results in striking morphological alterations, including membrane ruffling and numerous pseudopodial protrusions, increased cell motility, and anchorage-independent (invasive) growth. These changes are prevented by treatment with monoclonal antibodies directed at transforming growth factor-beta (TGF-beta). In vivo, cyclosporine enhances tumour growth in immunodeficient SCID beige mice; anti-TGF-beta monoclonal antibodies but not control antibodies prevent the cyclosporine-induced increase in the number of metastases. Our findings suggest that immunosuppressants like cyclosporine can promote cancer progression by a direct cellular effect that is independent of its effect on the host's immune cells, and that cyclosporine-induced TGF-beta production is involved in this. PMID- 10028971 TI - RGD peptides induce apoptosis by direct caspase-3 activation. AB - Synthetic peptides containing the arginine-glycine-aspartate (RGD) motif have been used extensively as inhibitors of integrin-ligand interactions in studies of cell adhesion, migration, growth and differentiation, because the RGD motif is an integrin-recognition motif found in many ligands. Here we report that RGD containing peptides are able to directly induce apoptosis without any requirement for integrin-mediated cell clustering or signals. We show that RGD-containing peptides enter cells and directly induce autoprocessing and enzymatic activity of procaspase-3, a pro-apoptotic protein. Using the breast carcinoma cell line MCF 7, which has a functional deletion of the caspase-3 gene, we confirm that caspase 3 is required for RGD-mediated cell death. In addition to an RGD motif, pro caspase-3 also contains a potential RGD-binding motif, aspartate-aspartate methionine (DDM), near the site of processing to produce the p12 and p17 subunits. On the basis of the ability of RGD-DDX interactions to trigger integrin activation, we suggest that RGD peptides induce apoptosis by triggering conformational changes that promote pro-caspase-3 autoprocessing and activation. These findings provide an alternative molecular explanation for the potent proapoptotic properties of RGD peptides in models of angiogenesis, inflammation and cancer metastasis. PMID- 10028972 TI - A positive response to perinatal HIV. PMID- 10028973 TI - Laser to the heart: magic but costly, or only costly? PMID- 10028974 TI - Preventing HIV infection: lessons from Mwanza and Rakai. PMID- 10028975 TI - Link between psychiatric dysfunction and dizziness. PMID- 10028976 TI - Science versus clinical adventurism in treatment of azoospermia. PMID- 10028977 TI - Secret out-of-court settlements in drug-injury cases. PMID- 10028978 TI - Medicine and politics of medical journalism. PMID- 10028979 TI - Transmyocardial laser revascularisation in patients with refractory angina: a randomised controlled trial. AB - BACKGROUND: Transmyocardial laser revascularisation (TMLR) is used to treat patients with refractory angina due to severe coronary artery disease, not suitable for conventional revascularisation. We aimed in a randomised controlled trial to assess the effectiveness of TMLR compared with medical management. METHODS: 188 patients with refractory angina were randomly assigned TMLR plus normal medication or medical management alone. At 3 months, 6 months, and 12 months after surgery (TMLR) or initial assessment (medical management) we assessed exercise capacity with the treadmill test and the 12 min walk. FINDINGS: Mean treadmill exercise time, adjusted for baseline values, was 40 s (95% CI -15 to 94) longer in the TMLR group than in the medical-management group at 12 months (p=0.152). Mean 12 min walk distance was 33 m (-7 to 74) further in TMLR patients than medical-management patients (p=0.108) at 12 months. The differences were not significant or clinically important. Perioperative mortality was 5%. Survival at 12 months was 89% (83-96) in the TMLR group and 96% (92-100) in the medical management group (p=0.14). Canadian Cardiovascular Society score for angina had decreased by at least two classes in 25% of TMLR and 4% of medical-management patients at 12 months (p<0.001). INTERPRETATION: Our findings show that the adoption of TMLR cannot be advocated. Further research may be appropriate to assess any potential benefit for sicker patients. PMID- 10028980 TI - Control of sexually transmitted diseases for AIDS prevention in Uganda: a randomised community trial. Rakai Project Study Group. AB - BACKGROUND: The study tested the hypothesis that community-level control of sexually transmitted disease (STD) would result in lower incidence of HIV-1 infection in comparison with control communities. METHODS: This randomised, controlled, single-masked, community-based trial of intensive STD control, via home-based mass antibiotic treatment, took place in Rakai District, Uganda. Ten community clusters were randomly assigned to intervention or control groups. All consenting residents aged 15-59 years were enrolled; visited in the home every 10 months; interviewed; asked to provide biological samples for assessment of HIV-1 infection and STDs; and were provided with mass treatment (azithromycin, ciprofloxacin, metronidazole in the intervention group, vitamins/anthelmintic drug in the control). Intention-to-treat analyses used multivariate, paired, cluster-adjusted rate ratios. FINDINGS: The baseline prevalence of HIV-1 infection was 15.9%. 6602 HIV-1-negative individuals were enrolled in the intervention group and 6124 in the control group. 75.0% of intervention-group and 72.6% of control-group participants provided at least one follow-up sample for HIV-1 testing. At enrolment, the two treatment groups were similar in STD prevalence rates. At 20-month follow-up, the prevalences of syphilis (352/6238 [5.6%]) vs 359/5284 [6.8%]; rate ratio 0.80 [95% CI 0.71-0.89]) and trichomoniasis (182/1968 [9.3%] vs 261/1815 [14.4%]; rate ratio 0.59 [0.38-0.91]) were significantly lower in the intervention group than in the control group. The incidence of HIV-1 infection was 1.5 per 100 person-years in both groups (rate ratio 0.97 [0.81-1.16]). In pregnant women, the follow-up prevalences of trichomoniasis, bacterial vaginosis, gonorrhoea, and chlamydia infection were significantly lower in the intervention group than in the control group. No effect of the intervention on incidence of HIV-1 infection was observed in pregnant women or in stratified analyses. INTERPRETATION: We observed no effect of the STD intervention on the incidence of HIV-1 infection. In the Rakai population, a substantial proportion of HIV-1 acquisition appears to occur independently of treatable STD cofactors. PMID- 10028981 TI - Epidemic of fatal encephalopathy in preschool children in Burkina Faso and consumption of unripe ackee (Blighia sapida) fruit. AB - BACKGROUND: On March 21, 1998, the Regional Health Authority of Bobo-Dioulasso, Burkina Faso, asked the Centre Muraz to investigate an unexplained outbreak of epidemic fatal encephalopathy (EFE). We aimed to identify the cause of this epidemic. METHODS: We identified cases retrospectively through review of health service records and interviews of family members, village chiefs, and local healers. Active surveillance was started in administrative divisions within the study area in April, 1998, to identify further EFE cases. We did a case-control study of households to investigate the risk from various environmental and health factors. Blood and urine samples were collected if possible and urine dicarboxylic acid concentrations measured by gas chromatography. FINDINGS: 29 cases of EFE were identified from January to May, 1998. Estimated age-specific attack rates (2-6 years) ranged from 31 to 847 per 100,000 population (p<0.001). The most common symptoms were hypotonia, vomiting, convulsions, and coma. All children died in 2-48 h. The only factor associated with EFE was the presence of ackee trees (Blighia sapida) within 100 m of households (odds ratio 5.1 [95% CI 1.8-14.7] p=0.001). Poisoning with unripe ackee fruits was suggested by urine concentrations of dicarboxylic acids four to 200 times higher in cases (n=2) than in controls (n=3). CONCLUSION: Consumption of unripe ackee fruit probably caused this epidemic and may lead to a substantial number of unexplained deaths in preschool children in west Africa every year. Educational campaigns have the potential to prevent these deaths. PMID- 10028982 TI - Angiotensin-converting-enzyme gene insertion/deletion polymorphism and response to physical training. AB - BACKGROUND: The function of local renin-angiotensin systems in skeletal muscle and adipose tissue remains largely unknown. A polymorphism of the human angiotensin converting enzyme (ACE) gene has been identified in which the insertion (I) rather than deletion (D) allele is associated with lower ACE activity in body tissues and increased response to some aspects of physical training. We studied the association between the ACE gene insertion or deletion polymorphism and changes in body composition related to an intensive exercise programme, to investigate the metabolic effects of local human renin-angiotensin systems. METHODS: We used three independent methods (bioimpedance, multiple skinfold-thickness assessment of whole-body composition, magnetic resonance imaging of the mid-thigh) to study changes in body composition in young male army recruits over 10 weeks of intensive physical training. FINDINGS: Participants with the II genotype had a greater anabolic response than those with one or more D alleles for fat mass (0.55 vs -0.20 kg, p=0.04 by bioimpedance) and non-fat mass (1.31 vs -0.15 kg, p=0.01 by bioimpedance). Changes in body morphology with training measured by the other methods were also dependent on genotype. INTERPRETATION: II genotype, as a marker of low ACE activity in body tissues, may conserve a positive energy balance during rigorous training, which suggests enhanced metabolic efficiency. This finding may explain some of the survival and functional benefits of therapy with ACE inhibitors. PMID- 10028983 TI - Thiamine deficiency and malaria in adults from southeast Asia. AB - BACKGROUND: Thiamine deficiency (beriberi) is common in some parts of southeast Asia. Acute thiamine deficiency can mimic many complications of malaria, such as encephalopathy and lactic acidosis. We examined the incidence of thiamine deficiency in adults admitted to hospital with malaria in Thailand. METHODS: For this prospective study, we recruited consecutive patients with malaria or other febrile illness who presented to Paholpolpayuhasena Hospital, Kanchanaburi, Thailand, between May and July, 1992. We used the activation coefficient (alpha) for transketolase activity in erythrocytes to measure thiamine deficiency (defined as alpha>1.31) in patients with severe and uncomplicated malaria and in controls (patients' relatives and healthy volunteers). To exclude the possibility of interference in the assays, transketolase activity was also measured in erythrocytes used to culture parasites. FINDINGS: 12 (52%) of 23 patients with severe malaria and ten (19%) of 54 patients with uncomplicated malaria had alpha values above the normal range (p<0.0001 and p=0.0014, respectively, compared with controls), which indicated severe thiamine deficiency. Thiamine deficiency was more severe in patients with cerebral malaria than in those with uncomplicated malaria and the controls (p=0.008). INTERPRETATION: In adults admitted to hospital in Thailand, thiamine deficiency commonly complicates acute falciparum malaria, particularly in severe infections, and could contribute to dysfunction of the central nervous system. PMID- 10028984 TI - Autologous haemopoietic stem-cell transplantation in four patients with refractory juvenile chronic arthritis. AB - BACKGROUND: Autologous haemopoietic stem-cell transplantation (AHSCT) had been described as a possible treatment for severe autoimmune disease refractory to conventional treatment. We report the first four children with severe forms of juvenile chronic arthritis (JCA) treated with AHSCT. METHODS: We studied three children with systemic JCA and one child with polyarticular JCA. Unprimed bone marrow was taken 1 month before AHSCT. T-cell depletion of the graft was done with CD2 and CD3 antibodies. We used a preparative regimen of antithymocyte globulin (20 mg/kg), cyclophosphamide (200 mg/kg) and low-dose total body irradiation (4 Gy). Methotrexate and cyclosporin were stopped before AHCST, prednisone was tapered after 2 months. FINDINGS: Our patients showed a drug-free follow-up of 6-18 months with a marked decrease in joint swelling, pain, and morning stiffness. Erythrocyte sedimentation rate, C-reactive protein, and haemoglobin returned to almost normal values within 6 weeks. Despite T-cell depletion there was a rapid immune reconstitution in three out of four children. Two patients developed a limited varicella zoster virus eruption, which was treated by aciclovir. INTERPRETATION: AHSCT for severe JCA was well tolerated and induced a remission of disease in four children with JCA that was resistant to conventional treatment. Prolonged prednisone-free growth catch-up and general well-being is a major therapeutic gain in such children. The actual follow-up is too short, however, for us to conclude that these children are completely cured of their disease. PMID- 10028985 TI - Spastic paraparesis after anaesthesia. PMID- 10028986 TI - Spontaneous rupture of spleen during peripheral blood stem-cell mobilisation in a healthy donor. PMID- 10028987 TI - Restoration of fertility by in-vitro spermatogenesis. PMID- 10028988 TI - Sex differences in suicide trends in England and Wales. PMID- 10028989 TI - Failure of early diagnosis in symptomatic Duchenne muscular dystrophy. PMID- 10028990 TI - Randomised cross-over study of patient-held records in oncology and palliative care. PMID- 10028991 TI - Major upper gastrointestinal bleeding and the use of calcium channel blockers. PMID- 10028992 TI - Analgesic effect of the cannabinoid analogue nabilone is not mediated by opioid receptors. PMID- 10028993 TI - Epidemic of transmissible spongiform encephalopathy in sheep and goats in Italy. PMID- 10028994 TI - Cultural invariance of likelihood ratios for the General Health Questionnaire. PMID- 10028995 TI - Identical differences. PMID- 10028996 TI - Progress in HIV-1 therapy continues on upward track. PMID- 10028997 TI - Parkinson's disease research moves on briskly. PMID- 10028998 TI - China attempts to soften its one-child policy. PMID- 10028999 TI - The menopause. AB - Menopause is diagnosed after 12 months of amenorrhoea resulting from the permanent cessation of ovarian function. The mean age at menopause is 51 years. The perimenopause, a time of changing ovarian function, precedes the final menses by several years. The physiology and clinical manifestations of this transition to menopause are not well understood; however, some symptoms, such as hot flashes, certainly begin in the perimenopause. Causal associations between menopause and several symptoms and diseases are proposed. The evidence for these associations varies and is reviewed. Hormone replacement therapy can be directed at symptom relief or at prevention or treatment of chronic diseases. Doses and routes of hormone replacement therapy vary by indication. Complications of hormone replacement therapy depend on the regimen used. Knowing the expected vaginal bleeding pattern for each hormone replacement therapy regimen is important, since unexpected bleeding may signal endometrial hyperplasia. Postmenopausal hormone therapy is a complex intervention that produces positive and negative specific health effects. Overall, based on observational studies, postmenopausal women who use hormones have a 30-50% lower all-cause mortality rate than those who do not use hormones. It is important to recognise that the value that individual women place on various health outcomes associated with hormone replacement therapy may differ. Thus, the decision to use hormone replacement therapy should be made jointly by each woman and her health-care provider, after careful consideration of possible benefits, risks, and her personal preferences. PMID- 10029000 TI - The bacteria craze of the 1880s. PMID- 10029001 TI - Restoring the literary to medical writing. PMID- 10029002 TI - ICON2 trial. EORTC-GCCG, NOCOVA, NCI-C, Scottish groups, and GOG. Gynaecologic Oncology Group. PMID- 10029003 TI - ICON2 trial. UK consensus statement on standard practice for chemotherapy in ovarian cancer. PMID- 10029004 TI - Sex differences in HIV-1 viral load and progression to AIDS. Swiss HIV Cohort Study. PMID- 10029005 TI - Sex differences in HIV-1 viral load and progression to AIDS. ICONA Study Group. Italian cohort of HIV-1 positive individuals. PMID- 10029006 TI - Sex differences in HIV-1 viral load and progression to AIDS. PMID- 10029007 TI - Vertigo. PMID- 10029008 TI - Atrial fibrillation. PMID- 10029009 TI - Positron emission tomography findings in heavy users of MDMA. PMID- 10029010 TI - Fatal MDMA intoxication. PMID- 10029011 TI - Fatal MDMA intoxication. PMID- 10029012 TI - Epidural analgesia and risk of caesarean section. PMID- 10029013 TI - Kidney cancer. PMID- 10029014 TI - Advertising of "Sandimmun Neoral". PMID- 10029015 TI - Sexual behaviour in travellers. PMID- 10029016 TI - Sexual behaviour in travellers. PMID- 10029017 TI - Inequalities in provision of health care for children in Scotland. PMID- 10029018 TI - The good old days! PMID- 10029019 TI - The Nobel chronicles. 1938: Corneille Jean Francois Heymans (1892-1968). PMID- 10029020 TI - Looks so bad, feels so good--Hollywood takes on social activism. PMID- 10029022 TI - Sketches from The Lancet. Turkish baths. PMID- 10029023 TI - The effects of varying fluid volume and rate of resuscitation during uncontrolled hemorrhage. AB - BACKGROUND: The role of rate and volume of infusion in survival from experimental uncontrolled hemorrhage was evaluated. METHODS: Hemorrhage was initiated using tail resection in 43 female rats assigned to the following five groups: nonresuscitated; resuscitated with moderate volume, slower rate; resuscitated with moderate volume, faster rate; resuscitated with high volume, slower rate; and resuscitated with high volume, faster rate. RESULTS: A trend toward improved survival was noted with faster rate of infusion (60 vs. 33.3% survival rate with moderate volume and 28.6 vs. 12.5% with high volume, compared with 16.7% in the nonresuscitated animals). CONCLUSION: Rapid infusion of moderate volume of isotonic saline improved survival in uncontrolled hemorrhage. Extreme volumes, infused rapidly, also resulted in higher survival rates compared with those observed in nonresuscitated rats. PMID- 10029024 TI - Controlled resuscitation for uncontrolled hemorrhagic shock. AB - OBJECTIVE: To test the hypothesis that controlled resuscitation can lead to improved survival in otherwise fatal uncontrolled hemorrhage. METHODS: Uncontrolled hemorrhage was induced in 86 rats with a 25-gauge needle puncture to the infrarenal aorta. Resuscitation 5 minutes after injury was continued for 2 hours with lactated Ringer's solution (LR), 7.3% hypertonic saline in 6% hetastarch (HH), or no fluid (NF). Fluids infused at 2 mL x kg(-1) x min(-1) were turned on or off to maintain a mean arterial pressure (MAP) of 40, 80, or 100 mm Hg in six groups: NF, LR 40, LR 80, LR 100, HH 40, and HH 80. Blood loss was measured before and after 1 hour of resuscitation. RESULTS: Survival was improved with fluids. Preresuscitation blood loss was similar in all groups. NF rats did not survive 4 hours. After 72 hours, LR 80 rats (80%) and HH 40 rats (67%) showed improved survival over NF rats (0%) (p < 0.05). Rebleeding increased with MAP. Attempts to restore normal MAP (LR 100) led to increased blood loss and mortality. CONCLUSION: Controlled resuscitation leads to increased survival compared with no fluids or standard resuscitation. Fluid type affects results. Controlled fluid use should be considered when surgical care is not readily available. PMID- 10029025 TI - Complement activation mediates intestinal injury after resuscitation from hemorrhagic shock. AB - BACKGROUND: Endothelial cell injury after hemorrhage and resuscitation (HEM/RES) might contribute to intestinal hypoperfusion and mucosal ischemia. Our recent work suggests that the injury might be the result of complement activation. We hypothesized that HEM/RES causes complement-mediated endothelial cell dysfunction in the small intestine. METHODS: Male Sprague-Dawley rats (195-230 g) were anesthetized and HEM to 50% of baseline mean arterial pressure for 60 minutes. Just before RES, animals received either soluble complement receptor-1 (sCR1, 15 mg/kg) to inhibit complement activation or saline vehicle. Resuscitation was with shed blood and an equal volume of saline. Two hours after RES, the small bowel was harvested to evaluate intestinal nitric oxide synthase activity (NOS), neutrophil influx, histology, and oxidant injury. RESULTS: HEM/RES induced tissue injury, increased neutrophil influx, and reduced NOS activity by 50% (vs. SHAM), all of which were completely prevented by sCR1 administration. There were no observed differences in oxidant injury between the groups. CONCLUSION: Histologic tissue injury, increased neutrophil influx, and impaired NOS activity after HEM/RES were all prevented by complement inhibition. Direct oxidant injury did not seem to be a major contributor to these alterations. Complement inhibition after HEM might ameliorate reperfusion injury in the small intestine by protecting the endothelial cell, reducing neutrophil influx and preserving NOS function. PMID- 10029026 TI - Injuries of the gastrointestinal tract from blunt trauma in children: a 12-year experience at a designated pediatric trauma center. AB - INTRODUCTION: Nonoperative management of solid organ injury from blunt trauma in children has focused concern on potential delays in diagnosis of hollow viscus injury with resultant increases in morbidity, mortality, and cost. This study of a large pediatric trauma database will review the issues of difficulty and/or delay in diagnosis as it relates specifically to definitive treatment and outcome. METHODS: We surveyed 11,592 consecutive admissions to a designated pediatric trauma center from 1985 to 1997 to identify children with documented injury of the gastrointestinal (GI) tract from blunt trauma. The records were extensively analyzed specifically in regard to mechanism of injury, type and site of injury, time to diagnosis, operative treatment, complications, and final outcome. RESULTS: The 79 children identified, 4 months to 17 years old, included 27 females and 52 males. Mechanism of injury included 15 restrained and 7 unrestrained passengers, 15 pedestrians, 15 child abuse victims, 10 bike handlebar intrusions, 8 discrete blows to the abdomen, 4 bike versus auto, 3 falls, and 2 crush injuries. There were 51 perforations, 6 avulsions, and 22 lesser injuries including contusions. Injury of the small bowel was most common, 44 cases, followed by the duodenum, 18 cases, colon, 17 cases, and stomach, 6 cases. In 45 children, diagnosis was made quickly by a combination of obvious clinical findings, plain x-ray and/or initial computed tomographic findings mandating urgent operative intervention. Diagnosis was delayed beyond 4 hours in 34 children, beyond 24 hours in 17 children and was made by persistent clinical suspicion, aided by delayed computed tomographic findings of bowel wall edema or unexplained fluid. The six deaths were caused by severe head injury. Complications included two delayed abscesses and two cases of intestinal obstruction. All 73 survivors left the hospital with normal bowel function. CONCLUSIONS: Injury to the GI tract from blunt trauma in children is uncommon (<1%). The majority of GI tract injuries (60%) are caused by a discrete point of energy transfer such as a seatbelt (19%), a handle bar (13%), or a blow from abuse (19%), or other blows and is unique to this population. Although diagnosis may be difficult and often delayed, this did not result in excessive morbidity or mortality. Safe and effective treatment of GI tract injuries is compatible with nonoperative management of most other injuries associated with blunt abdominal trauma in children, while reducing the risk of nontherapeutic laparotomy. PMID- 10029027 TI - Pregnant women and car restraints: beliefs and practices. AB - OBJECTIVE: Motor vehicle collisions are a leading cause of death and disability in pregnant women. The purpose of this study was to examine current restraint practices by pregnant women. Additionally, the beliefs and knowledge of pregnant women about restraint laws and effectiveness were studied. METHODS: From May of 1997 to January of 1998, women were surveyed at initial prenatal visit at four obstetrical clinics. Data collected included age, gravida, ethnicity, educational level attained, payor source, restraint use, and knowledge of effectiveness of restraint use. RESULTS: A total of 807 women completed surveys. Most always wore restraints before pregnancy, but increased restraint use during pregnancy (79% vs. 86%, chi2, p = 0.02). Only 52% used restraints properly. Significantly fewer women believed restraints were beneficial to mother and fetus in late pregnancy compared with early pregnancy. Only 21% of women were educated on proper restraint use during pregnancy. Comparison by payor mix showed no difference in use or education received. CONCLUSIONS: Most women use restraints and continue to do so during pregnancy, but they use them improperly. Pregnant women are familiar with mandatory restraint laws but are less informed about restraint use in pregnancy. Few women receive education from health care providers about proper restraint use. This study highlights the need for aggressive educational efforts to improve car restraint use in pregnant women, thereby reduce maternal and fetal injury and death. PMID- 10029028 TI - The use of a temporary vena caval interruption device in high-risk trauma patients unable to receive standard venous thromboembolism prophylaxis. PMID- 10029029 TI - Colonic resection in trauma: colostomy versus anastomosis. AB - OBJECTIVES: The management of colonic trauma is well established for simple injuries with primary repair, and ileocolostomy for right-sided injuries that undergo colonic resection. Segmental colon resection for injuries to the left colon can be managed with either an end colostomy or primary anastomosis. A retrospective review was performed to evaluate the outcome and complications associated with colonic resection for trauma to determine the risk factors associated with anastomotic leakage. METHODS: A retrospective review included patients undergoing colonic resection for trauma. The patients were stratified into colostomy, ileocolostomy, and colocolostomy groups. Patient demographics and colon-related complications were collected. Comparison between the colostomy and colocolostomy groups was performed to determine the difference in outcome. The outcome of right-sided colon injuries managed by either an ileocolonic or colocolonic anastomosis was compared. Analysis was performed to identify the factors associated with an increased risk of anastomotic leakage. RESULTS: One hundred forty patients over a 66-month period were included in the analysis. Overall, 41% (57 of 140) of patients developed a colon-related complication; 28% (39 of 140) of patients developed an abscess. Overall, the anastomotic leak rate was 13% (7 of 56) in the colocolostomy group, 4% (2 of 56) in the ileocolostomy group. Right-sided colon injuries managed with a colocolonic anastomosis had a higher incidence of anastomotic leakage than ileocolonic anastomosis, i.e., 14 versus 4% respectively. Of the seven patients who developed a leak from a colocolonic anastomosis, two patients died (29%). Univariate analysis identified an Abdominal Trauma Index Score > or = 25 (p = 0.03) or hypotension in the emergency department (p = 0.001) to be associated with increased risk of developing an anastomotic leak from a colocolonic anastomosis. CONCLUSION: Colonic injuries that are managed with resection are associated with a high complication rate regardless of whether an anastomosis or colostomy is performed. Colonic resection and anastomosis can be performed safely in the majority of patients with severe colonic injury, including injuries to the left colon. For injuries of the right colon, an ileocolostomy has a lower incidence of leakage than a colocolonic anastomosis. For injuries to the left colon, there remains a role for colostomy specifically in the subgroups of patients with a high ATI or hypotension, because these patients are at greater risk for an anastomotic leak. The role of resection and primary anastomosis versus colostomy in colonic trauma requires further investigation. PMID- 10029030 TI - Operative treatment of acetabular fractures through the extensile Henry approach. AB - OBJECTIVE: The purpose of this study was to evaluate the previously unreported application of the extensile Henry approach to the operative treatment of acetabular fractures. METHODS: Thirty-one cases were retrospectively reviewed at an average follow-up of 18.5 months. RESULTS: There were 8 simple and 23 complex associated fracture patterns. The average operative time was 4.5 hours, and the average blood loss was 1,160 mL. Reduction was anatomic in 26 patients (84%), satisfactory in 4 patients (13%), and unsatisfactory in 1 patient (3%). Radiographic results at follow-up were 25 excellent results, 4 good results, and 2 poor results. Twenty-six patients reported no limitation of ordinary activities, whereas five patients had to modify their activities because of pain. No heterotopic ossification occurred in 24 patients (77%). In the seven patients with heterotopic ossification, only one patient had a significant decrease in hip range of motion. Additional complications were two cases of superficial wound infection, one case of hardware failure, and two cases of avascular necrosis of the femoral head. There were no iatrogenic injuries to the sciatic nerve, nor was there any development of flap necrosis. CONCLUSION: The extensile Henry approach is a versatile approach offering an excellent exposure for surgical treatment of acetabular fractures. The rate of complications is comparable with or lower than that of other surgical approaches. By providing a direct exposure of the posterior pelvis, the extensile Henry approach has the advantage of minimizing the risk of iatrogenic injury to the sciatic nerve. In addition, the incidence of clinically significant heterotopic ossification may be reduced through the use of low-dose radiation prophylaxis. PMID- 10029031 TI - Brain tissue oxygenation during hemorrhagic shock, resuscitation, and alterations in ventilation. AB - OBJECTIVES: Recently developed polarographic microelectrodes permit continuous, reliable monitoring of oxygen tension in brain tissue (PbrO2). The aim of this study was to investigate the feasibility and utility of directly monitoring PbrO2 in cerebral tissue during changes in oxygenation or ventilation and during hemorrhagic shock and resuscitation. We also sought to develop a model in which treatment protocols could be evaluated using PbrO2 as an end point. METHODS: Licox Clark-type polarographic probes were inserted in the brain tissue of 16 swine to monitor PbrO2. In eight swine, changes in PbrO2 were observed over a range of fractional concentrations of inspired O2 (FiO2) as well as during periods of hyperventilation and hypoventilation. In eight other swine, PbrO2 was monitored during a graded hemorrhage of up to 70% estimated blood volume and during the resuscitation period. RESULTS: When FiO2 was elevated to 100%, PbrO2 increased from a baseline of 15+/-2 mm Hg to 36+/-11 mm Hg. Hyperventilation while breathing 100% oxygen resulted in a 40% decrease in PbrO2 (p < 0.05), whereas hypoventilation increased PbrO2 to 88 mm Hg (p < 0.01). A graded hemorrhage to 50% estimated blood volume significantly reduced PbrO2, mean arterial pressure, and intracranial pressure (p < 0.01). Continued hemorrhage to 70% estimated blood volume resulted in a PbrO2 of 2.9+/-1.5 mm Hg. After resuscitation, PbrO2 was significantly elevated, reaching 65+/-13 mm Hg (p < 0.01), whereas mean arterial pressure and cerebral perfusion pressure simply returned to baseline. CONCLUSION: Directly measured PbrO2 was highly responsive to changes in FiO2, ventilatory rate, and blood volume in this experimental model. In particular, hypoventilation significantly increased PbrO2, whereas hyperventilation had the opposite effect. The postresuscitation increase in PbrO2 may reflect changes in both O2 delivery and O2 metabolism. These experiments set the stage for future investigations of a variety of resuscitation protocols in both normal and injured brain. PMID- 10029032 TI - The utility of head computed tomography after minimal head injury. AB - OBJECTIVE: To determine if patients who present with a history of loss of consciousness who are neurologically intact (minimal head injury) should be managed with head computed tomography (CT), observation, or both. METHODS: We prospectively studied patients who presented to our urban Level I trauma center with a history of loss of consciousness after blunt trauma and a Glasgow Coma Scale score of 15. All patients underwent CT of the head and were subsequently admitted for 24 hours of observation. RESULTS: A total of 1,170 patients with minimal head injury were studied during a 35-month period. All patients had Glasgow Coma Scale scores of 15 on arrival and had a history of either loss of consciousness or amnesia to the event. Two hundred forty-seven patients (21.1%) were intoxicated with drugs or alcohol on admission; 39 patients (3.3%) had abnormalities detected by CT, including 18 intracranial bleeds; 21 patients (1.8%) had changes in therapy as a direct result of their CT results, including 4 operative procedures. No patient with negative CT results deteriorated during the subsequent observation period. CONCLUSION: CT is a useful test in patients with minimal head injury because it may lead to a change in therapy in a small but significant number of patients. Subsequent hospital observation adds nothing to the CT results and is not necessary in patients with isolated minimal head injury. PMID- 10029033 TI - Standardized management of intracranial pressure: a preliminary clinical trial. AB - OBJECTIVE: To test a standardized protocol for management of intracranial pressure (ICP) after severe head injury (i.e., traumatic brain injury), consistent with published guidelines. METHODS: We compared prospective use of a standardized protocol for ICP management in 12 patients with severe head injuries and retrospective ICP management using preprinted hospital orders in combination with ad hoc physician orders in 12 historical control patients with severe head injuries. With the standardized protocol, flow-chart decision logic diagrams were applied at patient bedside by critical care practitioners, with nursing shift review. RESULTS: ICP and its variation during the first 6 intensive care unit days was less for the standardized protocol- than for the preprinted order managed group (p <0.001), indicating better process control with the standardized protocol. ICP exceeded 25 mm Hg for less time for the standardized protocol group (182 hours; 15+/-23 hours/patient) than for prescribed order group (429 hours; 36+/-28 hours/patient) (p = 0.03). On average, ICP exceeded 20 mm Hg for 2.3 days for the standardized protocol-managed group and for 4.7 days for the prescribed order-managed group. Cerebral perfusion pressure was significantly greater and its variation less for the standardized protocol- than for the preprinted order managed group. Fewer interventions were made for ICP management for the standardized protocol- than for the preprinted order-managed patients (601 vs. 876), suggesting more effective nursing time using the standardized protocol. CONCLUSION: ICP management was more consistent, and intracranial hypertension was better controlled, in patients managed according to a standardized, data-driven protocol for escalation and weaning of therapies in response to immediate patient needs. We recommend computerized implementation and a randomized clinical trial to compare the protocol with prescribed orders. PMID- 10029034 TI - The effect of hypoxia/reoxygenation on the cellular function of intestinal epithelial cells. AB - BACKGROUND: Previously, using in vivo models, we have demonstrated that ischemia/reperfusion can increase intestinal mucosal permeability, promote bacterial translocation, and induce gut cytokine production. Because of the cellular heterogeneity of the gut, however, studies investigating the direct effects of hypoxia/reoxygenation on intestinal epithelial cells are confounded in in vivo model systems. Consequently, this study examines oxidant-mediated enterocyte injury using an in vitro intestinal enterocyte hypoxia/reoxygenation model system. METHODS: Two intestinal epithelial cell lines, IEC-6 and Caco-2, were seeded onto 3-microm filters in a Transwell bicameral system and grown until tight junction integrity was established. Cells were subjected to hypoxia in a sealed chamber with 95% nitrogen and 5% carbon dioxide and incubated at 37 degrees C for 60 or 90 minutes. Reoxygenation was initiated by replacing the media and putting the cells in an environment of room air plus 5% carbon dioxide. Permeability and bacterial translocation were assayed by measuring the phenol red concentration and culturing the bacteria that crossed the cell monolayer and reached the basal chamber of the bicameral system. Monolayer tight junction integrity was monitored by serial measurements of transepithelial electrical resistance (TEER), and cell viability was assessed by trypan blue dye. RESULTS: IEC-6 cell monolayers subjected to 60 or 90 minutes of hypoxia showed significantly higher permeability to phenol red, with 54+/-5% and 57+/-5% of the dye crossing the monolayers, respectively, compared with normoxic control (38+/ 2%; p < 0.01). Caco-2 cell monolayers also had increased permeability to phenol red, with 24+/-6% and 20+/-4% of the phenol red crossing the monolayer after 60 or 90 minutes of hypoxia, respectively, compared with 8+/-3% in the normoxic controls (p < 0.01). At 3 hours after challenge with Escherichia coli, the monolayers subjected to 60 or 90 minutes of hypoxia had significantly increased bacterial translocation (IEC-6 cells, p < 0.05; Caco-2 cells, p < 0.01) compared with controls. The increased permeability of the hypoxic Caco-2 and IEC-6 monolayers was associated with a decrease in TEER beginning as early as 1 hour after reoxygenation (p < 0.01). Cell viability, however, was not decreased. CONCLUSION: These results indicate that hypoxia/reoxygenation can directly impair cellular function as manifested by increased monolayer permeability to phenol red, increased E. coli bacterial translocation, and a decrease in TEER values. PMID- 10029035 TI - The effects of diaspirin cross-linked hemoglobin on hemodynamics, metabolic acidosis, and survival in burned rats. AB - OBJECTIVE: Diaspirin cross-linked hemoglobin (DCLHb) is a vasoactive hemoglobin based oxygen carrier or "blood substitute" that has been shown to improve base deficit in several experimental studies of hemorrhagic shock. Our objective was to determine if the addition of DCLHb to the resuscitation regimen would improve hemodynamic parameters, metabolic acidosis, and survival in our rat burn shock model compared with currently used resuscitation therapy. METHODS: This was a randomized, controlled, experimental rat study. Male Wistar rats, weighing 200 to 250 g, were surgically prepared for an acute study. After placement of indwelling catheters, baseline hemodynamic values (mean arterial pressure, cardiac output, systemic vascular resistance, stroke volume, and base excess) were obtained. Thirty-two rats were used in the study, and they were either subjected to a 30% scald burn (experimental group) or sham burned (control group). The experimental animals were immediately intravenously resuscitated and followed for 6 hours. The resuscitation was based on the Parkland formula (4 mL/kg for each 1% of total body surface area [TBSA] burn), with 50% of the calculated fluid amount to be administered at a constant rate during the first 8 hours after burn. The animals were resuscitated for 6 hours and received between 9.00 and 11.25 mL of fluid depending on weight. The experimental animals were randomly assigned to one of three treatment groups: group I, lactated Ringer's solution; group II, lactated Ringer's solution-human serum albumin; group III, lactated Ringer's solution DCLHb. Group I (n = 8) received 4 mL/kg lactated Ringer's solution for each 1% of TBSA burn. Group II (n = 8) received 2 mL/kg lactated Ringer's solution and 2 mL/kg human serum albumin for each 1% of TBSA burn. Group III (n = 8) received 2 mL/kg lactated Ringer's solution and 2 mL/kg DCLHb for each 1% of TBSA burn. The sham group (n = 8) was not burned and was not resuscitated. Animals that survived up to 6 six hours were killed. RESULTS: We found that mean arterial pressure, cardiac output, stroke volume, and base excess were all improved in the DCLHb lactated Ringer's solution-treated animals compared with the other experimental treatment groups. The 6-hour mortality rates were zero of eight (lactated Ringer's solution-DCLHb group), zero of eight (sham group), three of eight (lactated Ringer's solution-human serum albumin group), and six of eight (lactated Ringer's solution only group). CONCLUSION: Early resuscitation with DCLHb is superior to non-oxygen-carrying resuscitative fluids in improving hemodynamics and survival in this model of burn shock. DCLHb might improve general tissue perfusion in the acute postburn period, and it could be useful in the early management of patients with severe burns. PMID- 10029036 TI - Does growth hormone augment brain edema caused by brain injury? A study with a freeze brain injury model in the rat. AB - OBJECTIVE: Because of the known sodium and water retention associated with growth hormone (GH) therapy, it is crucial to evaluate the safety of GH after brain injury. To clarify this issue, we investigated whether GH affects brain edema in a rat brain freeze-injury model. METHODS: Male Wistar rats (n = 29) were divided into four groups according to the substance injected (GH vs. normal saline) and whether the brain was injured or not. The subcutaneous injections of GH (0.8 IU/kg) or saline were given 24 hours apart. In the injury groups, after the second injection, an aluminum rod (4-mm diameter) cooled to -50 degrees C was placed on the exposed dura mater in the right parietal region for 4 minutes, under anesthesia. At 4 hours after the insult, brain and skeletal muscle were excised and their water content was measured by drying. RESULTS: Freeze injury of the brain caused an increase in water and sodium content in skeletal muscle. GH injection augmented this edema in skeletal muscle. Freeze injury of the brain also caused an increase in water and sodium content in the injured hemisphere of the brain. GH injection did not exacerbate this edema in injured brain tissue. Neither freeze injury nor GH injection caused brain edema in the noninjured hemisphere or in the cerebellum. CONCLUSION: GH administration did not augment brain edema caused by brain injury in our model. PMID- 10029037 TI - Polymorphonuclear neutrophil chemiluminescence in whole blood from blunt trauma patients with multiple injuries. AB - BACKGROUND: Studies using isolated polymorphonuclear neutrophils (PMNs) indicate that trauma is associated with altered function of PMNs. Because isolation of PMNs can itself alter the function of these cells, we examined the relationships among measures of injury severity and several indices of PMN function using whole blood samples from trauma patients. METHODS: Whole blood samples were obtained from 12 blunt trauma patients with multiple injuries in the intensive care unit of a Level I trauma center within 24 hours of admission and from 11 healthy volunteers. Samples were assayed for PMN chemiluminescence (CL) in response to a complement receptor 3 (CR3)-dependent agonist and for CD11b (CR3) expression. Common clinical parameters were correlated with CL and CR3 expression. RESULTS: The CL ratio (i.e., unprimed/primed CL) was significantly correlated with initial base deficit (BD), Injury Severity Score (ISS), CR3 expression, units of packed red blood cells transfused during the interval before blood sampling, and length of intensive care unit stay (survivors only). In contrast, BD did not correlate with units of red blood cells transfused or length of stay. Similarly, ISS did not correlate with length of stay. CONCLUSION: Significant correlations were observed between CL ratios and CR3 expression, ISS, initial BD, length of stay, and units of blood given. These data suggest that measuring CL produced by PMNs in whole blood is a potentially useful way to assess injury severity. Whereas the initial BD and ISS are indicators of how badly injured a patient is at the time of entry into a trauma center, the CL ratio may be a more useful indicator of both injury severity and prognosis. PMID- 10029038 TI - Epidural hematoma in infants: a different entity? AB - BACKGROUND: Epidural hematoma (EDH) in infants may be difficult to diagnose. The mechanism of injury and the clinical presentation are different from those in older children. We characterized the clinical and radiologic parameters of EDH in infants and correlated them with outcome. Because there are no optimal prognostic tools or clear guidelines to perform computed tomography in this unique population, a new approach of neurotrauma scoring is suggested. METHODS: Eleven infants (<2 years old) operated on for EDH were studied. Children's Glasgow Coma Scale (CCS) score was applied, and diagnosis was confirmed by computed tomography. RESULTS: Age was 13+/-5 months. Seven infants (63.6%) fell from less than 1 m. CCS score on admission was 10.7+/-3.9. Five infants (45%) were unconscious, yet two (18.2%) had CCS scores of 15. Pupillary abnormalities were found in two infants and lateralizing signs in five infants. Eight infants (72.7%) had subgaleal hematomas. Mortality and morbidity were 9% each. CONCLUSION: We suggest that a Trauma Infant Neurologic Score be used when dealing with EDH in infants. Lateralizing signs, pupillary abnormalities, mechanism of trauma, and scalp injuries should be included because these are objective relevant parameters. PMID- 10029039 TI - Treatment of femoral neck nonunions with a sliding compression screw: comparison with and without subtrochanteric valgus osteotomy. AB - BACKGROUND: The aim of this prospective study was to investigate and compare the results of treatment of femoral neck nonunions using a sliding compression screw (SCS) with and without subtrochanteric valgus osteotomy (SVO). METHODS: Thirty two consecutive patients with femoral neck nonunions, which sustained no osteonecrosis of the femoral head based on bone scan study, were prospectively treated with SCS with (21 patients) or without (11 patients) SVO. The indication for SCS with SVO was a femoral neck nonunion with leg shortening of more than 1.5 cm. SCS without SVO was for leg shortening of less than 1.5 cm. RESULTS: Seventeen patients with osteotomy and nine patients without osteotomy were followed for at least 2 years (range, 2-8 years). All femoral neck fractures healed, with a union period of 4.6+/-1.0 months (95% confidence interval, 4.1-5.1 months) for osteotomy cases and 4.6+/-1.1 months (95% confidence interval, 3.8 5.4 months) for nonosteotomy cases (p = 0.83). However, in the osteotomy group, two patients sustained osteonecrosis of the femoral head, and nonunion remained in 1 patient at the osteotomy site (complication rate, 18%; 3 of 17 patients). There were no complications in the nonosteotomy group (p = 0.26). The average lengthening achieved from osteotomy was 1.0 to 1.5 cm (p < 0.001). CONCLUSION: Using SCS without SVO to treat femoral neck nonunions can result in a very satisfactory outcome. It is thus preferred for indicated patients. SCS without SVO, however, cannot concomitantly correct a femoral neck shortening; furthermore, shortening may deteriorate because of a telescoping effect. For patients with evident shortening, therefore, combined SVO with SCS is more suitable. PMID- 10029040 TI - Posterior shoulder dislocation associated with fracture of the humeral anatomic neck: treatment guidelines and long-term outcome. AB - OBJECTIVE: We describe here 10 cases of posterior shoulder dislocation associated with fracture of the humeral anatomic neck. METHODS: Patients were treated according to our uniform treatment guidelines, in which only the dislocated humeral head (closed, if possible) was reduced, without any concomitant repositioning or internal fixation for fractures. RESULTS: Reduction resulted in an acceptable repositioning of the fractured fragments in all but one case. Anatomic neck fractures were impacted by applying longitudinal pressure for stabilization. Although early physiotherapy was initiated, redisplacement of the bone fragments did not occur. Of nine patients who were followed for more than 2 years, complete recovery of function was achieved in all but two patients. The completely detached humeral head became avascular necrotic accompanied by subchondral collapse in one case, and in the other case the displaced lesser tuberosity caused a decreased range of movement. CONCLUSION: We recommend initially treating such patients by either open or closed reduction of the dislocated humeral head and impaction of the fracture, with neither repositioning nor internal fixation of any of the fractured fragments. A completely detached humeral head or bone fragments displaced more than 10 mm after reduction of the dislocated humeral head contraindicate the use of this method. PMID- 10029041 TI - Magnetic resonance imaging findings in cerebral fat embolism: correlation with clinical manifestations. AB - OBJECTIVES: Cerebral fat embolism (CFE) is a serious complication after fracture of long bones. The mortality rate of CFE may be high. However, recent progress in treatment may decrease the mortality. We studied the validity of magnetic resonance imaging (MRI) to detect and grade severity of CFE in 11 patients with CFE. METHODS: Glasgow Coma Scale score, PaO2, PaCO2 at the onset, and minimal hemoglobin and platelet levels were monitored, and phagocytes in bronchoalveolar lavage fluid were counted. Brain computed tomographic and MRI scans were performed serially. MRI findings were graded into four categories according to the severity of T2-weighted images. RESULTS: High-intensity T2 signals were identified in the various brain regions as early as 4 hours after onset of CFE. The maximum MRI grade significantly correlated with Glasgow Coma Scale score at the onset of CFE (p < 0.01). High-intensity T2 signal lesions fused and enlarged with time. In most cases, they diminished within 2 weeks. Three patients had persistent morbidity. CONCLUSION: MRI-T2-weighted imaging seems to be the most sensitive imaging technique for diagnosing CFE, and correlates well with the clinical severity of brain Injury. With the aid of proper treatment for pulmonary fat embolism, CFE is a potentially reversible disease that can have a good outcome. PMID- 10029042 TI - Study of the outcome of patients transferred to a level I hospital after stabilization at an outlying hospital in a rural setting. AB - OBJECTIVE: To determine the characteristics and outcome of transferred trauma patients in a rural setting. METHODS: We conducted a case-control study of all trauma admissions to a rural Level I trauma center to examine a 3.5-year (1993 1996) comparison of trauma patients admitted directly with those transferred (RTTP) after being initially stabilized at an outlying hospital. We used prehospital times, Injury Severity Score (ISS), LD50ISS (the ISS at which 50% of patients died), Revised Trauma Score, probability of survival, Acute Physiology and Chronic Health Evaluation II, and observed survival as main outcome measures. RESULTS: RTTPs (39.4%) spent an average of 182+/-139 minutes at the outlying hospital and 72+/-42 minutes in transport to the trauma center. Proportionately more head/neck and patients with multiple injuries composed the RTTP group. The RTTP were more severely injured (ISS 11.1+/-8.5; Acute Physiology and Chronic Health Evaluation II 16.2+/-5.8; Revised Trauma Score 7.44+/-1.1) than the trauma patients admitted directly (ISS 7.9+/-5.3; Acute Physiology and Chronic Health Evaluation II 13.1+/-6.3; Revised Trauma Score 7.8+/-0.4; p < 0.05). However, both groups had the same LD50ISS (ISS = 35). When logistic regression was applied with death as the dependent variable, both ISS and age contributed significantly (p = 0.0001) but transfer status did not (p = 0.473). CONCLUSION: Rural trauma centers admit a high percentage of RTTP. These RTTP have a higher injury severity and acuity than their trauma patients admitted directly counterparts. Trauma care in rural areas that involves initial stabilization at outlying hospitals does not adversely affect mortality. PMID- 10029043 TI - The relationship between socioeconomic factors and gang violence in the City of Los Angeles. AB - OBJECTIVE: To investigate the relationship between community-level socioeconomic factors and the incidence of gang-related homicide in the city of Los Angeles. METHODS: An ecological group-level analysis was conducted to correlate the 5-year incidence rates (from 1988 through 1992) of gang-related homicide with community level socioeconomic statistics for the 18 geographically distinct Los Angeles Police Department divisions. Eight socioeconomic factors were examined: (1) log mean per capita income, (2) proportion employed, (3) proportion high school graduates, (4) proportion single-parent families, (5) proportion male, (6) proportion younger than 20 years of age, (7) proportion African American, and (8) proportion Hispanic. Pearson correlation coefficients were calculated for the interrelationships among the study variables and gang-related homicide. Adjusted regression estimates were calculated from a multiple linear regression model. RESULTS: The overall 5-year gang-related homicide rate for the city was 48.8 per 100,000, with a range of 5.2 to 173.5 per 100,000 among the different Los Angeles Police Department divisions. Pearson correlation coefficients revealed that the strongest negative correlations with gang-related homicide were log mean per capita income and proportion employed, and the strongest positive correlations were proportion single-parent families and proportion younger than 20 years of age. With mutual adjustment of all variables, only log mean per capita income and proportion employed were significantly associated with gang-related homicide. CONCLUSION: At the community level, gang-related homicide in Los Angeles is most closely associated with lower income and unemployment. These relationships may provide important insights into the causes of gang formation and gang violence. PMID- 10029044 TI - Complete masking of a severe open-book pelvic fracture by a pneumatic antishock garment. PMID- 10029045 TI - Unilateral lower extremity compartment syndrome in the quadriplegic patient: a possible association with the use of elastic bandages. PMID- 10029046 TI - Epidural metastatic abscess: a rare complication of an infected osteosynthesis in a distal lower leg fracture. PMID- 10029047 TI - Closed posterior dislocation of the ankle without associated fracture in a child. PMID- 10029048 TI - Surgical implications of failed endovascular therapy for postraumatic femoral arteriovenous fistula repair. PMID- 10029049 TI - Freezing soft tissue injury from propane gas. PMID- 10029050 TI - Sildenafil (Viagra) has been reported to be an effective treatment for erectile dysfunction. PMID- 10029051 TI - Ultrasound is an effective triage tool to evaluate blunt abdominal trauma in the pediatric population. PMID- 10029052 TI - Euthanasia in its active and passive forms has challenged our society. PMID- 10029053 TI - My visit to the gynecologist. PMID- 10029054 TI - The Sock Test for evaluating activity limitation in patients with musculoskeletal pain. AB - BACKGROUND AND PURPOSE: Assessment within rehabilitation often must reflect patients' perceived functional problems and provide information on whether these problems are caused by impairments of the musculoskeletal system. Such capabilities were examined in a new functional test, the Sock Test, simulating the activity of putting on a sock. SUBJECTS AND METHODS: Intertester reliability was examined in 21 patients. Concurrent validity, responsiveness, and predictive validity were examined in a sample of 337 patients and in subgroups of this sample. RESULTS: Intertester reliability was acceptable. Sock Test scores were related to concurrent reports of activity limitation in dressing activities. Scores also reflected questionnaire-derived reports of problems in a broad range of activities of daily living and pain and were responsive to change over time. Increases in age and body mass index increased the likelihood of Sock Test scores indicating activity limitation. Pretest scores were predictive of perceived difficulties in dressing activities after 1 year. CONCLUSION AND DISCUSSION: Sock Test scores reflect perceived activity limitations and restrictions of the musculoskeletal system. PMID- 10029055 TI - Energy cost of propulsion in standard and ultralight wheelchairs in people with spinal cord injuries. AB - BACKGROUND AND PURPOSE: Wheelchair- and subject-related factors influence the efficiency of wheelchair propulsion. The purpose of this study was to compare wheelchair propulsion in ultralight and standard wheelchairs in people with different levels of spinal cord injury. SUBJECTS: Seventy-four subjects (mean age=26.2 years, SD=7.14, range=17-50) with spinal cord injury resulting in motor loss (30 with tetraplegia and 44 with paraplegia) were studied. METHOD: Each subject propelled standard and ultralight wheelchairs around an outdoor track at self-selected speeds, while data were collected at 4 predetermined intervals. Speed, distance traveled, and oxygen cost (VO2 mL/kg/m) were compared by wheelchair, group, and over time, using a Bonferroni correction. RESULTS: In the ultralight wheelchair, speed and distance traveled were greater for both subjects with paraplegia and subjects with tetraplegia, whereas VO2 was less only for subjects with paraplegia. Subjects with paraplegia propelled faster and farther than did subjects with tetraplegia. CONCLUSION AND DISCUSSION: The ultralight wheelchair improved the efficiency of propulsion in the tested subjects. Subjects with tetraplegia, especially at the C6 level, are limited in their ability to propel a wheelchair. PMID- 10029056 TI - Development of the physical therapy outpatient satisfaction survey (PTOPS). AB - BACKGROUND AND PURPOSE: The purposes of this 3-phase study were (1) to identify the underlying components of outpatient satisfaction in physical therapy and (2) to develop a test that would yield reliable and valid measurements of these components. SUBJECTS: Three samples, consisting of 177, 257, and 173 outpatients from 21 facilities, were used in phases 1, 2, and 3, respectively. METHODS AND RESULTS: In phase 1, principal component analyses (PCAs), reliability checks, and correlations with social desirability scales were used to reduce a pool of 98 items to 32 items. These analyses identified a 5-component model of outpatient satisfaction in physical therapy. The phase 2 PCA, with a revised pool of 48 items, indicated that 4 components rather than 5 components represented the best model and resulted in the 34-item Physical Therapy Outpatient Satisfaction Survey (PTOPS). Factor analyses conducted with phase 2 and phase 3 data supported this conclusion and provided evidence for the internal validity of the PTOPS scores. The 4-component scales were labeled "Enhancers," "Detractors," "Location," and "Cost." Responses from subsamples of phase 3 subjects provided evidence for validity of scores in that the PTOPS components of "Enhancers," "Detractors," and "Cost" appeared to differentiate overtly satisfied patients from overtly dissatisfied patients. "Location" and "Enhancer" scores discriminated subjects with excellent attendance at scheduled physical therapy sessions from those with poor attendance. CONCLUSION AND DISCUSSION: In this study, we identified components of outpatient satisfaction in physical therapy and used them to develop a test that would yield valid and reliable measurements of these components. PMID- 10029057 TI - Hospital restructuring and the changing nature of the physical therapist's role. AB - BACKGROUND AND PURPOSE: This study was conducted to identify role behavior changes of acute care physical therapists and changes in the organizational and professional context of hospitals following restructuring. METHODS: A Delphi technique, which involved a panel of 100 randomly selected acute care physical therapy managers, was used as the research design for this study. Responses from rounds 1 and 2 were synthesized and organized into exhaustive and mutually exclusive categories for round 3. Data obtained from round 3 were used to develop a comprehensive perspective on the changes that have occurred. RESULTS: Changed role behaviors in patient care and professional interaction, including increased emphasis on evaluation, planning, teaching, supervising, and collaboration, appeared to be extensions of unchanged role behaviors. Reported changes in the structural and professional context of physical therapy services included using critical pathways to guide care, providing services system-wide, and using educational activities and meetings to maintain a sense of community. The importance of professionalism to physical therapists' work was identified and related to specific role behavior changes. CONCLUSION AND DISCUSSION: The changing role of physical therapists in acute care hospitals includes an increased emphasis on higher-level skills in patient care and professional interaction and the continuing importance of professionalism. PMID- 10029058 TI - Statistical inference by confidence intervals: issues of interpretation and utilization. AB - This article examines the role of the confidence interval (CI) in statistical inference and its advantages over conventional hypothesis testing, particularly when data are applied in the context of clinical practice. A CI provides a range of population values with which a sample statistic is consistent at a given level of confidence (usually 95%). Conventional hypothesis testing serves to either reject or retain a null hypothesis. A CI, while also functioning as a hypothesis test, provides additional information on the variability of an observed sample statistic (ie, its precision) and on its probable relationship to the value of this statistic in the population from which the sample was drawn (ie, its accuracy). Thus, the CI focuses attention on the magnitude and the probability of a treatment or other effect. It thereby assists in determining the clinical usefulness and importance of, as well as the statistical significance of, findings. The CI is appropriate for both parametric and nonparametric analyses and for both individual studies and aggregated data in meta-analyses. It is recommended that, when inferential statistical analysis is performed, CIs should accompany point estimates and conventional hypothesis tests wherever possible. PMID- 10029059 TI - Osteopenia in the patient with cancer. AB - Osteopenia is defined as a reduction in bone mass. It is commonly known to occur in elderly people or women who are postmenopausal due to hormonal imbalances. This condition, however, can result because of many other factors, such as poor nutrition, prolonged pharmacological intervention, disease, and decreased mobility. Because patients with cancer experience many of these factors, they are often predisposed to osteopenia. Currently, patients with cancer are living longer and leading more fulfilling lives after treatment. Therefore, it is imperative that therapists who are responsible for these patients understand the risk factors for osteopenia and their relevance to a patient with cancer. PMID- 10029060 TI - Mutational inactivation of the xeroderma pigmentosum group C gene confers predisposition to 2-acetylaminofluorene-induced liver and lung cancer and to spontaneous testicular cancer in Trp53-/- mice. AB - Mice that are genetically engineered to mimic the human hereditary cancer-prone DNA repair-defective disease xeroderma pigmentosum (XP) are highly predisposed to UV radiation-induced skin cancer. It is not clear, however, whether XP mice or humans are predisposed to cancers in other tissues associated with exposure to environmental carcinogens. To test the importance of nucleotide excision repair in protection against chemical carcinogenesis in internal organs, we treated XPC mutant (XPC-/-) mice with 2-acetylaminofluorene and NOH-2-acetylaminofluorene. We observed a significantly higher incidence of chemically induced liver and lung tumors in XPC-/- mice compared with normal and heterozygous littermates In addition, the progression of liver tumors in XPC-/- Trp53+/- mice is accelerated compared with XPC-/- Trp53+/+ animals. Finally, we demonstrate a higher incidence of spontaneous testicular tumors in XPC-/- TrpS3-/- double mutant mice compared with XPC+/+ Trp53-/- mice. PMID- 10029061 TI - Arsenic targets tubulins to induce apoptosis in myeloid leukemia cells. AB - Arsenic exhibits a differential toxicity to cancer cells. At a high concentration (>5 microM), As2O3 causes acute necrosis in various cell lines. At a lower concentration (0.5-5 microm), it induces myeloid cell maturation and an arrest in metaphase, leading to apoptosis. As2O3-treated cells have features found with both tubulin-assembling enhancers (Taxol) and inhibitors (colchicine). Prior treatment of monomeric tubulin with As2O3 markedly inhibits GTP-induced polymerization and microtubule formation in vitro but does not destabilize GTP induced tubulin polymers. Cross-inhibition experiments indicate that As2O3 is a noncompetitive inhibitor of GTP binding to tubulin. These observations correlate with the three-dimensional structure of beta-tubulin and suggest that the cross linking of two vicinal cysteine residues (Cys-12 and Cys-213) by trivalent arsenic inactivates the GTP binding site. Furthermore, exogenous GTP can prevent As2O3-induced mitotic arrest. PMID- 10029062 TI - A fluorescent orthotopic bone metastasis model of human prostate cancer. AB - Here, we report a fluorescent spontaneous bone metastatic model of human prostate cancer developed by surgical orthotopic implantation of green fluorescent protein (GFP)-expressing prostate cancer tissue. Human prostate cancer PC-3 cells were transduced with the pLEIN expression retroviral vector containing the enhanced GFP and neomycin resistance genes. Stable GFP high-expression PC-3 clones were selected in vitro with G418, which were then combined and injected s.c. in nude mice. For metastasis studies, fragments of a single highly fluorescent s.c. growing tumor were implanted by surgical orthotopic implantation in the prostate of a series of nude mice. Subsequent micrometastases and metastases were visualized by GFP fluorescence throughout the skeleton, including the skull, rib, pelvis, femur, and tibia The central nervous system, including the brain and spinal cord, was also involved with tumor, as visualized by GFP fluorescence. Systemic organs, including the lung, plural membrane, liver, kidney, and adrenal gland, also had fluorescent metastases. The metastasis pattern in this model reflects the bone and other metastatic sites of human prostate cancer. Thus, this model should be very useful for the study and development of treatment for metastatic androgen-independent prostate cancer. PMID- 10029063 TI - PTCH2, a novel human patched gene, undergoing alternative splicing and up regulated in basal cell carcinomas. AB - By a combination of cDNA library screening, rapid amplification of cDNA ends analysis, and BAC sequencing, a novel human patched-like gene (PTCH2) has been cloned and sequenced. The genomic organization is similar to PTCH1 with 22 exons and, by radiation hybrid mapping, PTCH2 has been localized to chromosome 1p33-34, a region often lost in a variety of tumors. Several alternatively spliced mRNA forms of PTCH2 were identified, including transcripts lacking segments thought to be involved in sonic hedgehog binding and mRNAs with differentially defined 3' terminal exons. In situ hybridization revealed high expression of PTCH2 transcripts in both familial and sporadic basal cell carcinomas in similarity to what has been observed for PTCH1, suggesting a negative regulation of PTCH2 by PTCH1. This finding tightly links PTCH2 with the sonic hedgehog/PTCH signaling pathway, implying that PTCH2 has related, but yet distinct, functions than PTCH1. PMID- 10029064 TI - Inactivation of the DNA repair gene O6-methylguanine-DNA methyltransferase by promoter hypermethylation is a common event in primary human neoplasia. AB - The DNA repair protein O6-methylguanine DNA methyltransferase (MGMT) removes alkyl adducts from the O6 position of guanine. MGMT expression is decreased in some tumor tissues, and lack of activity has been observed in some cell lines. Loss of expression is rarely due to deletion, mutation, or rearrangement of the MGMT gene, but methylation of discrete regions of the CpG island of MGMT has been associated with the silencing of the gene in cell lines. We used methylation specific PCR to study the promoter methylation of the MGMT gene. All normal tissues and expressing cancer cell lines were unmethylated, whereas nonexpressing cancer cell lines were methylated. Among the more than 500 primary human tumors examined, MGMT hypermethylation was present in a subset of specific types of cancer. In gliomas and colorectal carcinomas, aberrant methylation was detected in 40% of the tumors, whereas in non-small cell lung carcinomas, lymphomas, and head and neck carcinomas, this alteration was found in 25% of the tumors. MGMT methylation was found rarely or not at all in other tumor types. We also analyzed MGMT expression by immunohistochemistry in relation to the methylation status in 31 primary tumors. The presence of aberrant hypermethylation was associated with loss of MGMT protein, in contrast to retention of protein in the majority of tumors without aberrant hypermethylation. Our results suggest that epigenetic inactivation of MGMT plays an important role in primary human neoplasia. PMID- 10029065 TI - Methylation-associated silencing of the tissue inhibitor of metalloproteinase-3 gene suggest a suppressor role in kidney, brain, and other human cancers. AB - Tissue inhibitor of metalloproteinase-3 (TIMP-3) antagonizes matrix metalloproteinase activity and can suppress tumor growth, angiogenesis, invasion, and metastasis. Loss of TIMP-3 has been related to the acquisition of tumorigenesis. Herein, we show that TIMP-3 is silenced in association with aberrant promoter-region methylation in cell lines derived from human cancers. TIMP-3 expression was restored after 5-aza-2'deoxycytidine-mediated demethylation of the TIMP-3 proximal promoter region. Genomic bisulfite sequencing revealed that TIMP-3 silencing was related to the overall density of methylation and that discrete regions within the TIMP-3 CpG island may be important for the silencing of this gene. Aberrant methylation of TIMP-3 occurred in primary cancers of the kidney, brain, colon, breast, and lung, but not in any of 41 normal tissue samples. The most frequent TIMP-3 methylation was found in renal cancers, which originate in the tissue that normally expresses the highest TIMP-3 levels. This methylation correlated with a lack of detectable TIMP-3 protein in these tumors. Together, these data show that methylation-associated inactivation of TIMP-3 is frequent in many human tumors. PMID- 10029066 TI - Survey of gene amplifications during prostate cancer progression by high throughout fluorescence in situ hybridization on tissue microarrays. AB - Prostate cancer development and progression is driven by the accumulation of genetic changes, the nature of which remains incompletely understood To facilitate high-throughput analysis of molecular events taking place in primary, recurrent, and metastat prostate cancer, we constructed a tissue microarray containing small 0.6-mm cylindrical samples acquired from 371 formalin-fixed blocks, including benign prostatic hyperplasia (n = 32) and primary tumors (n = 223), as well as both locally recurrent tumors (n = 54) and metastases (n = 62) from patients with hormone-refractory disease. Fluorescence in situ hybridization (FISH) was applied to the analysis of consecutive tissue microarray sections with probes for five different genes. High-level (> or =3X) amplifications were very rare (<2%) in primary prostate cancers However, in metastases from patients with hormone-refractory disease, amplification of the androgen receptor gene was seen in 22%, MYC in 11%, and Cyclin-D1 in 5% of the cases. In specimens from locally recurrent tumors, the corresponding percentages were 23, 4, and 8%. ERBB2 and NMYC amplifications were never detected at any stage of prostate cancer progression. In conclusion, FISH to tissue microarray sections enables high throughput analysis of genetic alterations contributing to cancer development and progression. Our results implicate a role for amplification of androgen receptor in hormonal therapy failure and that of MYC in the metastatic progression of human prostate cancer. PMID- 10029067 TI - Frequent silencing of the GPC3 gene in ovarian cancer cell lines. AB - GPC3 encodes a glypican integral membrane protein and is mutated in the Simpson Golabi-Behmel syndrome. Simpson-Golabi-Behmel syndrome, an X-linked condition, is characterized by pre- and postnatal overgrowth as well as by various other abnormalities, including increased risk of embryonal tumors. The GPC3 gene is located at Xq26, a region frequently deleted in advanced ovarian cancers. To determine whether GPC3 is a tumor suppressor in ovarian neoplasia, we studied its expression and mutational status in 13 ovarian cancer cell lines. No mutations were found in GPC3, but its expression was lost in four (31%) of the cell lines analyzed. In an of the cases where GPC3 expression was lost, the GPC3 promoter was hypermethylated, as demonstrated by Southern analysis. Expression of GPC3 was restored by treatment of the cells with the demethylating agent 5-aza-2' deoxycytidine. A colony-forming assay confirmed that ectopic GPC3 expression inhibited the growth of ovarian cancer cell lines. Our results show that GPC3, a gene involved in the control of organ growth, is frequently inactivated in a subset of ovarian cancers and suggest that it may function as a tumor suppressor in the ovary. PMID- 10029068 TI - Stable inhibition of nuclear factor kappaB in cancer cells does not increase sensitivity to cytotoxic drugs. AB - Several reports indicated that nuclear factor kappaB (NF-kappaB) activation by cytokines, cytotoxic drugs, or ionizing radiation protects cells against apoptosis. Therefore, we investigated the consequence of NF-kappaB inhibition on the efficiency of antineoplastic agents. HPB, HCT116, MCF7, and OVCAR-3 cells stably expressing a dominant negative IkappaBalpha inhibitor showed a decreased NF-kappaB activation following treatment with tumor necrosis factor a and various chemotherapeutic agents. However, there was no difference in survival between parental cells and cells expressing mutated IkappaBalpha. These studies suggest that, at least in these cell lines, stable NF-kappaB inhibition did not modify the response to cytotoxic drugs. PMID- 10029070 TI - Increased levels of human papillomavirus type 16 DNA in a subset of prostate cancers. AB - Whether oncogenic human papilloma viruses (HPVs) are involved in the pathogenesis of prostate cancers has been a subject of great controversy. To clarify the contradictory results of investigations, with the aim of detecting viral nucleic acids in prostate cancers, we have carried out a comparative quantitation of the HPV16-E6 sequence in 84 prostate specimens. Using single-tube quantitative competitive PCR, we characterized 47 prostate cancers and 37 control tissues of benign prostatic hyperplasia. A subgroup of the prostate tumors (10 of 47; 21%) was detected as having significantly higher copy numbers of HPV16-E6 sequences when compared to the control tissue (1 of 37; 3%), using a cutoff value of 300 copies per 12,500 diploid cells (two-sided Fisher's exact test, P = 0.02). Our results indicate that the oncogenic HPV16 might contribute to the development of a subset of prostate tumors. PMID- 10029069 TI - hMSH5: a human MutS homologue that forms a novel heterodimer with hMSH4 and is expressed during spermatogenesis. AB - MutS homologues have been identified in nearly all organisms examined to date. They play essential roles in maintaining mitotic genetic fidelity and meiotic segregation fidelity. MutS homologues appear to function as a molecular switch that signals genomic manipulation events. Here we describe the identification of the human homologue of the Saccharomyces cerevisiae MSH5, which is known to participate in meiotic segregation fidelity and crossing-over. The human MSH5 (hMSH5) was localized to chromosome 6p22-21 and appears to play a role in meiosis because expression is induced during spermatogenesis between the late primary spermatocytes and the elongated spermatid phase. hMSH5 interacts specifically with hMSH4, confirming the generality of functional heterodimeric interactions in the eukaryotic MutS homologue, which also includes hMSH2-hMSH3 and hMSH2-hMSH6. PMID- 10029071 TI - Cloning and characterization of the promoter region of human telomerase reverse transcriptase gene. AB - Activation of telomerase is one of the rate-limiting steps in human cell immortalization and carcinogenesis Human telomerase is composed of at least two protein subunits and an RNA component. Regulation of expression of the catalytic subunit, human telomerase reverse transcriptase (hTERT), is suggested as the major determinant of the enzymatic activity. We report here the cloning and characterization of the 5'-regulatory region of the hTERT gene. The highly GC rich content of the 5' end of the hTERT cDNA spans to the 5'-flanking region and intron 1, making a CpG island. A 1.7-kb DNA fragment encompassing the hTERT gene promoter was placed upstream of the luciferase reporter gene and transiently transfected into human cell lines of fibroblastic and epithelial origins that differed in their expression of the endogenous hTERT gene. Endogenous hTERT expressing cells, but not nonexpressing cells, showed high levels of luciferase activity, suggesting that the regulation of hTERT gene expression occurs mainly at the transcriptional level. Additional luciferase assays using a series of constructs containing unidirectionally deleted fragments revealed that a 59-bp region (-208 to -150) is required for the maximal promoter activity. The region contains a potential Myc oncoprotein binding site (E-box), and cotransfection of a c-myc expression plasmid markedly enhanced the promoter activity, suggesting a role of the Myc protein in telomerase activation. Identification of the regulatory regions of the hTERT promoter sequence will be essential in understanding the molecular mechanisms of positive and negative regulation of telomerase. PMID- 10029072 TI - Peripheral-type benzodiazepine receptor (PBR) in human breast cancer: correlation of breast cancer cell aggressive phenotype with PBR expression, nuclear localization, and PBR-mediated cell proliferation and nuclear transport of cholesterol. AB - Aberrant cell proliferation and increased invasive and metastatic behavior are hallmarks of the advancement of breast cancer. Numerous studies implicate a role for cholesterol in the mechanisms underlying cell proliferation and cancer progression. The peripheral-type benzodiazepine receptor (PBR) is an Mr 18,000 protein primarily localized to the mitochondria. PBR mediates cholesterol transport across the mitochondrial membranes in steroidogenic cells. A role for PBR in the regulation of tumor cell proliferation has also been shown. In this study, we examined the expression, characteristics, localization, and function of PBR in a battery of human breast cancer cell lines differing in their invasive and chemotactic potential as well as in several human tissue biopsies. Expression of PBR ligand binding and mRNA was dramatically increased in the highly aggressive cell lines, such as MDA-231, relative to nonaggressive cell lines, such as MCF-7. PBR was also found to be expressed at high levels in aggressive metastatic human breast tumor biopsies compared with normal breast tissues. Subcellular localization with both antibodies and a fluorescent PBR drug ligand revealed that PBR from the MDA-231 cell line as well as from aggressive metastatic human breast tumor biopsies localized primarily in and around the nucleus. This localization is in direct contrast to the largely cytoplasmic localization seen in MCF-7 cells, normal breast tissue, and to the typical mitochondrial localization seen in mouse tumor Leydig cells. Pharmacological characterization of the receptor and partial nucleotide sequencing of PBR cDNA revealed that the MDA-231 PBR is similar, although not identical, to previously described PBR. Addition of high affinity PBR drug ligands to MDA-231 cells increased the incorporation of bromodeoxyuridine into the cells in a dose dependent manner, suggesting a role for PBR in the regulation of MDA-231 cell proliferation. Cholesterol uptake into isolated MDA-231 nuclei was found to be 30% greater than into MCF-7 nuclei. High-affinity PBR drug ligands regulated the levels of cholesterol present in MDA-231 nuclei but not in MCF-7. In addition, the PBR-dependent MDA-231 cell proliferation was found to highly correlate (r = 0.99) with the PBR-mediated changes in nuclear membrane cholesterol levels. In conclusion, these data suggest that PBR expression, nuclear localization, and PBR mediated cholesterol transport into the nucleus are involved in human breast cancer cell proliferation and aggressive phenotype expression, thus participating in the advancement of the disease. PMID- 10029073 TI - COOH-terminal domain of p53 modulates p53-mediated transcriptional transactivation, cell growth, and apoptosis. AB - The tumor suppressor protein p53 contributes to the control of cell cycle checkpoints and stress-induced apoptosis and is frequently mutated in many different types of human cancers. The COOH terminus of p53 modulates the transcriptional and apoptotic activities of the protein. Although COOH-terminal mutants of p53 are uncommon, we proposed that these p53 mutants nevertheless contributed to the selective clonal expansion of the cancer cells. Therefore, we analyzed the tumor-derived p53 COOH-terminal domain (CTD) mutants (352D/H, 356G/W, 342-stop, 360-del, and 387-del) functionally. The results have revealed that all mutants have impaired apoptotic activity when compared with wild-type p53. However, some of these mutants still transcriptionally transactivate p21Waf/Cip1 and inhibit cell growth. Interestingly, of the tumor-derived CTD mutants, oligomerization-defective mutant 342-stop was the only one that did not exhibit sequence-specific DNA binding or failed to transactivate p21Waf1/Cip1, Bax, and IGF-BP3 transcriptionally. The failure to inhibit cell growth by this tumor-derived CTD mutant supports the hypothesis that p53 sequence-specific transcriptional transactivity to p21Waf1/Cip1 is correlated with induction of cell cycle arrest and that the p53 transcriptional transactivity requires oligomerization of the p53 protein. These and other data indicate that the CTD of p53 is an important component of p53-mediated apoptosis and cell growth arrest and that inactivation of the apoptotic function, but not the inhibition of growth, is an important step during human tumorigenesis. PMID- 10029074 TI - Isolation and characterization of a rat homologue of the human tuberous sclerosis 1 gene (Tsc1) and analysis of its mutations in rat renal carcinomas. AB - In the Eker rat, a germ-line mutation in the homologue of the human tuberous sclerosis gene (Tsc2) causes renal cell carcinomas (RCs) with a complete penetrance in all heterozygotes. Tsc2 mutations have also been found in a subset of chemically induced non-Eker rat RCs. Because tuberous sclerosis patients with alteration of either of the two predisposing genes (TSC1 and TSC2) show identical symptoms, the products of these two genes are thought to be involved in a common biological pathway. In this study, to analyze the possible overlap between the functions of Tsc2 and Tscl gene products, we isolated and characterized a rat homologue of the TSC1 gene (Tsc1). The rat Tsc1 gene, which has an identical exon intron structure to that of human TSC1 and is localized on rat chromosome 3, has been shown to encode a protein (hamartin) that is highly homologous to the human counterpart with an approximately 86% amino acid sequence identity. Using PCR single-strand conformational polymorphism analysis, we identified two splicing donor site mutations in one chemically induced rat RC (1 of 15). This suggests that alterations of the Tsc1 gene may be involved in the development of a subset of rat RCs. PMID- 10029075 TI - Breast carcinoma: vascular density determined using CD105 antibody correlates with tumor prognosis. AB - Angiogenesis is essential for tumor growth and metastasis. There are conflicting reports as to whether microvessel density (IMD) in breast cancers is associated with prognosis. This could be due to the use of different antibodies to endothelial cell markers, variation in tissue pretreatment protocols, and nonstandardized counting methods. We have assessed the IMD in 106 breast carcinomas using a pan-endothelial marker, CD34, and a recently described mAb to CD105, which preferentially reacts with endothelial cell in angiogenic tissues. IMD values (separated as above or below median) for CD105 expression showed a statistically significant correlation with overall (P = 0.0029) and disease-free survival (P = 0.0362). In contrast, blood vessel counts using a panendothelial marker CD34 did not correlate with overall or disease-free survival (P = 0.2912 and P = 03153, respectively). When IMD values were subdivided into quartiles and assessed for their prognostic values, there was a statistically significant difference in the overall survival across CD105, but not CD34, values (P = 0.0017 and P = 0.7997, respectively) and also disease-free survival (P = 0.0431 and P = 0.5066, respectively). Further analysis of IMD values demonstrated that there were no deaths in the lowest quartile for CD105 and it differed from the other three quartiles. However, examination of clinical details of patients in the lowest quartile failed to reveal clustering of patients known to be associated with low-risk factors. Multivariate analysis confirmed that IMD values using CD105 were an independent prognostic factor. These results suggest that the ability to quantitatively distinguish between tumor neovascularization and preexisting vessels may be important in the assessment of tumor angiogenesis, but requires confirmation in a greater number of patients with a longer follow-up. PMID- 10029076 TI - 1,25-Dihydroxyvitamin D3 enhances the susceptibility of breast cancer cells to doxorubicin-induced oxidative damage. AB - 1,25-Dihydroxyvitamin D3 (1,25(OH)2D3), the hormonal form of vitamin D, has anticancer activity in vivo and in vitro. Doxorubicin exerts its cytotoxic effect on tumor cells mainly by two mechanisms: (a) generation of reactive oxygen species (ROS); and (b) inhibition of topoisomerase II. We studied the combined cytotoxic action of 1,25(OH)2D3 and doxorubicin on MCF-7 breast cancer cells. Pretreatement with 1,25(OH)2D3 resulted in enhanced cytotoxicity of doxorubicin. The average enhancing effect after a 72-h pretreatment with 1,25(OH)2D3 (10 nM) followed by a 24-h treatment with 1 microg/ml doxorubicin was 74+/-9% (mean +/- SE). Under these experimental conditions, 1,25(OH)2D3 on its own did not affect cell number or viability. 1,25(OH)2D3 also enhanced the cytotoxic activity of another ROS generating quinone, menadione, but did not affect cytotoxicity induced by the topoisomerase inhibitor etoposide. The antioxidant N acetylcysteine slightly reduced the cytotoxic activity of doxorubicin but had a marked protective effect against the combined action of 1,25(OH)2D3 and doxorubicin. These results indicate that ROS are involved in the interaction between 1,25(OH)2D3 and doxorubicin. 1,25(OH)2D3 also increased doxorubicin cytotoxicity in primary cultures of rat cardiomyocytes. Treatment of MCF-7 cells with 1,25(OH)2D3 alone markedly reduced the activity, protein, and mRNA levels of the cytoplasmic antioxidant enzyme Cu/Zn superoxide dismutase, which indicated that the hormone inhibits its biosynthesis. This reduction in the antioxidant capacity of the cells could account for the synergistic interaction between 1,25(OH)2D3 and doxorubicin and may also suggest increased efficacy of 1,25(OH)2D3 or its analogues in combination with other ROS-generating anticancer therapeutic modalities. PMID- 10029077 TI - Survival in familial, BRCA1-associated, and BRCA2-associated epithelial ovarian cancer. United Kingdom Coordinating Committee for Cancer Research (UKCCCR) Familial Ovarian Cancer Study Group. AB - The natural history of hereditary and BRCA1- and BRCA2-associated epithelial ovarian cancer may differ from that of sporadic disease. The purpose of this study was to compare the clinical characteristics of BRCA1- and BRCA2-associated hereditary ovarian cancer, hereditary ovarian cancer with no identified BRCA1/2 mutation, and ovarian cancer in population-based controls. BRCA1 and BRCA2 mutation testing was carried out on index cases from 119 families with site specific epithelial ovarian cancer or breast-ovarian cancer. We estimated overall survival in 151 patients from 57 BRCA1 and BRCA2 mutation families and compared it with that in 119 patients from 62 families in which a BRCA1/2 mutation was not identified. We compared clinical outcome and data on tumor histopathology, grade, and stage. We also compared survival in familial epithelial ovarian cancer, whether or not a mutation was identified, with that of an age-matched set of population control cases. Overall survival at 5 years was 21% (95% confidence interval, 14-28) in cases from BRCA1 mutation families, 25% (8-42) in BRCA2 mutation families, and 19% (12-26) in families with no identified mutation (P = 0.91). Survival in familial ovarian cancer cases as a whole was significantly worse than for population controls (P = 0.005). In the familial cases, we found no differences in histopathological type, grade, or stage according to mutation status. Compared to population control cases, mucinous tumors occurred less frequently in the familial cases (2 versus 12%, P<0.001), and a greater proportion of the familial cases presented with advanced disease (83% stage III/IV versus 56%; P = 0.001). We have shown that survival in familial ovarian cancer cases is worse than that in sporadic cases, whether or not a BRCA1/2 mutation was identified, perhaps reflecting a difference in biology analogous to that observed in breast cancer. PMID- 10029078 TI - Suppression of angiogenesis, tumorigenicity, and metastasis by human prostate cancer cells engineered to produce interferon-beta. AB - We determined whether the IFN-beta gene can be used to suppress angiogenesis, tumor growth, and metastasis of human prostate cancer cells growing in the prostate of nude mice. Highly metastatic PC-3M human prostate cancer cells were engineered to constitutively produce murine IFN-beta subsequent to infection with a retroviral vector containing murine IFN-beta cDNA. Parental (PC-3M-P), control vector-transduced (PC-3M-Neo), and IFN-beta-transduced (PC-3M-IFN-beta) cells were injected into the prostate (orthotopic) or subcutis (ectopic) of nude mice. PC-3M-P and PC-3M-Neo cells produced rapidly growing tumors and regional lymph node metastases, whereas PC-3M-IFN-beta cells did not. PC-3M-IFN-beta cells also suppressed the tumorigenicity of bystander nontransduced prostate cancer cells. PC-3M-IFN-beta cells produced small tumors (3-5 mm in diameter) in nude mice treated with anti-asialo GM1 antibodies and in severe combined immunodeficient/Beige mice. Immunohistochemical staining revealed that PC-3M-IFN beta tumors were homogeneously infiltrated by macrophages, whereas control tumors contained fewer macrophages at their periphery. Most tumor cells in the control tumors were stained positive by an antibody to proliferative cell nuclear antigen; very few were positively stained by terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick-end labeling. In sharp contrast, PC-3M-IFN beta tumors contained fewer proliferative cell nuclear antigen-positive cells and many terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick-end labeling positive cells. Staining with antibody against CD31 showed that control tumors contained more blood vessels than PC-3M-IFN-beta tumors. PC-3M-IFN-beta cells were more sensitive to lysis mediated by natural killer cells in vitro or to cytostasis mediated by macrophages than control transduced cells. Conditioned medium from PC-3M-IFN-beta cells augmented splenic cell-mediated cytolysis to control tumor cells, which could be neutralized by antibody against IFN-beta. Collectively, the data suggest that the suppression of tumorigenicity and metastasis of PC-3M-IFN-beta cells is due to inhibition of angiogenesis and activation of host effector cells. PMID- 10029079 TI - SDZ PSC 833, the cyclosporine A analogue and multidrug resistance modulator, activates ceramide synthesis and increases vinblastine sensitivity in drug sensitive and drug-resistant cancer cells. AB - Resistance to chemotherapy is the major cause of cancer treatment failure. Insight into the mechanism of action of agents that modulate multidrug resistance (MDR) is instrumental for the design of more effective treatment modalities. Here we show, using KB-V-1 MDR human epidermoid carcinoma cells and [3H]palmitic acid as metabolic tracer, that the MDR modulator SDZ PSC 833 (PSC 833) activates ceramide synthesis. In a short time course experiment, ceramide was generated as early as 15 min (40% increase) after the addition of PSC 833 (5.0 microM), and by 3 h, [3H]ceramide was >3-fold that of control cells. A 24-h dose-response experiment showed that at 1.0 and 10 microM PSC 833, ceramide levels were 2.5- and 13.6-fold higher, respectively, than in untreated cells. Concomitant with the increase in cellular ceramide was a progressive decrease in cell survival, suggesting that ceramide elicited a cytotoxic response. Analysis of DNA in cells treated with PSC 833 showed oligonucleosomal DNA fragmentation, characteristic of apoptosis. The inclusion of fumonisin B1, a ceramide synthase inhibitor, blocked PSC 833-induced ceramide generation. Assessment of ceramide mass by TLC lipid charring confirmed that PSC 833 markedly enhanced ceramide synthesis, not only in KB-V-1 cells but also in wild-type KB-3-1 cells. The capacity of PSC 833 to reverse drug resistance was demonstrated with vinblastine. Whereas each agent at a concentration of 1.0 microM reduced cell survival by approximately 20%, when PSC 833 and vinblastine were coadministered, cell viability fell to zero. In parallel experiments measuring ceramide metabolism, it was shown that the PSC 833/vinblastine combination synergistically increased cellular ceramide levels. Vinblastine toxicity, also intensified by PSC 833 in wild-type KB-3-1 cells, was as well accompanied by enhanced ceramide formation. These data demonstrate that PSC 833 has mechanisms of action in addition to P-glycoprotein chemotherapy efflux pumping. PMID- 10029080 TI - Rapamycin causes poorly reversible inhibition of mTOR and induces p53-independent apoptosis in human rhabdomyosarcoma cells. AB - The mammalian target of rapamycin (mTOR) has been shown to link growth factor signaling and posttranscriptional control of translation of proteins that are frequently involved in cell cycle progression. However, the role of this pathway in cell survival has not been demonstrated. Here, we report that rapamycin, a specific inhibitor of mTOR kinase, induces G1 cell cycle arrest and apoptosis in two rhabdomyosarcoma cell lines (Rh1 and Rh30) under conditions of autocrine cell growth. To examine the kinetics of rapamycin action, we next determined the rapamycin sensitivity of rhabdomyosarcoma cells exposed briefly (1 h) or continuously (6 days). Results demonstrate that Rh1 and Rh30 cells were equally sensitive to rapamycin-induced growth arrest and apoptosis under either condition. Apoptosis was detected between 24 and 144 h of exposure to rapamycin. Both cell lines have mutant p53; hence, rapamycin-induced apoptosis appears to be a p53-independent process. To determine whether induction of apoptosis by rapamycin was specifically due to inhibition of mTOR signaling, we engineered Rh1 and Rh30 clones to stably express a mutant form of mTOR that was resistant to rapamycin (Ser2035-->Ile; designated mTOR-rr). Rh1 and Rh30 mTOR-rr clones were highly resistant (>3000-fold) to both growth inhibition and apoptosis induced by rapamycin. These results are the first to indicate that rapamycin-induced apoptosis is mediated by inhibition of mTOR. Exogenous insulin-like growth factor (IGF)-I protected both Rh1 and Rh30 from apoptosis, without reactivating ribosomal p70 S6 kinase (p70S6K) downstream of mTOR. However, in rapamycin treated cultures, the response to IGF-I differed between the cell lines: Rh1 cells proliferated normally, whereas Rh30 cells remained arrested in G1 phase but viable. Rapamycin is known to inhibit synthesis of specific proteins but did not inhibit synthesis or alter the levels of mTOR. To examine the rate at which the mTOR pathway recovered, the ability of IGF-I to stimulate p70S6K activity was followed in cells treated for 1 h with rapamycin and then allowed to recover in medium containing > or =100-fold excess of FK506 (to prevent rapamycin from rebinding to its cytosolic receptor FKBP-12). Our results indicate that, in Rh1 cells, rapamycin dissociates relatively slowly from FKBP-12, with a t1/2 of approximately 17.5 h. in the presence of FK506, whereas there was no recovery of p70S6K activity in the absence of this competitor. This was of interest because rapamycin was relatively unstable under conditions of cell culture having a biological t1/2 of approximately 9.9 h. These results help to explain why cells are sensitive following short exposures to rapamycin and may be useful in guiding the use of rapamycin analogues that are entering clinical trials as novel antitumor agents. PMID- 10029082 TI - Improvement of systemic 5-aminolevulinic acid-based photodynamic therapy in vivo using light fractionation with a 75-minute interval. AB - We have studied different single and fractionated illumination schemes after systemic administration of 5-aminolevulinic acid (ALA) to Improve the response of nodular tumors to ALA-mediated photodynamic therapy. Tumors transplanted on the thigh of female WAG/Rij rats were transdermally illuminated with red light (633 nm) after systemic ALA administration (200 mg/kg). The effectiveness of each treatment scheme was determined from the tumor volume doubling time. A single illumination (100 J/cm2 at 100 mW/cm2, 2.5 h after ALA administration) yielded a doubling time of 6.6+/-1.2 days. This was significantly different from the untreated control (doubling time, 1.7+/-0.1 days). The only treatment scheme that yielded a significant improvement compared to all other schemes studied was illumination at both 1 and 2.5 h after ALA administration (both 100 J/cm2 at 100 mW/cm2) and resulted in a tumor volume doubling time of 18.9+/-2.9 days. A possible mechanism to explain this phenomenon is that the protoporphyrin IX formed after administration of ALA is photodegraded by the first illumination. In the 75-min interval, new porphyrin is formed enhancing the effect of the second illumination. PMID- 10029081 TI - Antiangiogenesis treatment for gliomas: transfer of antisense-vascular endothelial growth factor inhibits tumor growth in vivo. AB - Presently, there is no effective treatment for glioblastoma, the most malignant and common brain tumor. Angiogenic factors are potentially optimal targets for therapeutic strategies because they are essential for tumor growth and progression. In this study, we sought a strategy for efficiently delivering an antisense cDNA molecule of the vascular endothelial growth factor (VEGF) to glioma cells. The recombinant adenoviral vector Ad5CMV-alphaVEGF carried the coding sequence of wild-type VEGF165 cDNA in an antisense orientation. Infection of U-87 MG malignant glioma cells with the Ad5CMV-alphaVEGF resulted in reduction of the level of the endogenous VEGF mRNA and drastically decreased the production of the targeted secretory form of the VEGF protein. Treatment of s.c. human glioma tumors established in nude mice with intralesional injection of Ad5CMV alphaVEGF inhibited tumor growth. Taken together, these findings indicate that the efficient down-regulation of the VEGF produced by tumoral cells using antisense strategies has an antitumor effect in vivo. This is the first time that an adenoviral vector is used to transfer antisense VEGF sequence into glioma cells in an animal model, and our results suggest that this system may have clinical and therapeutic utility. PMID- 10029083 TI - Identification of the human melanoma-associated chondroitin sulfate proteoglycan antigen epitope recognized by the antitumor monoclonal antibody 763.74 from a peptide phage library. AB - To identify the epitope of the melanoma-associated chondroitin sulfate proteoglycan (MCSP) recognized by the monoclonal antibody (mAb) 763.74, we first expressed random DNA fragments obtained from the complete coding sequence of the MCSP core glycoproteins in phages and selected without success for binders to the murine mAb 763.74. We then used a library of random heptapeptides displayed at the surface of the filamentous M13 phage as fusion protein to the NH2-terminal portion of the minor coat protein III. After three rounds of selection on the bound mAb, several phages displaying related binding peptides were identified, yielding the consensus sequence Val-His-Leu-Asn-Tyr-Glu-His. Competitive ELISA experiments showed that this peptide can be specifically prevented from binding to mAb 763.74 by an anti-idiotypic MK2-23 mouse:human chimeric mAb and by A375 melanoma cells expressing the antigen MCSP. We screened the amino acid sequence of the MCSP molecule for a region of homology to the consensus sequence and found that the amino acid sequence Val-His-Ile-Asn-Ala-His spanning positions 289 and 294 has high homology. Synthetic linear peptides corresponding to the consensus sequence as well as to the MCSP-derived epitope inhibit the binding of mAb 763.74 to the phages displaying the consensus amino acid sequence. Finally, the biotinylated consensus peptide absorbed to streptavidin-microtiter plates can be used for the detection of mAb 763.74 in human serum. These results show clearly that the MCSP epitope defined by mAb 763.74 has been identified. PMID- 10029084 TI - Tumor-induced interleukin-10 inhibits type 1 immune responses directed at a tumor antigen as well as a non-tumor antigen present at the tumor site. AB - Interleukin (IL)-10 is a potent immunosuppressive cytokine that has been found to be present at the tumor site in a wide variety of human cancers, including transitional cell carcinoma of the bladder. Using a murine bladder tumor (MB49), which we show to express the male transplantation antigen (HY), we tested the hypothesis that IL-10 at the tumor site can block the generation of a tumor specific type 1 immune response. We show that, despite its expression of HY, MB49 fails to prime for an HY-specific type 1 (IFN-gamma) response in normal female mice. Although MB49 does not constitutively produce IL-10, our data support a model whereby MB49 induces infiltrating cells to produce IL-10. This feature rendered the IL-10 knockout (KO) mouse, whose infiltrating cells are incapable of IL-10 production, a suitable model in which to study MB49 in the absence of IL 10. When injected into IL-10 KO mice, MB49 does prime for an HY-specific, type 1 immune response. Furthermore, IL-10 KO mice show prolonged survival and an increased capacity to reject tumors as compared with normal mice. We also tested the ability of tumor-induced IL-10 to inhibit immunization to a non-tumor antigen present at the tumor site. When vaccinia virus encoding beta-galactosidase (beta gal) is injected into the tumors of normal mice, no beta-gal-specific IFN-gamma response is mounted. However, when this same viral construct is injected into the tumors of IL-10 KO mice, it produces a strong beta-gal-specific, IFN-gamma response. These studies demonstrate that tumor-induced IL-10 can block the generation of a tumor-specific type 1 immune response as well as subvert attempts to elicit a type 1 immune response to a non-tumor antigen at the tumor site. PMID- 10029085 TI - Conserved mechanism of PLAG1 activation in salivary gland tumors with and without chromosome 8q12 abnormalities: identification of SII as a new fusion partner gene. AB - We have previously shown (K. Kas et al, Nat. Genet., 15: 170-174, 1997) that the developmentally regulated zinc finger gene pleomorphic adenoma gene 1 (PLAG1) is the target gene in 8q12 in pleomorphic adenomas of the salivary glands with t(3;8)(p21;q12) translocations. The t(3;8) results in promoter swapping between PLAG1 and the constitutively expressed gene for beta-catenin (CTNNB1), leading to activation of PLAG1 expression and reduced expression of CTNNB1. Here we have studied the expression of PLAG1 by Northern blot analysis in 47 primary benign and malignant human tumors with or without cytogenetic abnormalities of 8q12. Overexpression of PLAG1 was found in 23 tumors (49%). Thirteen of 17 pleomorphic adenomas with a normal karyotype and 5 of 10 with 12q13-15 abnormalities overexpressed PLAG1, which demonstrates that PLAG1 activation is a frequent event in adenomas irrespective of karyotype. In contrast, PLAG1 was overexpressed in only 2 of 11 malignant salivary gland tumors analyzed, which suggests that, at least in salivary gland tumors, PLAG1 activation preferentially occurs in benign tumors. PLAG1 over-expression was also found in three of nine mesenchymal tumors, i.e., in two uterine leiomyomas and one leiomyosarcoma. RNase protection, rapid amplification of 5'-cDNA ends (5'-RACE), and reverse transcription-PCR analyses of five adenomas with a normal karyotype revealed fusion transcripts in three tumors. Nucleotide sequence analysis of these showed that they contained fusions between PLAG1 and CTNNB1 (one case) or PLAG1 and a novel fusion partner gene, i.e., the gene encoding the transcription elongation factor SII (two cases). The fusions occurred in the 5' noncoding region of PLAG1, leading to exchange of regulatory control elements and, as a consequence, activation of PLAG1 gene expression. Because all of the cases had grossly normal karyotypes, the rearrangements must result from cryptic rearrangements. The results suggest that in addition to chromosomal translocations and cryptic rearrangements, PLAG1 may also be activated by mutations or indirect mechanisms. Our findings establish a conserved mechanism of PLAG1 activation in salivary gland tumors with and without 8q12 aberrations, which indicates that such activation is a frequent event in these tumors. PMID- 10029086 TI - Control of apoptosis in Epstein Barr virus-positive nasopharyngeal carcinoma cells: opposite effects of CD95 and CD40 stimulation. AB - The expression and function of CD95 and CD40 were investigated in malignant cells from EBV-positive undifferentiated nasopharyngeal carcinomas (NPCs). Large amounts of CD95 and CD40 expression were detected in 15 of 16 EBV-positive NPC specimens. In contrast, CD95 was not detected in two biopsies from patients with EBV-negative differentiated NPCs. We tested whether the CD95 apoptotic pathway was functional in NPC cells by treating two EBV-positive NPC tumor lines in vitro with a CD95 agonist. In both cases, NPC cells were extremely susceptible to CD95 mediated apoptosis, despite strong constitutive expression of Bcl-x. Combined CD40 and CD95 stimulation was used to investigate the possible anti-apoptotic activity mediated by CD40. The CD40 receptor was activated by incubating NPC cells with murine L cells producing CD154, the CD40 ligand. This treatment resulted in a strong inhibition of CD95-related cytotoxicity. Such an anti apoptotic effect of CD40 is well known for B lymphocytes, but has not previously been reported for epithelial cells. These data suggest that NPC tumor infiltrating lymphocytes, which often produce the CD40 ligand in situ, may increase the survival of malignant cells, thereby enhancing tumor growth in patients. PMID- 10029087 TI - Using computerized video time lapse for quantifying cell death of X-irradiated rat embryo cells transfected with c-myc or c-Ha-ras. AB - Rat embryo fibroblasts that had been transfected with the c-myc or c-Ha-ras oncogene were X-irradiated, after which individual cells and their progeny were followed in multiple fields for 5-6 days by computerized video time lapse microscopy to quantify the lethal events that resulted in loss of clonogenic survival. The loss of clonogenic survival of X-irradiated (9.5 or 2.5 Gy) REC:myc cells was attributed almost entirely to the cells dying by apoptosis, with almost all of the apoptosis occurring after the progeny had divided from one to four times. In contrast, the loss of clonogenic survival of X-irradiated REC:ras cells was attributed to two processes. After 9.5 Gy, approximately approximately 60% of the nonclonogenic cells died by apoptosis (with a very small amount of necrosis), and the other 40% underwent a senescent-type process in which some of the cells and their progeny stopped dividing but remained as viable cells throughout 140 h of observation. Both processes usually occurred after the cells had divided and continued to occur in the cells' progeny for up to five divisions after irradiation. Furthermore, the duration of the apoptotic process was shorter for REC:myc cells (0.5-1 h) than for REC:ras cells (4-5 h). By using computerized video time lapse to follow individual cells, we were able to determine the mode of cell death. This cannot be determined by conventional clonogenic survival experiments. Also, only by following the individual cells and their progeny can the true amount of apoptosis be determined. The cumulative percentage of apoptosis scored in whole populations, without distinguishing between the progeny of individually irradiated cells, does not reflect the true amount of apoptosis that occurs in cells that undergo postmitotic apoptosis after irradiation. Scoring cell death in whole populations of cells gives erroneous results because both clonogenic and nonclonogenic cells are dividing as nonclonogenic cells are apoptosing or senescing over a period of many days. For example, after 9.5 Gy, which causes reproductive cell death in 99% of both types of cells, the cumulative percentage of the cells scored as dead in the whole population at 60- 80 h after irradiation, when the maximum amount of cumulative apoptosis occurred, was approximately 60% for REC:myc cells, compared with only approximately 40% for REC:ras cells. PMID- 10029088 TI - Modulation of the cytotoxicity of 3'-azido-3'-deoxythymidine and methotrexate after transduction of folate receptor cDNA into human cervical carcinoma: identification of a correlation between folate receptor expression and thymidine kinase activity. AB - Cervical carcinoma is an AIDS-defining illness. The expression of folate receptors (FRs) in cervical carcinoma (HeLa-IU1) cells was modulated by stable transduction of FR cDNA encapsidated in recombinant adeno-associated virus-2 in the sense and antisense orientation (sense and antisense cells, respectively). Although sense cells proliferated slower than antisense or untransduced cells in vivo and in vitro in 2% (but not 10%) FCS, [methyl-3H]thymidine incorporation into DNA was significantly increased in sense cells in 10% serum; therefore, the basis for this discrepancy was investigated. The activity of thymidine kinase (TK) was subsequently directly correlated with the extent of FR expression in single cell-derived clones of transduced cells. This elevated TK activity was not a result of recruitment of the salvage pathway based on the presence of adequate dTTP pools, normal thymidylate synthase (TS) activity, persistence of increased thymidine incorporation despite the exogenous provision of excess 5,10-methylene tetrahydrofolate, and documentation of adequate folates in sense cells. The increase in TK activity conferred significant biological properties to sense cells (but not antisense or untransduced cells) as demonstrated by augmented phosphorylation of 3'-azido-3'-deoxythymidine (AZT) and concomitantly greater sensitivity to the cytotoxic effects of AZT. Conversely, sense cells were highly resistant to methotrexate, but this was reversed by the addition of AZT. The direct correlation of FR expression and TK activity indicates a previously unrecognized consequence of FR overexpression. PMID- 10029089 TI - Cadherin-11 is expressed in invasive breast cancer cell lines. AB - In several cancers, including breast cancer, loss of E-cadherin expression is correlated with a loss of the epithelial phenotype and with a gain of invasiveness. Cells that have lost E-cadherin expression are either poorly invasive with a rounded phenotype, or highly invasive, with a mesenchymal phenotype. Most cells lacking E-cadherin still retain weak calcium-dependent adhesion, indicating the presence of another cadherin family member. We have now examined the expression of the mesenchymal cadherin, cadherin-11, in breast cancer cell lines. Cadherin-11 mRNA and protein, as well as a variant form, are expressed in the most invasive cell lines but not in any of the noninvasive cell lines. Cadherin-11 is localized to a detergent-soluble pool and is associated with both alpha- and beta-catenin. Immunocytochemistry shows that cadherin-11 is localized to the cell membrane at sites of cell-cell contact as well as at lamellipodia-like projections, which do not interact with other cells. These results suggest that cadherin-11 expression may be well correlated with the invasive phenotype in cancer cells and may serve as a molecular marker for the more aggressive, invasive subset of tumors. Cadherin-11 may mediate the interaction between malignant tumor cells and other cell types that normally express cadherin-11, such as stromal cells or osteoblasts or perhaps even with the surrounding extracellular matrix, thus facilitating tumor cell invasion and metastasis. PMID- 10029090 TI - Vitamin E succinate (VES) induces Fas sensitivity in human breast cancer cells: role for Mr 43,000 Fas in VES-triggered apoptosis. AB - Fas (CD95/APO-1) is an important mediator of apoptosis. We show that Fas resistant MCF-7, MDA-MB-231, and MDA-MB-435 human breast cancer cells become responsive to anti-Fas (CD95) agonistic antibody-triggered apoptosis after pretreatment or cotreatment with vitamin E succinate (VES; RRR-alpha-tocopheryl succinate). In contrast, no enhancement of anti-Fas agonistic antibody-triggered apoptosis was observed following VES pretreatment or cotreatment with Fas sensitive primary cultures of human mammary epithelial cells, immortalized MCF 10A cells, or T47D human breast cancer cells. Although VES is itself a potent apoptotic triggering agent, the 6-h pretreatment procedure for Fas sensitization did not initiate VES-mediated apoptosis. The combination of VES plus anti-Fas in pretreatment protocols was synergistic, inducing 2.8-, 3.0-, and 6.3-fold enhanced apoptosis in Fas-resistant MCF-7, MDA-MB-231, and MDA-MB-435 cells, respectively. Likewise, cotreatment of Fas-resistant MCF-7, MDA-MB-231, and MDA MB-435 cells with VES plus anti-Fas enhanced apoptosis 1.9-, 2.0-, and 2.6-fold, respectively. Functional knockout of Fas-mediated signaling with either Fas neutralizing antibody (MCF-7-, MDA-MB-231-, and MDA-MB-435-treated cells) or Fas antisense oligomers (MDA-MB-435-treated cells only), reduced VES-triggered apoptosis by approximately 50%. Analyses of whole cell extracts from Fas sensitive cells revealed high constitutive expression of Mr 43,000 Fas, whereas Fas-resistant cells expressed low levels that were confined to the cytosolic fraction. VES treatment of the Fas-resistant cells caused a depletion of cytosolic Mr 43,000 Fas with a concomitant increase in Mr 43,000 membrane Fas. These data show that VES can convert Fas-resistant human breast cancer cells to a Fas-sensitive phenotype, perhaps by translocation of cytosolic Mr 43,000 Fas to the membrane and show that VES-mediated apoptosis involves Mr 43,000 Fas signaling. PMID- 10029091 TI - Bombesin stimulates adhesion, spreading, lamellipodia formation, and proliferation in the human colon carcinoma Isreco1 cell line. AB - The neuropeptide bombesin and its mammalian homologue, gastrin-releasing peptide (GRP), enhance proliferation in some but not all human tumor cell lines. The pathophysiological relevance of the bombesin/GRP receptor (GRP-R), which is expressed in 30% of human colon tumor cell lines and in 24-40% of native tumors, has not been clearly assessed at this time. We studied the effects of bombesin in the recently characterized human colon carcinoma Isreco1 cell line. Competitive reverse transcription-PCR showed a high GRP-R mRNA level in Isreco1 cells, and binding studies confirmed the expression of bombesin/GRP-subtype receptors (Kd = 0.42 nM; Bmax = 18,000 sites/cell). Exposure to bombesin resulted in an increase of intracellular calcium concentrations. Bombesin (1 nM) induced cell spreading at 24 h (21.7+/-1.6% versus 6.4+/-0.8% in control cells; P<0.01) and markedly increased the formation of lamellipodia. In addition, adhesion of Isreco1 cells to collagen I-coated culture dishes was stimulated in the presence of 1 nM bombesin (69+/-6% versus 42+/-1% in control cells; P<0.01). Finally, bombesin significantly increased [3H]thymidine uptake by Isreco1 cells in a dose-dependent manner, with a first significant response at 0.1 nM and a maximal effect at 100 nM bombesin (192.2+/-9.7% of control). These results clearly indicate that bombesin exerts morphological, adhesive, and proliferative effects on Isreco1 cells, suggesting that expression of the bombesin/GRP-R may contribute to the malignant properties of colon carcinoma cells. PMID- 10029092 TI - Elevation of the epidermal growth factor receptor and dependent signaling in human papillomavirus-infected laryngeal papillomas. AB - Laryngeal papillomas are benign tumors caused by human papillomaviruses types 6 and 11. This study addressed alterations in levels of signal transduction from the epidermal growth factor receptor (EGFR) in papillomas and cultured papilloma cells compared to normal tissue and cells. Mitogen-activated protein kinase (MAPK) was activated to a greater extent, phosphotyrosine was more abundant, and EGFR was overexpressed in laryngeal papillomas compared to normal laryngeal epithelium by Western blot analysis. The EGFR was 3 times more abundant in cultured papilloma cells than in normal laryngeal cells by Scatchard analysis and Western blot, without gene amplification or an increase in steady-state levels of mRNA. Following stimulation with EGF, a significant portion of the EGFR was recycled to the surface in papilloma cells, whereas in normal cells, it was not. Tyrosine kinase activity and activation of MAPK was more responsive to epidermal growth factor stimulation in papilloma cells than in uninfected primary laryngeal cells. PD153035, a specific inhibitor of the EGFR, and an EGFR-specific antibody that blocks ligand binding completely abrogated basal MAPK activation by endogenous ligands in laryngeal papilloma cells. These results demonstrated that infection of laryngeal epithelium by low-risk human papillomaviruses elevates the EGFR by posttranslational mechanisms, increasing its responsiveness to ligand mediated activation. They also showed that MAPK activation in laryngeal papillomas depends upon ligand-mediated EGFR stimulation. PMID- 10029094 TI - Cerebral fat embolism from cardiopulmonary bypass. PMID- 10029093 TI - Ovine MHC class II DRB1 alleles associated with resistance or susceptibility to development of bovine leukemia virus-induced ovine lymphoma. AB - For the further characterization of bovine leukemia virus (BLV)-induced leukemogenesis, we investigated the association between polymorphism of ovine leukocyte antigen (OLA)-DRB1 gene and tumor development after infection of sheep with BLV. We infected 28 sheep with BLV and cloned exon 2 of the OLA-DRB1 gene from asymptomatic animals and from animals with lymphoma Sequence analysis revealed that, among 12 healthy sheep without any evidence of tumor, ten (83.3%) carried DRB1 alleles encoding Arg-Lys (RK) at positions beta70/71 as compared with only 6 (37.5%) of the 16 sheep with lymphoma, which suggested that alleles encoding the RK motif might protect against development of tumors after infection by BLV. By contrast, alleles encoding Ser-Arg (SR) at positions beta70/71 were present at a significantly elevated frequency in sheep with lymphoma as compared with the healthy carriers, which indicated that OLA-DRB1 alleles encoding the SR motif might be positively related to susceptibility to tumor development. The two amino acids in these motifs line a pocket that accommodates the side chain of a bound peptide according to a model of the crystal structure of human leukocyte antigen (HLA)-DR1. To analyze immunoreactions of sheep with alleles that encoded RK or SR at beta70/71, we selected sheep with either the RK/SR genotypes or the SR/SR genotypes and immunized them with a mixture of multiple synthetic antigenic peptides that corresponded to T-helper, T-cytotoxic, and B-cell epitopes of the BLV envelope glycoprotein gp51. Two weeks after the last immunization, all of the sheep were challenged with BLV. Sheep with the RK/SR genotype produced neutralizing antibodies against BLV; they eliminated BLV completely within 28 weeks of the BLV challenge, and they gave strong lymphocyte-proliferative responses to the peptides used for immunization. Moreover, such animals did not develop lymphoma. By contrast, sheep with the SR/SR genotype continued to produce BLV throughout the experimental period and developed terminal disease. Our results indicate that the differences in immunoresponse were due to differences in major histocompatibility complex class II alleles and reflected the risk of BLV-induced leukemogenesis. In addition, it appears that susceptibility to tumor development may be determined to some extent by polymorphic residues binding to antigenic peptides directly within the binding cleft of the OLA-DR molecule. PMID- 10029095 TI - Molecular analysis of microdissected de novo glioblastomas and paired astrocytic tumors. AB - Glioblastoma multiforme (GBM) often displays morphological heterogeneity in that low-grade (LG) area with well-differentiated cells are commonly found adjacent to high-grade (HG) area with poorly-differentiated cells. This heterogeneity may cause difficulty in obtaining representative tumor samples. Nevertheless, the genetic composition of these cells has only been occasionally examined. In the present study, we examined 29 de novo glioblastomas in which distinct LG and HG areas of sufficient volumes could be identified. These areas were microdissected from paraffin-embedded tissues and analyzed for genetic alterations: p53 mutations and immunohistochemistry; allelic losses at 17p13.1, 9p21, and 10q23 25; and amplification of the epidermal growth factor receptor (EGFR) gene and immunohistochemistry. We also examined 14 paired astrocytic tumors, in which a primary Grade II astrocytoma progressed over a period of time to a Grade III or Grade IV tumor. Our findings showed that the LG areas of the de novo glioblastomas exhibited numerous genetic aberrations, the proportion of which was increased in the HG areas. Genetic abnormalities seen in the LG areas were conserved in the HG areas suggesting that these morphologically different cellular subsets were derived from a common transformed clone. Also, the LG areas were genetically different from Grade II astrocytomas of the paired tumor group, in spite of their morphological similarity. In particular, the LG areas had more deletions on 10q23-25 (75% vs 20%, p = 0.04), but fewer p53 mutations (24% vs 71%, p = 0.003) and less p53 protein labeling (45% vs 79%, p = 0.04). These differences suggest that LG and HG areas in de novo glioblastoma are genetically closer to each other compared with paired low- and high-grade tumors that have progressed over time. Moreover, only a small proportion (17%) of our de novo glioblastomas exhibited EGFR amplification while a high proportion (62%) showed either p53 mutations or allelic loss of 17p13.1. We speculate that some de novo GBMs with copious LG areas may constitute a separate group with rapid progression from Grade II astrocytomas. PMID- 10029096 TI - Distribution of inclusions in neuronal nuclei and dystrophic neurites in Huntington disease brain. AB - Recently, an N-terminal fragment of huntingtin was localized to neuronal intranuclear inclusions (NII), presumed to cause cellular dysfunction, and to inclusions in dystrophic neurites (IDN) in the neostriatum and neocortex of Huntington disease (HD) patients. In the present immunohistochemical study of autopsy brain of 2 juvenile-onset HD patients, 5 HD patients with adult-onset, and 5 controls, NII and IDN as stained with both N-terminal antiserum to huntingtin and ubiquitin antiserum were detected in the HD neostriatum, neocortex, and allocortex, but not in the HD pallidum, cerebellum, and substantia nigra nor in control brain. The frequency of NII in the HD neocortex was highest in the juvenile patients. Within the allocortex, NII and IDN were found in the entorhinal region, subiculum, and pyramidal cell layer of Ammon's horn. N terminal huntingtin antiserum also labeled intranuclear granular structures adjacent to the neuronal nuclear membrane in 5 HD patients, one control with idiopathic epilepsy, and one with Alzheimer disease. Our results show that NII formation in HD involves the allocortex in addition to the neostriatum and neocortex. The development of NII in the neocortex and allocortex in HD brain might contribute to the emergence of the cognitive and behavioral symptoms of the disease. PMID- 10029097 TI - In vitro adhesion and migration of T lymphocytes across monolayers of human brain microvessel endothelial cells: regulation by ICAM-1, VCAM-1, E-selectin and PECAM 1. AB - Increased lymphocyte traffic across an altered blood-brain barrier (BBB) is a prominent and early event in inflammatory and immune-mediated CNS diseases. The factors that control the entry of lymphocytes into the brain have not been fully elucidated. In this study, primary cultures of human brain microvessel endothelial cells (HBMEC) were used to investigate the role of endothelial cell (EC) adhesion molecules in the adhesion and migration of peripheral blood T lymphocytes across TNF-alpha treated and untreated monolayers. Adhesion of T cells to unstimulated HBMEC was minimal and few of the adherent cells migrated across the monolayers. Treatment of HBMEC with TNF-alpha augmented adhesion by 5 fold. The binding to activated EC was significantly, but not completely, inhibited by monoclonal antibodies (mAbs) to ICAM-1 and VCAM-1, whereas adhesion to unstimulated EC was blocked by mAb to ICAM-1 but not VCAM-1. Transendothelial migration of lymphocytes increased by up to 30-fold following treatment of HBMEC with TNF-alpha. Migration across activated monolayers, but not across untreated EC, was almost completely blocked by Ab to ICAM-1 and significantly inhibited by Abs to PECAM-1 and E-selectin. VCAM-1 was not utilized during transendothelial migration. Ultrastructurally, pseudopodia from lymphocytes contacted finger-like cytoplasmic projections on EC and eventually penetrated the EC cytoplasm at focal points along the apical surface. Migrating lymphocytes moved either through the EC cytoplasm or between adjacent EC across intercellular contacts. The overlying monolayers showed no evidence of disruption and intercellular junctions appeared intact over the migrated T cells. These studies indicate that adhesion and migration of T lymphocytes across the cerebral endothelial barrier are distinct processes that depend upon the activation state of EC and are controlled by diverse receptor-ligand interactions. PMID- 10029098 TI - Experimental investigation of cerebral contusion: histopathological and immunohistochemical evaluation of dynamic cortical deformation. AB - We used a new approach, termed dynamic cortical deformation (DCD), to study the neuronal, vascular, and glial responses that occur in focal cerebral contusions. DCD produces experimental contusion by rapidly deforming the cerebral cortex with a transient, nonablative vacuum pulse of short duration (25 milliseconds) to mimic the circumstances of traumatic injury. A neuropathological evaluation was performed on brain tissue from adult rats sacrificed 3 days following induction of either moderate (4 psi, n = 6) or high (8 psi, n = 6) severity DCD. In all animals, DCD produced focal hemorrhagic lesions at the vacuum site without overt damage to other regions. Examination of histological sections showed localized gross tissue and neuronal loss in the cortex at the injury site, with the volume of cell loss dependent upon the mechanical loading (p < 0.001). Axonal pathology shown with neurofilament immunostaining (SMI-31 and SMI-32) was observed in the subcortical white matter inferior to the injury site and in the ipsilateral internal capsule. No axonal injury was observed in the contralateral hemisphere or in any remote regions. Glial fibrillary acidic protein (GFAP) immunostaining revealed widespread reactive astrocytosis surrounding the necrotic region in the ipsilateral cortex. This analysis confirms that rapid mechanical deformation of the cortex induces focal contusions in the absence of primary damage to remote areas 3 days following injury. Although it is suggested that massive release of neurotoxic substances from a contusion may cause damage throughout the brain, these data emphasize the importance of combined injury mechanisms, e.g. mechanical distortion and excitatory amino acid mediated damage, that underlie the complex pathology patterns observed in traumatic brain injury. PMID- 10029099 TI - Axonal transport of N-terminal huntingtin suggests early pathology of corticostriatal projections in Huntington disease. AB - Aggregation of N-terminal mutant huntingtin within nuclear inclusions and dystrophic neurites occurs in the cortex and striatum of Huntington disease (HD) patients and may be involved in neurodegeneration. We examined the prevalence of inclusions and dystrophic neurites in the cortex and striatum of 15 adult onset HD patients who had mild to severe striatal cell loss (grades 1, 2 or 3) using an antibody that detects the N-terminal region of huntingtin. Nuclear inclusions were more frequent in the cortex than the striatum and were sparse or absent in the striatum of patients with low-grade striatal pathology. Dystrophic neurites occurred in both regions. Patients with low-grade striatal pathology had numerous fibers with immunoreactive puncta and large swellings within the striatal neuropil, the subcortical white matter, and the internal and external capsules. In the globus pallidus of 3 grade 1 cases, N-terminal huntingtin markedly accumulated in the perinuclear cytoplasm and in some axons but not in the nucleus. Findings suggest that in the earlier stages of HD, accumulation of N terminal mutant huntingtin occurs in the cytoplasm and is associated with degeneration of the corticostriatal pathway. PMID- 10029100 TI - Expression of transforming growth factor (TGF)-beta1, -beta2, and -beta3 isoforms and TGF-beta type I and type II receptors in multiple sclerosis lesions and human adult astrocyte cultures. AB - It is known that the pleiotropic cytokine transforming growth factor beta (TGF beta) has a regulatory role in the process of tissue repair and remodelling following injury. As reports on these molecules in multiple sclerosis (MS) lesion with different lesional activity are rare, we studied the cellular localization of TGF-beta1, -beta2, and -beta3 isoforms, and TGF-beta receptor type I (TGF betaR-I) and TGF-betaR-II expression by immunohistochemistry on postmortem brain tissue from MS and normal control cases. To validate the TGF-beta staining results we demonstrated that cultured human adult astrocytes that produce biological active TGF-beta2, and to a lesser extent TGF-beta1, were immunoreactive for all 3 TGF-beta isoforms. Moreover, at mRNA level TGF-beta1 was detected in MS and normal control brain tissue. In normal control brain tissue, TGF-beta isoforms were expressed in ramified microglia and TGF-beta2, and -beta3 on neuronal cells in the gray matter TGF-betaR-I and TGF-betaR-II expression was found on endothelial cells, astrocytes, microglia, and neurons. In active demyelinating MS lesions a strong to intense immunoreactivity was detected for all 3 TGF-beta isoforms in perivascular and parenchymal (foamy) macrophages and in hypertrophic astrocytes. Strong immunoreactivity for TGF-betaR-I and TGF-betaR II was found on macrophages in both parenchymal and perivascular areas and on hypertrophic astrocytes and endothelial cells in active demyelinating MS lesions. In chronic active and inactive MS lesions, all 3 TGF-beta isoforms and their receptors were strongly expressed in hypertrophic astrocytes. Our findings strongly suggest that the expression of the various TGF-beta isoforms and their receptor types found in MS lesions with different cellular activity participate in reactive processes leading to the formation of chronic MS lesions. PMID- 10029101 TI - Neurons may live for decades with neurofibrillary tangles. AB - Neurons containing neurofibrillary tangles (NFT) are one of the pathological hallmarks of Alzheimer disease (AD). It is known that this population of neurons express gene products and thus function to some degree, but it is unknown how long these neurons may survive with NFT. It is also thought that the formation of NFT results in the death of neurons. Using quantitative data on neuron loss and NFT formation as a function of disease duration, we have generated a computer program that models both the degeneration of CA1 hippocampal neurons and the formation of NFT in these neurons in AD. Modeling various neuron survival times with NFT and altering selected assumptions upon which the models are based, we arrive at the conclusions that 1) CA1 hippocampal neurons survive with NFT for about 20 years, and 2) NFT may not be obligatory for death of CA1 hippocampal neurons in AD. PMID- 10029103 TI - Fleecy amyloid deposits in the internal layers of the human entorhinal cortex are comprised of N-terminal truncated fragments of Abeta. AB - The deposition of amyloid in the brain is a hallmark of Alzheimer disease (AD). Amyloid deposits consist of accumulations of beta-amyloid (Abeta), which is a 39 43 amino-acid peptide cleaved from the Abeta-protein precursor (APP). Another cleavage product of APP is the P3-peptide, which consists of the amino acids 17 42 of the Abeta-peptide. In order to study the deposition of N-terminal truncated forms of Abeta in the human entorhinal cortex, serial sections from 16 autopsy cases with AD-related pathology were immunostained with antibodies against Abeta1 40, Abeta1-42, Abeta17-23, and Abeta8-17, as well as with the Campbell-Switzer silver impregnation for amyloid. In the external entorhinal layers (pre-beta and pre-gamma), sharply delineated diffuse plaques were seen. They were labeled by silver impregnation and by all Abeta-antibodies used. By comparison, in the internal layers (pri-alpha, pri-beta, and pri-gamma) blurred, ill-defined clouds of amyloid existed, in addition to sharply delineated diffuse plaques. These clouds of amyloid were termed "fleecy amyloid." Immunohistochemically, fleecy amyloid was stained by Abeta17-23 and Abeta1-42 antibodies, but not with antibodies against Abeta8-17 and Abeta1-40. Using the Campbell-Switzer technique, the fleecy amyloid deposits were found to be fine argyrophilic amyloid fibrils. Thus, the internal entorhinal layers are susceptible to a distinct type of amyloid, namely fleecy amyloid. This fleecy amyloid obviously corresponds to N terminal truncated fragments of Abeta1-42, probably representing the P3-peptide. These N-terminal truncated fragments of Abeta are capable of creating fine fibrillar "amyloid." PMID- 10029104 TI - The cutting edge: surgery sites on the World Wide Web. PMID- 10029102 TI - Astrocytoma adhesion to extracellular matrix: functional significance of integrin and focal adhesion kinase expression. AB - Evidence is accumulating implicating a role for integrins in the pathogenesis of cancer, a disease in which alterations in cellular growth, differentiation, and adhesive characteristics are defining features. In the present report we studied a panel of 8 human astrocytoma cell lines for their expression of integrin subunits by RT-PCR, and of integrin heterodimers by immunoprecipitation analyses. The functionality of integrin heterodimers was assessed using cell attachment assays to plastic or single matrix substrates. Downstream effects of integrin activation were studied by western blot analyses of FAK expression in human astrocytoma cell lines growing on plastic and on a fibronectin matrix, and in 13 primary human brain tumor specimens of varying histopathological grade. Furthermore, we studied tyrosine phosphorylation of FAK in astrocytoma cells growing on plastic versus fibronectin. Finally, we analyzed the effects of intermediate filament gene transfer on FAK phosphorylation in SF-126 astrocytoma cells. Our data show that astrocytoma cell lines express various integrin subunits by RT-PCR, and heterodimers by immunoprecipitation analyses. The beta1 and alphav integrin subunits were expressed by all astrocytoma cell lines. The alpha3 subunit was expressed by all cell lines except SF-188. By immunoprecipitation, the fibronectin receptor (alpha5beta1 integrin heterodimer) and the vitronectin receptor (alphavbeta3) were identified in several cell lines. Astrocytoma cell attachment studies to human matrix proteins suggested that these integrin heterodimers were functional. Using confocal laser microscopy, we showed that FAK was colocalized to actin stress fibers at sites of focal adhesion complexes. By western blot, FAK was variably but quite ubiquitously expressed in human astrocytoma cell lines, and in several primary human astrocytoma specimens. When U373 and U87 MG astrocytoma cells bind to a fibronectin matrix, FAK is phosphorylated. GFAP-transfected SF-126 human astrocytoma cells were shown to overexpress the phosphorylated form of FAK only when these cells were placed on a fibronectin matrix. This result is of interest because it suggests that manipulations of the astrocytoma cytoskeleton per se can bring about potential signaling changes that channel through integrins and focal adhesion sites leading to activation of key kinases such as FAK. PMID- 10029105 TI - Enabling students to deal with the disabled. PMID- 10029106 TI - Operation Smile volunteers travel far to transform lives. PMID- 10029107 TI - Test for diabetic tendency may aid risk factor studies. PMID- 10029108 TI - From the Centers for Disease Control and Prevention. Recommended childhood immunization schedule--United States, 1999. PMID- 10029109 TI - From the Centers for Disease Control and Prevention. Outbreak of Vibrio parahaemolyticus infection associated with eating raw oysters and clams harvested from Long Island Sound--Connecticut, New Jersey, and New York, 1998. PMID- 10029110 TI - Managing pain in elderly patients. PMID- 10029111 TI - Managing pain in elderly patients. PMID- 10029112 TI - Licensing boards and the stigma of mental illness. PMID- 10029113 TI - Licensing boards and the stigma of mental illness. PMID- 10029114 TI - Cardiovascular screening of high school athletes. PMID- 10029115 TI - Cardiovascular screening of high school athletes. PMID- 10029116 TI - Cardiovascular screening of high school athletes. PMID- 10029117 TI - Medical school courses in alternative medicine. PMID- 10029118 TI - Medical school courses in alternative medicine. PMID- 10029119 TI - Medical school courses in alternative medicine. PMID- 10029120 TI - Medical school courses in alternative medicine. PMID- 10029121 TI - Employment among recent residency program graduates. PMID- 10029122 TI - Comprehensive discharge planning and home follow-up of hospitalized elders: a randomized clinical trial. AB - CONTEXT: Comprehensive discharge planning by advanced practice nurses has demonstrated short-term reductions in readmissions of elderly patients, but the benefits of more intensive follow-up of hospitalized elders at risk for poor outcomes after discharge has not been studied. OBJECTIVE: To examine the effectiveness of an advanced practice nurse-centered discharge planning and home follow-up intervention for elders at risk for hospital readmissions. DESIGN: Randomized clinical trial with follow-up at 2, 6, 12, and 24 weeks after index hospital discharge. SETTING: Two urban, academically affiliated hospitals in Philadelphia, Pa. PARTICIPANTS: Eligible patients were 65 years or older, hospitalized between August 1992 and March 1996, and had 1 of several medical and surgical reasons for admission. INTERVENTION: Intervention group patients received a comprehensive discharge planning and home follow-up protocol designed specifically for elders at risk for poor outcomes after discharge and implemented by advanced practice nurses. MAIN OUTCOME MEASURES: Readmissions, time to first readmission, acute care visits after discharge, costs, functional status, depression, and patient satisfaction. RESULTS: A total of 363 patients (186 in the control group and 177 in the intervention group) were enrolled in the study; 70% of intervention and 74% of control subjects completed the trial. Mean age of sample was 75 years; 50% were men and 45% were black. By week 24 after the index hospital discharge, control group patients were more likely than intervention group patients to be readmitted at least once (37.1 % vs 20.3 %; P<.001). Fewer intervention group patients had multiple readmissions (6.2% vs 14.5%; P = .01) and the intervention group had fewer hospital days per patient (1.53 vs 4.09 days; P<.001). Time to first readmission was increased in the intervention group (P<.001). At 24 weeks after discharge, total Medicare reimbursements for health services were about $1.2 million in the control group vs about $0.6 million in the intervention group (P<.001). There were no significant group differences in post-discharge acute care visits, functional status, depression, or patient satisfaction. CONCLUSIONS: An advanced practice nurse-centered discharge planning and home care intervention for at-risk hospitalized elders reduced readmissions, lengthened the time between discharge and readmission, and decreased the costs of providing health care. Thus, the intervention demonstrated great potential in promoting positive outcomes for hospitalized elders at high risk for rehospitalization while reducing costs. PMID- 10029123 TI - Analysis of missed cases of abusive head trauma. AB - CONTEXT: Abusive head trauma (AHT) is a dangerous form of child abuse that can be difficult to diagnose in young children. OBJECTIVES: To determine how frequently AHT was previously missed by physicians in a group of abused children with head injuries and to determine factors associated with the unrecognized diagnosis. DESIGN: Retrospective chart review of cases of head trauma presenting between January 1, 1990, and December 31, 1995. SETTING: Academic children's hospital. PATIENTS: One hundred seventy-three children younger than 3 years with head injuries caused by abuse. MAIN OUTCOME MEASURES: Characteristics of head-injured children in whom diagnosis of AHT was unrecognized and the consequences of the missed diagnoses. RESULTS: Fifty-four (31.2%) of 173 abused children with head injuries had been seen by physicians after AHT and the diagnosis was not recognized. The mean time to correct diagnosis among these children was 7 days (range, 0-189 days). Abusive head trauma was more likely to be unrecognized in very young white children from intact families and in children without respiratory compromise or seizures. In 7 of the children with unrecognized AHT, misinterpretation of radiological studies contributed to the delay in diagnosis. Fifteen children (27.8%) were reinjured after the missed diagnosis. Twenty-two (40.7%) experienced medical complications related to the missed diagnosis. Four of 5 deaths in the group with unrecognized AHT might have been prevented by earlier recognition of abuse. CONCLUSION: Although diagnosing head trauma can be difficult in the absence of a history, it is important to consider inflicted head trauma in infants and young children presenting with nonspecific clinical signs. PMID- 10029124 TI - Geographic variation in the treatment of acute myocardial infarction: the Cooperative Cardiovascular Project. AB - CONTEXT: Quality indicators for the treatment of acute myocardial infarction include pharmacologic therapy, reperfusion, and smoking cessation advice, but these therapies may not be administered to all patients who could benefit from them. OBJECTIVE: To assess geographic variation in adherence to quality indicators for treatment of acute myocardial infarction. DESIGN: Inception cohort using data from the Health Care Financing Administration Cooperative Cardiovascular Project. SETTING: Acute care hospitals in the United States. PATIENTS: A total of 186800 Medicare beneficiaries hospitalized for treatment of confirmed acute myocardial infarction from February 1994 through July 1995. MAIN OUTCOME MEASURES: Adherence to quality indicators for pharmacologic therapy, reperfusion, and smoking cessation advice for patients judged to be ideal candidates for these therapies. The mean rates of adherence to these quality indicators for the entire United States were determined, and the 20th and 80th percentiles of the age- and sex-adjusted rates for each of 306 hospital referral regions were contrasted (mean rate [20th-80th percentiles]). RESULTS: Aspirin was used frequently both during hospitalization (86.2% [82.6%-90.1%]) and at discharge (77.8% [72.5% -83.9%]). Calcium channel blockers were withheld from most patients with impaired left ventricular function (81.9% [73.6%-90.8%]). Lower rates were seen in the use of angiotensin-converting enzyme inhibitors at discharge (59.3% [49.2%-69.2%]); reperfusion, using thrombolytic therapy or coronary angioplasty (67.2% [59.8%-75.1%]); prescription of beta-blockers at discharge (49.5% [35.8%-61.5%]); and for smoking cessation advice (41.9% [32.8% 51.3%]). CONCLUSIONS: Substantial geographic variation exists in the treatment of patients with acute myocardial infarction, and these gaps between knowledge and practice have important consequences. Therapies with proven benefit for AMI are underused despite strong evidence that their use will result in better patient outcomes. PMID- 10029125 TI - Increased pulse pressure and risk of heart failure in the elderly. AB - CONTEXT: Arterial stiffness increases with age. Thus, pulse pressure, an index of arterial stiffening, may predict congestive heart failure (CHF) in the elderly. OBJECTIVE: To study prospectively the association between pulse pressure and risk of CHF. DESIGN: Prospective cohort study. SETTING: The community-based East Boston Senior Health Project, East Boston, Mass. PATIENTS: A total of 1621 men and women (mean [SD] age, 77.9 [5.0] years) free of CHF who had blood pressure measurements taken in 1988-1989 and were followed up for 3.8 years. MAIN OUTCOME MEASURE: Incidence of CHF as ascertained by hospital discharge diagnosis (n = 208) and death certificates (n = 13). RESULTS: After controlling for age, sex, mean arterial pressure, history of coronary heart disease, diabetes mellitus, atrial fibrillation, valvular heart disease, and antihypertensive medication use, pulse pressure was an independent predictor of CHF. For each 10-mm Hg elevation in pulse pressure, there was a 14% increase in risk of CHF (95% confidence interval, 1.05-1.24; P = .003). Those in the highest tertile of pulse pressure (>67 mm Hg) had a 55% increased risk of CHF (P=.02) compared with those in the lowest (<54 mm Hg). Pulse pressure was more predictive than systolic blood pressure alone and was independent of diastolic blood pressure. CONCLUSION: Pulse pressure, an easily measurable correlate of pulsatile hemodynamic load, is an independent predictor of risk of CHF in this elderly cohort. PMID- 10029126 TI - Is physician detection associated with thinner melanomas? AB - CONTEXT: In cutaneous melanoma, tumor depth remains the best biologic predictor of patient survival. Detection of prognostically favorable lesions may be associated with improved survival in patients with melanoma. OBJECTIVE: To determine melanoma detection patterns and relate them to tumor thickness. DESIGN: Interview survey. SETTING AND PATIENTS: All patients with newly detected primary cutaneous melanoma at the Melanoma Center, Johns Hopkins Medical Institutions, between June 1995 and June 1997. MAIN OUTCOME MEASURE: Tumor thickness grouped according to detection source. RESULTS: Of the 102 patients (47 men, 55 women) in the study, the majority of melanomas were self-detected (55%), followed by detection by physician (24%), spouse (12%), and others (10%). Physicians were more likely to detect thinner lesions than were patients who detected their own melanomas (median thickness, 0.23 mm vs 0.9 mm; P<.001). When grouped according to thickness, 11 (46%) of 24 physician-detected melanomas were in situ, vs only 8 (14%) of 56 patient-detected melanomas. Physician detection was associated with an increase in the probability of detecting thinner (< or =0.75 mm) melanomas (relative risk, 4.2; 95% confidence interval, 1.4-11.1; P=.01). CONCLUSIONS: Thinner melanomas are more likely to have been detected by physicians. Increased awareness by all physicians may result in greater detection of early melanomas. PMID- 10029127 TI - Distribution of variable vs fixed costs of hospital care. AB - CONTEXT: Most strategies proposed to control the rising cost of health care are aimed at reducing medical resource consumption rates. These approaches may be limited in effectiveness because of the relatively low variable cost of medical care. Variable costs (for medication and supplies) are saved if a facility does not provide a service while fixed costs (for salaried labor, buildings, and equipment) are not saved over the short term when a health care facility reduces service. OBJECTIVE: To determine the relative variable and fixed costs of inpatient and outpatient care for a large urban public teaching hospital. DESIGN: Cost analysis. SETTING: A large urban public teaching hospital. MAIN OUTCOME MEASURES: All expenditures for the institution during 1993 and for each service were categorized as either variable or fixed. Fixed costs included capital expenditures, employee salaries and benefits, building maintenance, and utilities. Variable costs included health care worker supplies, patient care supplies, diagnostic and therapeutic supplies, and medications. RESULTS: In 1993, the hospital had nearly 114000 emergency department visits, 40000 hospital admissions, 240000 inpatient days, and more than 500000 outpatient clinic visits. The total budget for 1993 was $429.2 million, of which $360.3 million (84%) was fixed and $68.8 million (16%) was variable. Overall, 31.5% of total costs were for support expenses such as utilities, employee benefits, and housekeeping salaries, and 52.4% included direct costs of salary for service center personnel who provide services to individual patients. CONCLUSIONS: The majority of cost in providing hospital service is related to buildings, equipment, salaried labor, and overhead, which are fixed over the short term. The high fixed costs emphasize the importance of adjusting fixed costs to patient consumption to maintain efficiency. PMID- 10029128 TI - Clinical course of hypertrophic cardiomyopathy in a regional United States cohort. AB - CONTEXT: Hypertrophic cardiomyopathy (HCM) has been regarded as a disease that causes substantial disability, with annual mortality rates of up to 6%, based largely on reports from tertiary referral centers. OBJECTIVE: To assess the clinical course of HCM in a patient cohort more closely resembling the true disease state. DESIGN: Retrospective cohort study. SETTING: A regional cohort from Minnesota and adjoining regions, free of referral center bias, studied at Minneapolis Heart Institute. PATIENTS: Two hundred seventy-seven consecutively studied HCM patients, none referred for specialized HCM care, managed clinically in a standard fashion. MAIN OUTCOME MEASURES: Mortality and clinical course of HCM. RESULTS: During a mean (SD) follow-up of 8.1 (6.6) years, 45 patients died and 29 of these deaths were directly related to HCM; however, 8 of the 29 HCM deaths were not premature (occurring >75 years of age). Annual HCM mortality rate was 1.3% (0.7% for sudden cardiac death). Patients identified in adulthood (n = 234) showed no statistically significant difference in mortality when compared with expected mortality, as calculated for the general US or Minnesota populations (P=.17). Patients identified as children (n=43) showed decreased survival compared with the general population (P<.001). At most recent clinical evaluation, 192 patients (69%) had no or mild symptoms and 69 (25%) experienced incapacitating symptoms or HCM-related death; 53 (19%) of the patients had achieved estimated life expectancy of 75 years or older. More advanced symptoms at diagnosis-occurrence of atrial fibrillation (often associated with stroke), the presence of basal outflow obstruction of at least 30 mm Hg, and marked left ventricular wall thickness of more than 25 mm-were clinically important independent predictors of HCM mortality. CONCLUSIONS: In a regionally selected patient population most closely resembling the true disease state, HCM did not significantly increase the risk of premature death or adversely affect overall life expectancy. Prevailing misconceptions of HCM as a generally unfavorable condition may largely be related to the skewed patient referral patterns characteristic of tertiary care centers. Hypertrophic cardiomyopathy is nevertheless a highly complex disease capable of serious clinical consequences and premature death in some patients. PMID- 10029129 TI - The value of targeted case management during transitional care. PMID- 10029130 TI - The challenges of recognizing child abuse: seeing is believing. PMID- 10029131 TI - Service quality in health care. AB - Although US health care is described as "the world's largest service industry," the quality of service--that is, the characteristics that shape the experience of care beyond technical competence--is rarely discussed in the medical literature. This article illustrates service quality principles by analyzing a routine encounter in health care from a service quality point of view. This illustration and a review of related literature from both inside and outside health care has led to the following 2 premises: First, if high-quality service had a greater presence in our practices and institutions, it would improve clinical outcomes and patient and physician satisfaction while reducing cost, and it would create competitive advantage for those who are expert in its application. Second, many other industries in the service sector have taken service quality to a high level, their techniques are readily transferable to health care, and physicians caring for patients can learn from them. PMID- 10029132 TI - JAMA patient page: skin cancer. PMID- 10029133 TI - The radial transmission line as a broad-band shielded exposure system for microwave irradiation of large numbers of culture flasks. AB - The problem of simultaneously exposing large numbers of culture flasks at nominally equivalent incident power densities and with good thermal control is considered, and the radial transmission line (RTL) is proposed as a solution. The electromagnetic design of this structure is discussed, and an extensively bench tested realization is described. Referred to 1 W of net forward power, the following specific absorption rate (SAR) data were obtained: at 835.62 MHz, 16.0+/-2.5 mW/kg (mean+/-SD) with range (11-22); at 2450 MHz, 245+/-50 mW/kg with range (130-323). Radio-frequency interference from an RTL driven at roughly 100 W is so low as to be compatible with a cellular base station only 500 m distant. To avoid potential confounding by temperature differences among as many as 144 T-75 flasks distributed over 9 RTLs (six irradiates and three shams), temperature within all flasks was controlled to 37.0+/-0.3 degrees C. Experience with over two years of trouble-free operation suggests that the RTL offers a robust, logistically friendly, and environmentally satisfactory solution to the problem of large-scale in vitro experiments in bioelectromagnetics. PMID- 10029134 TI - Compact shielded exposure system for the simultaneous long-term UHF irradiation of forty small mammals. II. Dosimetry. AB - A four-antenna collinear array in an electromagnetically shielded chamber was designed and constructed to preferentially irradiate the brains of a large number of small mammals using cellular telephony microwave signals. Ten animals in special restrainers were positioned symmetrically around a centrally located antenna. These restrainers are resting on a circular structure made of acrylic plastic called a "carousel." Four carousels are stacked vertically, forming the array, inside a microwave anechoic chamber called a "chamberette." (Details of the design of this irradiator and of a 12-chamberette irradiation facility are given in a previous article.) In this article, the dosimetry on rats is reported. Both thermometric and thermographic measurements were performed. The average specific absorption rate (SAR) in brain tissue measured thermometrically was 0.85+/-0.34 W/kg per watt of net input power into the radiating antenna. This range agrees with the SAR levels reported in the literature for cellular telephones. Thermographic evaluation using splittable phantoms showed that most of the energy absorbed by the rats is concentrated in and around the brain. Moreover, it was found that the SAR in brain tissue can vary considerably for rats of similar weights, depending on position of the rats' heads inside the restrainers, and that there exists a significant dependence of SAR on animal weight. These variations may be of importance in the interpretation of results of lifelong studies. The data presented clearly show that the chamberette is, dosimetrically, a suitable irradiation system for electromagnetic bioeffects studies in the cellular communication frequency range, especially when a large number of laboratory animals is required. PMID- 10029135 TI - Diatom motility and low frequency electromagnetic fields--a new technique in the search for independent replication of results. AB - The hypothesis that exposure to a certain combination of static and alternating electromagnetic fields (EMFs) results in an increase in motility of the marine diatom Amphora coffeaeformis was tested. Diatom motility in three strains of A. coffeaeformis was positively correlated with extracellular calcium ion (Ca2+) concentration. The test apparatus consisted of two pairs of Helmholtz coils supported around the stage of a microscope linked to a video recorder and monitor. This system allowed real-time in vivo recordings of diatom speed under EMF and control exposures. The EMFs were calculated at calcium resonance values, previously found to cause enhanced motility. Computerised image analysis was used to calculate the distance moved by individual diatoms in 2-min periods before, during and after EMF or sham-EMF (control) exposure. The addition of EMF caused no significant increase in diatom motility. The results are discussed in relation to the use of diatom motility to measure EMF exposure effects. PMID- 10029137 TI - Heating of cardiovascular stents in intense radiofrequency magnetic fields. AB - We consider the heating of a metal stent in an alternating magnetic field from an induction heating furnace. An approximate theoretical analysis is conducted to estimate the magnetic field strength needed to produce substantial temperature increases. Experiments of stent heating in industrial furnaces are reported, which confirm the model. The results show that magnetic fields inside inductance furnaces are capable of significantly heating stents. However, the fields fall off very quickly with distance and in most locations outside the heating coil, field levels are far too small to produce significant heating. The ANSI/IEEE C95.1-1992 limits for human exposure to alternating magnetic fields provide adequate protection against potential excessive heating of the stents. PMID- 10029136 TI - Test facility for human exposure to AC and DC magnetic fields. AB - For more than a decade, Midwest Research Institute (MRI) has investigated the effects of exposure to 60 Hz electric and magnetic fields (EMF) on human physiology, performance, and biochemistry. This accumulated experience, new research directions, and limited resources made it important to design more comprehensive and operationally cost-effective exposure facilities. Here we describe the new, integrated laboratory exposure test facilities recently constructed at MRI and present data on relevant characteristics of the exposure systems. Concentric coil systems were developed to generate uniform magnetic fields within the three new exposure rooms, with rapid cancellation of the field to ambient levels in the rest of the laboratory. Control systems are fully automated, computer-based, and independent. These provide the operational flexibility needed to present fields of different magnitudes, frequencies, and polarization. The local geomagnetic field can be modulated and/or canceled, and both AC and DC fields can be presented in various combinations. Capabilities for conducting double-blind experiments with true active-sham exposure conditions were implemented using bifilar windings and applying current flow in the opposite direction for each wire in a pair. The new facilities provide a comprehensive capability for laboratory-based human research on the potential effects of exposure to AC and DC magnetic fields. PMID- 10029138 TI - Biochemical effects of high intensity constant magnetic fields on worker honey bees. AB - Hemolymph samples from adult bees that had completed their pupal development and emergence in a 7 Tesla field contained a lower percentage of glucose than controls, indicating that trehalase enzyme activity in honey bees is reduced in strong magnetic fields. Significantly more phospholipids were found in the intestines of magnetic field-exposed bees than in controls. No significant differences were found for fatty acids, triacylglycerols, or steroids. PMID- 10029139 TI - Changes of hydration of rats' tissues after in vivo exposure to 0.2 Tesla steady magnetic field. AB - Hydration and [3H]ouabain uptake by different tissues of adult male rats were measured immediately after exposure to homogenous 0.2 T steady magnetic field. A time-dependent decrease of hydration and adaptation, followed by disadaptation, was detected in brain and liver tissues in most of the rats after 3.5-5 h of exposure. The number of functional active ouabain binding receptors, which correlates with cell volume, was also decreased in brain, liver, and spleen and increased in kidney tissue after half an hour of exposure. It is suggested that cell hydration is a second messenger through which the SMF exerts its influence. PMID- 10029140 TI - Observations on the effects of low frequency electromagnetic fields on cellular transcription in Drosophila larvae reared in field-free conditions. AB - Drosophila larvae reared inside a micro-metal box with an internal field strength 0.004 microT, were treated with a magnetic field of 50 Hz, 8 microT. for 20 min. Control experienced 0.004 microT. Cellular transcript levels were assessed using slot blots and quantified using a Phosphorimager. Blots were hybridised using probes against HSP 70a, Histone 1.9, and Copia. The low frequency EMFs very significantly decreased transcript levels, indicating that experimental responses may be influenced by previous exposure or lack of previous exposure. PMID- 10029141 TI - Why compliance is not good enough. AB - Although reducing risks for medical devices is an element of product liability risk management, reducing risks for medical device manufacturers is the ultimate objective. With so much riding on the product development pipeline, what can manufacturers do to ensure a successful launch and healthy return on their investment? We argue in this editorial that the operating environment for the medical device industry is so dynamic that compliance is not enough. Instead, we suggest that risk abatement must become a part of a medical device manufacturer's operating strategy. We outline a robust risk abatement strategy involving corporate cultural changes, scenario modeling tools, and implementation systems. PMID- 10029142 TI - Extractable free monomers from self-cured dental sealants resulting from dispensing errors. AB - High performance liquid chromatography (HPLC) experiments were performed on a series of commercially available self-curing dental sealant materials that were deliberately mismixed. The goal of the experiments was to measure the amount of extractable sealant under conditions of nonideal processing as might happen clinically. The stoichiometry of the two component resins ranged from a 2/1 to a 1/2 catalyst to base mixture using a commercially available self-cure sealant that was to be mixed 1/1 based on the manufacturer's recommendations. Following fabrication the samples were immersed in an ethanol/water mixture as an extraction fluid that was then analyzed using HPLC. Values other than the 1-1 stoichiometry led to a statistically larger extractable content of bis-glycidyl methacrylate relative to the control. The extractable fraction of triethylene glycol dimethacrylate also increased with mismixing, although statistical differences varied somewhat more. Given the increased concerns about the effects of extractable monomers on the endocrine system, there may be an increased need to maintain proper stoichiometry in a clinical setting. PMID- 10029143 TI - Effect of behavioral stress on platelet reactivity on polymeric surfaces. AB - It is well known that stressful stimuli change blood functions and platelet parameters are altered in humans and animals subjected to stress. We have examined the influences of behavioral stress on the morphological responses of platelets on a standard biomaterial, polyethylene (PE). Male rabbits were used. Blood was collected from the marginal vein of the ear 2 times per subject: the first sample was used as the baseline; 1 week later, the second was preceded in half of the subjects by 20 min of immobilization stress. In vitro adhesion of platelets on the PE was evaluated. The exposure of animals to stress induced a dramatic change in platelet morphology and functions on the PE: a higher degree of platelet adhesion, increased platelet spreading, and the appearance of pseudopodia. In the unstressed subjects there were no modifications of the platelets on the PE with respect to the baseline. The present experiment emphasizes for the first time the possible problems involved with the varying physiological conditions of patients before and after any biomaterial application surgery and of subjects who supply the blood for hemocompatibility tests performed on biomaterials. Therefore, in assessments of the performance of different biomaterials, the reactivity of blood factors in the patients should be considered and the test of blood compatibility should be performed with blood collected from donors in appropriate physiological conditions. PMID- 10029144 TI - Totally implantable artificial hearts and left ventricular assist devices: selecting impermeable polycarbonate urethane to manufacture ventricles. AB - In the development of a new generation of totally implantable artificial hearts and left ventricular assist devices (VADs) for long-term use, the selection of an acceptable material for the fabrication of the ventricles probably represents one of the greatest challenges. Segmented polyether urethanes used to be the material of choice due to their superior flexural performance, acceptable blood compatibility, and ease of processing. However, because they are known to degrade and to be readily permeable to water, they cannot meet the rigorous requirements needed for a new generation of implantable artificial hearts and VADs. Therefore, the objective of the present study was to identify alternative polymeric materials that would be satisfactory for fabricating the ventricles, and in particular, to determine the water permeability through membranes made from four commercial polycarbonate urethanes (Carbothane PC3570A, Chronoflex AR, Corethane 80A, and Corethane 55D) in comparison to those made from two traditional polyether urethanes (Tecoflex EG80A and Tecothane TT-1074A). In addition to determining the rate of water transmission through the six membranes by exposing them to deionized water, saline, and albumin-Krebs solution under pressure and measuring the displacement of liquid by means of a recently developed capillary method, the inherent surface and chemical properties of the six membranes were characterized by SEM, contact angle measurements, FTIR, DSC, and GPC techniques. The results of the study demonstrated that the rate of water transmission through the four polycarbonate urethane membranes was significantly lower than through the two polyether urethanes. In fact the lowest values were recorded with the two Corethane membranes, and the harder type 55D polymer had a lower value (2.7 x 10( 7) g/s cm2) than the softer 80A version (3.3 x 10(-7) g/s cm2). This level of water vapor permeability, which appears to be controlled primarily by a Fickian diffusion mechanism, is between 2 and 4 times lower than that obtained with traditional polyether urethane membranes of equivalent thickness. The superior performance of the polycarbonate urethanes is likely due to the inherently lower chain mobility of the carbonate structure in the soft segment phase. In addition, the study shows that additional impermeability to water vapor can be achieved by selecting a polyurethane polymer with a high hard segment content, an aromatic rather than aliphatic diisocyanate comonomer, and a more hydrophobic surface. The use of a higher molecular weight polyurethane is not necessarily efficacious if the above requirements are not met. As expected by Raoult's Law, the study found that the use of physiological media instead of deionized water further decreases the rate of water vapor transmission. Because none of today's commercial polyurethanes are totally impervious to water vapor transmission, additional work is needed to develop permeable polymers or to apply additional treatments to existing candidates to achieve an acceptable impermeable ventricle material. PMID- 10029145 TI - Failure of glove hole detection device for synthetic gloves. AB - Holes in latex gloves can be reliably detected by commercially available electronic devices. The purpose of this study was to compare the performance of an electronic glove hole detection device using latex gloves to that of neoprene, vinyl, and nitrile latex-free gloves. The electronic hole detection device accurately detected holes in the latex gloves during the 2-h study. In contrast, the latex-free gloves were immediately conductive of electricity in the absence of holes. Consequently, electronic glove hole detection devices cannot be reliably used with latex-free gloves. PMID- 10029146 TI - Tensile set behavior of Foley catheter balloons. AB - The removal of indwelling urinary balloon catheters from patients is usually associated with many problems. The problems such as balloon deflation failure; encrustations on balloons, eyes, and lumen; and catheter associated infections are widely discussed in the literature. The tensile set exhibited by the catheter balloon material could also play a role and further complicate the removal process. This article addresses this issue by comparing the tensile set behavior of the balloon material from three commercially available Foley catheters. The balloon materials were subjected to aging in synthetic urine at 37 degrees C for 28 days to simulate clinical conditions. The deflation time of catheter balloons aged in similar conditions were also measured. It was found that different brands of catheters exhibited statistically significant differences in their properties. The tensile set data of the aged samples could be correlated with the deflation time of the balloons. The clinical significance of the tensile set is also highlighted. PMID- 10029147 TI - Bone bonding strength of calcium phosphate ceramic coated strain gauges. AB - Although strain transfer from bone to gauge has been used as an indication of the extent of bone bonding to calcium phosphate ceramic (CPC) coated strain gauges, interface strength measurements have not been reported. In order to develop bone bonded gauges that remain attached to bone surfaces for long periods, the strength of the CPC-bone interface must be optimized. A shear test to assess the interface strength of the CPC-bone interface was developed using the femora of 120-day-old male rats. The mean interface strength of a blended CPC coating bonded to the femora of the rats for 6 weeks in vivo was 4.8+/-2.4 MPa, and one specimen achieved a strength of nearly 10 MPa. This mean strength value is higher then the CPC-gauge interface strength reported in early studies, but it is lower than recently developed heat treated CPC-gauge interfaces that have average strengths of approximately 7.0+/-2.0 MPa. PMID- 10029148 TI - Histological and compositional evaluations of three types of calcium phosphate cements when implanted in subcutaneous tissue immediately after mixing. AB - To evaluate the soft tissue response of calcium phosphate cement (CPC), consisting of an equimolar mixture of tetracalcium phosphate (TTCP) and dicalcium phosphate anhydrous (DCPA) under conditions close to those encountered in actual surgical procedures, we implanted three types of CPC [conventional CPC (c-CPC), fast-setting CPC (FSCPC), and antiwashout type FSCPC (aw-FSCPC; formerly called nondecay type FSCPC or nd-FSCPC)] subcutaneously in the abdomens of rats immediately (1 min) after mixing. At 1 week after surgery, histological examination and compositional analysis were performed using light microscopy and powder X-ray diffraction (XRD), respectively. The implanted c-CPC was crumbled completely, whereas FSCPC and aw-FSCPC retained their shape. Large vesicles containing copious inflammatory effusion were subcutaneously formed around the c CPC. Histologically, many foreign-body giant cells were collected around the c CPC, and moderate inflammatory cell infiltration was observed at 1 week after surgery. In contrast, the FSCPC and aw-FSCPC were covered with a thin layer of granulation tissue that included few giant cells and presented slight inflammatory cell infiltration, and no effusion was observed. The XRD analysis of the c-CPC revealed the presence of some unreacted DCPA even 1 week after implantation, whereas almost no DCPA was found in the FSCPC or aw-FSCPC. In conclusion, it was found that CPC does not always show excellent tissue response. When c-CPC is implanted subcutaneously in rats immediately after mixing, it fails to set and causes a severe inflammatory response. Therefore, the type of CPC should be chosen according to the clinical particulars. CPC should be used in a manner that assures its setting reaction. We recommend the use of FSCPC and aw FSCPC for surgical applications, such as orthopedics, plastic and reconstructive surgery, and oral and maxillofacial surgery, where the cement might otherwise crumble due to the pressure before setting. PMID- 10029149 TI - Pressurization of bioactive bone cement in vitro. AB - We have developed a bioactive bone cement consisting of MgO-CaO-SiO2-P2O5-CaF2 glass-ceramic powder (AW glass-ceramic powder), silica glass powder as an inorganic filler, and bisphenol-a-glycidyl methacrylate (bis-GMA) based resin as an organic matrix. The efficacy of this bioactive bone cement was investigated by evaluating its pressurization in a 5-mm hole and small pores using a simulated acetabular cavity. Two types of acetabular components were used (flanged and unflanged sockets) and a commercially available polymethylmethacrylate (PMMA) bone cement (CMW 1 Radiopaque Bone Cement) was selected as a comparative control. Bioactive bone cement exerted greater intrusion volume in 5-mm holes than PMMA bone cement in both the flanged and unflanged sockets 10 minutes after pressurization (p < 0.05). In the small pores the bioactive and PMMA bone cements exerted almost identical intrusion volumes in flanged and unflanged sockets 10 min after pressurization. The intrusion volume in the flanged socket 10 minutes after pressurization was greater than that in the unflanged socket in all groups (p < 0.05). These results show that bioactive bone cement intrudes deeper into anchor holes than PMMA bone cement. PMID- 10029150 TI - Characterization of acrylic bone cement using dynamic mechanical analysis. AB - Dynamic mechanical analysis (DMA) was used to characterize the properties of acrylic bone cement with the addition of tricalcium phosphate (TCP), hydroxyethyl methacrylate (HEMA), and ethylene glycol dimethacrylate (EGDMA). The glass transition temperature of acrylic bone cement is >100 degrees C; the cement has a flat modulus response near human body temperature. The height of the damping peak decreases and becomes broader with increasing TCP content. Thus, TCP is incompatibile with acrylic bone cement. When the frequency is changed from high to low, the damping peak shifts to low temperature. The shift in damping peak with frequency indicates that this relaxation is time-dependent. When acrylic bone cement contains TCP with HEMA and EGDMA, the incompatibility between acrylic bone cement and TCP can be ameliorated. PMID- 10029151 TI - Morphology of in vitro generated ultrahigh molecular weight polyethylene wear particles as a function of contact conditions and material parameters. AB - Osteolysis in total joint replacements has been linked to ultrahigh molecular weight polyethylene (UHMWPE) wear particles. Although the biological response to these UHMWPE particles is poorly understood at present, it has been demonstrated that particle size and morphology are important factors in such a response. The goal of the present study was twofold: to develop a comprehensive set of particle size and shape descriptors, and to use these descriptors to analyze the effects of different contact conditions and material parameters during the wear process on the size and morphology of UHMWPE wear debris. The three parameters studied were average contact stress (6.9 and 13.8 MPa), macromolecular orientation of the UHMWPE with respect to the wear direction (0 degrees , 45 degrees , and 90 degrees ), and UHMWPE initial surface roughness (Ra = 1 and 3 microm). Tests were performed using pin on disk or cylinder on plate systems for 3 million cycles each. The results indicated that the initial surface roughness of the UHMWPE test samples had no effect on the morphology of UHMWPE wear particles. However, particle size and morphology were a function of the average contact stress and molecular orientation of the UHMWPE. PMID- 10029152 TI - Ligament graft initial fixation strength using biodegradable interference screws. AB - The objective of this study was to evaluate the initial fixation strength of three types of biodegradable interference screws [an Endo Fix, 7 x 25 mm polyglycolic acid, non-self-tapping (Acufex); a biodegradable interference screw, 7 x 23 mm poly-L-lactic acid, self-tapping (Arthrex); a Bioscrew, 7 x 25 mm poly L-lactic acid, self-tapping (Linvatec)] in comparison to a titanium interference screw (Linvatec, 7 x 25 mm) in anterior cruciate ligament reconstruction using a bone-patellar tendon-bone graft. Porcine lower limbs were used. To control for specimen related bias, bone mineral density of each tibia was measured. All specimens were loaded to failure. Failure mode was determined by visual analysis. The maximum load to failure [mean (SD)] was 785 (87) N (titanium screw), 555 (60) N (Acufex), 592 (211) N (Arthrex), and 844 N (Linvatec). The primary fixation strength of the titanium screw and the Linvatec screw was significantly higher (p < 0.05) than the primary fixation strength of the Arthrex screw and the Acufex screw. There was no difference in bone mineral density between the groups. With respect to primary fixation strength, all biodegradable screws were strong enough to allow accelerated rehabilitation. From this point of view the biodegradable screws may be a reasonable alternative to titanium interference screws. PMID- 10029153 TI - A miniature specimen mechanical testing technique scaled to articulating surface of polyethylene components for total joint arthroplasty. AB - The small punch test was developed to investigate the mechanical behavior of polyethylene using miniature specimens (< 14 mg) measuring 0.5 mm in thickness and 6.4 mm in diameter. The objective of this study was to demonstrate the feasibility and reproducibility of the small punch test when applied to clinically relevant polyethylenes. Mechanical behavior was characterized during 66 tests performed on GUR4150HP and GUR4120 specimens following alternate sterilization methods and 4 weeks of accelerated aging at 80 degrees C. The small punch test was found to be highly reproducible with regard to characterizing the ductility, ultimate strength, and fracture resistance of sterilized and aged polyethylene. In the future, the small punch test can be used to directly measure mechanical properties near the articulating surface of retrieved components. PMID- 10029154 TI - A new radiolucent system for vertebral body replacement: its stability in comparison to other systems. AB - Anterior intervention of metastatic lesions of the spine can accomplish relief of pain, spinal decompression, and restoration of spinal stability. Ventral vertebral body replacements have been developed to provide these conditions but there have been problems with loosening at the implant-bone interface, mechanical failure, and X-ray artifacts from the metal. Intraoperative stability of the vertebral body replacement is especially critical to avoid loosening of the implant and to achieve long-term bony incorporation. This study compared the biomechanical performance in vitro of a new radiolucent system for vertebral body replacement to three currently marketed systems. The new system features a composite bioglass-polyurethane body and a new configuration of polymeric fastening hardware. Range of motion, neutral zone, and several interfacial motion parameters were measured under pure moments of 3.75 Nm in the three anatomical directions. The new system provided the significantly highest restraint of motion for all parameters. Mechanically, the new system is preferable at least initially to a sampling of systems representative of those currently used. PMID- 10029155 TI - Comparison of Zeeman Background Corrected Atomic Absorption Spectrometric and Inductively Coupled Plasma Mass Spectrometric detection of trace elements in electrothermally vaporized serum. AB - There is continued interest in the measurement of degradation products of metallic implants in biological tissues and fluids. A study was conducted to compare analytical results obtained by the Zeeman Background Corrected Atomic Absorption Spectrometric and Inductively Coupled Plasma Mass Spectrometric techniques on a uniform set of triple-element (Ti, Al, and V) spiked human serum specimens over concentration ranges up to 20 ppb (20 ng/ml). The results indicate that the two methods are comparable. The positive and negative aspects of each method of instrumental analysis are discussed. PMID- 10029156 TI - Protective effects of BB-10010 treatment on chemotherapy-induced neutropenia in mice. AB - Chemotherapy-induced neutropenia is a major dose-limiting factor in the management of cancer patients. Most chemotherapeutic agents are active against proliferating cells, interfering with DNA replication and/or mitosis. A number of chemokines, notably macrophage inflammatory protein-1 alpha [MIP-1alpha], have been reported to induce cell-cycle arrest in immature hematopoietic progenitors, raising the possibility that chemokines, such as MIP-1alpha, could be used to reduce or even eliminate the hematologic toxicity of cycle-active chemotherapy. We tested the effectiveness of BB-10010 [a genetically engineered analog of human MIP-1alpha] in vivo against three different cytotoxic drugs [cyclophosphamide (Cy), 5-fluorouracil (5-FU) and cytosine arabinoside (Ara-C)] commonly used in cancer therapy. BB-10010 treatment reduced the toxicity of all three agents, though the precise mode of protection varied with the cytotoxic drug used. BB 10010 reduced the neutropenic interval in Cy-treated mice without affecting the neutropenic nadir, whereas the absolute neutrophil counts [ANC] of both 5-FU and Ara-C treated mice were significantly higher throughout the neutropenic interval for mice receiving BB-10010 prior to chemotherapy. These findings indicate that the ability to manipulate the cell cycle of hematopoietic progenitors with chemokines, such as BB-10010/MIP-1alpha and other negative regulators, may be exploited to reduce chemotherapy-induced neutropenia; furthermore, the fact that BB-10010 is effective against several different cytotoxic agents is cause for guarded optimism that this approach may be generally applicable, and, once optimized for patient use, may prove to be of significant clinical benefit. PMID- 10029157 TI - Interferon-gamma impairs physiologic downregulation of cyclin-dependent kinase inhibitor, p27Kip1, during G1 phase progression in macrophages. AB - Cell cycle progression of mouse macrophage cells was impaired by interferon-gamma (IFN-gamma). The blockage of G1/S transition was associated with diminution of cyclin-dependent kinase-2 (CDK2)-associated kinase activities. The expression of p21Cip1 was not upregulated by IFN-gamma. Instead, the physiologic downregulation of p27Kip1 necessary for normal cell cycle progression did not take place sufficiently in the presence of IFN-gamma. During normal cell cycle progression, the levels of p27Kip1 were maximal at early G1 and then decreased gradually. In the presence of IFN-gamma, however, the levels of p27Kip1 discontinued to decrease at a late mid G1 point and were consistently as high as, or higher than, levels observed there. The steady, relatively high-level attachment of p27Kip1 to CDK2 contributed to the insufficient formation of active cyclin/CDK2, possibly deferring cells from entering S phase. PMID- 10029158 TI - IL-1beta mediates diethyldithiocarbamate-induced granulocyte colony-stimulating factor production and hematopoiesis. AB - Diethyldithiocarbamate (DDTC) exhibits chemoprotective effects via reduced myelosuppression in mice treated with various chemotherapeutic agents. The mechanism of DDTC-mediated chemoprotection is believed to involve the induction and release of several cytokines, including interleukin-1 beta (IL-1beta), tumor necrosis factor-alpha (TNF-alpha), and granulocyte colony-stimulating factor (G CSF). In the present study the roles of IL-1beta and TNF-alpha in DDTC-mediated G CSF induction were examined using human long-term bone marrow cultures (hLTBMCs). Administration of IL-1 receptor antagonist (IL-1ra) to DDTC-treated hLTBMCs obviated the G-CSF induction profile and blocked the resultant colony proliferation, indicating that IL-1beta mediates DDTC-induced G-CSF release and hematopoiesis. IL-1beta mRNA levels were increased threefold over control following DDTC treatment of hLTBMCs, implying that DDTC induces IL-1beta at the level of transcription. Conversely, studies involving inhibition of DDTC-induced TNF-alpha synthesis, with the inhibitor MNX 160, had no effect on DDTC-induced G CSF release or colony proliferation. These findings taken together strongly suggest that IL-1beta mediates the chemoprotective effects of DDTC. PMID- 10029159 TI - Interleukin-10 inhibits burst-forming unit-erythroid growth by suppression of endogenous granulocyte-macrophage colony-stimulating factor production from T cells. AB - Numerous cytokines released from accessory cells have been shown to exert either stimulatory or inhibitory growth signals on burst-forming unit-erythroid (BFU-E) growth. Because of its cytokine synthesis-inhibiting effects on T cells and monocytes, interleukin-10 (IL-10) may be a potential candidate for indirectly affecting erythropoiesis. We investigated the effects of IL-10 on BFU-E growth from normal human peripheral blood mononuclear cells (PBMC) using a clonogenic progenitor cell assay. The addition of recombinant human IL-10 to cultures containing recombinant human erythropoietin suppressed BFU-E growth in a dose dependent manner (by 55.2%, range 47.3-63.3%, p < 0.01, at 10 ng/mL). In contrast, no inhibitory effect of IL-10 was seen when cultivating highly enriched CD34+ cells. BFU-E growth from PBMC also was markedly suppressed in the presence of a neutralizing anti-granulocyte-macrophage colony-stimulating factor (GM-CSF) antibody (by 48.7%, range 32.9-61.2% inhibition,p < 0.01), but not by neutralizing antibodies against granulocyte colony-stimulating factor and interleukin-3. This suggests a stimulatory role of endogenously released GM-CSF on BFU-E formation. Also, the addition of exogenous GM-CSF completely restored IL 10-induced suppression of BFU-E growth. To determine the cellular source of GM CSF production, we analyzed GM-CSF levels in suspension cultures containing PBMC that were either depleted of monocytes or T cells. Monocyte-depleted PBMC showed spontaneous production of increasing amounts of GM-CSF on days 3, 5, and 7, respectively, which could be suppressed by IL-10, whereas GM-CSF levels did not increase in cultures containing T-cell-depleted PBMC. Our data indicate that IL 10 inhibits the growth of erythroid progenitor cells in vitro, most likely by suppression of endogenous GM-CSF production from T cells. PMID- 10029160 TI - Tumor necrosis factor p55 receptor (TNF-RI) mediates the in vitro inhibition of hepatic erythropoietin production. AB - Tumor necrosis factor alpha (TNFalpha) is thought to contribute to the blunted erythropoietin (Epo) production in inflammatory diseases. The present study was carried out to find out as to whether the 55 kD (TNF-RI) or the 75 kD (TNF-RII) receptor is responsible for the TNFalpha-induced inhibition of hepatic Epo synthesis. When the effects of two receptor-specific mutants were compared, only the TNF-RI-specific isoform proved to suppress the formation of immunoreactive Epo in the human hepatoma cell lines HepG2 and Hep3B, similar to the effect of wild-type TNFalpha. Anti-TNFalpha antibody restored Epo production in TNFalpha- or TNF-RI mutant-treated cultures. By gel shift assay NF-kappaB binding to DNA was demonstrated following the addition of TNFalpha or TNF-RI-specific mutant to HepG2 cells, while the TNF-RII-specific mutant was ineffective. Finally, immunoreactive TNF-RI, but not TNF-RII, fragments were measurable in cell culture supernatants. Taken together, these results suggest that the inhibition of hepatic Epo production by TNFalpha is mediated by TNF-RI signaling. PMID- 10029161 TI - Dominant negative effect of a truncated erythropoietin receptor (EPOR-T) on erythropoietin-induced erythroid differentiation: possible involvement of EPOR-T in ineffective erythropoiesis of myelodysplastic syndrome. AB - We isolated a human leukemic cell line UT-7/GM from UT-7, which can differentiate into mature erythroid cells with erythropoietin (EPO) treatment. Using this cell line, we examined the effect of a truncated human EPO receptor (EPOR-T) on EPO induced erythroid differentiation. Transfection studies revealed that UT-7/GM cells expressing exogenous EPOR-T were likely to undergo apoptosis even in the presence of EPO. In addition, EPOR-T-transfected cells could not differentiate into hemoglobin-positive cells after administration of EPO. These results suggest that EPOR-T is a negative regulator of EPO-induced anti-apoptosis and EPO-induced erythroid differentiation. The EPOR-T form was expressed in seven of nine cases of myelodysplastic syndrome but not in normal controls. In patients with myelodysplastic syndrome, dysregulated expression of EPOR-T may cause apoptosis and blockage of erythroid differentiation, resulting in ineffective erythropoiesis. PMID- 10029162 TI - Protection of retrovirus-induced disease by transplantation of bone marrow cells transduced with MuLV env gene via retrovirus vector. AB - Fv-4 is a mouse gene that dominantly confers resistance to infection by ecotropic murine leukemia virus (MuLV). We have demonstrated previously that bone marrow chimeras in which hematopoietic cells were replaced with cells expressing Fv-4 resistant (Fv-4r) gene product became refractory to Friend leukemia virus (FLV) induced leukemogenesis. To induce in vivo resistance against retrovirus-induced diseases by retroviral vector-mediated gene transduction, we introduced Fv-4 env gene into bone marrow cells of FLV-susceptible C3H/He (C3H) mice with retroviral vector (pLSF) derived from murine Friend spleen focus forming virus (SFFV) and the cells were transplanted into lethally irradiated C3H mice. After the bone marrow transplantation, Fv-4r gene product was successfully expressed on erythroid and myeloid cells, while lymphoid cells were only weakly expressing Fv 4r gene product. The C3H mice expressing relatively higher amounts of Fv-4r gene product were rendered resistant to FLV-induced erythroleukemia, while mice expressing lower amounts of the Fv-4r gene product were still susceptible. Effective protection of FLV-induced leukemia in these mice suggested that the Fv 4r gene expression by erythroid cells that were the major target of FLV infection might be critical for resisting FLV-induced leukemia. Thus, gene therapy model by transducing Fv-4r env gene using bone marrow transplantation would provide a useful protection model system of retrovirus-induced diseases. PMID- 10029163 TI - Adoptive transfer of genetically modified human hematopoietic stem cells into preimmune canine fetuses. AB - To develop a surrogate model system for assaying gene transfer into human hematopoietic stem cells (HSCs) with in vivo repopulating potential, we injected human marrow cells transduced with a reporter retroviral vector in long-term marrow cultures (LTMCs), into the yolk sacs of preimmune canine fetuses. Of eight mid-gestation fetuses injected through the exteriorized uterine wall and under ultrasound guidance, seven were born alive. One puppy died in the neonatal period accidentally. The remaining six puppies are all healthy at 31 months of age. There was no evidence for graft-versus-host disease or any untoward effects of in utero adoptive transfer of transduced human LTMC cells. All puppies were chimeras. Human cells, detected by fluorescence in situ hybridization, were present in blood, declining from 38% to 0.05% between 10 and 44 weeks after birth. Corresponding numbers for marrow were from 20% to 0.05%. Human cells were also detected in assays of hematopoietic cell progenitors and in stimulated blood cultures. All six puppies were positive for the presence of proviral DNA at various time-points after birth. In three dogs, provirus was detected up to 41 weeks after birth in blood or marrow, and in one dog up to 49 weeks in blood. These data support the further development of this large-animal model system for studies of human hematopoiesis. PMID- 10029164 TI - Targeted transfection of the IL-3 gene into primary human hematopoietic progenitor cells through the c-kit receptor. AB - We recently showed that an antibody-mediated gene transfer procedure termed antifection can be used for targeted gene delivery into lymphoid cells in vitro and in vivo. We here report that antifection also is effective for targeted gene transfer to immature hematopoietic cells. A human IL3-expressing plasmid was chemically linked to an anti-human CD117 antibody. Delivery of the IL3 plasmid into IL-3-dependent myeloid TF-1 cells (bearing the CD117 antigen) was specific and resulted in the transient proliferation of the targeted cells in the absence of exogenous IL-3. Transfection of primary human CD34+ hematopoietic stem/progenitor cells led to transient production of IL-3 and transient proliferation of the target cells. Interestingly, by using a semisolid progenitor cell assay, we found that transfected primary CD34+ cells were able to generate normal numbers of cell colonies in the absence of exogenous IL-3. Polymerase chain reaction analysis confirmed the presence and expression of the IL-3 transgene in the progenitor-derived colonies. In conclusion, our data show that CD117 is a suitable cell surface target to specifically transfer gene by antifection into primary CD34+ cells and that delivery of IL-3 gene in these cells resulted in the expression of a functional IL-3 able to support cell growth in absence of exogenous cytokine. Thus, antifection may provide new therapeutic modality relying on the transient production of appropriate growth factors acting via autocrine and/or paracrine mechanisms. PMID- 10029165 TI - Priming with G-CSF effectively enhances low-dose Ara-C-induced in vivo apoptosis in myeloid leukemia cells. AB - We investigated the role of apoptosis in chemotherapy for hematologic malignancies. Twelve consecutive patients with acute myelogenous leukemia (AML) or refractory anemia with excess of blasts in transformation (RAEB-t) who were not tolerable for standard-dose chemotherapy were treated with CAG regimen (low dose cytosine arabinoside [Ara-C] plus aclarubicin with concurrent administration of granulocyte colony-stimulating factor [G-CSF]). Bone marrow mononuclear cells obtained before the commencement of the chemotherapy were cultured with various concentrations (0-10(-5) M) of Ara-C in the presence or absence of 10 ng/mL of G CSF, and the resultant cell proliferation/cytotoxicity was assayed. In all but one patient, half killing concentration (LC50) of Ara-C was significantly reduced in the presence of G-CSF (by 400- and 1.45-fold, median: 21-fold). Furthermore, LC(50) values in responders assayed in the presence of 10 ng/mL of G-CSF were significantly lower than those in nonresponders (p = 0.02). In vitro killing tests using a G-CSF-dependent leukemic cell line suggested that addition of G-CSF potentiates Ara-C-induced cytotoxicity through the mechanism of apoptosis. We thus assayed apoptosis in peripheral blood leukemic cells during CAG chemotherapy by flow cytometry using 7-amino-actinomycin D. Peak percentages of apoptosis in responders were significantly higher than those in nonresponders (p = 0.02). These results collectively suggest that apoptosis plays an important role for eradicating leukemic cells by CAG chemo-therapy. PMID- 10029166 TI - Detection and quantitation of genetically marked acute myeloid leukemia by competitive polymerase chain reaction after autologous bone marrow transplantation: a preclinical model for minimal residual disease. AB - Preclinical models and methods aimed at detecting and quantitating minimal residual disease (MRD) after autologous bone marrow transplantation (BMT) for acute myeloid leukemia (AML) could facilitate assessment of innovative therapeutic strategies for their antileukemic potential. Among the various techniques exploited to identify MRD, polymerase chain reaction (PCR) proved to be a valuable tool in instances in which clonogeneic markers are involved during the evolution of disease. In human AML, however, detection of MRD by PCR is limited to a minority of subgroups, as clonospecific markers are absent or presently unknown. Although gene labeling has proved to be efficient in detecting marker-devoid leukemia cells in preclinical models, detection and quantitation by PCR have not yet been considered. We therefore developed an experimental model in which detection and quantitation of genetically marked murine AML cells are based on a highly sensitive two-step nested PCR and competitive PCR protocol, respectively. We further demonstrated its applicability to a murine syngeneic BMT model that was designed to monitor minimal numbers of gene-tagged AML cells at various time intervals after transplantation. Our results showed that detection and quantitation could reproducibly be achieved at levels as low as one in 10(6) and 10(5) cells, respectively. PMID- 10029167 TI - Expression of murine CD34 by fetal liver NK cell progenitors. AB - Although 14.5-day murine fetal liver (FL) has few, if any, mature natural killer (NK) cells, culture of FL with recombinant human IL-2 (rhIL-2) and stroma from irradiated NK longterm bone marrow cultures (NK-LTBMC) allows proliferation and differentiation of NK cell progenitors. Using this system, NK cell progenitors were found in both CD34+ and CD34- sorted subpopulations of FL. The CD34 antigen was expressed by 14+/-1.3% of whole FL cells, while mature NK cells cultured from NK cell precursors in FL did not express the CD34 antigen. Anti-TER-119 mAb reacted with 84%+/-10.3% of the FL cells, and NK cell progenitors were enriched in the TER-119- subpopulation. After coculture with rhIL-2 and stroma, neither TER-119- nor TER-119+ cells expressed antigens associated with T cells (CD3, CD4, and CD8) or myeloid cells (Gr-1 and Mac-1). Only the TER-119 subpopulation generated NK1.1+ (77%) and B220+ (87%) cells. Within the TER-119 subpopulation, both CD34+ and CD34- cells generated cytolytic and NK1.1+ cells after culture. By a limiting dilution assay (LDA) of the Lin (i.e., negative for NK1.1, CD3, CD4, CD8, B220, Gr-1, and TER-119) CD34 positive or negative subpopulations, the calculated mean frequency of NK cell progenitors was about 1/100 for the CD34+Lin subpopulation and about 1/(200-300) for the CD34-Lin- subpopulation. In kinetic studies, we found that NK1.1 antigen expression continued to increase with time in culture for both the CD34+Lin- and CD34-Lin- fractions. In contrast, the percentage of CD34+ cells decreased rapidly and produced CD34- cells, and the CD34- population remained CD34-. These data suggest that both CD34+ and CD34- subpopulations of FL can differentiate into NK cells when cocultured for 13 days with irradiated NK-LTBMC stroma and rhIL-2, and that CD34+ progenitors differentiate to CD34- precursors, which in turn differentiate to CD34- mature NK cells. PMID- 10029168 TI - Differential effects of CD4+ and CD8+ cells on lymphocyte development from human cord blood cells in murine fetal thymus explants. AB - The possibility that mature lymphocytes play a role in the regulation of human T cell development was studied in the experimental model of fetal thymus organ cultures (FTOC), by reconstituting lymphocyte-depleted murine fetal thymus (FT) lobe with cells isolated from human umbilical cord blood (CB). Cultures were incubated with human cytokines (IL-7, FLT-3 ligand and Steel Factor), or remained untreated. When CD4+, or CD8+ CB cells, were co-cultured with FT explants, they expanded and maintained their original phenotypic markers, with no significant effect of the cytokines. Cultures of human hematopoietic stem cells (CD34+) gave rise to CD4+CD8- cells, which were mainly CD3-, with no indication of further intermediate developmental stages. However, a limited number of CD4+CD8+ (double positive [DP]) cells were detected when the CD34- cells were co-cultured with CD4+ cells from the same CB samples. In contrast, FT with unseparated CB cells resulted in the different CD4/CD8 subsets, and their numbers increased in the presence of cytokines. The appearance of DP cells depended on the presence of either CD4+ or CD8+ cells in the cultured CB samples. Hence, DP cells were not detected when the CB was depleted of CD4+ and CD8- cells ("depCB") before culture, and they appeared when depCB were co-cultured with either CD4+ or CD8+ cells. In contrast, CD4+ cells inhibited the development of CD8+CD3+ cells, and this was most pronounced in the absence of the cytokines. There was no symmetrical down-regulatory effect of CD8+ cells on the development of CD4+CD3+ cells. Addition of IL-15 to the cytokine mixture led to an increased proportion of CD56+ cells in cultures of CD34+ cells. The presence of CD4+, and not CD8+ cells, interfered with this process. Our results thus imply differential effects of CD4+ and CD8+ cells on thymocytopoiesis. PMID- 10029169 TI - Cord blood is better than bone marrow for generating megakaryocytic progenitor cells. AB - Thrombocytopenia remains an important problem for patients post high-dose chemotherapy and hematopoietic stem cell transplantation. The study of megakaryocytes, the direct precursors of platelets, has been hampered by their relatively low frequency in hematopoietic tissues. In an attempt to obtain a large number of functional megakaryocytic cells, we established a serum-free culture system to grow megakaryocytic progenitor cells derived from normal human bone marrow (BM) and cord blood (CB). Highly purified (purity >95%) CD34+ cells were obtained using magnetic cell sorting (MACS) followed by fluorescence activated cell sorting (FACS). The cells were cultured in a serum-free culture system for 3 weeks in the presence of a single dose of MGDF (50 ng/mL). On days 0, 5, 8, 12, 14, 18, and 21 of culture, the cellularity and morphology were examined. Megakaryocytic cells were monitored by detecting the expression of GPIIIa (CD61), GPIIb/IIIa (CD41) and GPIb (CD42b), and the distribution of megakaryocyte (MK) ploidy was analyzed by two-color flow cytometry. MGDF alone induced maximal nucleated cell expansion at day 14, resulting in a 38.20+/-10.47 fold increase in cell number for CB and a 5.08+/-1.30-fold increase in cell number for BM. On day 14 of the culture, the percentage of CD41-/CD14- cells derived from CB reached 73.54%+/-6.01% giving an absolute number of CD41+/CD14- cells of 27.25+/-2.23 x 10(4)/mL (27,250-fold increase), whilst the percentage of CD41+/CD14- cells derived from BM was only 29.21%+/-5.63% with an absolute number of 1.36+/-0.26 x 10(4)/mL (680-fold increase). Increased expression of GPIIIa occurred the earliest in culture, followed by GPIIb/IIIa, and then GPIb. The majority (81.6%-92.6%) of megakaryocytes (CD41+ cells) on day 14 of culture were 2N, although we did detect some 4N, 8N and greater ploidy cells. In conclusion, CD34+ cells stimulated by MGDF alone generated highly enriched MK progenitor cells at day 14 of serum-free culture. CB stem and progenitor cells have a greater proliferative response to MGDF alone than those derived from BM and may, therefore, prove to be a better source of cells for MK expansion. PMID- 10029170 TI - Expression and function of cell adhesion molecules on fetal liver, cord blood and bone marrow hematopoietic progenitors: implications for anatomical localization and developmental stage specific regulation of hematopoiesis. AB - The mechanism of localization, migration, and regulation of hematopoiesis at different stages of ontogeny is not well understood, but may relate to the specific adhesive interactions between hematopoietic stem cells and their microenvironment at different ontogenic stages. We studied the expression of cell adhesion molecules (CAM) on fetal liver (FL), umbilical cord blood (UCB) and adult bone marrow (ABM) CD34+ cells, and the adhesion of committed progenitors (CFC) from all three sources to ABM stromal layers and purified extracellular matrix proteins. Compared to ABM CFC, significantly more UCB CFC and fewer FL CFC adhered to ABM stroma. Adhesion of FL CFC to fibronectin (FN), the 75 kD RGD containing FN fragment and the 33-66 kD COOH-terminal heparin binding FN fragment was also significantly less than that of ABM CFC. Like ABM CFC, the adhesion of FL CFC was mediated through alpha4beta1 and alpha5beta1 integrins. Of note, more FL CD34+ cells expressed alpha5 integrins and the number of alpha4, alpha5 and beta1 integins per cell (mean channel frequency) was similar or higher for FL CD34+ cells than ABM CD34+ cells. Further, treatment of FL CFC with a beta1 integrin activating antibody (8A2), increased adhesion of FL CFC to FN to the same level as that of 8A2 treated ABM CFC. This suggests that the alpha4beta1 and alpha5beta1 integrins on FL CD34+ cells may be present in a low avidity/affinity state. We also show that unlike ABM, FL CD34+ cells expressed alpha2 and that approximately 20% FL CFC adhered to collagen IV. Further, alpha2beta1 integrin on FL CFC was functional since their engagement, either by adhesion to collagen IV or through blocking alpha2 antibodies, transmitted proliferation inhibitory signals. In contrast to alpha4b and alpha5beta1 integrin dependent adhesion, alpha2beta1 dependent adhesion of FL CFC to collagen IV was not enhanced after treatment with 8A2. The reason for this is not clear but suggests that alpha2 integrins on FL CFC are maximally activated. This novel adhesive interaction with collagen IV, reminiscent of that described for CML progenitors, may have a role in the extramedullary localization of FL hematopoiesis or its developmental stage specific regulation by its microenvironment. Studies to evaluate these possibilities are underway. PMID- 10029171 TI - SZF1: a novel KRAB-zinc finger gene expressed in CD34+ stem/progenitor cells. AB - The identification and study of genes expressed in hematopoietic stem/progenitor cells should further our understanding of hematopoiesis. Transcription factors in particular are likely to play important roles in maintaining the set of genes that define the stem/progenitor cell. We report here the identification of a putative KRAB-zinc finger gene (SZF1) from a cDNA library prepared from human bone marrow CD34+ cells. Characterization of SZF1 implicates its role in hematopoiesis. The predicted protein contains a highly conserved KRAB domain at the NH2 terminus and four zinc fingers of the C2H2 type at the COOH terminus. Two alternatively spliced products of SZF1 were isolated, which predict proteins of 421 (SZF1-1) and 361 (SZF1-2) amino acids, differing from each other only at the carboxy terminus. The two transcripts of SZF1 have different expression patterns. SZF1-2 is ubiquitously expressed, as indicated by Northern blot, RNase protection, and reverse transcriptase polymerase chain reaction. SZF1-1 expression, in contrast, was detected only in CD34+ cells. We recently isolated the promoter region for the stem/progenitor cell expressed FLT3/FLK-2/STK-1 gene and used this region to generate a reporter construct to test the effect of SZF1 expression. Cotransfection of the reporter construct with SZF1 constructs showed that SZF1-2 repressed transcription three- to fourfold, whereas SZF1-1 showed a lower level of repression. The expression pattern of SZF1 transcripts and the transcriptional repression of a CD34+-specific promoter demonstrate a possible role for SZF1 in hematopoietic stem/progenitor cell differentiation. PMID- 10029173 TI - A fragment of alpha-actinin promotes monocyte/macrophage maturation in vitro. AB - Conditioned media (CM) from cultures of HL-60 myeloid leukemia cells grown on extracellular bone marrow matrix contains a factor that induces macrophage-like maturation of HL-60 cells. This factor was purified from the CM of HL-60 cells grown on bone marrow stroma by ammonium sulfate precipitation, then sequential chromatography on DEAE, affi-gel blue affinity, gel exclusion, and wheat germ affinity columns, followed by C-4 reverse phase HPLC, and SDS-PAGE. The maturation promoting activity of the CM was identified in a single 31 kD protein. Amino acid sequence analysis of four internal tryptic peptides of this protein confirmed significant homology with amino acid residues 48-60, 138-147, 215-220, and 221-236 of human cytoskeletal alpha-actinin. An immunoaffinity purified rabbit polyclonal anti-chicken alpha-actinin inhibited the activity of HL-60 conditioned media. A 27 kD amino-terminal fragment of alpha-actinin produced by thermolysin digestion of chicken gizzard alpha-actinin, but not intact alpha actinin, had maturation promoting activity on several cell types, including blood monocytes, as measured by lysozyme secretion and tartrate-resistant acid phosphatase staining. We conclude that an extracellular alpha-actinin fragment can promote monocyte/macrophage maturation. This represents the first example of a fragment of a cytoskeletal component, which may be released during tissue remodeling and repair, playing a role in phagocyte maturation. PMID- 10029172 TI - Interleukin-13 is involved in functional maturation of human peripheral blood monocyte-derived dendritic cells. AB - Dendritic cells (DCs) are professional antigen presenting cells (APCs) that are required for the initiation of the immune response. DCs have been shown to be generated from hematopoietic stem cells, but relatively little is known about the regulation underlying differentiation and activation of DCs. Here, we report that recombinant human (rh)IL-13 induces functional maturation of rhGM-CSF plus rhIL-4 generated monocyte-derived immature DCs. Incubation of these immature DCs with rhIL-13 or rhTNF-alpha for 2 days resulted in increased surface expression of CD1a, CD11c, CD86 and HLA-DR. The DCs treated with rhIL-13 or rhTNF-alpha, but not rhIL-4, for 2 days were more efficient than unstimulated DCs in the primary autologous/allogeneic T-cell response whereas the antigen (Ag)-specific T-cell response was suppressed. The treatment of DCs with rhIL-13 as well as rhTNF-alpha for 4 days down-modulated endocytic capacity for FITC-dextran (FITC-DX) and lucifer yellow (LY), and induced surface expression of CD83. Morphological, phenotypical, and functional analyses revealed that the monocytes cultured with rhGM-CSF plus rhIL-13 gave rise to a DC type more mature than rhGM-CSF plus rhIL 4-induced DCs. These findings revealed a new role for rhIL-13 in regulating both the maturation and activation of DCs. PMID- 10029174 TI - HL-60 cells degrade alpha-actinin to produce a fragment that promotes monocyte/macrophage maturation. AB - An amino-terminal fragment of alpha-actinin can promote monocyte/macrophage maturation. This fragment was initially isolated from media of HL-60 myeloid leukemia cells cultured on extracellular bone marrow matrix. To determine the source of this fragment in this culture system, we investigated whether HL-60 cells grown on bone marrow stroma have increased intracellular levels of alpha actinin that may be released into the media during cell apoptosis. HL-60 cells grown on matrix showed no evidence of increased cellular alpha-actinin compared to cells grown on plastic substrata as measured by flow cytometry. In addition, there was no evidence of increased apoptosis as determined by DNA fragmentation assays or flow cytometry. However, 100 kD alpha-actinin was found in the extracellular matrix of bone marrow stroma by Western blot analysis and immunofluorescence microscopy. The alpha-actinin content in the stroma was markedly decreased after exposure to HL-60 cells. Furthermore, lysates of HL-60 cells or of peripheral blood monocytes can degrade exogenous alpha-actinin to produce a 31 kD fragment, which promotes monocyte/macrophage maturation. We conclude that when alpha-actinin is present in the extracellular matrix, it can be modified by HL-60 cells to produce a maturation promoting 31 kD fragment. PMID- 10029175 TI - Differential effect on U937 cell differentiation by targeting transcriptional factors implicated in tissue- or stage-specific induced integrin expression. AB - The inhibition of transcription factor functions was used to define their role in phorbol ester-induced cellular differentiation of a monocytic cell line, U937. We demonstrate a differential effect on cell adhesion and differentiation: antisense or competitive binding with double-stranded oligonucleotides antagonized the functions of AP-1, NF-kappaB, and PU.1 transcriptional factors. In the presence of phorbol 12-myristate 13-acetate (PMA), U937 cells attached to the plastic surface and cells were characterized by marked expression of beta2-integrin molecules on the cell surface. We show that the in vivo differentiation of U937 cells appears to occur normally in the absence of AP-1 activity. In contrast, the addition to the cell culture of phosphorothioate oligonucleotides that contained the NF-kappaB or PU.1 binding sites significantly inhibited U937 differentiation. The absence of NF-kappaB led to pleiotropic effects with a clear reduction in the expression of integrin and other lineage-specific myeloid antigens on the cell surface. In contrast, the absence of PU.1 had a more restricted effect on integrin expresion on the cell surface, probably as a result of blockage of CD18 gene expression. PMID- 10029176 TI - Ultrastructure of primitive hematopoietic stem cells isolated using probes of functional status. AB - The most primitive hematopoietic stem cells capable of longterm reconstitution of the entire hematopoietic system following transplantation are characterized by their ability to exclude both Rhodamine 123 and Hoechst 33342 dyes (Rh/Ho(dull)), and are an appropriate target population for the determination of stem cell ultrastructure. We have used a fluorescence-activated cell sorter to enrich to near purity these rare, highly quiescent cells. Analysis of the in vitro growth characteristics of Rh/Ho(dull) cells demonstrated an obligatory requirement for multiple growth factors, with 62% of the sorted population having the capacity to form colonies in the presence of CSF-1 + IL-1alpha + IL-3 + SCF. The Rh/Ho(dull) cells were small, with profiles having a mean diameter of 4.6 microm. Ultrastructural examination showed numerous ribosomes and several mitochondria in the thin rim of cytoplasm surrounding the nucleus, with other cytoplasmic organelles revealed in serial sections. The cells were generally homogeneous in appearance apart from the nucleus, which had an irregular shape with a single deep indentation. The heterochromatin around the margin was distinctly more pronounced in about 50% of nuclei. The findings provide a basis for studying the structural changes that occur with progressive differentiation of early hematopoietic cells. PMID- 10029177 TI - A comparative study of the cell cycle status and primitive cell adhesion molecule profile of human CD34+ cells cultured in stroma-free versus porcine microvascular endothelial cell cultures. AB - Porcine microvascular endothelial cells (PMVECs) plus cytokines support a rapid proliferation and expansion of human CD34+CD38- cells that are capable of multilineage engraftment within the bone marrow of a secondary host. CD34+CD38- cells contain the self-renewing, long-term culture-initiating cells (LTC-IC) that are ideal targets for retroviral gene transfer experiments. Previous experiments attempting retroviral infection of CD34+CD38- cells have failed partly because these cells do not enter cell cycle in response to cytokine combinations. In this study, we determined the cell cycle status and the cell adhesion molecule profile on purified CD34+ cells and the CD34+CD38- subset before and after ex vivo expansion on PMVECs. Purified human CD34+ cells were cocultured with PMVECs for 7 days in the presence of optimal concentrations of granulocyte/macrophage-colony stimulating factor (GM-CSF) + interleukin (IL)-3 + IL-6 + stem cell factor (SCF) + Flt-3 ligand. The total CD34+ population and the CD34+CD38- subset increased 8.4- and 67-fold, respectively, with absolute increases in the number of colony forming unit-granulocyte macrophage (CFU-GM) (28.2-fold), CFU-Mix (8.7 fold), and burst-forming unit-erythroid (BFU-E) (4.0-fold) progenitor cells. After 7 days of coculture with PMVECs, 44% of the CD34+CD38+ subset were found to be in G1, and 51% were in G2/S/M phase of the cell cycle. More remarkably, 53% of the CD34+CD38 subset were in G1, and 17% were in G2/S/M phase after 7 days of PMVEC coculture. In contrast, only 22% of the CD34+CD38- subset remaining after 7 days of stroma free culture were in G1, and 6% were in G2/S/M phase. Despite the high level of cellular activation and proliferation induced by PMVEC coculture, the surface expression of adhesion molecules CD11a (LFA-1), CD11b, CD15s (sialyl-Lewis x), CD43, and CD44 (HCAM) on the total CD34+ population was maintained, and the surface expression of CD49d (VLA-4), CD54 (ICAM), CD58, and CD62L (L selectin) increased after ex vivo expansion. In contrast, CD34+ cells expanded on stroma free cultures showed lower and more variable expression of CD62L and CD15s. These findings demonstrate that the primitive CD34+CD38- subset of marrow progenitor cells can be induced to enter cell cycle and can be significantly expanded ex vivo on a hematopoietic supportive microenvironment (PMVECs) while preserving the expression of cell adhesion molecules that may be important in stem cell homing and engraftment. PMID- 10029178 TI - Umbilical cord blood banking for unrelated transplantation: evaluation of cell separation and storage methods. AB - Cost-efficient umbilical cord blood (UCB) banking requires well-standardized methods of volume reduction and storage. To compare UCB fractionation using a technique of hydroxyethyl starch (HES) sedimentation with the Ficoll (double) and Percoll methods, 50 whole units was allocated randomly to each procedure. HES resulted in a significantly better recovery of mononuclear cells (87.5%), granulocyte/macrophage colony-forming units (CFU-GM) (88.4%), and CD34- cells (87.4%) and lesser volume reduction (85.5%). HES was the least laborious, time consuming, and expensive of the three procedures, costing 3.4- and 4.4-fold less than the Ficoll and Percoll methods, respectively. Five units processed by each method was frozen in 4.5-mL cryotubes under optimal conditions. After thawing, the greatest degree of recovery of viable nucleated cells and number of CFU-GM per unit were obtained using the HES procedure. Using 4.5-mL cryotubes, the calculated number of units that could be stored in 600-L containers was 3.8- and 2.2-fold higher for Ficoll- and Percoll-separated than for HES-separated units, respectively. Nevertheless, the higher direct costs of the density gradient separation procedures outweighed their lower storage cost. For long-term cryopreservation, we assessed the freezing of HES-processed units in 50-mL cryobags and their specifically designed canisters. We found cell recoveries similar to those obtained with cryotubes, but storage capacity was decreased. Special racks designed for these canisters resulted in a 5-fold increase over the number of units stored in standard cryobags. This system also is feasible for Percoll- and Ficoll-separated units, resulting in comparable storage costs for the three separation methods. We conclude that this HES procedure and the 50-mL cryobags constitute a cost-efficient system for large-scale UCB banking. PMID- 10029179 TI - The influence of interleukin (IL)-4 and IL-13 on human dendritic cell differentiation from CD34+ progenitor cells: the importance of the source of serum. PMID- 10029180 TI - Problems raised by the in vitro generation of dendritic cells for use in immunotherapy. PMID- 10029182 TI - Skin morphology and its role in thermoregulation in mole-rats, Heterocephalus glaber and Cryptomys hottentotus. AB - The skin structure of 2 Bathyergid rodents, the naked mole-rat (Heterocephalus glaber) and the common mole-rat (Cryptomys hottentotus) is compared, to investigate whether thermoregulatory differences may be attributed to different skin features. Histological and ultrastructural studies of the dorsal skin of these closely related species show morphological and structural similarities but differences in the degree of skin folding, thickness of the integument and dermal infrastructure were evident. The skin of the common mole-rat conforms with expected morphological/histological arrangements that are commonly found in mammalian skin. Many features of the skin of the naked mole-rat, such as the lack of an insulating layer and the loosely folded morphological arrangement contribute to poikilothermic responses to changing temperatures of this mammal. Further evidence for poikilothermy in the naked mole-rat is indicated by the presence of pigment containing cells in the dermis, rather than the epidermis, as commonly occurs in homeotherms. Lack of fur is compensated by a thicker epidermal layer and a marked reduction in sweat glands. Differences in skin morphology thus contribute substantially to the different thermoregulatory abilities of the 2 Bathyergids. The skin morphology is related to the poor thermoinsulatory ability of the animals while simultaneously facilitating heat transfer from the environment to the animal by thigmothermy and/or other behavioural means. PMID- 10029181 TI - Fibrocartilage in tendons and ligaments--an adaptation to compressive load. AB - Where tendons and ligaments are subject to compression, they are frequently fibrocartilaginous. This occurs at 2 principal sites: where tendons (and sometimes ligaments) wrap around bony or fibrous pulleys, and in the region where they attach to bone, i.e. at their entheses. Wrap-around tendons are most characteristic of the limbs and are commonly wider at their point of bony contact so that the pressure is reduced. The most fibrocartilaginous tendons are heavily loaded and permanently bent around their pulleys. There is often pronounced interweaving of collagen fibres that prevents the tendons from splaying apart under compression. The fibrocartilage can be located within fascicles, or in endo or epitenon (where it may protect blood vessels from compression or allow fascicles to slide). Fibrocartilage cells are commonly packed with intermediate filaments which could be involved in transducing mechanical load. The ECM often contains aggrecan which allows the tendon to imbibe water and withstand compression. Type II collagen may also be present, particularly in tendons that are heavily loaded. Fibrocartilage is a dynamic tissue that disappears when the tendons are rerouted surgically and can be maintained in vitro when discs of tendon are compressed. Finite element analyses provide a good correlation between its distribution and levels of compressive stress, but at some locations fibrocartilage is a sign of pathology. Enthesis fibrocartilage is most typical of tendons or ligaments that attach to the epiphyses of long bones where it may also be accompanied by sesamoid and periosteal fibrocartilages. It is characteristic of sites where the angle of attachment changes throughout the range of joint movement and it reduces wear and tear by dissipating stress concentration at the bony interface. There is a good correlation between the distribution of fibrocartilage within an enthesis and the levels of compressive stress. The complex interlocking between calcified fibrocartilage and bone contributes to the mechanical strength of the enthesis and cartilage-like molecules (e.g. aggrecan and type II collagen) in the ECM contribute to its ability to withstand compression. Pathological changes are common and are known as enthesopathies. PMID- 10029183 TI - Neurite outgrowth-regulating properties of GABA and the effect of serum on mouse spinal cord neurons in culture. AB - Time-lapse photography was used to examine the effects of gamma-aminobutyric acid (GABA) on the outgrowth and motility of neurites in cultures from mouse spinal cord. GABA at concentrations of 100, 10 and 1 microM caused significant inhibition of neurite outgrowth and the motility of growth cones was significantly reduced by treatment with 100 and 10 microM GABA. This effect was mimicked by the GABA(B) receptor agonist baclofen, whereas the GABA(A) receptor agonist muscimol had no effect. The effect of GABA on outgrowth and motility seems to be dependent on the type of serum employed. The results reported here were obtained only when heat-inactivated serum was used and not when non heat inactivated serum was added to the culture medium. They suggest that GABA has a role in the regulation of process outgrowth within the embryonic mouse spinal cord. PMID- 10029184 TI - In oculo transplants of myometrium from postpartum guinea pigs fail to support sympathetic reinnervation. AB - Sympathetic nerves to the enlarged fetus-containing region of the uterus undergo degenerative changes during late pregnancy and show slow regrowth after parturition. It is not known whether this unusual response of sympathetic nerves to smooth muscle hypertrophy is due to the sensitivity of short adrenergic neurons to hormonal changes, or whether the nerves respond to changes in the neurotrophic capacity of the target. We have investigated this question using in oculo transplantation. Small pieces of myometrium from the uterine horn of virgin guinea pigs, or from the region previously occupied by the placenta and fetus in postpartum guinea pigs, were transplanted into the anterior eye chamber. After 3 wk in oculo, the pattern of reinnervation of the transplants was assessed on whole mount stretch preparations stained for tyrosine hydroxylase. The histology of the transplants was examined in toluidine blue-stained semithin sections. Myometrial transplants from virgin donors and uterine artery transplants from both virgin and postpartum donors became organotypically reinnervated by sympathetic fibres from the host iris. In contrast, sympathetic nerves did not reinnervate myometrial transplants from postpartum donors, although they approached the transplants and became distributed in the surrounding connective tissue. All transplanted tissues showed a normal histological appearance. Both the myometrium and uterine artery from postpartum donors retained a hypertrophic appearance after 3 wk in oculo. We interpret these results to indicate that the degeneration of sympathetic nerves in late pregnancy, as well as their slow regrowth to the uterus after delivery, may be due to changes in uterine smooth muscle rather than a particular sensitivity of short adrenergic neurons to hormonal changes. PMID- 10029185 TI - The degenerative fate of germ cells not conforming to stage in the pubertal golden hamster testis. AB - In the golden hamster (Mesocricetus auratus), pubertal establishment of spermatogenesis includes a defined period (d 26-30 of life) during which elongation of spermatids is selectively arrested. The resulting appearance of germ cell associations not conforming to stage and the phenomenon of desynchronisation-related germ cell degeneration are analysed both quantitatively and qualitatively by means of light and 'retrospective' electron microscopy. From d 26 onwards, the portion of tubules containing non-stage conforming germ cell associations gradually increases up to 37.5% of sectioned tubules on d 32. Concomitantly, the degree of desynchronisation rises to a maturational gap between spermatids and associated younger germ cells of 7 stages of the seminiferous epithelium cycle, i.e. of fully half a cycle. Beyond d 32, the frequency of desynchronised tubule segments decreases again. Some of the arrested round spermatids and, eventually, all belatedly elongating spermatids degenerate and are lost from the epithelium. Thus a regular maturation of advanced spermatids does not succeed under non-stage conforming conditions. Possibly it is not the desynchronisation between the associated germ cell generations and the spermatids by itself that impedes normal further development of the latter cells. Instead this may be due to the maturational delay of the stage-aberrant cells by several stages compared to the seminiferous epithelium as a whole and, especially, in relation to the stage-conditioned functional state of the neighbouring Sertoli cells. PMID- 10029186 TI - Modified cuspal relationships of mandibular molar teeth in children with Down's syndrome. AB - A total of 50 permanent mandibular 1st molars of 26 children with Down's syndrome (DS) were examined from dental casts and 59 permanent mandibular 1st molars of normal children were examined from 33 individuals. The following measurements were performed on both right and left molars (teeth 46 and 36 respectively): (a) the intercusp distances (mb-db, mb-d, mb-dl, db-ml, db-d, db-dl, db-ml, d-dl, d ml, dl-ml); (b) the db-mb-ml, mb-db-ml, mb-ml-db, d-mb-dl, mb-d-dl, mb-dl-d angles; (c) the area of the pentagon formed by connecting the cusp tips. All intercusp distances were significantly smaller in the DS group. Stepwise logistic regression, applied to all the intercusp distances, was used to design a multivariate probability model for DS and normals. A model based on 2 distances only, mb-dl and mb-db, proved sufficient to discriminate between the teeth of DS and the normal population. The model for tooth 36 for example was as follows: p(DS) = (e(30.6-5.6(mb-dl)+25(mb-db)))/(1 + e(30.6 5.6(mb-dl)+25(mb db))). A similar model for tooth 46 was also created, as well as a model which incorporated both teeth. With respect to the angles, significant differences between DS and normals were found in 3 out of the 6 angles which were measured: the d-mb-dl angle was smaller than in normals, the mb-d-dl angle was higher, and the mb-dl-d angle was smaller. The dl cusp was located closer to the centre of the tooth. The change in size occurs at an early stage, while the change in shape occurs in a later stage of tooth formation in the DS population. PMID- 10029187 TI - Morphometric study of the equine navicular bone: variations with breeds and types of horse and influence of exercise. AB - Navicular bones from the 4 limbs of 95 horses, classified in 9 categories, were studied. The anatomical bases were established for the morphometry of the navicular bone and its variations according to the category of horse, after corrections were made for front or rear limb, sex, weight, size and age. In ponies, navicular bone measurements were smallest for light ponies and regularly increased with body size, but in horses, navicular bone dimensions were smallest for the athletic halfbred, intermediate for draft horse, thoroughbreds and sedentary halfbreds and largest for heavy halfbreds. The athletic halfbred thus showed reduced bone dimensions when compared with other horse types. Navicular bones from 61 horses were studied histomorphometrically. Light horses and ponies possessed larger amounts of cancellous bone and less cortical bone. Draft horses and heavy ponies showed marked thickening of cortical bone with minimum intracortical porosity, and a decrease in marrow spaces associated with more trabecular bone. Two distinct zones were observed for the flexor surface cortex: an external zone composed mainly of poorly remodelled lamellar bone, disposed in a distoproximal oblique direction, and an internal zone composed mainly of secondary bone, with a lateromedial direction for haversian canals. Flexor cortex external zone tended to be smaller for heavy ponies than for the light ponies. It was the opposite for horses, with the largest amount of external zone registered for draft horses. In athletic horses, we observed an increase in the amount of cortical bone at the expense of cancellous bone which could be the result of reduced resorption and increased formation at the corticoendosteal junction. Cancellous bone was reduced for the athletic horses but the number of trabeculae and their specific surfaces were larger. Increased bone formation and reduced resorption could also account for these differences. PMID- 10029188 TI - Maternal adrenocortical hormones maintain the early development of pancreatic B cells in the fetal rat. AB - To investigate the effect of maternal adrenocortical hormones on the development of fetal pancreatic islet cells, pregnant rats were adrenalectomised on d 6 of gestation. On d 12-16 the growth patterns of fetal insulin-producing B cells, glucagon-producing A cells, and somatostatin-producing D cells were observed histometrically. Maternal adrenalectomy resulted in growth retardation of fetal B cells on d 12-15. Maternal corticosterone therapy prevented this retardation. Maternal adrenalectomy, however, did not affect the developmental patterns of A and D cells. By Western blotting and immunohistochemistry, glucocorticoid receptors were demonstrated to be present in the islet cells from d 12 to d 15. These results suggest that maternal adrenocortical hormones, glucocorticoids in particular, maintain the early development of fetal pancreatic B cells through their specific intracellular glucocorticoid receptor. PMID- 10029189 TI - Identifying homologous anatomical landmarks on reconstructed magnetic resonance images of the human cerebral cortical surface. AB - Guided by a review of the anatomical literature, 36 sulci on the human cerebral cortical surface were designated as homologous. These sulci were assessed for visibility on 3-dimensional images reconstructed from magnetic resonance imaging scans of the brains of 20 normal volunteers by 2 independent observers. Those sulci that were found to be reproducibly identifiable were used to define 24 landmarks around the cortical surface. The interobserver and intraobserver variabilities of measurement of the 24 landmarks were calculated. These reliably reproducible landmarks can be used for detailed morphometric analysis, and may prove helpful in the analysis of suspected cerebral cortical structured abnormalities in patients with such conditions as epilepsy. PMID- 10029190 TI - Evaluation of pulmonary volumetric morphometry at the light and electron microscopy level in several species of passerine birds. AB - The lungs of 3 small passerine species, having similar body mass but different diurnal activity patterns, were analysed morphometrically to assess the relationship between diurnal activity and pulmonary volumetry at the light and electron microscope levels. The percentage volumes of the major lung and exchange tissue components of the 3 species--an aerial insectivore, a foliage gleaner/nectarivore and a ground forager--were strikingly similar, and consistent with literature values for other passerine species. The only significant difference found was exchange tissue plasma volume and pulmonary haematocrit, with the ground-foraging, low activity Malurus splendens having significantly lower values than the other 2 species. This may indicate that cardiovascular parameters are more important determinants of metabolic activity in small passerines than aspects of pulmonary anatomy. PMID- 10029191 TI - Morphology of intraepithelial corpuscular nerve endings in the nasal respiratory mucosa of the dog. AB - Corpuscular nerve endings in the nasal respiratory mucosa of the dog were investigated by immunohistochemical staining specific for protein gene product 9.5 by light and electron microscopy. In the nasal respiratory mucosa, complex corpuscular endings, which displayed bulbous, laminar and varicose expansions, were distributed on the dorsal elevated part of the nasal septum and on the dorsal nasal concha. The endings were 300-500 microm long and 100-250 microm wide. Some axons gave rise to a single ending while others branched into 2 endings. Cryostat sections revealed that the corpuscular endings were located within the nasal respiratory epithelium. On electron microscopy, immunoreactive nerve terminals that contained organelles, including mitochondria and neurofilaments, were observed within the epithelial layer near the lumen of the nasal cavity. Some terminals contacted the goblet cell. Such terminal regions were covered by the cytoplasmic process of ciliated cells and were never exposed to the lumen of the nasal cavity. These nerve endings are probably activated by pressure changes. PMID- 10029192 TI - Developmental changes in mucosubstances revealed by immunostaining with antimucus monoclonal antibodies and lectin staining in the epithelium lining the segment from gizzard to duodenum of the chick embryo. AB - The mucosubstances in the epithelium lining the segment from gizzard to duodenum during development of the chick embryo was studied histochemically using monoclonal antibodies against gizzard mucus and lectins, with attention to the regional differentiation of the epithelium in this segment. The anterior limit of epithelial CdxA mRNA expression detected by in situ hybridisation, which served as the position of the gizzard-duodenal boundary, was clearly found from d 3. Granules positive for some antibodies or lectins were found in the region ranging from the posterior part of the gizzard to the duodenum at d 3, which was followed by an increase in the number of granules and a gradual enlargement of the granule positive area to the anterior part of the gizzard over 4-6 d. From d 4, the epithelia of the gizzard body and of the pyloric or duodenal region came to be differently stained with some antibodies or lectins. From d 10, each region showed a specific pattern of staining. The epithelia of the gizzard body and pyloric region contained abundant mucus granules with a different staining pattern. In the duodenum the number of stained granules was low except in occasional goblet cells. Thus the epithelia of the gizzard body, pyloric region and duodenum may produce different mucosubstances and the regional differentiation in these epithelia may start at rather early stages soon after the formation of digestive tube. PMID- 10029193 TI - Possible role of serotonin in Merkel-like basal cells of the taste buds of the frog, Rana nigromaculata. AB - Merkel-like basal cells in the taste buds of the frog were examined by fluorescence histochemistry, immunohistochemistry and electron microscopy. There were about 16-20 basal cells arranged in a radial fashion at the base of each taste bud. These cells were strongly immunopositive for serotonin antiserum. They were characterised by the presence of numerous dense-cored granules in the cytoplasm ranging from 80 to 120 nm in diameter, and of microvilli protruding from the cell surface. For 4 mo after sensory denervation by cutting the gustatory nerves, all cell types of the taste bud were well preserved and maintained their fine structure. Even at 4 mo after denervation, the basal cells exhibited a strong immunoreaction with serotonin antiserum. To investigate the function of serotonin in the basal cells in taste bud function, serotonin deficiency was induced by administration of p-chlorophenylalanine (PCPA), an inhibitor of tryptophan hydroxylase, and of p-chloroamphetamine (PCA), a depletor of serotonin. After administration of these agents to normal and denervated frogs for 2 wk, a marked decrease, or complete absence, of immunoreactivity for serotonin was observed in the basal cells. Ultrastructurally, degenerative changes were observed in both types of frog; numerous lysosome-like myelin bodies were found in all cell types of the taste buds. The number of dense-cored granules in the basal cells also was greatly decreased by treatment with these drugs. Serotonin in Merkel-like basal cells appears to have a trophic role in maintenance of the morphological integrity of frog taste bud cells. PMID- 10029194 TI - Embryonal feather growth in the chicken. AB - Prenatal feather growth development in the chicken was studied in 7 body regions in HH stages 27-45, using direct measurements, specific histological and immunohistochemical methods, and scanning electron microscopy. The results from measurements of absolute length values, and, particularly, growth rate development in each HH stage revealed a distinct phase of most intensive growth in HH stage 40-41, which was preceded by feather follicle insertion and accompanied by the occurrence of alpha-keratins in barbule cells. Specific regional evaluation demonstrated that growth in the feather follicles of abdominal skin generally showed the slowest progression from absolute values and that in the feather filaments of the developing wings the most rapid progression occurred during HH stage 40-41 from growth rate values. PMID- 10029195 TI - Mucosa and taste buds of the human epiglottis. PMID- 10029196 TI - Glutamate receptors in the cingulate cortex, hippocampus, and cerebellar vermis of alcoholics. AB - This study tests the hypothesis that glutamate receptors are altered in the brains of alcoholics as a result of chronic alcohol neurotoxicity. Excessive release of the excitatory neurotransmitter glutamate may damage postsynaptic neurons by increasing calcium flux through N-methyl-D-aspartate (NMDA) receptor gated ion channels. Alcohol has opposite effects on the NMDA receptor, depending on the duration of exposure. Acute exposure to alcohol inhibits ion flow through NMDA receptors, whereas chronic exposure upregulates the number of these receptors and thereby increases ion flow. Acute withdrawal from alcohol results in hyperexcitability and seizures in the presence of upregulated NMDA receptors, making postsynaptic neurons vulnerable to excitotoxic damage. For this study, 13 grossly and histologically normal brains from alcoholics and 13 brains from nonalcoholic controls were selected from our brain bank. The two groups were matched for age, postmortem interval, and storage time. Maximal binding and affinities of NMDA receptors were determined by quantitative autoradiography in the cingulate cortex, the cornu Ammonis of the hippocampus, and in the cerebellar vermis. Binding was determined with an agonist, L-[3H]glutamate, with a competitive antagonist, [3H]CGP-39653, and with an antagonist binding in the channel interior, [3H]MK-801. No significant differences were found in receptor densities or affinities between alcoholics and controls. Real differences were not likely to be obscured by nonalcohol-related variables because the groups were closely matched for age, autopsy delay, time in storage, and central nervous system medications. Various diseases causing acute and chronic hypoxia did not significantly affect receptor density or affinity. Liver diseases and thiamine deficiency were excluded. A long-lasting upregulation of the number or affinity of NMDA receptors is not a key feature of chronic alcoholics. PMID- 10029197 TI - Acquisition of a fixed ratio schedule in adult male rats neonatally exposed to ethanol and/or cocaine. AB - Acquisition of an operant learning task for sucrose reinforcement was examined in rats after neonatal exposure to ethanol and/or cocaine. Subjects were raised using an artificial rearing procedure from postnatal days 4 to 11 and were intragastrically fed a milk diet containing either ethanol (6 g/kg/day), cocaine (60 mg/kg/day), the combination (6 g/kg/day + 60 mg/kg/day), or an isocaloric control diet. There was also a suckled sham control. Adult male offspring (postnatal day 65 to postnatal day 68) were shaped to lever press for sucrose reinforcement and then began daily 15-min sessions of fixed ratio (FR) training. The number of days to acquire an FR 20 was measured. Neonatal exposure to the ethanol/cocaine combination significantly increased the number of days to reach the FR 20. There was also a trend for fewer of these subjects to reach the FR 20, although this difference was not statistically significant. These results suggest that subjects neonatally exposed to the ethanol/cocaine combination have difficulty learning an operant task. This impairment was unique to the ethanol/cocaine combination group and suggests that polydrug exposure during development may have a more adverse outcome than exposure to ethanol or cocaine alone. PMID- 10029198 TI - Mutation of putative phosphorylation sites in the 5-hydroxytryptamine3 receptor does not eliminate its modulation by ethanol. AB - The function of the 5-hydroxytryptamine3 (5-HT3) receptor is enhanced by ethanol, but the amino acid residue(s) that confers sensitivity to ethanol remains to be identified. Phosphorylation of the related GABA(A) receptor has been implicated in conferring its sensitivity to ethanol. In common with the GABA(A) receptor, the 5-HT3 receptor contains multiple consensus sites for protein kinases. To evaluate the possibility that phosphorylation of the 5-HT3 receptor underlies its ethanol sensitivity, we examined the ability of ethanol to enhance 5-HT-mediated currents in a mutant 5-HT3 receptor containing no intracellular serines, threonines, or tyrosines. Mutation of these 13 residues in the intracellular loops produced a modest leftward shift in the 5-HT concentration response curve, with the EC50's for 5-HT decreasing from 0.839 +/- 0.03 microM in the wild-type receptor to 0.713 +/- 0.03 microM in the mutant receptor. Cooperativity of the 5 HT binding sites was enhanced by the mutations, with Hill coefficients of 2.92 for the wild-type receptor and 3.74 for the mutant receptor, respectively. In oocytes expressing mutant receptors, ethanol (50 to 200 mM) enhanced the currents produced by low concentrations of 5-HT by approximately 5 to 45%, which was not statistically different from the potentiation produced by ethanol in wild-type receptors. These results suggest that ethanol enhancement of the 5-HT3 receptor function does not require receptor phosphorylation. PMID- 10029199 TI - Effects of alcohol and nicotine on developing olfactory bulb: loss of mitral cells and alterations in neurotransmitter levels. AB - Previous research from our laboratory has shown that [ethanol (EtOH)] exposure during the brain growth spurt is detrimental to olfactory bulb development. This study extends those findings by examining the effects of EtOH, nicotine (NIC), and the combination of these drugs (EtOH/NIC) on olfactory bulb mitral cell numbers, as well as on various major neurotransmitter levels in neonatal rats. An artificial rearing paradigm was used in the present studies. These artificially reared pups were given 4 g/kg/day of EtOH and/or 6 mg/kg/day of NIC on postnatal day (PD) 4 to PD 9, except in the case of the acute neurochemistry study, in which the pups received treatment on PD 9 only. An artificially reared gastrostomy control group (GC) and a suckle control group were included. The mean total numbers of mitral cells in the EtOH and NIC groups were significantly reduced from that of the GC, as well as the volume of the left main olfactory bulb. There was no difference among any of the groups in mitral cell density. As for neurochemistry data, there was no difference in neurotransmitter levels among any of the groups in the repeat exposure regimen. There were, however, changes after the acute exposure (exposure on PD 9 only). Both serotonin and GABA levels were significantly increased only after NIC exposure. However, norepinephrine levels were significantly decreased after acute exposure in all three drug treatment groups, compared with that of the control group. Except for the GC control group, dopamine levels were not detected consistently after acute exposure to EtOH, NIC, or EtOH/NIC. Collectively, these findings demonstrate that exposure to EtOH or NIC individually during the brain growth spurt results in developmental deficits in the olfactory bulb, suggesting that both EtOH and NIC are neuroteratogens. Furthermore, this study demonstrated the capability of NIC to antagonize (protect) EtOH-induced mitral cell loss in the developing olfactory bulb. PMID- 10029200 TI - Characterization of adducts of ethanol metabolites with cytochrome c. AB - Cytochrome c (cyt c) is found in the mitochondria of all mammalian cells where hydrogen peroxide is produced as a byproduct of the electron transport chain. In the presence of peroxide cyt c generates a ferryl heme and radicals at Tyr residues (Barr et al., 1996). These radicals can be transferred to Trp residues within the protein or to Tyr- and Trp-containing peptides (Deterding et al., 1998). We report that addition of ethanol to this system of cyt c plus peroxide results in replacement of the Tyr/Trp radicals by 1-hydroxyethyl radicals (HER), and covalent binding of up to 10 mol of ethanol per mol of cyt c. In the absence of exogenously added peroxide, ethanol incorporation to cyt c is attained also with a reconstituted system of the ethanol-inducible cytochrome P-4502E1 isozyme. Comparative studies with myoglobin and apomyoglobin suggest that the heme is necessary for ethanol adduction of the protein to occur. Structural analysis by mass spectrometry of the tryptic digestion fractions of adducted cyt c is consistent with several peptides bearing one-to-three acetaldehyde moieties on Lys residues, and three distinct Tyr/Trp-containing peptides: P[28-53], P[56-73], P[73-91] carrying one-to-two HER. The x-ray crystallographic structure of cyt c shows that the Tyr/Trp residues in the adducted peptides are in close proximity to the heme. In conclusion, our data show that ethanol metabolites alkylate cyt c under oxidative stress and point to HER-Tyr/Trp adducts as plausible markers of alcoholism. PMID- 10029201 TI - Alcohol rapidly lowers plasma testosterone levels in the rat: evidence that a neural brain-gonadal pathway may be important for decreased testicular responsiveness to gonadotropin. AB - Alcohol is reported to suppress testosterone (T) secretion in the adult male rat. Decreases in the circulating levels of luteinizing hormone (LH) and/or the activity of testicular steroidogenic enzymes have been proposed as putative mechanisms underlying this inhibitory effect. We have recently provided functional evidence for a neural pathway between the brain and the male gonads that plays an important role in the ability of brain proinflammatory cytokines to blunt testicular responsiveness to human chorionic gonadotropin (hCG). The present work was designed to test the hypothesis that a similar pathway might be implicated in the inhibitory influence of alcohol on T secretion. Alcohol, administered intraperitoneally or intragastrically, significantly prevented the T response to the gonadotropin. This effect was significant within 15 min of drug treatment. In the intragastric model (the only one used for this type of experiment), the effect of alcohol was not altered by prior blockade of LH release, which suggests that it is independent of changes in the activity of the pituitary gonadotrophs. The lowest effective dose of alcohol, delivered intraperitoneally, was 2.0 g/kg. The intracerebroventricular injection of the alpha- and beta-adrenergic receptor antagonists phentolamine and propranolol significantly reversed the inhibitory influence of alcohol when it was administered 15 min, but not 60 min, before hCG. Collectively, our results indicate that (1) alcohol induces a rapid and profound decrease in plasma T levels that is secondary to decreased testicular responsiveness to hCG; and (2) at least part of this acute inhibitory action of alcohol may depend on the activation of a neural, adrenergic-dependent pathway between the brain and the testes. PMID- 10029202 TI - Effects of ethanol on alpha-adrenergic and beta-adrenergic agonist-stimulated beta-endorphin release and cAMP production in hypothalamic cells in primary cultures. AB - We have previously shown that low concentrations of ethanol rapidly stimulate beta-endorphin (beta-EP) release from hypothalamic neurons in primary cultures and that chronic exposures to these concentrations of ethanol desensitize beta-EP neurons to ethanol challenges. We have also shown that chronic ethanol desensitizes dibutyryl cAMP-, adenosine-, and prostaglandin E1-stimulated beta-EP release and the cAMP content in hypothalamic neurons. In this study, we determined the effects of ethanol (50 mM) on beta-adrenergic agonist (isoproterenol) or alpha-adrenergic agonist (l-phenylephrine)-induced beta-EP release and cellular contents of cAMP to identify whether ethanol causes heterologous desensitization of the adenylate cyclase system in this neuronal cell population. Both isoproterenol and l-phenylephrine increased beta-EP levels in culture media and elevated the cAMP content in cell extracts in a concentration (0.1 and 10 microM)-dependent fashion between 3 to 6 hr. A 50 mM dose of ethanol increased beta-EP and cAMP levels at 3 hr, but it did not elevate beta-EP and cAMP levels after 48 hr of exposure. Acute exposure (3 hr) of these cells to ethanol moderately enhanced the isoproterenol-stimulated and l phenylephrine-stimulated levels of media beta-EP and intracellular levels of cAMP. However, chronic exposure (48 hr) to ethanol reduced the magnitude of both alpha- and beta-adrenergic receptor agonist-stimulated beta-EP release and cAMP production. These results confirm our previous findings that the ethanol action on beta-EP secretion is mediated by the cAMP system and further suggest that chronic ethanol causes heterologous desensitization of the adenylate cyclase system in the beta-EP neuronal cell population. PMID- 10029203 TI - Effects of prenatal exposure to alcohol on the release of adenocorticotropic hormone, corticosterone, and proinflammatory cytokines. AB - Prenatal alcohol exposure has been shown to produce hyperresponsiveness of the hypothalamic-pituitary-adrenal (HPA) axis to immune challenges. Because cytokines, which are released in response to immune challenges, are known to activate the HPA axis, this study determined whether altered release of cytokines contribute to the HPA hyperresponsiveness to immune challenges observed after prenatal alcohol exposure. Pregnant dams were exposed to alcohol vapors (6-7 hr daily) between days 7 and 18 of gestation. At postnatal days 45 and 60, control (C) and prenatal alcohol-exposed (E) offspring were subjected to three different types of immune challenges: injections of interleukin-1beta or endotoxin (lipopolysaccharide), or turpentine-induced tissue injury. We observed the expected higher plasma adrenocorticotropic hormone and corticosterone levels in E compared with C rats, and this HPA hyperresponsiveness was greater in E females compared with E males. Plasma tumor necrosis factor-alpha or interleukin-6 responses were comparable in the C and E groups. Females exhibited significantly higher corticosterone, tumor necrosis factor-alpha, and interleukin-6 responses than males. These results indicate that (1) prenatal alcohol exposure produces HPA hyperresponsiveness to immune challenges; (2) prenatal alcohol treatment does not influence the release of cytokines to immune challenges; and (3) there are gender differences in the secretory pattern of corticosterone and cytokines to immune challenges. Therefore, these data do not support the hypothesis that cytokines play a role in the hyperresponsiveness of the HPA axis to immune challenges observed after prenatal alcohol exposure. PMID- 10029204 TI - Reversal of chronic ethanol-induced testosterone suppression in peripubertal male rats by opiate blockade. AB - Teenage drinking continues to be a significant problem in the U.S., as well as abroad. We have previously demonstrated that opiate blockade with naltrexone, a drug currently used in patients to diminish alcohol craving, prevented the fall in serum testosterone seen after acute ethanol (EtOH) exposure in young, peripubertal male rats. To follow-up on this reversal, a series of experiments was performed to determine if naltrexone would also prevent the testosterone suppression caused by chronic EtOH exposure. Peripubertal rats either 45 days old (mid-pubertal) or 55 days old (late pubertal) were fed an EtOH-containing liquid diet or pair-fed control diet for 14 days. Each animal was implanted with either a naltrexone containing or placebo pellet before starting the liquid diet. In each age group, EtOH alone significantly suppressed testosterone, whereas naltrexone prevented this fall, although it had no effect alone. Serum luteinizing hormone was also suppressed by EtOH; however, naltrexone did not abrogate this fall. In the 45-day-old animals, beta-luteinizing hormone mRNA levels rose significantly in the EtOH group, but not when naltrexone was coadministered with EtOH. There was no change in hypothalamic luteinizing hormone releasing hormone (LHRH) mRNA, pro-LHRH, or LHRH in any group at either age. Thus, naltrexone is able to partially prevent the EtOH-induced suppression of gonadal testosterone of young, adolescent male rats. This effect appears to be mediated directly at gonadal level, because hypothalamic and pituitary hormone changes were minor and nonsignificant. PMID- 10029205 TI - Ethanol-induced apoptosis to stable HepG2 cell lines expressing human cytochrome P-4502E1. AB - In a previous study (Wu and Cederbaum, J. Biol. Chem. 271:23914-23919, 1996), ethanol was shown to be cytotoxic to HepG2 cells, which were transduced to express human cytochrome P-4502E1 (CYP2E1) but not to control HepG2 cells. The goal of the current study was to evaluate whether this toxicity was apoptotic in nature. Incubation of CYP2E1-expressing HepG2 cells with 100 mM ethanol for 2 days produced morphological changes and DNA fragmentation (in situ labeling, flow cytometry, and DNA ladder formation) indicative of apoptosis. No changes were observed in the control HepG2 cells that do not express CYP2E1. Ethanol-induced apoptosis was also observed in HepG2 cells transiently transfected to express CYP2E1. The ethanol-induced apoptosis was prevented by 4-methylpyrazole, an inhibitor of ethanol oxidation by CYP2E1, and by trolox, an antioxidant that prevents lipid peroxidation. Ethanol treatment of the cells expressing CYP2E1 resulted in increased activities of caspases 1 and 3. An inhibitor of these caspases prevented the ethanol-induced apoptosis in the stable cell lines and the transiently transfected cell lines. Ethanol did not cause apoptosis in a HepG2 cell line overexpressing bcl-2 plus CYP2E1, but did cause apoptosis in cell lines expressing CYP2E1 in the absence of bcl-2. These experiments demonstrate that ethanol can produce apoptosis in HepG2 cells that express CYP2E1. Increased production of reactive oxygen species and lipid peroxidation can be associated with apoptotic cell death. The prevention of the ethanol-induced apoptosis by 4 methylpyrazole and by trolox suggests that production of a prooxidative state as a consequence of ethanol oxidation by CYP2E1 results in eventual activation of caspases such as caspases 1 and 3, which can trigger the apoptotic process. PMID- 10029206 TI - Role of protein kinase C in ethanol-induced activation of adenylyl cyclase. AB - Ethanol is known to enhance the activity of adenylyl cyclase (AC) in a number of cells and tissues. Recent work has suggested that the various isoforms of AC show differential sensitivity to ethanol, with Type VII AC being most sensitive. However, the mechanism of action of ethanol is unclear. In the present work, we investigated the effect of ethanol on AC activity in the human erythroleukemia (HEL) cell line, platelets, and AC VII-transfected HEK 293 cells. The HEL cells contain abundant amounts of mRNA for Type VII AC. We found that both ethanol and phorbol dibutyrate (PDBu) treatment enhanced agonist (prostaglandin E1; PGE1) stimulated AC activity in HEL cells, as well as in platelets and HEK 293 cells transfected with AC VII. Inhibitors of protein kinase C (PKC) blocked the stimulatory effects of both ethanol and PDBu. However, the effects of ethanol and PDBu on AC activity were additive, suggesting that the mechanisms of action of ethanol and PDBu were not identical. Furthermore, a 30-min exposure of HEL cells to ethanol attenuated (desensitized) the ability of ethanol, but not PDBu, to enhance agonist-activated AC activity. On the other hand, a 30-min pretreatment with PDBu attenuated the AC response to the phorbol ester, but not to ethanol; but, after a 20 hr preincubation with phorbol ester, the ability of both PDBu and ethanol to enhance prostaglandin E1-stimulated AC activity was completely eliminated. Finally, pretreatment of HEL cells with pertussis toxin blocked the effect of PDBu, but not ethanol, on AC activity. The results support the involvement of phorbol ester-sensitive PKC(s) in ethanol's enhancement of agonist activated activity of AC in HEL cells, but suggest that the mechanism of ethanol's action is different from that of PDBu. The findings with pertussis toxin suggest that PDBu activation of PKC(s) may affect AC activity through phosphorylation of a G1 protein, whereas ethanol may act by promoting phosphorylation of a different substrate (e.g., AC VII). PMID- 10029207 TI - Ethanol-induced expression of c-Fos differentiates the FAST and SLOW selected lines of mice. AB - The effect of ethanol on the number of Fos-like immunoreactive (Fos-li) neurons was previously studied in the C57BL/6J (B6) and DBA/2J (D2) inbred mouse strains (Hitzemann and Hitzemann, 1997). Data obtained suggested that the locomotor activation response to ethanol found in the D2 but not the B6 strain was associated with an increase in the number of Fos-li neurons (a putative measure of synaptic activity) in the central nucleus of the amygdala (CeA), but not in other brain regions, including the basal ganglia. Supporting results were obtained in B6D2 F2 intercross animals (Demarest et al., 1998) those animals exhibiting a marked locomotor activation response to ethanol also showed a significant increase in the number of Fos-li neurons in the CeA. The current study extends this line of investigation to the FAST and SLOW selected lines of mice (Shen et al., 1995). Twenty-eight SLOW and FAST mice (taken evenly from both replicate lines) were randomly assigned to receive either saline or ethanol (1.5 g/kg). One hour later, the animals were sacrificed, and the number of Fos-li neurons were determined using standard immunocytochemical techniques. Both the FAST and SLOW lines showed a marked increase (>300%) in the number of Fos-li neurons in the lateral aspect of the CeA; however, in the capsular division, only the FAST line showed an increase (>500%). In several brain regions, the basal (saline) response was markedly higher in the SLOW line; these regions included the subthalamic nucleus, the entopeduncular nucleus, the substantia nigra compacta, and the ventral tegmental area. Furthermore, it was found that ethanol decreased the number of Fos-li neurons in the ventral tegmental area of the SLOW but not FAST mice. These data suggest a substantial involvement of the basal ganglia in the segregation of the FAST and SLOW lines. PMID- 10029208 TI - Polyenylphosphatidylcholine opposes the increase of cytochrome P-4502E1 by ethanol and corrects its iron-induced decrease. AB - Dietary iron overload damages membrane phospholipids and decreases microsomal cytochromes P-450. We wondered whether this might also pertain to cytochrome P 4502E1 (2E1) and whether polyenylphosphatidylcholine (PPC), a 94-96% pure mixture of linoleate-rich polyunsaturated phosphatidylcholines that protects against alcohol-induced liver injury, also affects 2E1, either in the presence or absence of iron. Accordingly, rats were fed for 8 weeks our standard liquid diet containing ethanol (36% of energy) or isocaloric carbohydrates, with either PPC (3 g/1000 Cal) or equivalent amounts of linoleate (as safflower oil). 2E1 was assessed by Western blots and by two of its characteristic enzyme activities: the microsomal ethanol oxidizing system (MEOS), evaluated by the conversion of ethanol to acetaldehyde (determined by head space GC), and p nitrophenolhydroxylase (PNP) activity, measured by HPLC with UV detection of 4 nitrocatechol. With ethanol (36% of energy) replacing carbohydrates, 2E1 content increased 10-fold, with a corresponding increase in PNP and MEOS activities, but when carbonyl iron (5 g/1000 Cal) was added, the induction was significantly reduced. This iron-induced decrease was corrected by PPC. PPC is rich in linoleate, but when the latter was given as triglycerides (safflower oil), there was no effect, whereas hepatic nonheme iron content was the same in both these groups. It also was found that in the absence of iron, the ethanol-mediated induction of 2E1 and its corresponding enzyme activities were significantly less with PPC (< 0.001) than with safflower oil. In addition, in alcohol-fed animals, PPC decreased the oxidative stress (as determined by F2-isoprostanes), which reflects yet another hepatoprotective effect of PPC. PMID- 10029209 TI - Age at first drink and risk for alcoholism: a noncausal association. AB - Prior research indicates risk for alcoholism is increased among individuals who begin to drink at an early age. We replicate and extend these findings, addressing causal and noncausal explanations for this association. Structured psychiatric interviews, including assessment of lifetime DSM-IV alcohol abuse and alcohol dependence (AD), were conducted with 8746 adult twins ascertained through a population-based twin registry. We found strong evidence for an association between early drinking onset and risk for AD, but less evidence for an association with alcohol abuse. The results of twin-pair analyses suggest that all of the association between early drinking and later AD is due to familial sources, which probably reflect both shared environmental and genetic factors. These results suggest the association between drinking onset and diagnosis is noncausal, and attempts to prevent the development of AD by delaying drinking onset are unlikely to be successful. PMID- 10029210 TI - Validity of the Obsessive Compulsive Drinking Scale (OCDS): does craving predict drinking behavior? AB - OBJECTIVE: The Obsessive Compulsive Drinking Scale (OCDS), a 14-item, self-report questionnaire, was developed to measure alcohol-related craving. The OCDS may provide a measure of the state of illness among alcohol-dependent individuals and may have value in predicting subsequent drinking behavior. The present study was conducted to evaluate the factor structure and the concurrent, construct, and predictive validity of the OCDS. METHODS: Data on desire to drink and on drinking behavior were obtained from 127 alcohol-dependent subjects who participated in a 12-week outpatient pharmacotherapy trial and a 3-month posttreatment follow-up. RESULTS: Principal components analysis of the OCDS indicated that three factors best described its structure: obsessions, drinking control and consequences, and alcohol consumption. Data also supported the concurrent and discriminant validity of the OCDS. However, the OCDS total score showed limited validity in predicting drinking during a posttreatment follow-up period. Furthermore, the only empirically derived factor that predicted drinking during this period was the alcohol consumption factor. CONCLUSIONS: As might be expected, the OCDS questions on drinking behavior predict subsequent drinking behavior. However, the instrument does not appear to provide a general measure of alcohol-related illness. The utility of the OCDS in studies of alcoholism treatment outcome requires clearer definition. PMID- 10029211 TI - Contribution of carbohydrate deficient transferrin to gamma glutamyl transpeptidase in evaluating progress of patients in treatment for alcoholism. AB - Eight previous investigations have suggested that conjoint consideration of findings on tests for gamma glutamyl transpeptidase (GGT) and carbohydrate deficient transferrin (CDT) substantially enhances sensitivity of screening for alcohol problems while minimally diminishing specificity. Using results from a large clinical trial, the current study evaluated the two tests singly and in combination as measures of three clinically important treatment outcome criteria: any drinking, at least one day of heavy drinking, and at least three consecutive days of heavy drinking during the past month. When scored by quartile, CDT is slightly better at screening for alcohol problems in males than GGT. However, CDT seems less accurate in females than GGT. Use of the two tests in consort moderately improves the individual test accuracy in predicting drinking status for both genders. PMID- 10029212 TI - Substance use, injury, and risk-taking dispositions in the general population. AB - Alcohol consumption has been found to be associated with injury occurrence and with risk-taking dispositions, and these dispositions, themselves, have been found to be associated with injury. Few studies have analyzed both alcohol consumption and risk-taking dispositions, or illicit drug use, on risk of injury across all types of injuries. Data on risk perception, risk-taking/impulsivity, sensation seeking, alcohol and drug use, demographic characteristics, and injury in the last year are reported from the 1995 National Alcohol Survey of 4925 respondents living in households in the 48 contiguous states. Moderate drinking, alcohol treatment, drug use, simultaneous use of alcohol and drugs, and risk taking dispositions were all positively associated with reporting an injury. In multiple logistic regression, only risk-taking dispositions maintained significance when other variables were controlled. In separate regressions by ethnicity, risk-taking dispositions were significant predictors of injury for whites, whereas none of the variables were significant for blacks or Hispanics. Data suggest that risk-taking dispositions may be more important predictors of injury than either drinking or drug use variables, but this may vary by ethnicity. Risk-taking disposition may influence the effectiveness of strategies to reduce alcohol-related injuries; future research is important, therefore, for informing intervention and prevention efforts. PMID- 10029213 TI - Do patients with alcohol dependence use more services? A comparative analysis with other chronic disorders. AB - OBJECTIVE: The primary purpose of this research was to compare the service use of patients diagnosed with alcohol dependence to the service use of patients diagnosed with other chronic illnesses. The secondary purpose was to determine the impact of comorbid alcoholism on the service use of patients with chronic illnesses. METHODS: The sample included 67,878 veterans diagnosed with alcohol dependence, depression, or diabetes who were treated by the Department of Veterans Affairs in 1993. The number of inpatient days and outpatient visits over a 4-year period (1991 to 1995) were compared using regression models to control for differences in casemix. RESULTS: Controlling for casemix, patients treated for alcohol dependence had significantly fewer outpatient visits than patients treated for either depression or diabetes. Patients treated for alcohol dependence also had significantly fewer inpatient days than patients treated for depression, but significantly more inpatient days than patients treated for diabetes. Comorbid alcoholism was prevalent among patients treated for depression and diabetes. Comorbid alcoholism increased the number of inpatient days for patients treated for depression or diabetes and increased the number outpatient visits for patients with depression. However, comorbid alcoholism decreased the number of outpatient visits for patients treated for diabetes. CONCLUSIONS: Results suggest that patients with alcohol use disorders should not be singled out as being more costly to treat than patients with other chronic illnesses. These findings are in stark contrast to those from studies comparing individuals with alcohol use disorders to relatively healthy individuals sampled from at-risk populations. PMID- 10029214 TI - Sleep-disordered breathing in alcoholics. AB - Sleep apnea and related disorders contribute to disturbed sleep in abstinent alcoholics. In an earlier report from our group, sleep-disordered breathing was common and increased with age in a cohort of 75 abstinent alcoholics. We now report an extension of the previous work that includes studies of an additional 103 abstinent alcoholics undergoing treatment for alcoholism (total sample = 188) and a comparison group of 87 normal subjects. The presence and severity of sleep disordered breathing was assessed with polysomnography. Among the alcoholics, sleep-disordered breathing (defined as 10 or more apneas plus hypopneas per hour of sleep) was present in 3% of 91 subjects under age 40, 17% of 83 subjects age 40 to 59, and 50% of 14 subjects age 60 or over. Subjects with sleep-disordered breathing were more likely to be male and had more severe sleep disruption and nocturnal hypoxemia and more complaints related to daytime sleepiness than subjects without sleep-disordered breathing. In a multiple linear regression analysis, age and body mass index were significant predictors of the presence of sleep-disordered breathing, whereas smoking history and duration of heavy drinking were not predictors after controlling for the effects of age and body mass index. Our findings suggest that sleep-disordered breathing contributes significantly to sleep disturbance in a substantial proportion of older alcoholics and that symptomatic sleep-disordered breathing increases with age in alcoholics. Sleep-disordered breathing, when combined with existing cardiovascular risk factors, may contribute to adverse health consequences in alcoholics. PMID- 10029215 TI - Longitudinal changes in predictor profiles of abstinence from alcohol use among male veterans. AB - We examined variations in predictors of abstinence depending on the timing of follow-up after alcohol treatment using data from 298 males who completed inpatient treatment at a Midwestern VA Alcoholism Treatment Unit. Our findings indicate fluidity of abstinence and relapse across subjects in the 12 months posttreatment. We also found substantial shifts in the salience of predictors even across short periods of continued abstinence. Methodologically, these findings demonstrate the importance of multiple and closely spaced follow-up points in outcomes research. Substantively, our data support previous findings concerning the impact of increased medical severity, positive employment history, and depression on treatment outcomes. PMID- 10029216 TI - Alcohol dependence and abuse diagnoses: concurrent validity in a nationally representative sample. AB - The Alcohol Dependence Syndrome concept has had a widespread influence on the major nosological classification systems, most recently with its operationalization as DSM-IV alcohol dependence. Although many studies have provided evidence of the validity of the Alcohol Dependence Syndrome in clinical samples, little validation work has been conducted in general population samples on DSM-IV alcohol dependence or the distinction of DSM-IV alcohol dependence from DSM-IV alcohol abuse. We therefore examined the cross-sectional validity of DSM IV alcohol dependence and abuse in 27,616 household residents who participated in a 1992 national survey on alcohol use disorders. Validity was investigated by testing the association of a set of five "criterion" variables, external to the alcohol diagnostic criteria, with dependence and abuse diagnoses. Results indicated that dependence diagnoses were significantly associated with all criterion variables when compared with those with no diagnosis and also when compared with alcohol abuse. This supported the separation of dependence from abuse. Abuse diagnoses were associated with some, but not all, criterion variables when compared with subjects with no diagnosis. This report replicates many aspects of a similar investigation in a community sample of household residents. Implications for the next steps in research are discussed. PMID- 10029217 TI - Implications of depression on outcome from alcohol dependence: a 3-year prospective follow-up. AB - The prognostic implications of comorbid depression for outcome from alcohol dependence are unclear. It has been suggested that drinking may represent self medication of depressive disorders and, alternatively, that the pharmacological properties of alcohol induce episodes of depression. In the present study, these questions were investigated by following 84 alcohol-dependent individuals seeking treatment (34% women) for 3 years in a naturalistic, prospective design. During the follow-up period, depressive and drinking outcomes were significantly related. However, there was no evidence that drinking reliably preceded depressive episodes or that depressive episodes precipitated heavy drinking. Despite their high co-occurrence, this study did not find evidence of a strong, direct causal relationship between these phenomena. PMID- 10029218 TI - Localized proton magnetic resonance spectroscopy of the cerebellum in detoxifying alcoholics. AB - An increased daily alcohol consumption results in neurological symptoms and morphological central nervous system changes, e.g. shrinkage of the frontal lobes and the cerebellar vermis. Brain shrinkage can be due to neuronal loss, gliosis, or alterations of (cell) membrane constitutes/myelin. Neuronal, glial, and metabolic changes can be measured in vivo with proton magnetic resonance spectroscopy. A total of 11 alcoholics and 10 age-matched volunteers were examined by magnetic resonance imaging and localized magnetic resonance spectroscopy at an echo time of 135 and 5 msec. Peak integral values were calculated for N-acetylaspartate (NAA), choline (Cho), myo-inositol (ml), glutamate/glutamine (Glx), and normalized to phosphocreatine/creatine (Cr). Patients had a significant shrinkage of the cerebellar vermis. NAA/Cr and Cho/Cr ratios were reduced in both sequences, but the NAA/Cr reduction was only significant in long echo time, although the Cho/Cr reduction was significant in short echo time. The ml/Cr and Glx/Cr ratios did not show any significant difference between volunteers and patients. The decrease of NAA/Cr in alcohol dependent patients is consistent with neuronal loss. The Cho/Cr decrease and an unchanged ml/Cr may reflect cell membrane modification or myelin alterations in alcohol-dependent patients. These changes lead to brain shrinkage, although hydration effects and gliosis are less likely. PMID- 10029219 TI - Glial cell loss in the hippocampus of alcoholics. AB - Alcohol abuse is often accompanied by cognitive impairment. Memory and concentration problems, especially, are described in neuropsychologically tested abstinent alcoholics. This impairment seems to be reversible, because a neuropsychological study has reported that after >5 years of abstinence, former alcoholics performed normally compared with a control group. The neuropathological correlate to the cognitive impairment associated with alcoholism is still under debate. Hippocampus is an area of the brain primarily involved in learning and memory, and the hippocampus is affected in several demential diseases. Over recent years, it has become evident that the glial cells in the brain, especially the astrocytes, play a central part in many activities that are critical to the normal functions of the brain. The total number of neuron and glial cells in the hippocampus was estimated in five severely affected alcoholics and five controls with an unbiased stereological technique: the optical fractionator. A statistically significant loss of 37% of the glial cells was found globally in the hippocampus of the alcoholics compared with controls. A reduction of astrocytes and oligodendrocytes and, to a lesser degree, microglial cells accounted for this loss. No loss of neurons was found in the hippocampus from alcoholics. The loss of glial cells and the potential for regeneration of these cells after cessation of alcohol abuse is discussed in the light of the results of clinical studies of former alcoholics. PMID- 10029220 TI - Drinking, menstrual cycle, and female sexuality: a diary study. AB - Sexual feelings in connection with alcohol intake were investigated in 97 Finnish women aged 18 to 35 years. The subjects were drawn from a population sample and included both oral contraceptive users and nonusers. Structured diaries were used to monitor sexual feelings and alcohol intake during one menstrual cycle for each subject. Alcohol drinking was found to be significantly associated with elevated sexual interest and arousal in the post- and intermenstrual phases. We suggest that these phase-dependent effects could be due to known alcohol-mediated testosterone elevations. PMID- 10029221 TI - Clinical use of benzodiazepines and decreased memory activation in anxious problem drinkers. AB - Clinical use of benzodiazepines (BZDs) may improve treatment outcome in anxious problem drinkers. Decreased activation of alcohol-related memories by negative affective cues may partly explain the beneficial effects of BZDs. To explore this possibility, the present study assessed semantic priming of alcohol words by negative affective words in anxious problem drinkers who received their standard dose of BZD and in unmedicated controls. Two groups of nine subjects each were matched on levels of anxiety, alcohol use, and alcohol dependence before performing a lexical decision task. Medicated subjects displayed significantly less activation than did unmedicated subjects on trials containing negative affective primes and alcohol-related targets, but displayed equivalent activation on control trials with neutral, categorized words. Degree of activation also correlated with a drug's affinity for the BZD receptor. These preliminary results suggest that BZD-induced amnesia may contribute to the therapeutic effects of these drugs in anxious problem drinkers. PMID- 10029222 TI - Phases of alcohol problem prevention research. AB - We build on precedents from other health research to present a phases model of research for alcohol problem prevention that accommodates the special characteristics of this research. We propose a five-level model, in which research moves along a series of relevant continua: from basic to more and more applied research; from descriptive hypothesis-generating pilot studies to full fledged, methodologically sophisticated, hypothesis-testing studies; from smaller to larger samples for testing; from greater to lesser control of experimental conditions; from more artificial "laboratory" environments to real-world geographically defined communities; from testing the effects of single prevention strategies to more complex studies of multiple strategies integrated into intervention systems; and from research-driven outcome studies to "demonstration" projects that evaluate the capacity of various types of communities to implement prevention programs based on prior evaluations. The five phases of research are: (1) foundational research to define and determine the prevalence of specific alcohol-involved problems, establish causal factors and processes that yield the specific problems or increase the risk of a problem, and provide the foundations for the development of effective prevention interventions; (2) developmental (preliminary effectiveness) studies to develop and test the likely effectiveness, safety, and costs of new interventions or to assess the effectiveness, safety, and costs of an existing intervention; (3) efficacy studies to determine the effects, safety, and costs of an intervention under optimal conditions of implementation (or availability or enforcement) and acceptance (or adoption at the community, organizational, or group level; or participation, compliance, or adherence at the individual level); (4) effectiveness studies of the real-world effectiveness of preventive interventions with purposeful or natural variation in implementation and acceptance; and (5) demonstration studies of the effects of interventions when widely disseminated. The proposed phases model for alcohol problem prevention research presented herein differs in significant ways from the models established by other National Institutes of Health agencies. Greater emphasis is placed on natural experiments, on methods development along the whole research continuum, on collapsing or combining research phases when appropriate, on recognizing the critical importance of behavioral parameters early as well as late in the research sequence, and on extending the research continuum to embrace diffusion and dissemination (i.e., technology transfer) studies. We also include examples of phased research in existing alcohol studies and a discussion of relevant issues, including cost, special populations, methods, and dissemination. If systematically followed, this model has the potential to contribute to wider testing and dissemination of prevention interventions of known effectiveness. PMID- 10029223 TI - Occupational medicine in Korea. PMID- 10029224 TI - Environmental contamination and human exposure to manganese--contribution of methylcyclopentadienyl manganese tricarbonyl in unleaded gasoline. AB - The organomanganese compound MMT (methylcyclopentadienyl manganese tricarbonyl), an antiknock additive in unleaded gasoline, has been used in Canada since 1976. Indeed, Canada is the only country where MMT is almost exclusively used. In October 1995, by court decision the Environmental protection Agency (EPA) granted Ethyl's waiver for the use of MMT in the United States. Paradoxically, in 1997 the federal government of Canada adopted a law (C-29) that banned both the interprovincial trade and the importation for commercial purposes of manganese based substances, including MMT. However, MMT is currently widely used in Canada because of substantial stockpiling, and six Canadian provinces are challenging the law in the courts. Moreover, MMT has been approved for use in Argentina, Australia, Bulgaria, Russia, and conditionally, in New Zealand. It has been suggested by some scientists that combustion of MMT may be a significant source of exposure to inorganic Mn in urban areas. The crucial question is whether Mn contamination from industrial sources combined with the additional contamination that would result from the widespread use of MMT would lead to toxic effects. Our research efforts have attempted to assess the environmental/ecosystem Mn contamination arising from the combustion of MMT in abiotic and biotic systems as well as human exposure. The experimental evidence acquired so far provides useful information on certain environmental consequences of the use of MMT as well as raising a number of questions. Our results gave evidence indicating that roadside air, soils, plants, and animals may be contaminated by Mn. As well, some specific groups of the population could have a higher level of exposure to Mn. Nevertheless, the levels of exposure remain below international guide values. Further studies and further characterization of dose-response relationships are thus needed to provide successful implementation of evidence-based risk assessment approaches. PMID- 10029225 TI - Exposure-response relationships in rhinitis and conjunctivitis caused by methyltetrahydrophthalic anhydride. AB - OBJECTIVE: To examine exposure-response relationships in the occurrence of symptoms of the eyes and airways in workers exposed to methyltetrahydrophthalic anhydride (MTHPA). METHODS: A population of 111 workers from 2 condenser plants (A and B) using epoxy resin with MTHPA underwent a questionnaire survey and serology investigations, and data obtained on 95 subjects in assembly and inspection lines were analyzed for this study. RESULTS: In all, 24 (65%) of 37 workers in plant A and 38 (66%) of 58 workers in plant B had positive MTHPA specific IgE. The air levels of MTHPA detected in assembly and inspection lines were higher in plant A than in plant B (geometric mean 25.5-63.9 and 4.93-5.49 microg/m3, respectively). IgE-sensitized workers in each plant had significantly (P < 0.05) more complaints regarding the eyes and nose than did unsensitized workers, suggesting that there is an IgE-mediated mechanism in most of these symptoms. The sensitized workers in plant A had higher frequencies for symptoms of the eyes, nose, and pharynx than did those in plant B (P < 0.02). Furthermore, only 15% of persons often displayed work-related symptoms among the 20 symptomatic workers in plant B as compared with 73% of the 26 symptomatic workers in plant A (P < 0.0001). These results can be explained by the difference in the MTHPA levels measured in the lines between the two plants. In plant B the minimal level of MTHPA that was associated with work-related symptoms was 15-22 microg/m3, which was lower than the geometric mean levels detected in assembly and inspection lines in plant A. CONCLUSIONS: These results suggest that MTHPA exposure at levels above 15 microg/m3 should be avoided to prevent the development of occupational allergic diseases in most workers. PMID- 10029226 TI - Liver function in workers exposed to N,N-dimethylformamide during the production of synthetic textiles. AB - OBJECTIVE: In a factory producing synthetic fibers the hepatotoxic effects of the solvent N,N-dimethylformamide (DMF) were investigated in 126 male employees, especially with regard to the combination effects of DMF exposure and ethyl alcohol consumption. A collective of similar structure from the same factory served as a control collective. METHODS: Reference is made to the results of air measurements and biological monitoring presented in a previous publication. The DMF concentrations in the air ranged from < 0.1 (detection limit) to 37.9 ppm (median 1.2 ppm). Concentrations of the DMF metabolite N-methylformamide (NMF) in urine were 0.05-22.0 mg/l (preshift) and 0.9-100.0 mg/l (postshift), corresponding to 0.02-44.6 mg/g creatinine (preshift) and 0.4-62.3 mg/g creatinine (postshift). A standardized anamnesis was drawn up for relevant previous illnesses and other factors influencing liver function. The laboratory tests included parameters especially relevant to the liver (e.g., AST, ALT, gamma GT, hepatitis B and C antibodies, and carbohydrate-deficient transferrin). RESULTS: The results indicate a statistically significant toxic influence of DMF on liver function. Alcohol has a synergistic effect. The effects of DMF and those of alcohol are dose-dependent. Under the existing workplace conditions the hepatotoxic effects of alcohol are more severe than those of DMF. In the exposed group there was a statistically significantly greater number of persons who stated that they had drunk less since the beginning of exposure (13% versus 0). This corresponded with the data on symptoms occurring after alcohol consumption (71% versus 4%). In the work areas with lower-level exposure to DMF there was greater alcohol consumption. It corresponded to that of the control collective not exposed to DMF. CONCLUSION: In this study we tried to differentiate and quantify the interaction between DMF exposure and alcohol consumption and the influence of both substances on liver function. The experience gained from former occupational health surveillance in DMF-exposed persons and from the present study show that there are individual differences in tolerance of interactions between DMF and ethyl alcohol. Further studies are necessary for the evaluation of these individual degrees of susceptibilitiy. PMID- 10029227 TI - Expression of lymphocyte subpopulations, cytokine serum levels, and blood and urinary trace elements in asymptomatic atopic men exposed to an urban environment. AB - The objective of this study was to analyze the role of some trace metals in the immune system of nonallergic or atopic men. One of these elements (Zn) is essential for immune function, whereas others, present in the urban environment, are known to be allergenic (Ni and Cr) or toxic (Pb). Serum levels of interleukin (IL) 2, 4, 5, and 13 and of interferon-y and immunoglobulins, blood lymphocyte subsets, blood concentrations of Pb and Zn, serum levels of Zn, and urinary Cr and Ni concentrations were determined in 17 nonallergic men (mean age 34 years) and 17 healthy nonsymptomatic atopic men living in urban areas. The mean blood concentration of Pb (a marker of exposure to toxic agents) was 11 microg/dl in both groups, which showed similar levels of blood Zn and of urinary Ni and Cr, whereas the serum Zn concentration was lower in the atopic group. Serum IgE levels were much higher in atopic men than in nonallergics, whereas serum IL-2, IL-5, and IL-13 concentrations were lower, possibly due to binding to tissue receptors and cells. Moreover, in atopic subjects, numbers of blood CD4+-CD45RO "virgin" lymphocytes were significantly lower and the CD4+ -CD45RO+/CD4+ -CD45RO- ratio was more elevated, indicating an activation of the immune system. Serum IgE levels of atopic men, in contrast to those of nonallergic subjects, were correlated with CD19+ and CD5--CD19+ B lymphocytes. Blood Pb levels of both groups of men were correlated with CD4+, CD4+-CD45RO+, and HLA-DR+ [activated T-, B-, CO4+ -C. and natural killer (NK) cells] lymphocytes; in particular, blood Pb levels of the nonallergic men were also significantly correlated with CD25+ cells activated by IL-2, whereas those of the atopic men were also correlated with CD3- HLA-DR+ (B- and NK-cells) and CD5--CD19+ lymphocytes. Besides serum Zn levels, urinary Ni and Cr of nonallergic men were correlated with several immune parameters; in particular, urinary Cr was correlated with serum IL-5 and IgE and urinary Ni was correlated with CD4+ -CD45RO+ and CD3+ -CD25+ lymphocytes. This correlation of Ni and Cr, also found in previous studies in nonallergic subjects, confirms the hypothesis that these metals are involved in mechanisms of immune response regulation and that allergy to Ni or Cr represents an alteration of physiological mechanisms. Previous experimental studies have demonstrated that Pb exerts immunomodulatory effects on CD4+ and B- lymphocytes, enhancing the production of Th2-like cytokines and IgE. These experimental results confirm those of this study, showing in atopic men the correlation of B-lymphocytes with both blood Pb and serum IgE levels. This suggests that Pb may enhance the incidence of atopy in populations exposed to an urban environment. PMID- 10029228 TI - Outcome of occupational asthma due to platinum salts after transferral to low exposure areas. AB - OBJECTIVE: To assess the health effects of transferral to low-exposure jobs on subjects with occupational asthma (OA). METHODS: We performed a cross-sectional survey of 83 workers in 2 platinum (Pt) refineries and 2 catalyst production plants, all with diagnosed OA due to Pt salts. In all, 9 workers (group A; 11%) continued to be exposed at the time of examination, 16 subjects (group B; 19%) had been transferred to other workplaces within the production building, 39 subjects (group C; 47%) had been transferred to areas outside the building but inside the plant, and 19 subjects (group D; 23%) had left the plant. The median period from transferral to examination was 54 months (lower quartile 23 months, upper quartile 84 months, n = 74). Symptoms, skin-prick tests (SPT) with environmental allergens and Pt salt, total serum IgE, lung function, and bronchial hyperresponsiveness were assessed by standard procedures. RESULTS: Asthma symptoms were reported by all subjects in the production area but by only 37 of 74 subjects (50%) after transferral, with no difference being found between groups B, C, and D. Both the proportion of subjects sensitized to Pt salts (100%, 88%, 67%, and 42% in groups A, B, C, and D, respectively) and the degree of sensitization were associated with exposure (P < 0.0002). Total IgE was higher in group A as compared with groups B, C, or D (P < 0.002). There was no association between bronchial hyperresponsiveness and exposure. Although no univariate difference in FEV1 was found between the groups, regression analysis showed an association between FEV1 and exposure (P < 0.002). In all, 13 subjects demonstrated a predicted FEV1 value of <80% (22%, 6%, 10%, and 32% in groups A, B, C, and D, respectively). They were older (median 49 versus 37 years; P < 0.002) and had worked over longer periods in high-exposure areas in spite of symptoms (median 43 versus 10 months; P < 0.003). Fifteen subjects of groups C or D had been removed from areas B previously, eight of them due to respiratory symptoms. CONCLUSIONS: For the majority of subjects with OA due to Pt salts transfer to low exposure areas as defined in this study may not be associated with a more unfavorable outcome as compared with complete removal from exposure sources. PMID- 10029229 TI - The influence of personal protection, environmental hygiene and exposure to pesticides on the health of immigrant farm workers in a desert country. AB - OBJECTIVES: Farm workers in developing countries tend not to use protective measures while handling pesticides. This study investigates the use of personal protection equipment and the practice of safety and hygiene procedures in the handling of pesticides in agriculture. METHODS: Through a multi-stage sampling technique, one-fifth of the farms in a region were selected and all the farm workers at these farms were included in the study. A comparison population matching in age, socio-economic status and stay in the region was selected. A specifically designed questionnaire was used to collect information on the use of protective measures and the practice of safety and hygiene during work and on the disposal of empty pesticide containers. Blood pressure and erythrocyte acetylcholinesterase (AChE) activity were measured in the exposed and the unexposed populations. RESULTS: Protective equipment was worn by a minority of farm workers - gloves, by 35%; work coveralls, by 36%; a scarf to cover the nose and mouth, by 39%; and shoes at work, by 79%. With regard to personal hygiene measures, 83% of the workers changed clothes after work and the same proportion took a shower after work; 63% and 46% drank and ate while at work respectively; and 11% used articles of domestic use in the preparation of pesticides on the farm. Most of the farm workers (96%) were asked to prepare pesticides for spraying by the foreman and 61% were asked to spray the pesticides on the crops. AChE activity was highly significantly depleted in the exposed population as compared with the unexposed population. CONCLUSIONS: AChE depletion was found to be negatively associated with the use of gloves, of work coveralls, and of a scarf to cover the nose and mouth and with the implementation of safety and hygiene procedures on the farm. AChE depletion was positively associated with the frequency of pesticide spraying. PMID- 10029230 TI - Estimation of the percutaneous absorption of styrene in an industrial situation. AB - OBJECTIVE: This field study was designed to compare the level of styrene absorbed percutaneously with that absorbed by inhalation in a real situation in the fiberglass-reinforced polyester industry. METHODS: The study protocol consisted of comparisons of the patterns of urinary excretion of styrene metabolites by four groups of workers, all of whom performed the same task at the same time in the same workshop but wore the following different protective equipment: total protection with an insulating suit and mask, respiratory equipment only, percutaneous protection only, and no protection. RESULTS: The urinary excretion level of the group with total protection did not significantly differ from that of the group with respiratory protection only. CONCLUSIONS: Precutaneous absorption is not a particularly important pathway for styrene absorption during stratification work in the polyester industry. Completely insulating personal protective equipment provides no greater level of protection than does a respirator at positive pressure alone. PMID- 10029231 TI - Occupational chronic exposure to organic solvents XVII. Ambient and biological monitoring of workers exposed to xylenes. AB - OBJECTIVE: Ambient-air and biological monitoring of occupational xylene exposure were carried out on 2 groups of workers (13 and 10 men, respectively) exposed to a mixture of xylenes during the production of paints or during spraying. METHODS: Personal ambient-air monitoring was performed for one complete work shift. Blood and urine samples were collected directly at the end of the shift. Biological monitoring was based on the determination of the concentration of xylenes in blood and on the quantification of the sum of the three methylhippuric acids in urine. RESULTS: Average xylene ambient-air concentrations were 29 ppm (production) and 8 ppm (spraying), ranging from 5 to 58 ppm and from 3 to 21 ppm, respectively. The concentrations of xylenes in blood ranged from 63 to 715 microg/l and from 49 to 308 microg/l, with average values being 380 and 130 microg/l, respectively. Accordingly, the workers engaged in paint production also excreted more methylhippuric acids in their urine (average 1221 mg/l, range 194 2333 mg/l) than did the sprayers (average 485 mg/l, range 65-1633 mg/l). DISCUSSION: Our results as well as a literature review indicate that occupational xylene exposure on average barely exceeds the threshold limit value of 100 ppm as proposed by both American and German institutions. Biological monitoring based on the determination of xylenes in blood and of methylhippuric acids in urine provides sufficient sensitivity and specificity for occupational health surveillance. The results also confirm the current limit values (BAT values) proposed by the Deutsche Forschungsgemeinschaft for xylenes in blood (1500 microg/l) and methylhippuric acids in urine (2000 mg/l). PMID- 10029232 TI - Health reasons for leaving the profession as determined among Finnish hairdressers in 1980-1995. AB - BACKGROUND: Selection into and out of a profession is a known phenomenon in jobs such as hairdressing, in which the workers are exposed to agents and conditions capable of causing work-related symptoms and diseases. OBJECTIVE: To assess the risk for departure from the profession due to health and other reasons among hairdressers as compared with women engaged in commercial work. METHODS: We used a self-administered questionnaire to provide data on 3484 female hairdressers and 3357 referents with regard to their reasons for leaving the profession during the 15-year follow-up period of 1980 1995, for which the relative risks (RR) and 95% confidence intervals (CI) were calculated. The data were collected in August 1995. RESULTS: Of the reasons studied, only the concern for health increased the risk of leaving the profession (RR 1.33; 95% CI 1.16-1.52) among hairdressers. The risk of hairdressers having to leave the profession (1) because of asthma or hand eczema was 3.5 times as great as that found among the control group, (2) because of a strain injury of the wrist or elbow was 2.7 times as great, and (3) because of diseases of the neck or shoulders was 1.7 times as great. The risk of leaving the profession was approximately 20% higher for hairdressers who had suffered at some point in their lives from an atopic disease. CONCLUSIONS: Hairdressers suffering from atopic diseases, hand eczema, and strain injuries of the elbow and wrist are at higher risk of leaving the profession. Active modes of intervention are needed to maintain their working ability. The tools available in the occupational health service are: information on hazards, optimization of working conditions, personal protection, and timely medical care and rehabilitation. PMID- 10029233 TI - Report on the status of the external quality-control programs for occupational medical and environmental-medical toxicological analyses in biological materials in Germany. PMID- 10029234 TI - N-tert-butyl-alpha-phenylnitrone protects against 3,4 methylenedioxymethamphetamine-induced depletion of serotonin in rats. AB - The present study examined the effect of N-tert-butyl-alpha-phenylnitrone (PBN) on 3,4-methylenedioxmathamphetamine (MDMA)-induced depletion of serotonin in the CNS. Rats were treated with two concurrent injections of MDMA (20 mg/kg, s.c.), PBN (50-400 mg/kg dissolved in ethanol, 50 mg/ml of 25% ethanol, i.p.), saline or 25% ethanol, alone or in combination, 6 h apart, and sacrificed 5 days later. Rectal temperature was measured prior to and hourly following the drug injection for 5 h. Monoamine levels in the tissue were measured by HPLC. Density of the 5 HT transporters was assayed by [3H]paroxetine binding. Rectal temperature of rats increased after MDMA, decreased after PBN, ethanol, PBN plus ethanol, and MDMA plus ethanol, and was not significantly altered after MDMA plus PBN. Levels of 5 HT and 5-HIAA in the frontal cortex, hippocampus, striatum, and brain stem of rats decreased significantly after MDMA or MDMA plus ethanol, but not after MDMA plus PBN, PBN plus ethanol (PBN dissolved in ethanol), or ethanol as compared to the saline controls. Levels of 5-HT and 5-HIAA in the brain tissues of rats treated with MDMA plus PBN were elevated as compared to those treated with MDMA plus saline. Similar results were observed in the density of 5-HT transporters in the frontal cortex and hippocampus. These results indicate that scavenging of free radicals of MDMA metabolites or reactive oxygen species by PBN and with lowering of body temperature protected against MDMA-induced depletion of serotonin transmitter. PMID- 10029235 TI - Comparison between the decrease of dopamine transporter and that of L-DOPA uptake for detection of early to advanced stage of Parkinson's disease in animal models. AB - Early diagnosis of Parkinson's disease (PD) is important for the potential application of neuroprotective therapies. The purpose of this study was to assess the detection of the early changes of PD by either imaging the dopamine transporter (DAT) or uptake of L-3,4-dihydroxyphenylalanine (L-DOPA). An early to advanced stage model of PD was induced in rats by stereotaxic injection of 1-10 microg 6-hydroxydopamine (6-OHDA) into the substantia nigra pars compacta. Using adjacent sections of the same animals, the binding of [I-125]beta-CIT, which labels DAT and the uptake of [C-14]L-DOPA, were evaluated 4 weeks after induction of the lesion. Any decrease in dopaminergic neurons was evaluated by in situ hybridization histochemistry (ISH) by detection of DAT mRNA-positive neurons. In addition, the expression levels of DAT, dopa decarboxylase (DDC), and vesicular monoamine transporter (VMAT2) in each neuron were studied with ISH. Our results show a decrease in both [I-125]beta-CIT binding and [C-14]L-DOPA uptake in parallel with a decrease in DA neurons from early to advanced stage models of PD. The decrease in [C-14]L-DOPA uptake was smaller than that in [I-125]beta-CIT binding in the same animal (P < 0.0001). Expression levels of DAT, DDC, and VMAT2 mRNAs were also decreased with the progression of the disease. Although ISH failed to detect the origin of the discrepancy between [I-125]beta-CIT and [C 14]L-DOPA levels, it was concluded that [C-14]L-DOPA levels underestimated the decrease of dopaminergic neurons and that [I-125]beta-CIT levels more precisely reflected the decrease. PMID- 10029236 TI - Agonist- and antagonist-induced plasticity of rat 5-HT1A receptor in hippocampal cell culture. AB - We examined the response and regulation of 5-HT1A receptor on hippocampal cultured fetal neurons grown in the absence of serotonin and steroids using three experimental designs: 1) functional response using an antibody against phosphorylated cyclic adenosine monophosphate response element binding protein (pCREB); 2) transcriptional regulation using in situ hybridization; and 3) translational expression using antipeptide 5-HT1A receptor antibody. Pretreatment of cultured hippocampal cells with the agonist 8-hydroxy-2-(di-N-propylamino) tetralin (8-OH-DPAT) (10(-8) M) or ipsapirone (IPS) (10(-9) M) for 10 min blocked the forskolin-stimulated increase in pCREB immunoreactivity. In situ hybridization radioautography revealed that IPS (10(-9) M) decreased the 5-HT1A receptor mRNA expression (-33%) after a 24-h treatment. The decrease in 5-HT1A receptor mRNAwas accompanied by a change in protein immunoreactivity using a 5 HT1A receptor antipeptide antibody. Computer-assisted morphometric analyses showed a reduction in the 5-HT1A receptor immunoreactive (IR) intensity as compared to control 24 h after treatment with 8-OH-DPAT (10(-7)-10(-12) M) and IPS (10(-9) M). Thus, fetal hippocampal neurons have a functional 5-HT1A receptor that is downregulated at both the transcription and translation levels. In addition, we found increased 5-HT1A receptor-IR intensity (+17% approximately +39%) 24 h after treatment with the antagonist N-[2-[4-(2-methoxyphenyl)-1 piperazinyl]ethyl]-N-(2-pyridinyl) cyclohexane carboxamide (WAY 100635) (10(-7) 10(-12) M). Our results indicate that the 5-HT1A receptor is sensitive to both agonists (downregulation) and antagonists (upregulation) in hippocampal fetal neurons grown in the absence of serotonin and steroids. PMID- 10029237 TI - Norepinephrine promotes long-term potentiation in the adult rat hippocampus in vitro. AB - We previously found a reduction in the ability of a single 100 Hz x 1 sec tetanus to induce long-term potentiation (LTP) in the CA1 region of hippocampal slices prepared from adult animals. To determine whether this reduction in LTP generation results from changes in neuromodulator function, we examined the ability of several neuromodulators to promote LTP in slices prepared from mature rats. Although acetylcholine, N-methyl-D-aspartate, and an agonist at metabotropic glutamate receptors failed to promote LTP, administration of norepinephrine allowed robust LTP. The effects of norepinephrine were mimicked by an alpha1-adrenergic agonist and were blocked by an alpha1-receptor antagonist. Beta-adrenergic agonists and antagonists were ineffective. These results suggest that norepinephrine acting via alpha1-adrenoceptors may be an important cofactor in promoting lasting synaptic plasticity in the adult central nervous system and that changes in adrenergic function may contribute to maturation- or aging associated changes in memory function. PMID- 10029238 TI - Heparin modulates the single channel kinetics of reconstituted AMPA receptors from rat brain. AB - Glutamate receptors specifically activated by alpha-amino-3-hydroxy-5 methylisoxazole-4-propionic acid (AMPA) have been reported to interact with the highly sulfated glycosaminoglycan, heparin, and to subsequently express lower binding affinity for [3H]AMPA. The present study examined whether heparin also modifies the kinetic properties of single channel activity expressed by isolated AMPA receptors from rat forebrain. Upon application of 280 nM AMPA, the partially purified receptors reconstituted in lipid bilayers expressed bursting channel activity that was inhibited by dinitroquinoxaline-2-3,-dione (DNQX). Treating the receptors with heparin (10 microg/ml) produced no change in conductance but the mean burst length for 280 nM AMPA was nearly doubled. Heparin also prolonged the lifetime of open states of the individual ion channels 3-5-fold, perhaps by causing a decrease in the closing rate constant for channel gating. Heparin had no effect on the lifetime of the closed state or on the amplitude of currents. The single channel open time was voltage-dependent and an increase of applied voltage caused a decrease in the heparin effect on channel open times. While the lifetime of the open channel was increased 3-4 times by heparin at 20 mV, there was no significant change induced at 43 mV. The equivalent electric charge of the channel gate was increased by 40%. The heparin effects were specific as another polysaccharide, dextran, and a monomeric constituent of heparin, glucosamine 2,3 disulfate, failed to have any effect on the receptors. These findings suggest that heparin-containing extracellular matrix components can interact with AMPA receptors and influence their functional properties. PMID- 10029239 TI - Dopamine D3 receptor mutant and wild-type mice exhibit identical responses to putative D3 receptor-selective agonists and antagonists. AB - Previous studies using a variety of drugs with different affinities for the dopamine (DA) D3 receptor suggested that this receptor is involved in regulating motor activity and hypothermia. However, the in vivo selectivity of many of these compounds has been repeatedly questioned. To examine the precise roles of the DA D3 receptor in motor activity and hypothermic responses, we used mutant mice lacking the DA D3 receptor to evaluate the in vivo effects of several putative D3 receptor-selective agonists and antagonists. Using automated photocell activity chambers, we observed that the decreases in locomotor activity produced by putative D3 receptor-selective agonists as well as increases in locomotor activity produced by putative D3 receptor antagonists are identical in D3 receptor mutant and wild-type mice. In addition, the hypothermia produced by the putative D3 receptor-selective agonist PD 128907 is identical in both groups of mice. Based on these findings, we propose that D3 receptors are unlikely to be involved in these effects and we caution that the putative D3 ligands that have been used to reach conclusions regarding the functional roles of D3 receptors lack the necessary in vivo selectivity to support such conclusions. PMID- 10029240 TI - Quantitative immunoelectron microscopic colocalization of GABA and enkephalin in the ventrocaudal periaqueductal gray of the rat. AB - In the present ultrastructural study in the ventrocaudal periaqueductal gray (PAG) of the rat, the relationship and the association between GABAergic and enkephalinergic neuronal elements were investigated using postembedding colocalization immunogold electron microscopic technique in order to establish the precise relationship between these two important neurotransmitters in this part of the brain stem. The GABA-like neuronal elements were immunoreacted with 20 nm gold particles and the enkephalin (ENK)-like immunoreactive neurons were labeled with 10 nm gold particles. Double labeling of sections with ENK and GABA produced colocalization in 23.3% and 1.2% of axon terminals and dendrites, respectively. Most of the double-labeled terminals contained more GABA-like than ENK-like immunolabeling. Approximately 19.4% of the labeled axon terminals and 8.5% of the labeled dendrites contained only GABA-like immunoreactivity, while 24% of the immunolabeled dendrites were immunoreactive with only ENK-like immunoreactivity. The synapses between the two kinds of immunolabeled neuronal profiles appear to be both asymmetrical and symmetrical. GABA-like immunolabeled terminals contained small, clear, pleomorphic or round vesicles and were found to make synapses with ENK-like immunolabeled and nonimmunolabeled dendrites, whereas most of the ENK-like immunolabeled axon terminals contained dense-cored vesicles. Approximately half of the axon terminals (51%) and dendrites (56%) in the ventrolateral PAG were not labeled for either GABA or for ENK immunoreactivity. The results are discussed in terms of GABAergic inhibition of antinociceptive mechanisms in the ventrolateral PAG and of the activation of these mechanisms by ENK neurotransmitter. PMID- 10029241 TI - Augmentation of locomotor activity by chronic phencyclidine is associated with an increase in striatal NMDA receptor function and an upregulation of the NR1 receptor subunit. AB - Phencyclidine (PCP) is a drug of abuse that produces schizophrenia-like symptoms in humans and increases locomotor activity and stereotypic behavior in rodents. PCP-induced alteration in rat locomotor activity is thought to be mediated by an inhibition of N-methyl-D-aspartate (NMDA) receptors in the striatum and other brain regions. In this study, rats treated chronically with PCP (20 mg/kg once per day for 5 days) showed a marked increase in locomotor activity following a PCP challenge (3.2 mg/kg) administered after either 3 or 8 days of withdrawal. In biochemical assays, the release of striatal [14C]GABA by NMDA was enhanced by about 77% by chronic PCP treatment, whereas [3H]ACh release was increased by about 31% in tissue from PCP-treated rats. Even though binding experiments with 1 [1-(2-thiethyl)cyclohexyl]piperidyl-3,4 3H(N) ([3H]TCP) showed no alteration in the Kd or Bmax in whole striatum, quantitative immunocytochemical experiments found an upregulation in the NR1 subunit in the cell bodies and neuropil of cortical and striatal regions of the forebrain following chronic PCP treatment. An increase in the size of NR1-immunoreactive cells in the forebrain was also observed following chronic PCP treatment. Together, these data may help in understanding the mechanisms underlying the adaptive response to chronic reduction in glutamatergic NMDA transmission that has been postulated to be involved in the etiology of schizophrenia. PMID- 10029242 TI - Dynamics of provirus load and lymphocyte subsets after interleukin 2 treatment in HIV-infected patients. AB - The association of antiretroviral agents plus interleukin 2 (IL-2) represents an efficient approach to the treatment of HIV+ subjects. While the effects of IL-2 on the immune system have been investigated, little is known concerning its impact on HIV dynamics. Two antiretroviral drugs control HIV viremia, but have minimal effects on the proviral load, a predictor of disease progression and response to therapy. The aim of this study was to define the effect of rIL-2 on HIV proviral copy numbers and its relationship to changes in CD4+ and CD8+ subsets. Twelve HIV+ patients with CD4 cell counts between 200 and 500 cells/mm3 were treated with six cycles of subcutaneous rIL-2, in combination with zidovudine and didanosine. This regimen resulted in a rapid and durable decrease in proviral load in the peripheral blood, in an increase in CD8+ lymphocytes, and in the emergence of a CD4+CD45RA+ T subset. These results demonstrate that the rationale for IL-2 administration to HIV+ patients may depend not only on its effects on the immune system, but also on the reduction of the number of infected cells, reinforcing the notion that IL-2 can have a favorable impact on the natural history of HIV infection. PMID- 10029243 TI - Therapeutic vaccination with p24-VLP and zidovudine augments HIV-specific cytotoxic T lymphocyte activity in asymptomatic HIV-infected individuals. AB - This study evaluates the impact of therapeutic vaccination with p24-VLP and zidovudine on the induction or maintenance of HIV-specific cytotoxic lymphocyte activity in a cohort of asymptomatic patients with CD4 counts greater than 400 cells/microl. In a dummy, randomized, phase II clinical trial of the therapeutic vaccine, participants were randomized to one of three arms for 6 months: p24-VLP (500 microg) in alum monthly plus zidovudine 200 mg tds, alum adjuvant plus zidovudine, or p24-VLP plus placebo. Subjects were studied for a total of 52 weeks from baseline. Monitoring included viral load, CD4 and CD8 counts, markers of immune activation, delayed-type hypersensitivity (DTH) skin testing, and cytotoxic T lymphocyte (CTL) measurement. The nine subjects who received p24-VLP and zidovudine had an augmentation and/or broadening of their CTL response compared with baseline (p = 0.004). The eight subjects receiving p24-VLP and seven subjects receiving zidovudine did not have a statistically significant increase or broadening of CTL activity. The augmentation of the CTL response in the subjects who received p24-VLP and zidovudine was not associated with a decline in viral load or an increase in CD8 counts. This study suggests that HIV specific CTL activity can be augmented in HIV-infected individuals receiving p24 VLP and zidovudine, supporting the hypothesis of therapeutic vaccination in the presence of antiretroviral therapy. PMID- 10029244 TI - HIV-1MN recombinant glycoprotein 160 vaccine-induced cellular and humoral immunity boosted by HIV-1MN recombinant glycoprotein 120 vaccine. National Institute of Allergy and Infectious Diseases AIDS Vaccine Evaluation Group. AB - We evaluated prime-boost immunization with two recombinant envelope glycoprotein subunit vaccines (HIV-1MN recombinant gp160 vaccine in alum adjuvant [MN rgp160] and HIV-1MN recombinant gp120 vaccine in alum adjuvant [MN rgp120]) for safety and immunogenicity in healthy, HIV-1-uninfected adults. The rationale was to combine the helper T cell memory and binding antibody responses typically induced by rgp160 vaccines with the superior neutralizing antibody responses induced by rgp120 vaccines. In a double-blinded, controlled trial, volunteers were randomly assigned to receive MN rgp160 or adjuvant placebo, and a subset later received MN rgp120. The two vaccines were safe, but reactions to MN rgp160 and its adjuvant placebo exceeded those to MN rgp120. MN rgp160 induced IgG binding antibodies, including all IgG subclasses, to MN rgp160 in all vaccine recipients. HIV-1MN neutralizing and anti-V3 MN peptide-binding antibodies were observed in a majority of volunteers after the fourth MN rgp160 immunization, but at lower levels compared with immunization with MN rgp120 in historical controls. HIV-1 binding, neutralizing, and fusion inhibition antibodies were boosted to the highest levels among MN rgp160 recipients after MN rgp120 booster injections. MN rgp120 boosting appeared to alter the distribution of MN rgp160 vaccine-induced, anti-MN rgp160 IgG subclass antibodies. MN rgp160 induced helper T cell memory, measured by lymphocyte proliferation, Thl and Th2 cytokine production, and skin testing. Strategies including both subunit vaccines may help maximize antibody and helper T cell memory responses to HIV-1 envelope glycoprotein. PMID- 10029245 TI - Impact of HIV type 1 subtype variation on viral RNA quantitation. AB - We evaluated the performance of three HIV-1 RNA quantitation methods (Amplicor HIV-1 MONITOR-1.0, NASBA, and Quantiplex HIV RNA 2.0 [branched DNA (bDNA)]) using plasma specimens (N = 60) from individuals from Asia and Africa infected with one of three HIV-1 subtypes (A, Thai B [B'] or E; N = 20 each). Our results demonstrate that of the 20 subtype A specimens, 19 were quantifiable by the bDNA assay compared with 15 by the MONITOR-1.0 and 13 by NASBA. Of those quantifiable, the mean log10 difference was 0.93 between bDNA and MONITOR-1.0 and 0.46 between bDNA and NASBA. For subtype B' specimens, the correlation among methods was better with only 2 specimens missed by NASBA and 3 by the bDNA assay. However the missed specimens had viral burden near the lower limit (1000 copies/ml) for these assays. For the 20 subtype E specimens, MONITOR-1.0 and NASBA quantified RNA in 17 and 14 specimens, respectively, as compared with 19 specimens quantified by the bDNA assay. The correlation among different assays, especially between bDNA/NASBA and MONITOR-1.0/NASBA, was poor, although the mean log10 difference for subtype E specimens was 0.4 between bDNA and MONITOR-1.0 and only 0.08 between bDNA and NASBA. The addition of a new primer set, designed for non-B HIV 1 subtypes, to the existing MONITOR assay (MONITOR-1.0+) resulted in RNA detection in all 60 specimens and significantly improved the efficiency of quantitation for subtypes A and E. Our data indicate that HIV-1 subtype variation can have a major influence on viral load quantitation by different methods. Periodic evaluation and modification of these quantitative methods may be necessary to ensure reliable quantification of divergent viruses. PMID- 10029246 TI - Distribution of the human immunodeficiency virus coreceptors CXCR4 and CCR5 in fetal lymphoid organs: implications for pathogenesis in utero. AB - HIV entry into a cell requires the coordinate cell surface expression of CD4 and one of several chemokine coreceptors. Here we have examined the expression of the two most widely utilized HIV coreceptors, CXCR4 and CCR5, on various lymphoid tissues derived from the fetus. CXCR4 and CCR5 are differentially expressed on lymphocytes in different lymphoid organs, which may reflect the maturational and functional status of cells within the organ. The different levels of coreceptor expression on CD4+ cells in the various organs may directly affect the targeting of CXCR4- and CCR5-tropic strains of HIV toward different fetal lymphoid tissues during in utero infection. PMID- 10029247 TI - Increased association of glycoprotein 120-CD4 with HIV type 1 coreceptors in the presence of complex-enhanced anti-CD4 monoclonal antibodies. AB - CD4-specific monoclonal antibodies (CG1, CG7, and CG8), which bind with a 5- to 10-fold higher avidity to preformed CD4-gp120 complexes than to CD4, were previously shown to recognize newly identified conformational epitopes in the D1 CDR3 region of CD4. In the current study, these and other complex-enhanced MAbs were tested in three separate assays of HIV-1 coreceptor (CXCR4/CCR5) recruitment. In these assays, the CD4-specific MAbs CG1, -7, and -8 stabilized the association of coreceptor, gp120, and CD4 in trimolecular complexes. In contrast, the gp120-specific, complex-enhanced MAbs 48d and 17b were inhibitory. These data suggest that conformational changes in the CDR3 region of CD4-D1, induced by gp120 binding, may be involved in coreceptor association and thus play a positive role in the HIV-1 cell fusion process. PMID- 10029248 TI - Altered expression of CD4, CD54, CD62L, and CCR5 in primary lymphocytes productively infected with the human immunodeficiency virus. AB - Infection of T cells with HIV-1 induces loss of CD4 and HLA class I from the cell surface. In the present article we have investigated whether changes in expression of other cell surface molecules could be related to HIV infection. To detect HIV-infected cells at the single-cell level, peripheral blood lymphocytes were infected in vitro with HIV-HSA, a reporter virus encoding the murine heat stable antigen. Expression of HSA on activated primary lymphocytes was an efficient indicator of productive infection. Expression of the majority of the cell surface proteins studied was unaffected by HIV infection (HLA class I, II, CD11a, CD18, CD25, CD27, CD28, CD29, CD30, CD31, CD38, CD44, CD45R0, CD49d, CD57, CD94, CD95, and CXCR4). However, phenotypic changes specific to the productively infected cells were detected. Expression of the CD4 molecule was progressively lost and this was closely associated with loss of CD62L expression, a molecule involved in T cell homing into the lymph nodes. By contrast, T cells productively infected with this T-tropic reporter virus were enriched for CD54, and for CCR5, the main coreceptor for M-tropic viruses. Given the roles of CD62L, CD54, and CCR5 in lymphocyte trafficking, these results suggest that cells productively infected with HIV might have altered homing patterns in vivo. PMID- 10029249 TI - Increased expression of CD80 and CD86 in in vitro-infected CD3+ cells producing cytoplasmic HIV type 1 p24. AB - Determining the effects of HIV infection on the expression of cell surface molecules has been limited by an inability to differentiate between productively infected cells and those without productive infection. We inoculated human peripheral blood mononuclear cells from healthy, human immunodeficiency virus type 1 (HIV) antibody-negative donors with HIV; noninoculated cells were also examined. Using multiparameter flow cytometry, we differentiated cells actively producing HIV cytoplasmic p24 antigen during acute, in vitro HIV infection from those not producing detectable cytoplasmic p24. For both resting and PHA stimulated cells inoculated with HIV (R/H and P/H), a higher proportion of p24+ cells expressed CD25, compared with p24-cells (p = 0.031 and p = 0.008, respectively), consistent with either increased viral replication in stimulated cells or increased stimulation secondary to productive HIV infection. Findings were similar for the expression of CD38, HLADR, and CD28. A striking proportion of p24+ cells expressed CD80 or CD86, antigens not usually expressed by CD3+ lymphocytes. The increased expression appeared to be independent of stimulation status in that it occurred in both the R/H and P/H treatment groups but not in resting or PHA-stimulated uninfected cells. CD28 expression was generally comparable between CD3+ cells that did and did not express CD80 or CD86. Multiparameter flow cytometry, in association with improved techniques for cell permeabilization and cytoplasmic fluorescent staining, should prove useful in examining the effects of productive HIV infection on surface and cytoplasmic cellular molecules. Using this approach, we found an association between productive infection and increased expression of CD80 and CD86. This association has implications for HIV disease pathogenesis and, potentially, HIV therapy. PMID- 10029250 TI - Virus threshold determines disease in SIVsmmPBj14-infected macaques. AB - Simian immunodeficiency virus (SIV) variant SIVsmmPBj14 is unique in producing an acutely lethal enteropathic syndrome in pigtail macaques. To determine whether the nature of the PBj14 disease would be attenuated by decreasing virus input and to relate tissue virus burden to the severity of disease, we infected pigtail macaques with serial 10-fold doses of SIVsmmPBj14 clone bcl.3 spanning 10(-2) through 10(4)TCID50. The results revealed a strikingly narrow difference between minimum infectious and fatal disease-inducing doses and a close association between enteric lymphoid tissue virus burden and disease. All animals infected with as much as 10(4) TCID50 through as little as 100 TCID50 of virus died of the lethal PBj14 syndrome between 7 and 13 days postinfection. Animals receiving 10( 1) TCID50 became infected (PCR+) but did not develop clinical disease. Animals receiving 10(-2) TCID50 did not become infected. The clinical syndrome was surprisingly similar in all affected macaques, although the time to disease onset and total survival time increased slightly as virus input decreased from 10(4) to 10 degrees TCID50. Highest terminal virus loads in plasma, gut-associated lymphoid tissue (GALT), and lymph nodes and greatest lesion severity were attained at intermediate levels of virus input (10(1) to 10(2) TCID50), probably owing to optimal time for virus amplification in target tissues. The present study reinforces others on the PBj14 system, suggesting that once a threshold level of virus replication is attained in intestinal lymphoid tissues, the cascade of events precipitating the lethal PBj14 syndrome is triggered irreversibly. PMID- 10029251 TI - Effect of complement consumption by cobra venom factor on the course of primary infection with simian immunodeficiency virus in rhesus monkeys. AB - Cobra venom factor (CVF)-induced consumption of complement proteins was used to investigate the role of complement in vivo in the immunopathogenesis of simian immunodeficiency virus of macaques (SIVmac) infection in rhesus monkeys. Repeated administration of CVF was shown to deplete complement to <5% of baseline hemolytic activity of serum complement for 10 days in a normal monkey. Three groups of SIVmac-infected animals were then evaluated: monkeys treated with CVF resulting in complement depletion from days -1 to 10 postinfection, monkeys treated with CVF resulting in complement depletion from days 10 to 21 postinfection, and control monkeys that received no CVF. CD8+ SIVmac-specific cytotoxic T lymphocyte (CTL) generation and CD4+ T lymphocyte depletion during primary infection were not affected by CVF treatment. Viral load, assessed by measurements of plasma p27gag antigen and viral RNA, was transiently higher during the first 4 weeks following infection in the CVF-treated monkeys and the subsequent clinical course in these treated animals was accelerated. These results suggest that complement proteins may participate in immune defense mechanisms that decrease virus replication following the initial burst of intense viremia during primary SIVmac infection. However, we cannot rule out that the observed increased virus replication was induced by immune activation resulting from the administration of a foreign antigen to these monkeys. PMID- 10029252 TI - In vivo cell and tissue tropism of SIVsmmPBj14-bcl.3. AB - To gain insight into the unique pathogenicity of simian immunodeficiency virus (SIV) variant PBj14, which produces an acutely lethal enteropathic syndrome in infected pigtail macaques, we investigated the cell and tissue tropisms of a highly pathogenic biologic clone (bcl.3) of SIVsmmPBj14. To compare the relative amount of viral antigen in lymphoid organs of infected macaques we used an objective semiquantitative immunohistochemistry (sQIHC) assay. We found that in all animals viral antigen load was greater in alimentary-associated lymphoid tissues (gut-associated lymphoid tissue [GALT], tonsil, mesenteric and retropharyngeal lymph nodes) than in non-alimentary-associated lymphoid tissues (spleen, thymus, inguinal and axillary lymph nodes). Moreover, in six of nine animals examined, virus load in GALT was greater than that in any other lymphoid tissue. To determine whether the acute pathogenicity and prolific replication of SIVsmmPBj14 might be explained by a broader in vivo cell tropism than is typical of SIVs, we used cell subset separation and nested PCR. We found that the primary target cells in mesenteric lymph node for SIVsmmPBj14 were CD4+ T lymphocytes. However, the virus also infected macrophages, as well as CD8+ T cells and B cells, albeit at low frequencies. These results suggest that alimentary lymphoid tissue localization rather than unusual cell phenotype tropism distinguishes the singular pathogenesis of SIVsmmPBj14. PMID- 10029253 TI - Dual transmission of subtype A and D HIV type 1 viruses from a Ugandan woman to her infant. PMID- 10029254 TI - Outbreak of severe neurologic involvement associated with Enterovirus 71 infection. AB - Enterovirus 71 has been associated with several outbreaks, as well as sporadic cases, of central nervous system infection and has a worldwide distribution. Seven children with encephalitis and five with aseptic meningitis caused by Enterovirus 71 were seen at Otsu Municipal Hospital during the summer of 1997. The infections were confirmed serologically, although detection of the viral genome in cerebrospinal fluid was unsuccessful. Seven children were diagnosed as having hand-foot-and-mouth syndrome, two were diagnosed as having herpangina, and three patients younger than 12 months old developed no eruptions. The skin or mucosal manifestations of this outbreak demonstrated considerable variation. The Enterovirus 71 strain that caused the outbreak had a strong neurovirulent tendency. Among the patients with encephalitis, symptoms originating from the impairment of diencephalon were seen in four patients, and those originating from cerebellar impairment were seen in two patients. Brain magnetic resonance imaging in one patient revealed an abnormality in the pons. The neurologic manifestations associated with Enterovirus 71 infection may be characterized by involvement of the cerebellum, brainstem, and diencephalon. Enterovirus 71 is one of the pathogenic viruses that cause hand-foot-and-mouth syndrome, as well as a variety of other clinical manifestations. The most important of these is neurologic disease, especially in infants and young children. PMID- 10029255 TI - N-acetyl-beta-glucosaminidase and beta-galactosidase activity in children receiving antiepileptic drugs. AB - To evaluate renal tubular function in children receiving antiepileptic drugs the urinary activity of two lysosomal enzymes, N-acetyl-beta-glucosaminidase and beta galactosidase, were measured. The enzyme levels were determined before the administration of antiepileptic drugs and 8 months after. Fourteen epileptic children received valproate, and 17 received carbamazepine. The urinary activity of these enzymes in 25 healthy control patients also was examined. Increased N acetyl-beta-glucosaminidase activity was found in 50% of patients taking valproate and in 17.6% of patients taking carbamazepine. Increased beta galactosidase activity was found in 28.5% of patients taking valproate and 11.7% of patients taking carbamazepine compared with the results before treatment. On the basis of these results, it is suggested that patients taking antiepileptic drugs, especially valproate, may demonstrate minor signs of tubular dysfunction. In those patients who use these drugs at increased dosage levels or for long periods, the possibility of tubular dysfunction may be increased, and these dysfunctions may manifest in clinical symptoms. PMID- 10029256 TI - Electroencephalogram confirmatory rate in neonatal seizures. AB - The electroencephalogram (EEG) is confirmatory in 70% of children and adults with seizures, although gestation- and etiology-specific EEG confirmatory rates in neonates have not been well defined. All neonates treated for seizures and who underwent EEG were identified from 4,575 neonates admitted between 1985 and 1996 to a neonatal intensive care unit. The relationship between EEG findings (epileptiform discharges and background abnormalities) and gestation, mortality rate, and seizure etiology was examined using the Student t test. One hundred eighty-three neonates treated for seizures underwent a total of 352 EEGs: 144 of these neonates (79%) had an abnormal EEG (epileptiform discharges in 113 (60%) and nonepileptiform background abnormalities in 31). The EEG confirmatory rate increased with gestation (63% at 28 weeks vs 77% at term, P < 0.02). Etiology for seizures also influenced the EEG confirmatory rate: central nervous system (CNS) infection 95% (P < 0.05), hypoxic-ischemic encephalopathy 80% (P < 0.05), germinal matrix-intraventricular hemorrhage 65%, and CNS malformations 65%. The EEG confirmatory rate was predictive of neonatal mortality (19% vs 6%, P < 0.03). The EEG was directly confirmatory (epileptiform discharges) in 60% and supportive (nonepileptiform background abnormalities) in a further 17% of neonates with seizures. Gestation and etiology influence the EEG confirmatory rate in neonatal seizures. PMID- 10029258 TI - Conventional cerebral angiography in children with ischemic stroke. AB - A retrospective review of conventional cerebral angiograms of 46 children with ischemic stroke was undertaken. Comparison was made with findings on magnetic resonance imaging and magnetic resonance angiography where available. Thirty-six children (78%) underwent magnetic resonance angiography in addition to conventional cerebral angiography. Seven patients had normal cerebral angiograms. Magnetic resonance angiography was diagnostic in 25 of 28 patients with large vessel occlusion, stenosis, or moya-moya syndrome. Conventional angiography was abnormal in four of nine patients with a normal magnetic resonance angiography. All patients with normal conventional angiograms also had normal magnetic resonance angiograms. Conventional angiography, either diagnostic or yielding further information, altered management in five patients with arterial dissection, one patient with large vessel occlusion, one patient with large vessel stenosis, and four patients with arteritis. On the basis of this experience, a clinical algorithm for the use of conventional cerebral angiography in the investigation of ischemic stroke in children is proposed. PMID- 10029257 TI - Immature astrocytes in Fukuyama congenital muscular dystrophy: an immunohistochemical study. AB - Recent studies of Fukuyama congenital muscular dystrophy have focused on abnormalities of the basement membrane in muscle and brain. The cerebral cortex has a unique basement membrane at the glia limitans, which is intimately related to astrocytes in the developing brain, and the basement membrane may be partially produced by the astrocyte. In this study the cerebral astrocytes in six patients with Fukuyama congenital muscular dystrophy, including two fetal patients, were characterized by immunohistochemical study. In fetal Fukuyama congenital muscular dystrophy, astrocytes reacted less to antibodies of glial fibrillary acidic protein, S-100 protein, and alphaB-crystallin than control astrocytes, but in postnatal Fukuyama congenital muscular dystrophy, astrocytes reacted more to these antibodies and displayed beading of processes. Moreover, vimentin was positive in the astrocytes of two postnatal Fukuyama congenital muscular dystrophy patients. This astrocytic appearance may suggest immaturity of astrocytes in Fukuyama congenital muscular dystrophy. Astrocytes exhibiting beaded cytoplasmic processes were prominent at the subpia of the cortex and around vessels. The authors hypothesize that these immature astrocytes are unable to participate in the function of the cortical basement membrane, which is defective in Fukuyama congenital muscular dystrophy. Studies of neurons and meninges were similar to those of control subjects. PMID- 10029259 TI - Serial electroencephalographic findings in patients with MELAS. AB - To clarify the electroencephalographic characteristics of mitochondrial myopathy, encephalopathy, lactic acidosis, and strokelike episodes (MELAS), the medical records and electroencephalograms of six patients with MELAS and two of their relatives with MELA (mitochondrial myopathy, encephalopathy, and lactic acidosis, without strokelike episodes) were retrospectively reviewed. All have a point mutation in the mitochondrial DNA at nucleotide position 3243. The electroencephalograms (n = 79) were divided into four groups according to the time relation to the strokelike episode: (1) before the first strokelike episode, (2) within 5 days after the strokelike episode (acute stage), (3) between 6 days and 1 month after the strokelike episode (subacute stage), and (4) more than 1 month after the strokelike episode (chronic stage). In the acute stage, 10 of the 11 electroencephalograms (9 strokelike episodes in four patients) revealed focal high-voltage delta waves with polyspikes (FHDPS), which were recognized as ictal electroencephalogram. Ictal events during FHDPS included focal clonic or myoclonic seizure and migrainous headache. In the subacute and chronic stages, focal spikes or sharp waves and 14- and 6-Hz positive bursts were frequently recorded. The authors' results suggest that FHDPSs present a reliable and accurate indicator of a strokelike episode in patients with MELAS. PMID- 10029260 TI - Sixth nerve palsies in children. AB - The causes of sixth nerve palsies in 75 children, all of whom had undergone modern neuroimaging, were reviewed. Neoplasms or their neurosurgical removal was the most common cause (n = 34 [45%]); elevated intracranial pressure (nontumor) (15%), traumatic (12%), congenital (11%), inflammatory (7%), miscellaneous (5%), and idiopathic (5%) causes represented other categories but were less commonly present. Isolated sixth nerve palsies were relatively uncommon (9%). On the basis of the relatively high risk of neoplasm, the authors suggest neuroimaging early in the clinical course of children with sixth nerve palsies, even if the palsy is isolated. PMID- 10029261 TI - Stroke and seizures as the presenting signs of pediatric HIV infection. AB - The authors report two pediatric patients with definite human immunodeficiency virus infection whose initial presentation was stroke and seizure. The first patient was a 3-year-old female who developed acute hemiparesis as the first manifestation. The other, a 2-month-old infant, had focal seizures secondary to cerebral infarction. Investigations revealed ischemic infarction of the thalamus, hypothalamus, and internal capsule in the first patient and cerebral cortex in the second. Further investigations failed to demonstrate any other causes of these cerebral infarctions. Opportunistic infection of the central nervous system was not documented. The authors emphasize that cerebrovascular accident may be the initial presentation in human immunodeficiency virus infection in children. Human immunodeficiency virus infection must be included in the differential diagnosis, and testing for the disease is mandatory in the investigation of stroke in any child who is at risk of having this infection. PMID- 10029262 TI - Tuberculoma of the pons. AB - A case of a pontine tuberculoma in a 12-year-old male from Somalia is presented. Cranial magnetic resonance imaging, performed in Abu Dhabi 1 month before admission in Germany revealed a tumorous lesion in the pons with surrounding edema; a presumptive diagnosis of a pontine glioma was made. Chest radiograph disclosed a pulmonary infiltrate with cavitation, as well as hilar and left mediastinal lymphadenopathy, suggestive of active tuberculosis. Tuberculostatic therapy led to an improvement of the patient's clinical status and a significant reduction in the size of the pontine tuberculoma. Intracranial tuberculomas rarely are seen in industrialized countries. They should, however, be considered as an important part of the differential diagnosis of intracranial space occupying lesions. In most cases, as in this patient, conservative therapy provides good or excellent results. PMID- 10029263 TI - Transient thalamic changes on MRI in a child with hypernatremia. AB - Severe hypernatremia has been associated with a wide variety of central nervous system lesions. Neurologic sequelae are the usual outcome in those cases in which a lesion has been documented neuroradiologically. The authors report a 7-month old male with severe hypernatremia who developed obtundation after correction of the electrolyte imbalance. Magnetic resonance imaging revealed bilateral thalamic signal changes that resolved on follow-up study, in accordance with complete clinical recovery. To the authors' knowledge, bilateral thalamic signal changes are previously unreported findings associated with hypernatremia. Pertinent literature and the clinical course of the authors' patient are the basis for questioning currently recommended guidelines for the rate of correction of hypernatremia. PMID- 10029264 TI - SSPE following neonatal measles infection. AB - The authors report a case of subacute sclerosing panencephalitis in a child who had measles during the neonatal period. At 3 years, 6 months of age, over a period of a few weeks, the patient lost the ability to sit unaided as a result of progressive truncal ataxia, without apparent cognitive changes, simulating acute cerebellar ataxia. His symptoms improved in 1 month, and he was able to walk again with support, but mental alteration and periodic mild head nodding on awakening followed. His illness was diagnosed as subacute sclerosing panencephalitis on the basis of the elevated titers of measles antibodies in the cerebrospinal fluid. Measles infection before 1 year of age is a risk factor of subacute sclerosing panencephalitis, but reports about patients with neonatal measles infection are rare. Immaturity of the brain at the time of measles infection may not only be a risk factor but may also influence the clinical course of the disease. PMID- 10029265 TI - Technetium-99m-HmPAO brain SPECT in infantile Gaucher's disease. AB - The authors report serial technetium-99m hexamethylpropylene-amine-oxime brain single photon emission computed tomography (SPECT) findings in two infants with Gaucher's disease type 2. Detailed neurologic and laboratory examinations, including bone marrow biopsies and enzymatic assays, were described. Serial brain magnetic resonance imaging studies in one patient illustrated the progressive cerebral atrophy in the frontal and temporal lobes. The SPECT in both cases demonstrated positive findings of initial scattered hypoperfusion, with extending to hypoperfusion of the entire cerebrum after 4 months of clinical deterioration. These changes in the SPECT findings may reflect progressive degeneration of the cerebrum in Gaucher's disease type 2. Brain SPECT may provide useful information on cerebral flow and metabolic distribution corresponding to the neurologic deficits of neuronopathic Gaucher's disease. PMID- 10029266 TI - Ring chromosome 14 complicated with complex partial seizures and hypoplastic corpus callosum. AB - A Japanese male with mosaicism of ring chromosome 14 and chromosome 14 monosomy is described. He demonstrated the characteristic morphologic features of ring chromosome 14, in addition to mental retardation and epileptic seizures. Clusters of complex partial seizures, one of which originated in the left frontocentral region on electroencephalographic monitoring, were evident. His seizures responded to phenobarbital, and his mental and motor development was only mildly retarded. Magnetic resonance imaging revealed a hypoplastic corpus callosum, previously unknown in association with this syndrome. PMID- 10029267 TI - Cognitive deterioration associated with focal cortical dysplasia. AB - Surgery for an area of focal cortical dysplasia in a critical region is reported in a right-handed female manifesting intractable focal epilepsy and verbal cognitive deterioration. She developed the first seizure at 2 years of age and was treated with phenytoin and zonisamide, with good control until 10 years of age. Although seizures did not occur at 9 years of age, she manifested dyscalculia, right-left disorientation, and finger agnosia, and N-isopropyl-p iodoamphetamine single-photon emission computed tomography (SPECT) revealed focal hypoperfusion in the left parietal lobe. At 11 years of age, she developed regular nocturnal seizures and gradually lost the ability to understand the meaning of sentences. Verbal IQ declined from 94 to 63, and the area of hypoperfusion detected by interictal N-isopropyl-p-iodoamphetamine SPECT spread over the left parietotemporal lobes. Magnetic resonance imaging revealed focal cortical dysplasia mainly in the left parietal lobe, and ictal technetium-99m ethyl cysteinate dimer SPECT images demonstrated an area of hyperperfusion around the focal cortical dysplasia, including the left precentral gyrus. Because of the overlap between the epileptogenic and functional cortex, the authors concluded that cortical resection, including focal cortical dysplasia, was inappropriate in this patient. PMID- 10029268 TI - Cervicomedullary astrocytoma simulating a neuromuscular disorder. AB - A 12-year-old male developed progressive proximal upper extremity weakness over a 3- to 4-year period. The clinical findings of proximal upper extremity weakness and atrophy, prominent scapular winging, and no sensory deficits or upper motor neuron signs suggested a neuromuscular disorder. Electromyography was consistent with a chronic denervating disorder involving the upper cervical anterior horn cells or their axons. A cervical magnetic resonance image revealed a large intramedullary mass extending from the inferior aspect of the fourth ventricle down to the level of T2. A biopsy of the lesion was consistent with a low-grade astrocytoma. PMID- 10029269 TI - Acute near-total intrauterine asphyxia. PMID- 10029270 TI - Treatment of chronic hepatitis B: a need for consensus. PMID- 10029272 TI - Gastro-oesophageal reflux in infancy. AB - Gastro-oesophageal reflux (GOR) is a common phenomenon in infants, which may occur with or without accompanying symptoms. Although most infants presenting with regurgitation have a normal physical examination, it is now recognized that infants may also present with a wide variety of symptoms. Oesophagitis is associated with increased oesophageal acid exposure. The determination of cause and effect is difficult, as there are many aspects of reflux disease where cause and effect relationships are cyclic. Reflux disease is present when there is an imbalance between a number of factors that can contribute to a decrease, as well as an increase, of GOR. Oesophageal pH monitoring with a semi-disposable monocrysant antimony pH catheter with three sensors is very good at documenting oesophageal acidification and gastric buffering and, therefore, quantifies acid reflux frequency and duration. However, the interpretation of the data is complex as they are influenced by numerous factors, such as position, activity (sleep, crying), feeding (frequency and composition) or medication. The duration of buffering of gastric acidity during pH monitoring might, in the future, appear to be a relevant factor in the interpretation of oesophageal pH data. PMID- 10029271 TI - Treatment of chronic hepatitis B virus infection: an Asia-Pacific perspective. AB - Chronic hepatitis B infection is a serious health threat in the Asia-Pacific area. A consensus meeting on the treatment of chronic hepatitis B infection was conducted in Hong Kong, in August 1997. It was generally agreed that treatment of chronic hepatitis B infection should be based on the understanding of the natural history of chronic hepatitis B infection. To date, interferon alpha is the only Food and Drug Administration (FDA)-approved form of therapy for chronic hepatitis B infection. The overall response in Asian patients is unsatisfactory: approximately 15-20% will clear hepatitis B e antigen, but less than 5% will clear hepatitis B surface antigen. Newer immunomodulatory therapies are under trial. In contrast, nucleoside analogues, such as lamivudine (pending FDA approval) and famciclovir, have been shown to be potent suppressors of hepatitis B viral replication; however, their role as monotherapy in the treatment of chronic hepatitis B infection remains to be defined. Also, the issues of resistance to nucleoside analogues and withdrawal rebound need to be carefully studied. The future direction of therapy in chronic hepatitis B infection is probably a combination of nucleoside analogues or nucleoside analogues with immunomodulatory therapy. PMID- 10029273 TI - Mucosal macrophage inflammatory protein-1alpha activity in Helicobacter pylori infection. AB - Mucosal chemokines are considered to be important in the pathogenesis of Helicobacter pylori-associated gastritis. The aims of this study are to examine the levels of macrophage inflammatory protein-1alpha (MIP-1alpha) in organ cultures, the expression of MIP-1alpha mRNA and the cellular source of MIP 1alpha, using the antral mucosal specimens obtained from H. pylori-positive and negative patients. Enzyme-linked immunosorbent assay was used to measure the levels of MIP-1alpha in organ cultures of mucosal tissues and cell cultures of fractionated mucosal cells. The expression of MIP-1alpha mRNA and protein was analysed in fresh biopsy tissues with reverse transcriptase-polymerase chain reaction (RT-PCR) and double immunofluorescence microscopy, respectively. The mucosal specimens obtained from H. pylori-positive patients exhibited significantly higher values of MIP-1alpha activity in organ cultures with increased numbers of CD68+ macrophages, myeloperoxidase+ neutrophils and mononuclear cells in the lamina propria compared with those from H. pylori negative patients. The RT-PCR analysis detected MIP-1alpha mRNA in more than 50% of the specimens with H. pylori infection, but not in those without infection. In cell cultures, the macrophage fraction contained substantially higher amounts of MIP-1alpha on a per cell basis than the lymphocyte fraction and MIP-1alpha activity was not detected in cultures of gastric epithelial cells. This observation was also confirmed by a double immunofluorescence microscopic study in which most (>90%) MIP-1alpha-positive infiltrating cells were CD68+ macrophages. This study indicates that synthesis and secretion of MIP-1alpha are increased in H. pylori-infected antral mucosa and that mucosal macrophages are the main cell type responsible for this phenomenon. PMID- 10029274 TI - Omeprazole attenuates neutrophil-endothelial cell adhesive interaction induced by extracts of Helicobacter pylori. AB - In this study, the influence of omeprazole on the adhesive activity of neutrophils, provided by an extract of Helicobacter pylori, was determined. Human neutrophils were collected from peripheral blood and labelled with a fluorochrome. Helicobacter pylori (NCTC 11637) was cultured and its water extract was obtained by centrifugation of the bacterial suspension. Neutrophils were incubated with the extract in a plastic plate. Percentage adherence was calculated by measuring the fluorescence of floating and adherent cells. Rat mesenteric venule was prepared on an intravital microscope and the number of neutrophils which adhered to venular endothelium was counted. Neutrophil adherence to the plastic plate was increased by the presence of H. pylori extract. Pretreatment with omeprazole significantly decreased this adherence in a dose-dependent manner (10(-6)-10(-4)mol/L). Neutrophil adherence to the mesenteric venule was also increased by H. pylori extract and significantly inhibited by omeprazole. These results indicate that the neutrophil-endothelial adhesive interaction is inhibited by omeprazole, suggesting that omeprazole prevents neutrophil recruitment to the gastric mucosa associated with H. pylori infection. PMID- 10029275 TI - Optimal treatment for duodenal ulcer disease: a cost-decision analysis in Malaysian patients. AB - The aim of the present study was to determine the cost-efficiency of different duodenal ulcer disease treatment practices in Malaysia. Six Malaysian gastroenterologists met to discuss the direct costs related to Helicobacter pylori (HP) eradication treatment. Five treatment strategies were compared: (i) histamine H2 receptor antagonists (H2RA), acid suppression therapy for 6 weeks followed by maintenance therapy as needed; (ii) bismuth triple + proton pump inhibitor (PPI), bismuth (120 mg, q.i.d.), metronidazole (400 mg; t.i.d.), tetracycline (500 mg, q.i.d.) for 7 days and PPI, b.i.d., for 7 days; (iii) OAC, omeprazole (20 mg, b.i.d.), amoxycillin (1000 mg, b.i.d.) and clarithromycin (500 mg, b.i.d.) for 7 days; (iv) OMC, omeprazole (20mg, b.i.d.), metronidazole (400mg, b.i.d.) and clarithromycin (500 mg, b.i.d.) for 7 days; and (v) OAM, omeprazole (20 mg, b.i.d.), amoxycillin (1000 mg, b.i.d.) and metronidazole (400 mg, b.i.d.) for 7 days. A decision tree model was created to determine which therapy would be the most cost-effective. The model considered eradication rates, resistance to anti-microbial agents, compliance and cost implications of treatment regimens, physician visits and ulcer recurrences during a 1 year time period assumption. The H2RA maintenance therapy was the most expensive treatment at Malaysian Ringgit (MR) 2335, followed by bismuth triple therapy (MR 1839), OMC (MR 1786), OAM (MR 1775) and OAC, being the most cost-effective therapy, at MR 1679. In conclusion, HP eradication therapy is superior to H2RA maintenance therapy in the treatment of duodenal ulcer disease. Of the HP eradication regimens, OAC is the most cost-effective. PMID- 10029276 TI - Rat gastrointestinal motor responses mediated via activation of neurokinin receptors. AB - Natural neurokinins (NK) and their specific receptor agonists, including substance P (SP), neurokinin A (NKA), neurokinin B (NKB), septide, [NIe10]-NKA4 10 and senktide, were used to assess whether they could activate established NK receptors in rat gastrointestinal tract and central nervous system to alter gastric emptying or intestinal transit. Fasting rats were intubated with an orogastric catheter to feed them liquid radiochromium. Neurokinins and analogues (at 10(-10), 10(-9), 10(-8) and 10(-7) mol/kg) and vehicle (saline + 0.1% bovine serum albumin) were injected via an intraperitoneal route. Rats were killed 15 min later and the whole gut was removed. The radioactivity of the stomach and 10 equally divided small intestinal segments was counted to determine gastric emptying and the geometric centre of intestinal transit. Septide treatment at 10( 8) and 10(-7) mol/kg markedly delayed gastric emptying. All doses of NKA inhibited gastric emptying. However, other peptides did not influence gastric emptying. Both septide and NKB treatment at 10(-8) and 10(-7) mol/kg enhanced intestinal transit. Substance P or senktide treatment (10-(-7) mol/kg) also enhanced intestinal transit. Stasis of remaining radioactivity in the proximal intestine was found following SP, septide, NKA and NKB treatment, whereas accelerated transit in the distal intestine was induced following NKA, NKB and senktide treatment. In conclusion, the in vivo study of NK and their specific agonists manifests a selective influence of these compounds on rat gastrointestinal tract. This selective activation of stomach NK1 and NK2 receptors delays gastric emptying, whereas activation of intestinal NK1 and NK3 receptors enhances intestinal transit. PMID- 10029277 TI - Increased mucosal production of granulocyte colony-stimulating factor is related to a delay in neutrophil apoptosis in Inflammatory Bowel disease. AB - Tissue accumulation of polymorphonuclear neutrophils (PMN) in Inflammatory Bowel disease (IBD) might be, in part, due to a delay in apoptotic processes associated with the effects of their specific growth factors and inflammatory cytokines. We addressed this hypothesis by examining the activity of granulocyte colony stimulating factor (G-CSF) and granulocyte-macrophage CSF (GM-CSF) in the organ culture supernatants of colonic mucosal specimens and their regulatory effects on PMN apoptosis in patients with IBD. The contents of G-CSF and GM-CSF in the supernatants were measured by the enzyme-linked immunosorbent assays and PMN apoptosis was evaluated by acridine orange/ethidium bromide staining, respectively. Mucosal specimens obtained from patients with active IBD exhibited higher levels of G-CSF and GM-CSF activity than controls. Notably, the levels of G-CSF activity were approximately 1000-fold higher than those of GM-CSF activity. Freshly isolated PMN showed a time-related increase in the proportion of cells with characteristic features of apoptosis when they were incubated with the culture medium alone and exposure of PMN to recombinant G-CSF and GM-CSF caused a concentration-dependent inhibition of apoptosis. Incubation of PMN with the supernatants from patients with active IBD induced an inhibitory effect on PMN apoptosis; this effect was abrogated to a significant degree by pre-incubation of the supernatants with anti-G-CSF serum. This study suggests that PMN apoptosis may be delayed under the influence of soluble mediators, especially G-CSF, in the microenvironment of IBD-affected mucosa, thus providing possible mechanisms for tissue accumulation of PMN in IBD. PMID- 10029278 TI - Dextran sodium sulphate-induced colitis activity varies with mouse strain but develops in lipopolysaccharide-unresponsive mice. AB - Bacteria and their products have been implicated in the pathogenesis of chronic Inflammatory Bowel disease. The aim of this study was to investigate the potential role of lipopolysaccharides (LPS) in the development of intestinal injury by comparing the effects of the dextran sodium sulphate (DSS)-induced model of colitis in LPS-sensitive and -insensitive mice. Experimental colitis was induced in LPS-sensitive mice (C3H/He) and their LPS-insensitive congenic strain (C3H/HeJ). Colitis was assessed clinically using a disease activity index (derived from the three main clinical signs; diarrhoea, rectal bleeding and weight loss) and by histological scoring of the diseased colon. The clinical signs and disease activity index did not differ between the LPS-sensitive and insensitive costrains. Similarly, histological scores did not differ significantly for either C3H strain at any time point during exposure to DSS. However, there were differences in the inflammatory response when different strains were compared (C3H vs CBA): the effects of DSS in C3H mice were immediate, more severe and mainly involved the caecum and ascending colon. These findings suggest that LPS from colonic bacteria do not play a primary role in the initiation of DSS-induced colitis and demonstrate clear differences in the responsiveness of different mouse strains to DSS. PMID- 10029279 TI - Proliferation of hepatic metastases of colorectal carcinoma: relationship to primary tumours and prognosis after hepatic resection. AB - In this study, we determined the proliferation indices of liver metastatic tumours originating from colorectal carcinomas using Ki67 and argyrophil nucleolar organizer region associated proteins (AgNOR) stain. We examined the primary and metastatic tumours in 27 patients with liver metastasis and eight cases with non-metastatic colorectal carcinoma as a control.The number of AgNOR dots in metastatic tumours was significantly higher than in the respective primary tumours of the metastasis group or in non-metastatic colorectal carcinomas. The Ki67 labelling index was similar in all groups. The Ki67 labelling index and AgNOR counts did not correlate with each other. There was no significant relationship between proliferation indices and the duration of the disease-free period following hepatic resection for metastases or with prognosis after hepatectomy. We conclude that Ki67 and AgNOR are not useful indicators of prognosis in patients who undergo operation for liver metastasis of colorectal carcinomas. PMID- 10029280 TI - Distal colonic neoplasms predict proximal neoplasia in average-risk, asymptomatic subjects. AB - Flexible sigmoidoscopy has been recommended as a screening method to reduce the incidence of colorectal cancer in asymptomatic, average-risk subjects through the early detection and removal of polyps. However, the association between distal and proximal colonic neoplasia and, hence, the requirement for colonoscopic follow up of screen-detected distal neoplasms is unclear. Our aims were: (i) to evaluate the risk of having proximal neoplasms in those with distal colonic neoplasms; and (ii) to determine whether the risk was dependent on the number, size, histology or morphology of the distal lesions. We prospectively evaluated asymptomatic subjects in a flexible sigmoidoscopy based screening programme. Those with rectosigmoid neoplasia underwent colonoscopy. The number, size, histology and morphology of the polyps were recorded. Advanced lesions were defined as adenomas > 1 cm or with a villous component or severe dysplasia, carcinoma in situ or cancer. Adenomatous polyps were found in 17% (135) of screening flexible sigmoidoscopies. At colonoscopy, up to 30% of subjects with distal colonic neoplasms had synchronous proximal lesions at colonoscopy and up to 20% had advanced proximal lesions. The risk of proximal colonic neoplasia was increased in those with distal sessile colonic neoplasms but appeared independent of distal lesion size, number or morphology. In conclusion, distal colonic neoplasia predicts proximal neoplasia in up to 30% of subjects and these were advanced lesions in up to 20%. We recommend that all subjects with biopsy proven distal colonic neoplasia undergo colonoscopy. PMID- 10029281 TI - Growth inhibition and differentiation of the human colon carcinoma cell line, Caco-2, by constitutive expression of insulin-like growth factor binding protein 3. AB - The human colon carcinoma cell line, Caco-2, produces insulin-like growth factor binding protein-3 (IGFBP-3), the secretion of which correlates with markers of enterocyte differentiation. To investigate whether IGFBP-3 inhibits proliferation or induces differentiation, Caco-2 cells were stably transfected with an IGFBP-3 cDNA expression construct or pcDNA3 vector as a control. Accumulation of IGFBP-3 mRNA and secretion of the protein into conditioned medium 9 days after plating were readily detected in the transfected cells, whereas these parameters were undetectable in pcDNA3-transfected cells. Insulin-like growth factor binding protein-3-expressing cells grew at a rate similar to the controls for 6 days after plating, but achieved a much lower final density between days 10 and 12. By day 9 of culture, accumulation of sucrase-isomaltase mRNA, a marker of enterocytic differentiation of Caco-2 cells, was evident in the IGFBP-3 expressing cells, but was undetectable in the controls. These results indicate that IGFBP-3 may inhibit proliferation and induce early differentiation of Caco-2 cells. PMID- 10029282 TI - How soon can a virological sustained response be determined after withdrawal of interferon therapy in chronic hepatitis C? Tokyo-Chiba Hepatitis Research Group. AB - Hepatitis C virus (HCV)-RNA status and alanine aminotransferase (ALT) levels determined shortly after interferon (IFN) therapy in patients with chronic hepatitis C do not predict long-term response. To determine the virological sustained response after the completion of IFN therapy, HCV-RNA was measured at the end of treatment and at 3-4 months and 12 months after the completion of therapy in 537 patients with chronic hepatitis C. In 347 patients, HCV-RNA was not detected by polymerase chain reaction (PCR) at the completion of therapy and 175 of these patients (50%) were still PCR negative 12 months later. In contrast, of the 180 patients who were HCV-RNA negative at 3-4 months after completion of therapy, 99% remained negative at 12 months. Normal ALT levels were found in 80, 93 and 95% of patients who were negative for HCV-RNA either at the end of treatment or at 3-4 months and 12 months after the completion of therapy, respectively. Of patients who were HCV-RNA positive, 30, 15 and 20% were found to have normal ALT levels at the same respective time points. To determine a sustained virological response shortly after the completion of therapy, serum HCV RNA was serially examined in 66 patients negative for HCV-RNA at the end of therapy. Of 31 patients who relapsed, HCV-RNA reappeared in 33, 80, 97 and 100% of patients by 1, 2, 4 and 8 weeks after the completion of therapy. In conclusion, a sustained virological response could be determined with 97 and 99% certainty at 4 weeks and at 3-4 months after the completion of therapy, respectively. PMID- 10029283 TI - The effects of a high dose, short course of interferon on hepatitis C. AB - To shorten the period of interferon (IFN) treatment for chronic hepatitis C, we investigated the clinical efficacy of a regimen using a higher dose and a shorter treatment period. Fifty chronic hepatitis C patients who were hepatitis C virus (HCV)-RNA positive and who were histologically diagnosed as having chronic hepatitis, took part in the study. Virus levels were measured before and 2 weeks after starting the treatment. We administered natural IFNalpha, 10 MU, i.m. daily for 2 consecutive weeks and then three times per week for the subsequent 14 weeks (total dose 560 MU). Patients who were HCV-RNA negative at the completion of the therapy and 6 months later, were evaluated as sustained responders (SR; 32%). Those who were not HCV-RNA negative at the two time points were evaluated as non responders. Nucleotide and clone differences in the hypervariable region (HVR) and predictive factors for prognosis were also analysed. Low virus level and HCV RNA genotype 2a/2b were the predictors for good prognosis, whereas the numbers of nucleotide differences and clone differences in HVR were not. Sustained responder patients became HCV-RNA negative 2 weeks after starting the treatment at a significantly higher rate, whereas no non-responder patients were HCV-RNA negative at that time. The SR rate (32%) was equivalent to those reported in previous 24 week treatment studies. This IFN therapy using a higher dose and a shorter period was useful. PMID- 10029285 TI - Post-biopsy liver cyst: a rare complication of liver biopsy. AB - Liver biopsy rarely leads to complications in a non-cirrhotic liver. We describe here a case of a biliary cyst of the liver that developed after a liver biopsy. It was successfully treated with surgery. PMID- 10029284 TI - Comparing the treatment outcomes of endoscopic papillary dilation and endoscopic sphincterotomy for removal of bile duct stones. AB - To compare the clinical usefulness of endoscopic papillary dilation (EPD) and endoscopic sphincterotomy (EST) for removal of bile duct stones, 110 patients with stones up to 15 mm in diameter and less than 10 in number were randomly treated with either EPD (55 patients) or EST (55 patients). The patients were followed up for a median period of 23 months and endoscopic manometry with the administration of morphine was carried out in 17 patients who were observed more than 12 months after the procedures to evaluate the post-procedure papillary function. Duct clearance was achieved in 51 EPD (92.7%) and 54 EST patients (98.1%, not significantly different). Forty EPD (78.4%) and 51 EST patients (94.4%) achieved duct clearance in the initial procedure (P=0.02). Early complications occurred in one EPD (2.0%) and in three EST patients (5.6%, P=0.62). Complications during the follow-up period occurred in two EPD and eight EST patients. Recurrence of bile duct stones was observed in two EPD and three EST patients (P=0.98). Acute cholecystitis was observed in one EPD and five EST patients (P=0.06) and among patients with gall-bladder stones in situ, the rate of acute cholecystitis after EPD was significantly lower than that after EST (P=0.03). Endoscopic manometry showed the existence of a choledochoduodenal pressure gradient only after EPD, while papillary contractile function was observed after both procedures. In conclusion, both EPD and EST are safe therapeutic modalities, although EPD is more clinically effective in decreasing the risk of acute cholecystitis in patients with gall-bladder stones in situ and in preserving post-procedure papillary function. PMID- 10029286 TI - Images of interest. Gastrointestinal: gastrointestinal lymphangiomas. PMID- 10029287 TI - Images of interest. Hepatobiliary and pancreatic patient: thread-like vessels in an arteriogram. PMID- 10029288 TI - Non-transferrin-bound iron and cellular toxicity. PMID- 10029289 TI - Anticoagulant therapy, anti-platelet agents and gastrointestinal endoscopy. AB - BACKGROUND: The increasing use of anticoagulant therapy and anti-platelet agents in the primary and secondary prevention of cardiovascular, cerebrovascular and venous thromboembolic disease has increased the need for guidelines for managing these agents prior to gastrointestinal endoscopy, particularly if therapeutic manoeuvres are required. The continuation of anticoagulant therapy increases the risk of haemorrhagic complications of gastrointestinal endoscopy. Temporary suspension of anticoagulant therapy exposes the patient to the risk of thromboembolism associated with the underlying condition requiring anticoagulant treatment. CONCLUSIONS: This article reviews the literature and proposes guidelines for the management of patients taking anticoagulant and anti-platelet agents who require gastrointestinal endoscopy. PMID- 10029290 TI - Relationship between Helicobacter pylori infection and gastric metaplasia in the duodenal bulb in the pathogenesis of duodenal ulcer. AB - BACKGROUND: The aim of this study was to determine whether the amount of Helicobacter pylori and the extent of gastric metaplasia in the duodenal mucosa play critical roles in the pathogenesis of duodenal ulcer. METHODS: Duodenal and gastric biopsy specimens were obtained from H. pylori-positive patients with duodenal ulcer, gastric ulcer or chronic gastritis. The extent of gastric metaplasia was evaluated histologically and endoscopically using the methylene blue test. In this study, we performed competitive polymerase chain reaction, a highly sensitive and quantitative method for determining the amount of H. pylori gastric and duodenal mucosa. The prevalence and extent of gastric metaplasia and the amount of H. pylori in the duodenal bulb in the three patient groups were compared. The correlation between the amount of H. pylori in the duodenum and gastric antrum and extent of gastric metaplasia were also determined. RESULTS: The prevalence and extent of gastric metaplasia and the amount of H. pylori in the duodenal bulb in patients with duodenal ulcer were much higher than in patients with gastric ulcer or chronic gastritis. A positive correlation was found between the amount of H. pylori in the duodenum and the extent of gastric bulb and that in the antrum. CONCLUSIONS: The findings of this study indicate that H. pylori colonization in the duodenal bulb may play a critically important role in the pathogenesis of duodenal ulcer and that the amount of H. pylori in the duodenal bulb may be related to the amount of H. pylori in the gastric antrum and the extent of gastric metaplasia in the duodenal bulb. PMID- 10029291 TI - Differential Helicobacter pylori infection rates in two contrasting gastric cancer risk regions of South China. China Gastric Cancer Study Group. AB - BACKGROUND: Carriers of Helicobacter pylori are believed to have a three- to six fold increased risk of developing gastric cancer. We have recently conducted a simultaneous cross-sectional population study on the prevalence of H. pylori infection in a cohort of asymptomatic adult volunteers in two contrasting gastric cancer risk regions of South China, Hong Kong and Changle of Fujian. Their mean annual gastric cancer mortality has been approximately 7.5 and 75/100 000 population, respectively, since the beginning of the last decade. The aim of this study was to evaluate if H. pylori prevalence bears any relationship to gastric cancer mortality rates in these two southern regions of China. METHODS: Sera were obtained from 397 volunteers in Hong Kong. They were tested for anti-H.pylori immunoglobulin (Ig) G antibody by using a commercial enzyme-linked immunosorbent assay (ELISA) kit. Volunteers of Changle (1456) had upper endoscopy examination and were also tested for anti-H. pylori IgG antibody by the same ELISA method. RESULTS: The overall H. pylori infection prevalence was significantly higher in Changle (80.4%) than in Hong Kong (58.4%; P< 0.01). The high prevalence is associated with more atrophic gastritis. The overall risk of gastric cancer in people of Changle is approximately five-fold that of Hong Kong (adjusted odds ratio 4.9, 95% CI 2.5-9.8). CONCLUSIONS: It is concluded that the prevalence of H. pylori infection rates bear a direct relationship to gastric cancer mortality rates in these two southern regions of China. Thus, H. pylori most likely plays a significant aetiopathogenetic role in gastric carcinogenesis in subjects living in Changle. PMID- 10029292 TI - Non-transferrin-bound iron and hepatic dysfunction in African dietary iron overload. AB - BACKGROUND: Circulating iron is normally bound to transferrin. Non-transferrin bound iron (NTBI) has been described in most forms of iron overload, but has not been studied in African dietary iron overload. This abnormal iron fraction is probably toxic, but this has not been demonstrated. METHODS: High-pressure liquid chromatography was used to assay serum NTBI in 25 black African subjects with iron overload documented by liver biopsy and in 170 relatives and neighbours. Levels of NTBI were correlated with indirect measures of iron status and conventional liver function tests. RESULTS: Non-transferrin-bound iron (> 2 micromol/L) was present in 43 people, 22 of patients of whom underwent liver biopsy and 21 relatives and neighbours. All but four of these had evidence of iron overload on the basis of either liver biopsy or elevated transferrin and serum ferritin concentrations. Among all 195 subjects, the presence of NTBI in serum was independently related to elevations in alanine and aspartate aminotransferase activity and bilirubin concentration. This relationship between serum NTBI and hepatic dysfunction was confirmed in the subgroup of 25 subjects with iron overload documented by liver biopsy. Non-transferrin-bound iron correlated significantly with elevations in alanine and aspartate aminotransferase activities after adjustment for hepatic iron grades, inflammation and diet. CONCLUSIONS: Non-transferrin-bound iron was found to be commonly present in African patients with dietary iron overload and to correlate with transferrin saturation and serum ferritin concentration. The independent relationship between NTBI and elevated liver function tests suggests that it may be part of a pathway leading to hepatic injury. PMID- 10029293 TI - Does steatohepatitis impair liver regeneration? A study in a dietary model of non alcoholic steatohepatitis in rats. AB - BACKGROUND: Impaired liver regeneration is a feature of alcoholic hepatitis, but the relative importance of alcohol, nutritional imbalance and inflammatory mediators in causing this effect is unclear. Non-alcoholic steatohepatitis (NASH) is a form of liver disease with similar morphology to alcoholic hepatitis, but the effect of this disorder on liver regeneration is unclear. We, therefore, examined the status of liver regeneration in a rat nutritional model of hepatic steatosis with inflammation, which is morphologically identical to NASH in humans. METHODS: Male Wistar rats received a methionine-choline-deficient diet (MCDD) for 4 weeks before experiments and both isocaloric pair-fed and ad libitum fed rats were used as controls. Following partial hepatectomy (68%), the extent of hepatic regeneration was determined 24 h later using [3H]-thymidine incorporation and restitution of liver mass. RESULTS: There was no significant difference of [3H]-thymidine incorporation in MCDD-fed, pair-fed and ad libitum fed rats (80+/-27, 78+/-11 and 80+/-6.3 d.p.m./microg DNA, respectively). Similarly, restituted liver masses in three groups of rats were not significantly different (17+/-3.8, 18+/-1.8 and 17+/-3.1% initial liver weight, respectively). CONCLUSIONS: The similarities in hepatic histology and cytochrome P450 2E1 induction between this nutritional model of hepatic steatohepatitis and alcoholic steatohepatitis imply that these two disorders share pathogenetic mechanisms. However, liver regeneration is not altered by NASH in rats, indicating that the nutritional and inflammatory changes that appear similar to those of alcoholic liver disease do not cause impairment of liver regeneration. PMID- 10029294 TI - Serum matrix metalloproteinase-1 in patients with chronic viral hepatitis. AB - BACKGROUND AND AIMS: Previously we found that serum matrix metalloproteinase (MMP)-1 activity decreased with progression of chronic liver disease. Our objectives in the present study were to observe the change in the serum MMP-1 protein concentration using recently developed specific enzyme immunoassays for MMP-1 and MMP-1 complexed with tissue inhibitor of metalloproteinases (TIMP)-1 and to elucidate the clinical usefulness of the serum MMP-1 test in chronic viral hepatitis. We measured the serum concentrations of MMP-1 and MMP-1/TIMP-1 complex using these immunoassays in 64 patients with histologically characterized chronic viral hepatitis. RESULTS: Serum MMP-1 concentration was inversely related to the histological severity of chronic hepatitis (P< 0.0001). It was closely associated with the histological degree of periportal necrosis (P< 0.0001), intralobular necrosis (P< 0.005), portal inflammation (P<0.0001) and liver fibrosis (P< 0.05). The serum concentration of MMP-1/TIMP-1 complex was also related to the histological severity of chronic hepatitis (P< 0.0001). It was associated with the degree of portal inflammation (P< 0.05), but not with the degree of periportal necrosis, intralobular necrosis or liver fibrosis. As serum MMP-1 level was closely associated with the histological degree of necroinflammation, we examined the ability of the serum MMP-1 test to differentiate active and inactive forms of hepatitis with a receiver operating curve. The results were compared with those of serum procollagen type III N-peptide (PIIINP) test. We found that the serum MMP-1 test was superior to the serum PIIINP test in assessing liver necroinflammation. CONCLUSIONS: In addition to the previously reported changes in enzyme activity, MMP-1 proteins in serum decreased during histological progression of chronic hepatitis. The serum MMP-1 test may be useful clinically to differentiate active and inactive types of hepatitis in patients with chronic viral hepatitis. PMID- 10029295 TI - Findings and benefit of liver biopsies in 46 patients infected with human immunodeficiency virus. AB - AIMS: The aim of this work is to evaluate the role of liver biopsy and to determine the histological findings in patients infected with the human immunodeficiency virus (HIV) who have abnormal liver function tests (LFT). METHODS: We performed a percutaneous liver biopsy in 46 HIV-seropositive patients with abnormal LFT. Parts of biopsied tissue were used for bacterial and fungal culture and the rest was processed for histological examination including special staining. RESULTS: Of these 46 patients, 41 patients were males and five were females. The median age was 31+/-6 years. Mycobacterium tuberculosis was the most common histological finding (15 cases). Of 15 tuberculosis patients, 11 (73.3%) had lymphadenopathy and positive acid-fast bacilli (AFB) in node aspiration or biopsy. The other findings included AFB-negative granuloma (eight cases), histoplasmosis (six cases), cryptococcosis (six cases), penicillosis (four cases), viral hepatitis: hepatitis C virus (HCV; one case), hepatitis B virus and HCV infection (one case), fatty liver (two cases), drug-induced hepatitis (one case) and non-specific changes (five cases). There were double infections in three patients. We were able to demonstrate opportunistic infections in 41 cases (89.3%). CONCLUSIONS: Mycobacterium tuberculosis was the most common histological finding in HIV patients with abnormal LFT in Thailand. Liver biopsy was a useful procedure in evaluating abnormal LFT in HIV patients. PMID- 10029296 TI - Plasma levels of mevalonate and 7alpha-hydroxy-4-cholesten-3-one in chronic liver disease. AB - BACKGROUND AND AIMS: Cholesterol levels in blood tend to be preserved despite hepatic impairment, in contrast to albumin levels and other markers of liver function in patients with liver cirrhosis (LC). We reported previously that the levels of plasma mevalonate (MVA) and 7alpha-hydroxy-4-cholesten-3-one (7alpha3one) closely reflect hepatic synthetic rates of cholesterol and bile acids. The aim of this study was to examine the association between hepatic cholesterogenesis and bile acid synthesis in hepatocellular impairment using these indices. METHODS: The plasma indices were measured in patients with LC (n = 38) or chronic hepatitis (CH; n = 11) and in normal controls (n = 22). The severity of LC was assessed by the Child-Pugh score. RESULTS: There were no significant differences in plasma MVA levels between CH, LC and control groups. However, plasma 7alpha3one levels were significantly lower in LC than in CH and control groups (P< 0.01). While MVA levels did not correlate with the Child-Pugh score, there was a significant correlation between 7alpha3one level and Child Pugh score (P< 0.005). The plasma 7alpha3one level in controls correlated positively with MVA levels (P< 0.01); however, there was no significant correlation between these indices in CH and LC. CONCLUSION: In chronic liver disease, there was a tendency for hepatic cholesterogenesis to be sustained in the face of hepatocellular impairment, while bile acid synthesis declined in parallel with the severity of impairment. PMID- 10029298 TI - Reactive lymphoid hyperplasia of liver coexisting with chronic thyroiditis: radiographical characteristics of the disorder. AB - BACKGROUND: Reactive lymphoid hyperplasia of the liver is an extremely rare entity, with six cases reported so far. METHODS: We encountered a 47-year-old Japanese female with reactive lymphoid hyperplasia of the liver, which coexisted with chronic thyroiditis. The lesion was discovered incidentally as a hypo-echoic mass with a hyper-echoic rim at a routine ultrasonography examination. It increased from 12 to 17 mm diameter in 6 months. Radiological studies, such as contrast-enhanced computerized tomography (CT) and angiography demonstrated a hypervascular lesion. RESULTS: It was consequently diagnosed as a neoplasm with malignant potentiality and she underwent partial hepatectomy. The lesion was composed of small mature lymphocytes which formed prominent lymphoid follicles with germinal centres, scattered plasma cells and stromal fibrosis. Immunohistochemical study revealed polyclonal origins of the involved lymphocytes. DNA analysis for the immunoglobulin heavy gene and the T cell receptor beta gene using Southern blot hybridization showed no monoclonality. The following features have characterized the images in past cases, as well as ours: hypo-echoic mass, occasionally with a rim, in ultrasonography and hypervascularity, shown by angiography and enhanced CT. PMID- 10029297 TI - Sodium butyrate induces alkaline phosphatase gene expression in human hepatoma cells. AB - BACKGROUND AND AIMS: Butyrate, a natural product of colonic bacterial flora, has been reported to increase the activities of a number of enzymes, including alkaline phosphatase, (ALP) in several cancer cell lines. However, butyrate induced ALP gene expression in human hepatoma cells has not been previously demonstrated. In the present study, the effects of sodium butyrate on cell growth and proliferation, cellular activity and expression of ALP gene in human hepatoblastoma-derived HepG2 cells were investigated. METHODS: The HepG2 cells were treated with sodium butyrate (0-1 mmol/L) and the number of viable cells were counted at 24, 48 and 72 h after treatment. A [3H]-thymidine incorporation study was performed at different concentrations of sodium butyrate for 48 h. The cellular activity of ALP in HepG2 cells by sodium butyrate was measured by a substrate-specific enzymatic assay. To elucidate the effects of sodium butyrate on ALP gene expression, a northern blotting experiment employing hybridization with mouse placental ALP cDNA was performed. RESULTS: Cell growth and proliferation were dose-dependently inhibited by sodium butyrate. Cellular ALP activity was significantly increased in HepG2 cells in a time- and dose-dependent fashion by treatment with sodium butyrate and a maximum activity was observed at 48 h. These effects were reversible when sodium butyrate was removed from the culture medium. By northern blot analysis, the level of ALP messenger RNA was dose-dependently elevated by sodium butyrate. CONCLUSION: Butyrate, at a concentration relevant to the normal physiology of the liver, causes augmented expression of ALP mRNA in HepG2 cells. We assume that increased ALP synthesis in HepG2 cells by sodium butyrate results from an enhanced rate of transcription rather than translation of mRNA. PMID- 10029299 TI - Rhabdomyolysis and acute pancreatitis. AB - AIMS: To establish the incidence of rhabdomyolysis in patients with acute pancreatitis and to determine the effectiveness of myoglobin in assessing the severity of the disease. METHODS: Sixty-one patients having acute pancreatitis (33 males, 28 females, mean age 66 years, range 16-97 years) were studied; diagnosis of acute pancreatitis was based on the typical abdominal pain associated with elevated concentrations of serum lipase and further confirmed by imaging techniques. Rhabdomyolysis was defined as a level of serum myoglobin which is two or more times greater than the upper normal test limit. All patients had normal renal function at the time of the study, none had clinical and/or electrocardiographic signs of acute myocardial infarction and none were drug addicts. Forty-five patients had mild acute pancreatitis and 16 had the severe form of the disease. Serum myoglobin was determined using a nephelometric technique. RESULTS: Patients with mild pancreatitis had serum concentrations of myoglobin (median and range; 35.7, 24-713 microg/L) similar to those with severe pancreatitis (26.8, 24-710 microg/L). Twelve of the 61 patients with acute pancreatitis (20%) had serum myoglobin concentrations above the upper normal limit: eight of the 45 patients with mild pancreatitis (17.7%) and four of the 16 patients with severe pancreatitis (25.0%). Four of the 61 patients with acute pancreatitis (7%) had serum myoglobin levels more than twice the upper normal limit: two with mild disease and two with the severe form of pancreatitis. CONCLUSIONS: Rhabdomyolysis may occur asymptomatically in patients with acute pancreatitis, especially in those with the severe form of the disease. Serum myoglobin determination is not useful in establishing the severity of acute pancreatitis. PMID- 10029300 TI - Haemosuccus pancreaticus: a clinical challenge. AB - BACKGROUND: Haemosuccus pancreaticus is a rare complication of pancreatitis. It is a diagnostic problem for even the most astute clinician and a challenge for the expert endoscopist. We report a 25-year-old male patient who had all the features usually seen in haemosuccus pancreaticus patients: recurrent obscure upper gastrointestinal bleeding, pancreatitis, pseudocyst formation, ductal disruption, fistula and pancreatic ascites. The patient was treated by subtotal pancreatectomy, splenectomy and drainage of the pseudocyst. Although pancreatic duct communication with the surrounding vasculature could not be ascertained, we strongly believe the patient had haemosuccus pancreaticus because, over a follow up period of 3 years, the patient was not only ascites free, but did not experience any further upper gastrointestinal bleeding. We believe that in evaluating patients with recurrent obscure gastrointestinal bleeding, one should always remember that the pancreas is a part of the gastrointestinal tract and, like other organs, is prone to blood loss. PMID- 10029301 TI - Effect of venesection on bone mineral density in an eugonadal woman with haemochromatosis. AB - BACKGROUND: A 41-year-old premenopausal woman with newly diagnosed haemochromatosis was found to have osteopenia on screening bone mineral densitometry. METHODS AND RESULTS: Liver biopsy showed grade 3 haemochromatosis with an hepatic iron index of 4. Investigation for secondary factors for osteopenia revealed no cause. The patient was clinically and biochemically eugonadal. Following venesection of 8 L blood (4 g iron) over 17 months and calcium supplementation, her bone density rose significantly. Neck of femur bone density increased by 6.0% over 13 months and lumbar vertebral bone density increased by 7.2%. There are no previous reports of response of bone density to venesection in eugonadal patients or in women with haemochromatosis. PMID- 10029302 TI - Fifty years of gastroenterology in Australia. PMID- 10029303 TI - Images of interest. Gastrointestinal: adenocarcinoma of the lower oesophagus. PMID- 10029304 TI - Images of Interest. Hepatobiliary and pancreatic: an alcoholic man with a lesion in the splenic hilum. PMID- 10029305 TI - Molecular cloning and biochemical characterization of a VCP homolog in African trypanosomes. AB - Through reverse transcription-polymerase chain reaction using degenerate oligonucleotide primers, a VCP homolog was identified in African trypanosomes. Sequence analysis shows a 72 and 64% deduced amino acid identity, respectively, with mouse VCP and yeast Cdc48p. Southern analysis indicates tbVCP to have a single locus with two alleles. Antibodies generated against recombinant protein recognize a 95 kDa protein in whole cell lysates of both procyclic and bloodstream trypanosomes. There is an approximately four-fold greater expression of TbVCP protein in the procyclic stage of the trypanosome life cycle. Subcellular fractionation and immunofluorescence with anti-TbVCP antibodies indicate the majority of TbVCP to be cytoplasmically localized with a small subset associated with membranes. Sucrose velocity sedimentation and gel filtration size analysis studies suggest that TbVCP is a homohexameric particle as has been demonstrated with other VCP homologs. Also like other VCP homologs, TbVCP contains an NEM-inhibitable ATPase activity. This is the first characterization of an AAA (ATPases Associated with a variety of cellular Activities) family member in African trypanosomes. PMID- 10029306 TI - Molecular cloning of p67, a lysosomal membrane glycoprotein from Trypanosoma brucei. AB - We have previously characterized a highly glycosylated membrane protein (p67) in Trypanosoma brucei spp that is apparently targeted to lysosomes in a developmentally regulated manner. Antibody to native p67 identified a partial cDNA clone from a T. b. rhodesiense expression library and RT-PCR was used to complete the sequence of the cDNA. Equal levels of p67 transcript are detected in both procyclic and bloodstream stages of the life cycle. The 2771 nt cDNA contains a 1980 nt orf encoding a 659 amino acid polypeptide (72,567 Da). Hydropathy analysis predicts a Type I membrane topology (N to C): an N-terminal signal sequence, a large hydrophilic lumenal domain with 14 N-glycosylation sites, a trans-membrane domain (19 aa), and a short (24 aa) cytoplasmic domain. Peptide microsequencing of purified p67 identified nine residues identical to the deduced amino acid sequence, confirming the identity of the cDNA and defining the signal sequence cleavage site. Antibody to p67 protein produced in E. coli recognizes the same spectrum of native p67 glycoforms as the antibody used to clone the cDNA. All features of the deduced amino acid sequence are consistent with the known properties of the native protein and suggest a structure similar to mammalian LAMPS. The cytoplasmic domain contains two putative di-leucine targeting motifs similar to those involved in lysosomal targeting in vertebrate cells. Our results suggest that a single p67 polypeptide, or a group of highly related polypeptides, is synthesized in both bloodstream and procyclic trypanosomes and that subsequent post-translational processing and lysosomal targeting is subject to stage-specific regulation. PMID- 10029307 TI - Purification and characterization of Plasmodium falciparum hypoxanthine-guanine xanthine phosphoribosyltransferase and comparison with the human enzyme. AB - The human malaria parasite Plasmodium falciparum is auxotrophic for purines and relies on the purine salvage pathway for the synthesis of its purine nucleotides. Hypoxanthine-guanine-xanthine phosphoribosyltransferase (HGXPRT) is a key purine salvage enzyme in P. falciparum, making it a potential target for chemotherapy. Previous attempts to purify this enzyme have been unsuccessful because of the difficulty in obtaining cultured parasite material and because of the inherent instability of the enzyme during purification and storage. Other groups have tried to express recombinant P. falciparum HGXPRT but only small amounts of activity were obtained. The successful expression of recombinant P. falciparum HGXPRT in Escherichia coli has now been achieved and the enzyme purified to homogeneity in mg quantities. The measured molecular mass of 26 229+/-2 Da is in excellent agreement with the calculated value of 26232 Da. A method to stabilise the activity and to reactivate inactive samples has been developed. The subunit structure of P. Jilciparum HGXPRT has been determined by ultracentrifugation in the absence (tetramer) and presence (dimer) of KC1. Kinetic constants were determined for 5-phospho-alpha-D-ribosyl-1-pyrophosphate, for the three naturally occurring 6-oxopurine bases guanine, hypoxanthine, and xanthine and for the base analogue, allopurinol. Differences in specificity between the purified P. falciparum HGXPRT and human hypoxanthine guanine phosphoribosyltransferase enzymes were detected which may be able to be exploited in rational drug design. PMID- 10029308 TI - Characterisation and expression of the carbamate kinase gene from Giardia intestinalis. AB - The arginine dihydrolase pathway in Giardia intestinalis produces energy via the carbamate kinase (CBK, ATP:carbamate phosphotransferase, EC 2.7.2.2) reaction. Characterisation of the CBK gene from the Portland 1 strain indicated that it is located on either chromosome 3 or 4, does not appear to contain introns and is expressed in both the trophozoite and early cyst stages. Heterologous expression of CBK in Escherichia coli, using the pQE-30 expression system (QIAGEN), enabled a one-step purification of the recombinant enzyme via affinity chromatography. The expressed protein was identified by enzyme assay and mass spectrometry. The native and recombinant forms of the enzyme have similar physical properties and the recombinant enzyme appears to be active as the homodimer. PMID- 10029309 TI - Purification, characterization, and drug susceptibility of tubulin from Leishmania. AB - Past work suggests that tubulin from kinetoplastid parasites may present an excellent drug target. To explore this possibility, tubulin was purified on a milligram scale from Leishmania mexicana amazonensis promastigotes by sonication, DEAE-Sepharose chromatography, and one cycle of assembly-disassembly. Purified leishmanial tubulin is recognized by commercially available anti-tubulin antibodies and displays concentration dependent assembly in vitro. The vinca site agents vinblastine, maytansine, and rhizoxin bind to leishmanial tubulin as assessed by the quenching of intrinsic tubulin fluorescence and the alteration of the proteins reactivity with the sulfhydryl-specific reagent 5,5'-dithiobis(2 nitrobenzoic acid). They also interfere with the assembly of leishmanial tubulin at low micromolar concentrations. Electrophilic compounds such as phenyl arsenoxide and 4-chloro-3,5-dinitro-alpha,alpha,alpha-trifluorotoluene (chloralin), which are of interest as traditional and experimental antiparasitic agents, respectively, inhibit the assembly of leishmanial tubulin in vitro as well. Colchicine-site agents and trifluralin, on the other hand, have little or no effect on leishmanial tubulin in these assays. Maytansine, taxol, and the electrophiles block the growth of Leishmania donovani amastigote-like forms in vitro at low ( <1 microM) concentrations, while colchicine site agents, trifluralin, vinblastine, and rhizoxin are at least two orders of magnitude less toxic to the parasite. PMID- 10029310 TI - L-myo-Inositol 1-phosphate synthase from Entamoeba histolytica. AB - L-myo-Inositol 1-phosphate synthase (I-1-P synthase) catalyses the primary reaction for the synthesis of inositol in a variety of prokaryotes, eukaryotes and in the chloroplasts of algae and higher plants. Inositol is a precursor of essential macromolecules like membrane phospholipids, GPI anchor proteins and lipophosphoglycans, which play a determinant role in the pathogenesis of protozoan parasites such as Leishmania and Entamoeba. However, there is no report of I-1-P synthase or its gene from these organisms. The gene INO1 coding for this enzyme was first cloned from Saccharomyces cerevisiae and subsequently from several plants. Using molecular cloning techniques we have isolated and characterised the INO1 gene coding for the enzyme I-1-P synthase from Entamoeba histolytica. Simultaneously, we have purified and characterised the native enzyme from E. histolytica trophozoites and the cloned gene product from Escherichia coli. The gene product and the purified enzyme were both shown to be recognised by a heterologous anti-I-1-P synthase antibody from the phytoflagellate Euglena gracilis. Phylogenetic analysis of I-1-P synthase sequences from different eukaryotes suggest that it is highly conserved across species and the origin of this enzyme precedes the evolutionary divergence of modern eukaryotes. PMID- 10029311 TI - Peroxynitrite affects Ca2+ transport in Trypanosoma cruzi. AB - Macrophages play an important role against Trypanosoma cruzi infection, via superoxide, nitric oxide, and peroxynitrite production. Peroxynitrite has been shown to be highly cytotoxic against Trypanosoma cruzi epimastigotes. Calcium is involved in many vital functions of the parasites, being its intracellular concentration governed by several transport systems, involving mitochondrial and non-mitochondrial compartments. In this paper, we report the effect of peroxynitrite on the calcium uptake systems, as studied by digitonin permeabilized trypanosomes in the presence of arsenazo III. Peroxynitrite, at biologically relevant concentrations produced within phagosomes (250-750 microM), inhibited calcium uptake in a dose-dependent manner. Peroxynitrite decreased the mitochondrial membrane potential obtained in the presence of tetramethyl-p phenylenediamine (TMPD)/ascorbate. In addition, a decrease of the non mitochondrial Ca(2+)-uptake, concomitant with the inactivation of a Ca(2+) dependent ATPase activity, was observed. HPLC analyses of the cellular adenine nucleotide pool showed a time-dependent decrease of ATP content and energy charge of the parasite; however this drop in ATP levels was significantly delayed with respect to decrease of the ATP-dependent Ca(2+)-transport. We conclude that the disruption of calcium homeostasis by peroxynitrite may contribute to the observed cytotoxic effects of macrophages against T. cruzi. PMID- 10029312 TI - Stable transformation of Toxoplasma gondii based on a pyrimethamine resistant trifunctional dihydrofolate reductase-cytosine deaminase-thymidylate synthase gene that confers sensitivity to 5-fluorocytosine. AB - To improve genetic models available for the analysis of apicomplexan protozoan parasites, bacterial sequences encoding the 427 amino acid cytosine deaminase (CD) gene were fused, in-frame, to an engineered linker domain of the high level pyrimethamine resistant form of the parasite bifunctional dihydrofolate reductase thymidylate synthase (DHFR-TS) gene. Toxoplasma gondii was transformed with the plasmid containing the fused pyrimethamine resistant dihydrofolate reductase cytosine deaminase-thymidylate synthase (DHFRm2m3-CD-TS) gene and parasites were selected in a high level of pyrimethamine. Transfected parasites that acquired resistance to pyrimethamine were cloned and evaluated for expression of the CD genetic marker. CD transgenic parasites acquired a high sensitivity to 5 fluorocytosine due to the intraparasitic conversion of this non-toxic prodrug to the cytotoxic compound 5-fluorouracil. Exogenously supplied cytosine or uracil rescued the growth of CD transgenic T. gondii parasites that were cultured in the presence of cytotoxic concentrations of 5-fluorouracil or 5-fluorocytosine. Bacterial CD fused to the pyrimethamine resistant DHFR-TS marker provides a novel genetic tool for new positive and negative genetic selection strategies in several protozoan parasites. An advantage of the CD genetic marker is that it is derived from a bacterial gene and can therefore be used in nearly any parasite genetic background for negative selection. This novel system should facilitate new approaches for the development of improved model genetic systems for the biological investigation of apicomplexan parasites. PMID- 10029313 TI - Virulence in Trypanosoma cruzi infection correlates with the expression of a distinct family of sialidase superfamily genes. AB - The overall success of Trypanosoma cruzi depends on its ability to invade the host and establish a long-term infection. Little is known of the genetic factors responsible for observed differences in virulence from strain to strain in T. cruzi. A virulent T. cruzi line was derived from an attenuated parental line by two passages through mice. To identify virulence genes a subtraction library was constructed and screened for cDNA expressed exclusively in the virulent line. One cDNA hybridized to 3.5 and 4.5 Kb RNA present in virulent trypomastigotes but absent in attenuated trypomastigotes. Sequence analysis showed the cDNA to encode an 85 kDa protein with homology to members of the sialidase/trans-sialidase superfamily and has been designated vp85.1. The highest amino acid sequence similarity was to a previously described T. cruzi sialidase-homologue pseudogene [Takle, G.B., O'Conner, J., Young, A.J. and Cross, G.A.M. (1992) Mol. Biochem. Parasitol. 56, 117-128]. The vp85.1 amino acid sequence has higher homology to members of the 160 kDa flagellar-associated antigen family, FL-160, than to other 85 kDa expressed sialidase superfamily members. Southern blot analysis of virulent and attenuated lines demonstrated a complex hybridization pattern consistent with a multiple gene copy family that was identical in both lines. Antibody directed against recombinant vp85.1 peptide recognized proteins between 95 and 115 kDa in total virulent parasite lysates which were absent in attenuated lysates. Peptide N-glycosidase F treatment reduced the high molecular weight bands to 85 kDa, indicating vp85 is an N-linked glycoprotein. Immunofluorescence with anti-vp85.1 demonstrated surface localization of vp85.1 on virulent, but not attenuated, trypomastigotes. We postulate this new subfamily of trans-sialidases may play a role in virulence. PMID- 10029314 TI - Trypanosoma brucei poly(A) binding protein I cDNA cloning, expression, and binding to 5 untranslated region sequence elements. AB - Poly(A) binding protein I (PABPI) is a highly conserved eukaryotic protein that binds mRNA poly(A) tails and functions in the regulation of translational efficiency and mRNA stability. As a first step in our investigation of the role(s) of mRNA poly(A) tails in posttranscriptional gene regulation in Trypanosoma brucei, we have cloned the cDNA encoding PABPI from this organism. The cDNA predicts a protein homologous to PABPI from other organisms and displaying conserved features of these proteins, including four RNA binding domains that span the N-terminal two-thirds of the protein. Comparison of northern blot data with the cDNA sequence indicates an unusually long 3' untranslated region (UTR) of approximately three kilobases. The 5 UTR contains both A-rich and AU repeat regions, the former being a ubiquitous property of PABPI 5' UTRs. T. brucei PABPI, expressed as a glutathione-S-transferase fusion protein, bound to RNA comprised of its full length 5' UTR in UV cross-linking experiments. This suggests that PABPI may play an autoregulatory role in its own expression. Competition experiments indicate that the A-rich region, but not the AU repeats, are involved in this binding. PMID- 10029315 TI - The putative gamma-glutamylcysteine synthetase from Plasmodium falciparum contains large insertions and a variable tandem repeat. AB - The tripeptide glutathione plays a pivotal role in the maintenance of the thiol redox state of the cell and for the detoxification of reactive oxygen species. Glutathione is synthesized in two consecutive reactions by y-glutamylcysteine synthetase (gamma-GCS) and glutathione synthetase, respectively. The former enzyme represents the rate limiting step of the synthetic pathway. We have cloned the cDNA and gene of a putative gamma-GCS from Plasmodium falciparum. The contiguous cDNA sequences obtained from various cDNA libraries of P. falciparum K1 and 3D7 encompass 4206 bp or 4038 bp and encode polypeptides of 1119 and 1063 amino acids, respectively. The deduced amino acid sequences show four regions of homology (identity: 31.3-43.9%) to human and Trypanosoma brucei gamma-GCS. These regions are interrupted by three large insertions between 94 and 239 amino acids. Within the first insert a variable repetitive motif was identified, which is responsible for the differing sizes of the sequences. We have analysed this phenomenon in five additional P. falciparum strains and found a high degree of variability in the number of the repeated octamer (Y/C)S(N/D)LQQ(Q/R). Therefore the predicted molecular mass of the proteins from different P. falciparum strains ranges from 124.4 to 133.2 kDa, which is almost twice that of the catalytic subunit of the human host enzyme. Isolation of three genomic clones revealed that the gene does not contain introns. P. falciparum gamma-GCS transcription peaks in trophozoites (24-30 h) suggesting that the antioxidant glutathione is predominantly produced at a time where hemoglobin degradation and the simultaneous formation of reactive oxygen species is maximal. PMID- 10029316 TI - Ancylostoma secreted protein 1 (ASP-1) homologues in human hookworms. PMID- 10029317 TI - Glutamic acid/alanine-rich protein from Trypanosoma congolense is the functional equivalent of 'EP' procyclin from Trypanosoma brucei. PMID- 10029318 TI - Molecular identification of a 21.7 kDa schistosoma japonicum antigen as a target of the human IgE response. PMID- 10029319 TI - Simultaneous screening for HBV DNA and HCV RNA genomes in blood donations using a novel TaqMan PCR assay. AB - The risk of contracting hepatitis from blood transfusions is estimated to be 1 in 63000 in the case of hepatitis B virus (HBV) and 1 in 103000 in the case of hepatitis C virus (HCV). In some countries (Germany, USA and England, for example), molecular protocols are evaluated to detect viral genomes in blood donations in order to reduce the seroconversion period. However, no such method is available currently to screen large series samples for HBV and HCV. While strategies involving the pooling of plasma samples have been proposed and tested in Germany, there is the question of sensitivity. We developed a novel approach to screen for HBV and HCV based on the TaqMan technology that allows for the quantification of an amplified fragment during PCR analysis (Lee et al., 1993). This approach is more sensitive than other quantification methods. As a first step primers and probes were designed to detect the different sub-types of HBV and HCV genomes. We then optimized the reaction conditions in order to screen for the two viruses at the same time. The observed sensitivity is less than 50 molecules per ml for HBV and less than 50 molecules per ml for HCV. This assay is, to our knowledge, the first that allows the simultaneous detection of DNA and RNA viral genomes. In conclusion, this TaqMan approach could be used as a single test to screen for HBV and HCV genomes in a series of 96 samples in less than 5 h. Such an approach is a first step for development of automation allowing a systematic screening of blood donations. PMID- 10029320 TI - Histidine-tagging and purification of tobacco etch potyvirus helper component protein. AB - The coding sequence for a series of six histidines (his-tag) was inserted near the 5' terminus of the helper component (HC) coding region of tobacco etch potyvirus (TEV). Full length genomic clones containing the his-tag coding sequence were infectious and produced symptoms in tobacco (Nicotiana tabacuma) similar to those induced by wild-type TEV. The modified virus was genetically stable and the his-tag sequence was maintained through at least four cycles of aphid transmission. A protocol for purifying rapidly the HC protein, based on the affinity of its his-tag for Ni(2+)-charged resin, yielded large amounts of his tagged HC protein that was fully functional as demonstrated by aphid transmission experiments. PMID- 10029321 TI - Comparison of seven RNA extraction methods on stool and shellfish samples prior to hepatitis A virus amplification. AB - When choosing an extraction method, two parameters have to be considered: recovery of the viral material and elimination or inactivation of inhibitory substances. Seven techniques for extracting hepatitis A virus (HAV) from stool and shellfish samples were compared, in order to identify the protocol most suited to both types of sample and with the best extraction yield. The protocols tested were either techniques for the recovery and purification of total RNA, such as RNAzol, PEG-CETAB, GTC-silica and Chelex, or techniques for isolating specifically HAV using a nucleotide probe or a monoclonal antibody. For stool samples, RNAzol, PEG-CETAB, and magnetic beads with antibody allowed detection of the virus in 11/12 and 12/12 of samples. For shellfish samples, three protocols allowed RNA to be extracted in 90% of cases, RNAzol, PEG-CETAB, and GTC-silica. Their rapidity and low cost make RNAzol and GTC-silica the most suitable for routine diagnostic testing. reserved. PMID- 10029322 TI - Single-strand conformation polymorphism (SSCP) analysis as a tool for viroid characterisation. AB - The potential of routine single-strand conformation polymorphism (SSCP) analysis for viroid characterization has been evaluated. Electrophoresis of 311 cloned full length viroid DNA inserts recovered from a field isolate of citrus exocortis viroid (CEVd) showed shifts in the migration of the cDNA or/and hDNA strands in non-denaturing 14% polyacrylamide gels. Using a single set of electrophoresis conditions seven different groups of variants (containing one to six changes), which did not represent the overall variability among clones, were identified. The relationship between the different SSCP profiles observed among clones and the variation in their nucleotide sequences was confirmed by sequence analysis. Variations in the dimensions of the gel allowed higher resolution and therefore the detection of additional single nucleotide variations among clones initially clustered into the same group. The viroid region affected by specific changes could be established by SSCP analysis of partial viroid length DNA. The potential use of SSCP analysis as a tool to screen existing viroid populations in infected hosts prior to sequencing is discussed. PMID- 10029323 TI - One-tube fluorogenic reverse transcription-polymerase chain reaction for the quantitation of feline coronaviruses. AB - A one-tube reverse transcription-polymerase chain reaction (RT-PCR) for absolute feline coronavirus (FCoV) quantitation was developed. The assay is based on the 5' nuclease activity of the Thermus flavus (Tfl) polymerase and a fluorogenic probe which generates fluorescence when it is cleaved. The fluorogenic probe, also called TaqMan(TM) probe (Perkin Elmer, Foster City, USA), is an oligonucleotide designed to bind between the two PCR primers to the target cDNA and is labeled with a reporter and a quencher dye. In the intact probe, the quencher dye suppresses the fluorescence of the reporter dye by Forster-type energy transfer. During the polymerase extension steps the Tfl exonuclease activity cleaves the hybridised probe resulting in the generation of fluorescent emission of the reporter dye. The threshold cycle (C(T) value) indicates the increase of reporter fluorescence and is directly related to the initial amount of target cDNA or RNA, respectively. Fluorescence is monitored in real time after each cycle by a Perkin-Elmer ABI Prism 7700 Sequence Detector. After completion of amplification, the C(T) values of the samples are calculated back to a standard curve, generated by amplification of diluted standard molecules. The one tube RT-PCR described below allows precise quantitation, is highly sensitive, rapid (no separate reverse transcription step and no post-amplification steps), easy to handle, allows for a high sample throughput, shows a very good reproducibility, and can be executed with a low risk of contamination. The design of the primers probe combination enables the detection of all known FCoV strains and is also useful for the detection of canine coronavirus, transmissible gastroenteritis virus and porcine respiratory coronavirus. PMID- 10029324 TI - A simple, rapid method of nucleic acid extraction without tissue homogenization for detecting viroids by hybridization and RT-PCR. AB - A simple, rapid method of nucleic acid extraction on a microcentrifuge tube scale for detecting viroids is presented. Five distinct citrus viroids (CVds), chrysanthemum stunt viroid (CSVd), hop stunt viroid (HSVd), hop latent viroid (HLVd) and potato spindle tuber viroid (PSTVd) were detected in their natural host plants by hybridization using cRNA probes and reverse transcription polymerase chain reaction (RT-PCR). Nucleic acids (NA) were liberated from tissues by incubation in a buffer containing potassium ethyl xanthogenate (PEX) without tissue homogenization, and then precipitated with ethanol (NA-PEX). All the viroids except CVd-IV could be detected clearly in NA-PEX by hybridization. HSVd, HLVd and PSTVd could also be detected in NA-PEX by RT-PCR. Although CVds and CSVd could not be detected in NA-PEX by RT-PCR, they were detected after further purification: differential precipitation with 2-butoxyethanol and HCl treatment followed by ethanol-precipitation. In addition, PCR in the presence of tetramethylammonium chloride specifically amplified the cDNA of all five distinct CVds under the same temperature and cycle conditions. Since all the viroids could be detected in NA liberated by PEX, the amount of NA extracted by the method described here is sufficient for detecting viroids, enabling the processing of a large number of samples. PMID- 10029325 TI - Development of a competitive ELISA for detection of primates infected with monkey B virus (Herpesvirus simiae). AB - Two competitive ELISAs (C-ELISAs) are described that allow detection of antibodies against monkey B virus (BV, Cercopithecine herpesvirus 1). The assays utilize monoclonal antibodies (MABs) directed against the BV glycoprotein B (gB). Two of these MABs specifically recognize BV gB while a third MAB also reacts with the gB homologues of other primate alpha-herpesviruses (herpes simplexvirus-1, HSV-1: HSV-2; simian agent-8, SA8; and Herpesvirus papio-2, HVP2). A C-ELISA using the single cross-reactive MAB 3E8 allowed detection of host antibodies against HSV-1, HSV-2, SA8, HVP2 or BV, thus proving to be a sensitive assay for the detection of infection by any of these primate alpha-herpesviruses. The C ELISA using BV-specific MABs was less sensitive but did allow some discrimination between infection by BV versus other alpha-herpesviruses. It was also shown that a C-ELISA using HVP2 as antigen and the cross-reactive MAB 3E8 was as sensitive for detection of BV antibody in macaque sera as an assay employing BV antigen. This test format allows detection of BV-infected primates without the biohazards associated with preparation and use of BV antigen. PMID- 10029326 TI - Use of anti-glycoprotein monoclonal antibodies to characterize rabies virus in formalin-fixed tissues. AB - Seventy anti-rabies virus monoclonal antibodies (Mabs) were tested for reactivity with rabies and rabies-related viruses in formalin-fixed (FF) tissues. Forty three of the Mabs were directed against the glycoprotein and 27 were directed against the nucleocapsid as determined by enzyme immunoassays and neutralization tests. Twenty of the anti-glycoprotein Mabs and one of the anti-nucleocapsid Mabs reacted with the rabies challenge virus strain (CVS) in FF tissue. These 21 Mabs were screened against other lyssaviruses in FF tissues: five rabies virus strains (coyote, skunk, raccoon, red bat, and silver-haired bat), and four rabies-related viruses (Australian bat lyssavirus, Duvenhage virus, Lagos bat virus, and Mokola virus). One of the anti-glycoprotein Mabs was reactive with all the virus strains screened. Another of the anti-glycoprotein Mabs reacted with all of the rabies virus strains tested, but not with any of the rabies-related virus strains tested. The remaining Mabs had reactivity patterns that could be useful for characterizing lyssaviruses in FF tissues. PMID- 10029327 TI - Sheep poxvirus identification by PCR in cell cultures. AB - A simple, rapid and specific diagnostic polymerase chain reaction (PCR) method was developed for sheep poxvirus identification. The primers used were from the sequenced genomes of the capripox viruses KS-1 and InS-1. Six different sheep pox isolates were tested against two orf (parapox) and three animal herpesviruses as controls. Material from uninfected cell cultures was also used as control. The sensitivity of the PCR was approximately equivalent with each of the two primers and for the six sheep pox isolates. All the negative control virus DNAs were negative and differed clearly from those of the sheep pox strains. PMID- 10029328 TI - Diagnosis of dengue infection by detecting specific immunoglobulin M antibodies in saliva samples. AB - To investigate whether saliva could be used for diagnosis of recent dengue, serum and saliva samples were collected simultaneously from patients with suspected dengue infection. Sera (1:10 dilution) and saliva (undiluted) were tested by using an IgM capture enzyme linked immunosorbent assay (MAC-ELISA) with minor modifications (serum and saliva absorption for 3 h at 37 degrees C). The quality of saliva was evaluated by determining the IgG total concentration (enzyme immunoassay) which ranged from 2.7 to > 50 mg/l. Recent dengue infection was confirmed in 38 cases. Forty-six serum and saliva specimens were collected from these patients 1-30 days after the onset of symptoms. IgM was detected in 65.8% saliva samples. High rate of positivity ( > 80%) was observed for the saliva samples collected > or = 5 days after the onset of the disease. Fifty serum and saliva samples from other 32 patients with rash diseases were also tested and all the specimens were unreactive by MAC-ELISA. These results indicate that saliva may be a convenient non-invasive alternative to serum for diagnosis of recent dengue fever infection, especially for epidemiological studies during outbreaks of the disease. PMID- 10029329 TI - Highly sensitive detection of swine vesicular disease virus based on a single tube RT-PCR system and DIG-ELISA detection. AB - A highly sensitive detection of swine vesicular disease virus (SVDV) based on a single tube RT-PCR system and digoxigenin (DIG)-PCR-ELISA detection was developed. Using a one tube RT-PCR system, optimisation of the PCR conditions and optimisation of the microwell hybridisation and colourimetric detection of the amplicons resulted in a method that could detect viral RNA in infected tissue culture fluid with a titre as low as 0.1 TCID50/100 microl. The same sensitivity was obtained with SVDV-spiked faeces, if the samples were pre-treated with 1,1,2 trichlorotrifluoroethane/chloroform and subsequently concentrated using an ultrafiltration system and RNA extracted with the Purescript kit. The specificity of the test was validated on 27 SVDV strains belonging to four different groups. No cross-reactivity with genetically and symptomatically related viruses was detected using RNA of foot-and-mouth disease virus (FMDV), porcine enterovirus (PEV), vesicular stomatitis virus (VSV), Coxsackie B5 virus (CV-B5) and encephalomyocarditis virus (EMCV). The test was validated successfully on clinical samples, being slightly more sensitive and much faster than virus isolation on cell cultures. Moreover the possibility of automating the procedure will allow the processing of large numbers of clinical samples. PMID- 10029330 TI - Isolation of mutants of Aujeszky's disease virus with antigenically altered glycoprotein E by affinity chromatography using monoclonal antibodies. AB - An efficient method for isolation of virus mutants with antigenically altered proteins is described. The method is based on the separation of viruses with wild type and antigenically altered proteins by affinity chromatography using monoclonal antibodies (MAbs). A nonessential glycoprotein E (gE) of Aujeszky's disease virus (ADV) was chosen as a model for introducing the antigenic changes. The ADV strain Ka mutagenised with 5-bromo-2'-deoxyuridine was used for the selection of mutants that do not bind to gE-specific MAb conjugated to resin. After three rounds of isolation by affinity chromatography, the resulting viruses that escape the binding to MAb were plaque-purified by plating at limiting dilution, and virus isolates were tested by the gE-specific sandwich ELISA in which the selecting MAb was used as a capture antibody. About 70% of the ADV isolates tested were not recognised by the sandwich gE-ELISA. The analysis of some of virus isolates in indirect ELISA with a panel of 16 gE-specific MAbs revealed that at least several of the generated virus isolates were mutants expressing gE with alterations in the epitope of the selecting MAb 75/7, as well as in the majority of other conformation-dependent epitopes of gE. The method for the production of antigenically altered viruses by affinity chromatography using MAbs is simple and convenient, and can be utilised with MAbs irrespective of their virus-neutralising activity. PMID- 10029331 TI - Detection of antibodies against the core protein p24 of the bovine leukaemia virus in cattle for confirmatory serological testing. AB - An electrophoretic immunoblotting technique which was developed recently was evaluated for the identification of serum antibodies against the bovine leukaemia virus core protein p24 by using 167 sera from a bovine leukaemia virus-negative herd, and 144 sera from herds naturally infected with the virus. The sensitivity of the immunoblot was 97.4%, relative to sera which were positive in the polymerase chain reaction and in a commercial EBL-ELISA. The specificity of the immunoblot was 99.4%, for the sera from a cattle herd in which all animals were negative by a commercial EBL-ELISA, and it was 96.7% relative to sera which were negative by the polymerase chain reaction and by the agar gel immunodiffusion test from bovine leukaemia virus-infected cattle herds. A p24-specific ELISA was developed, using a monoclonal anti-p24 antibody for coating microtitre plates, a crude antigen preparation, and a monoclonal anti-bovine IgG-horse radish peroxidase conjugate as components. All reagents were commercially available. While the p24-ELISA worked well with sera from serial bleeds from calves infected experimentally with the bovine leukaemia virus and its sensitivity with sera from the naturally-infected cattle was 96.5%, its specificity was relatively low at 85.0 or 53.3%, respectively for the two negative sera groups. PMID- 10029332 TI - Mechanisms underlying the age-related decrement in the human sweating response. AB - To examine the mechanisms underlying the age-related decrement in the ability to sweat, seven older (64-76 years) and seven younger (20-24 years) men participated in a 60-min sweating test. The test consisted of placing the subject's lower legs in a water bath at 42 degrees C while sitting in a controlled environment of 35 degrees C ambient temperature and 45% relative humidity. The rectal (Trc) and skin temperatures, local sweating rates (m(sw): on the forehead, chest, back, forearm and thigh) and the frequency of sweat expulsion (f(sw)) were measured during the test. No group difference was observed in the mean body temperature (Tb) throughout the passive heating, although the older men had a higher Tre and a lower mean skin temperature during the last half of the 60-min test. There were no group differences in the Tb threshold for sweating, although the time to the onset of sweating tended to be longer for the older men regardless of body site. The m(sw) increased gradually for approximately 35 min after the start of heat exposure in the older men and for 30 min in the younger men and then reached a steady state. During the first half of the test, the older men had a significantly lower m(sw) at all sites. During the last half of the test, only m(sw) on the thigh was significantly lower in the older men than in the younger men. There was no group difference in the slope of f(sw) versus Tb (an indicator of the change in the central sudomotor response to thermal input). The slope of m(sw) versus f(sw) (an indicator of the change in peripheral activity in response to central sudomotor changes) was significantly lower on the thigh in the older men, but there were no differences for the other sites. These results suggest that in older men the lower thigh m(sw) observed during the last half of the heat test was possibly due to age-related modifications of peripheral mechanisms involving the sweat glands and surrounding tissues. It was not due to a change in the central drive to sudomotor function. Furthermore, the sluggish m(sw) responses in the older men appear to have been related to age-related modifications of the sensitivity of thermoreceptors in various body regions to thermal stimuli. They may also involve lower sweat glands' sensitivity to cholinergic stimulus or sluggish vasodilatation, and do not reflect age-related changes in the central drive. PMID- 10029333 TI - Shoulder muscle co-ordination during chronic and acute experimental neck-shoulder pain. An occupational pain study. AB - Little is known about the mechanisms leading to chronic neck-shoulder musculoskeletal disorders (MSD). The aim of the present study was to investigate and compare motor function during controlled, low load, repetitive work together with chronic or acute experimental neck-shoulder pain. The clinical study was performed on workers with (n = 12) and without (n = 6) chronic neck-shoulder pain. In the experimental study, experimental muscle pain was induced in healthy subjects by intra-muscular injection of hypertonic saline into the trapezius muscle (n = 10). The assessed parameters related to motor performance were: work task event duration, cutting forces, surface electromyogram (EMG) activity in four shoulder muscles, displacement of the centre of pressure, and arm and trunk 3D movements. For controlled cutting force levels, chronic and acute experimental pain provoked a series of changes: a decreased working rhythm and a protective reorganisation of muscle synergy (experimental study), higher EMG frequency contents which may indicate altered motor unit recruitment, and greater postural activity and a tendency towards increased arm and trunk movements. These pain related changes can play a role in the development of MSD. The present clinical and experimental study demonstrated similar interactions between motor co ordination and neck-shoulder pain in occupational settings. We therefore suggest that this experimental model can be used to study mechanisms related to MSD. Information on such modulatory processes may help in the design of new strategies aimed at reducing the development of MSD. PMID- 10029334 TI - Decreased serum levels of 1,25-(OH)2 vitamin D during 1 year of sunlight deprivation in the Antarctic. AB - French Antarctic territories harbor bases that are devoted to scientific and technical work. Living and working conditions during 1-year sojourns in such an environment are quite acceptable, but the confinement and the drop in ultraviolet B radiation exposure during winter months raise the problem of preservation of normal vitamin D status. Seasonal variations in 25-hydroxyvitamin D [25(OH)D] levels have been well documented, but the effect of sunshine deprivation on 1,25 dihydroxyvitamin D [1,25(OH)2D] levels is quite controversial. The aim of this study was to address this question under the exceptional conditions of lack of sunshine exposure. Fifteen male Caucasian subjects participating in a 1-year mission in Antarctica were investigated. They were subjected to seven blood samplings, one before and six during their sojourn. Serum levels of 25(OH)D, 1,25(OH)2D, osteocalcin, and ICTP were measured. We found that levels of 25(OH)D and 1,25(OH)2D significantly decreased in these subjects during the mission, minimum levels being observed 10 months after their departure from France. ICTP concentrations did not change throughout this study, but osteocalcin levels were found to be higher at the end of the sojourn than before departure, which could argue for the existence of bone remodeling changes. Further studies are now needed to fully investigate bone metabolism changes and to address the question of vitamin D supplementation during this kind of sojourn. PMID- 10029335 TI - Hypotension following mild bouts of resistance exercise and submaximal dynamic exercise. AB - Our purposes were (1) to examine resting arterial blood pressure following an acute bout of resistance exercise and submaximal dynamic exercise, (2) to examine the effects of these exercises on the plasma concentrations of atrial natriuretic peptide ([ANP]), and (3) to evaluate the potential relationship between [ANP] and post-exercise blood pressure. Thirteen males [24.3+/-(2.4) years] performed 15 min of unilateral leg press exercise (65% of their one-repetition maximum) and, I week later, approximately 15 min of cycle ergometry (at 65% of their maximum oxygen consumption). Intra-arterial pressure was monitored during exercise and for 1 h post-exercise. Arterial blood was drawn at rest, during exercise and at intervals up to 60 min post-exercise for analysis of haematocrit and [alphaANP]. No differences occurred in blood pressure between trials, but significant decrements occurred following exercise in both trials. Systolic pressure was approximately 20 mmHg lower than before exercise after 10 min, and mean pressure was approximately 7 mmHg lower from 30 min onwards. Only slight (non-significant) elevations in [alphaANP] were detected immediately following exercise, with the concentrations declining to pre-exercise values by 5 min post-exercise. We conclude that post-exercise hypotension occurs following acute bouts of either resistance or submaximal dynamic exercise and, in this investigation, that this decreased blood pressure was not directly related to the release of alphaANP. PMID- 10029336 TI - Lactate determination in exercise testing using an electrochemical analyser: with or without blood lysis? AB - The practical use of lactate electrochemical analysers in exercise testing has not been adequately examined. Initial studies have reported differences in lactate concentration between that measured spectrophotometrically and that measured electrochemically. The study described here was undertaken to compare, using the statistical technique of Bland and Altman (1986), two widely available methods of measuring lactate using lysed and non-lysed blood samples and the lactate thresholds derived from the measured lactate values using a log-log transform technique. Thirteen normal, healthy young adults (11 male) undertook progressive exercise tests to exhaustion. Arterialised venous blood samples were taken each minute and the lactate concentration therein was measured both spectrophotometrically and electrochemically and either with or without lysis of the blood samples. The lactate concentrations measured in lysed blood using both methods (182 pairs) were in close agreement. The electrochemical values obtained using non-lysed blood were systematically lower than spectrophotometric values (206 pairs), the difference becoming progressively greater at higher lactate concentrations. Results for the lactate threshold comparisons are given as mean difference (limits of agreement with 95% probability). Lactate thresholds (12 pairs) derived from lysed blood lactate concentrations measured spectrophotometrically and electrochemically were not significantly different -30 (240) ml O2 x min(-1). Lactate thresholds (11 pairs) derived from lysed spectrophotometric and non-lysed electrochemical measurements were also not significantly different + 20 (250) ml O2 x min(-1). Thus, despite the difference in the measured lactate concentrations, the derived lactate thresholds are in agreement and, therefore, electrochemical analysers can be used for lactate threshold determination using the log-log transform technique without sample lysis. PMID- 10029337 TI - Effect of exhausting stretch-shortening cycle exercise on the time course of mechanical behaviour in the drop jump: possible role of muscle damage. AB - The purpose of the present study was to investigate the effect of stretch shortening-cycle-induced muscle damage on the time course of mechanical behaviour in the drop jump. Ten healthy male subjects performed submaximal stretch shortening cycle (SSC) exercise on a special sledge apparatus. Exhaustion occurred on average within 3 min. A drop jump (DJ) test from a 50-cm height was performed before and immediately after the sledge exercise as well as 2 h, 2 days and 4 days later. The fatigue exercise showed relatively high blood lactate concentration [12.5 (SD 2.6) mmol x l(-1)] and an increase of serum creatine kinase (CK) activity delayed by 2 days [540 (SD 407) U x l(-1)]. The initial decline in the jump performance (before - immediately after) was related negatively to the early recovery in performance (immediately after 2 h) (P < 0.05). The early recovery of the knee joint moment at the end of stretch showed a negative correlation to the delayed decrease in DJ performance (2 h 2 days) (P < 0.01). Thus, the DJ performance showed an initial decline followed by an early recovery and a secondary decline. Both the initial decline and early recovery in the knee joint moment at the end of stretch were related to the corresponding initial (after 2 h) (P < 0.05) and secondary increases (2 h - 2 days) (P < 0.01) in CK. It is suggested that the early recovery as well as the initial decline in the knee joint function could depend on the degree of muscle damage. Delayed decrease in initial stiffness (2 h - 2 days) was negatively related to the corresponding changes in the knee joint angle at touch down in DJ (P < 0.001). These interactions would imply that the decrease in the stiffness regulation and the modulation of the prelanding motor control might be attributable to secondary muscle damage during 2 days after the SSC exercise. Therefore, it may be suggested that the changes in the DJ performance after the exhausting SSC exercise accompany the progress of muscle damage observed by the corresponding increase in serum CK concentration and the corresponding deterioration of stiffness regulation and motor control in DJ. PMID- 10029338 TI - The effects of long-term simulated microgravity on neuromuscular performance in men and women. AB - The effects are reported of prolonged exposure to simulated microgravity (strict bed rest in an antiorthostatic position -6 degrees head-down tilt, HDT) on voluntary and electrically evoked contractions of the triceps surae muscle in men (n = 6) and women (n = 4). The subjects served as their own controls. Bed rest is a model that has commonly been used to simulate spaceflight. Measurements made in the control condition (10-8 days before the beginning of HDT) and after 120-days of HDT (on the 3rd day after it ended) included examination of the properties of isometric maximal voluntary contractions (MVC), isometric twitch contractions (Pt) and tetanic contractions (Po). After HDT, the MVC decreased by means of 44% and 33%, P, by means of 36% and 11%, Po by means of 34% and 24%, in the men and the women, respectively. The difference between Po and MVC, expressed as a percentage of Po and referred to as force deficiency (FD), has also been calculated. The FD increased by means of 60% and 28.8% in the men and the women, respectively. Time-to-peak tension of the triceps surae muscle increased by means of 12% and 14% in the men and the women, respectively, but half-relaxation time decreased by means of 9% and 19%. Total contraction time increased by a mean of 23% in the men and decreased by a mean of 17% in the women. Force-velocity of properties of the triceps surae muscle calculated according to a relative scale of voluntary contraction development significantly decreased more in the women than the men. The calculations of the same properties of electrically evoked contraction development did not differ substantially from the initial physiological state. It can be concluded that not only were the contractile properties of the triceps surae muscle significantly different in the men and the women, but that the effects of exposure to simulated microgravity on these properties were also different. These differences may be explained by sex differences in the muscle tissue itself and in its maximal neural activation. PMID- 10029339 TI - Metabolic and cardioventilatory responses during a graded exercise test before and 24 h after a triathlon. AB - Previous studies have reported respiratory, cardiac and muscle changes at rest in triathletes 24 h after completion of the event. To examine the effects of these changes on metabolic and cardioventilatory variables during exercise, eight male triathletes of mean age 21.1 (SD 2.5) years (range 17-26 years) performed an incremental cycle exercise test (IET) before (pre) and the day after (post) an official classic triathlon (1.5-km swimming, 40-km cycling and 10-km running). The IET was performed using an electromagnetic cycle ergometer. Ventilatory data were collected every minute using a breath-by-breath automated system and included minute ventilation (V(E)), oxygen uptake (VO2), carbon dioxide production (VCO2), respiratory exchange ratio, ventilatory equivalent for oxygen (V(E)/VO2) and for carbon dioxide (V(E)/VCO2), breathing frequency and tidal volume. Heart rate (HR) was monitored using an electrocardiogram. The oxygen pulse was calculated as VO2/HR. Arterialized blood was collected every 2 min throughout IET and the recovery period, and lactate concentration was measured using an enzymatic method. Maximal oxygen uptake (VO2max) was determined using conventional criteria. Ventilatory threshold (VT) was determined using the V slope method formulated earlier. Cardioventilatory variables were studied during the test, at the point when the subject felt exhausted and during recovery. Results indicated no significant differences (P > 0.05) in VO2max [62.6 (SD 5.9) vs 64.6 (SD 4.8) ml x kg(-1) x min(-1)], VT [2368 (SD 258) vs 2477 (SD 352) ml x min(-1)] and time courses of VO2 between the pre- versus post-triathlon sessions. In contrast, the time courses of HR and blood lactate concentration reached significantly higher values (P < 0.05) in the pre-triathlon session. We concluded that these triathletes when tested 24 h after a classic triathlon displayed their pre-event aerobic exercise capacity, bud did not recover pretriathlon time courses in HR or blood lactate concentration. PMID- 10029340 TI - Training theory and taper: validation in triathlon athletes. AB - This paper defines a training theory with which to predict the effectiveness of various formats of taper in optimizing physical performance from a standardized period of training and taper. Four different taper profiles: step reduction vs exponential (exp) decay and fast vs slow exp decay tapers, were simulated in a systems model to predict performance p(t) resulting from a standard square-wave quantity of training for 28 days. The relative effectiveness of each of the profiles in producing optimal physical improvement above pre-taper criterion physical test standards (running and cycle ergometry) was determined. Simulation showed that an exp taper was better than a step-reduction taper, and a fast exp decay taper was superior to a slow exp decay taper. The results of the simulation were tested experimentally in field trials to assess the correspondence between simulation and real-training criterion physical tests in triathlon athletes. The results showed that the exp taper (tau = 5 days) group made a significantly greater improvement above a pre-taper standard (P < or = 0.05) than the step reduction taper group in cycle ergometry, and was better, but not significantly so, in a 5-km run. A fast exp taper group B (tau = 4 days) performed significantly better (P < or = 0.05) in maximal, cycle ergometry above a pre taper training standard than a slow exp taper group A (tau = 8 days) and was improved more, but not significantly so, than group A in a 5-km criterion run. The mean improvement on both physical tests by exp decay taper groups all increased significantly (P < or = 0.05) above their pre-taper training standard. Maximum oxygen uptake increased significantly in a group of eight remaining athletes during 2 weeks of final taper after three athletes left early for final preparations at the race site. PMID- 10029341 TI - Effects of hyperoxia on oxygen uptake kinetics in cystic fibrosis patients as determined by pseudo-random binary sequence exercise. AB - Patients with cystic fibrosis (CF) have been shown to exhibit impaired oxygen uptake (VO2) kinetics independent of their physical fitness. This study investigated whether oxygen supplementation improves VO2 kinetics in CF as determined by cycle ergometry at submaximal exercise intensities using a pseudo random binary sequence exercise test i.e. a simultaneous application of different frequencies of sinusoidal work. The subjects were 9 CF patients and 13 healthy controls (HC) and they exercised while breathing humidified and heated air with a fractional concentration of oxygen in inspired air (F(I)O2) of either 0.21 or 0.40. With a F(I)O2 of 0.21 the respiratory exchange ratio (R) was higher in CF than in HC both at rest (0.91 vs 0.81) and during exercise (0.97 vs 0.89). Oxygen saturation (SO2) was slightly lower in CF. but remained above 90% during exercise (92.7% vs 95.2%). Spectrum analysis revealed that in CF, the amplitude ratio (AR) between V02 and exercise intensity was lower over a wide frequency range (P < 0.05). In addition, CF showed a larger negative phase shift (PS) at lower frequencies (P < 0.005). With a F(I)O2 of 0.40, SO2 increased to about 97% in both groups; while R remained higher in CF (0.92) compared to HC (0.81). In the control group, the O2 supplement raised AR but the VO, kinetics of the CF patients were not significantly affected. In HC the enhanced AR during oxygen supplementation would suggest a cardiopulmonary limitation of VO2 at the onset of submaximal exercise. In CF patients low AR and PS would indicate an attenuated VO2 response attributable to an impaired oxygen utilization in the muscles because the oxygen supplement normalised SO2 but failed to improve R and VO2 kinetics. PMID- 10029342 TI - Jumping height in former elite athletes. AB - To evaluate lower-limb explosive strength with respect to lifetime athletic activity, we measured vertical jumping height on a contact mat in former male runners (n = 28). soccer players (n = 31), weightlifters (n = 29) and shooters (n = 29) (age range 45 68 years). There were no statistically significant age adjusted sport-group differences in jumping height, but differences by sport were evident among the subgroup of athletes without hip or knee osteoarthritis (n = 65) (P < 0.05). Thus, sports that increased jumping height also predisposed to lower-limb osteoarthritis. After adjustment for age and sport, the subjects without osteoarthritis jumped higher than those with osteoarthritis (n = 33) (P < 0.01). In a multiple linear regression analysis, age, reported hip and knee disability, and knee pain reduced jumping height. Hours spent in team-training during the past 12 months and the hours spent during their lifetime in power training were associated with improved vertical jumping height and together explained 41% of the difference among the subjects. The ability to jump even among athletes with hip or knee osteoarthritis would suggest that former elite athletes possess advanced lower limb muscle function. PMID- 10029343 TI - Effect of a pulsating anti-gravity suit on peak exercise performance in individual with spinal cord injuries. AB - The aim of this study was to examine effects of a pulsating pressure anti-gravity suit on the peak values of oxygen uptake (VO2) and power during maximal arm exercise in spinal-cord-injured (SCI) individuals. Five well-trained SCI men (with lesions at levels between T6 and L1) and seven well-trained able-bodied men (ABC) performed two incremental (10 W x min(-1)) arm-cranking tests. During one test the pressure in the anti-G suit pulsated between 4.7 kPa (35 mmHg) and 9.3 kPa (70 mmHg) every 2 s (PPG+), during the other test (PPG-) all the subjects wore the anti-G suit in a deflated state. Tests were performed in a counter balanced order. Peak VO2 in SCI was 1 ml x kg(-1) x min(-1) lower during PPG+ compared to PPG- (P = 0.05). Peak power and peak heart rate were not significantly different during PPG+ compared to PPG-. These results would suggest that no increase in work capacity can be obtained with a pulsating pressure anti gravity suit in either SCI or ABC. PMID- 10029344 TI - Pontine gliomas: a lesson to learn. PMID- 10029345 TI - Twins with different temporal lobe malformations: schizencephaly and arachnoid cyst. AB - The etiology and relationships between different forms of malformations of cortical development are poorly understood. Schizencephaly is generally regarded as unrelated to arachnoid cysts. As part of a systematic study of epilepsy in twins we observed a monozygotic twin pair discordant for temporal lobe epilepsy where the twin with epilepsy had unilateral temporal schizencephaly and periventricular heterotopia. The twin without epilepsy had an arachnoid cyst in the same temporal lobe. Although an incidental association is possible, this observation, together with occasional reports of schizencephaly and arachnoid cysts within one individual, suggests a shared pathogenic mechanism. Schizencephaly can be caused by both genetic and acquired factors. We propose that our observations in this twin pair are best explained by a genetic factor present in both twins, with an additional environmental insult resulting in schizencephaly in only one of the pair. PMID- 10029346 TI - A novel form of familial congenital muscular dystrophy in two adolescents. AB - We report on two brothers (the product of first-degree consanguineous marriage; aged 15 and 12 years) who presented with severe hypotonia at birth, proximal muscle weakness associated with delayed motor milestones but normal cognitive function. Investigations (at 4 years of age) revealed mildly elevated serum creatine kinase (CK) levels (300 and 824 IU/l; N < or = 210). Muscle biopsies showed minimal change myopathy, no neurogenic atrophy but remarkable type-1 fibre predominance (up to 85.5%) without fibre-type disproportion. Clinical examination at 12 and 9 years, respectively, showed mild facial weakness and high-arched palate in both patients. The younger sibling also had ptosis but otherwise normal external ocular muscles. They showed symmetric proximal muscle weakness and wasting associated with calf-muscle hypertrophy. They could walk independently. A repeat muscle biopsy showed advanced dystrophic changes in the younger patient at the age of 10 years. Virtually all the remaining fibres were type 1. Immunohistochemistry revealed normal expression of the dystrophin-glycoprotein complex (DGC), including dystrophin, beta-dystroglycan, alpha-(adhalin), beta-, gamma-, and delta-sarcoglycan, laminin-alpha2 chain (merosin) and syntrophin. Mild dystrophic features and type-1 fibre predominance (92.5%) were seen in the biopsy of the older patient, whereas immunohistochemistry showed normal expression of the DGC. Both cases also showed clear expression of integrin alpha7 at the muscle fibre surface and in the blood vessels. Three years later, they could still walk, but with difficulty, and the older brother showed enlargement of the tongue and echocardiographic features of left ventricular dilated cardiomyopathy. PMID- 10029347 TI - Mental retardation in amaurosis congenita of Leber. AB - A group of 229 patients with Leber's congenital amaurosis (ACL) was investigated for associated defects. We especially looked for the occurrence of mental retardation because the literature gives varying frequencies for this association. A percentage of 19.8% was found. This finding has consequences for genetic counseling. Special attention was given to how frequently sibling pairs occurred in which one patient was mentally retarded whereas the other functioned normally. We found 11 sibling pairs that were discordant with regard to their mental state. This observation proves that mental retardation could be one variable expression of ACL. PMID- 10029348 TI - MRI of the brain in the Cohen syndrome: a relatively large corpus callosum in patients with mental retardation and microcephaly. AB - Our purpose was to perform the first systematic brain magnetic resonance imaging (MRI) study of a substantial number of Cohen syndrome (MIM n:o 216550) patients. 18 Cohen patients and 26 healthy volunteers were examined by MRI (1.0 T). All Cohen patients had essential features of this syndrome: typical facial and structural features, mental retardation, microcephaly, ophthalmologic symptoms, granulocytopenia and cheerful psychic disposition. All our patients belong to the recently published study of refined mapping of the Cohen syndrome gene by linkage disequilibrium. As visual analysis of MR images revealed an impression of a large corpus callosum (CC), quantitative analysis was performed. Sagittal diameter of the body of the CC was larger than that of controls (p = 0.02), whereas all sagittal diameters of the brain stem were markedly smaller (p < 0.0001), as was the midline internal skull surface (MISS) (p < 0.0001). The CC surface did not significantly differ from that of controls significantly. Our main finding, a relatively enlarged corpus callosum, has not previously been reported to associate with mental retardation. Though MRI alone can not confirm the diagnosis and no definite measurements can be recommended for clinical use, any clinical suspicion of this syndrome receives reinforcement through MRI: a relatively enlarged corpus callosum in a microcephalic head and normal signal intensities of the grey and white matters. PMID- 10029349 TI - Familial cerebellar hypoplasia and pancytopenia without chromosomal breakages. AB - Two siblings manifested a neuro-haematologic syndrome characterised by low birth weight, failure to thrive, chronic persistent tongue ulceration, severe truncal ataxia and pancytopenia without either telangiectasia or chromosomal instability. One sibling died from sepsis and the cerebellum demonstrated reduced cellularity of the molecular and granular layers with relative preservation of Purkinje cells and minimal gliosis. A surviving sibling has shown haematologic progression to a myelodysplastic disorder. There was no evidence of any chromosomal instability following exposure of fibroblasts and lymphocytes to irradiation. Monosomy-7 was not present in the surviving sibling. We suspect that these two patients represent another example of the rare Hoyeraal-Hreidarsson syndrome and we are currently engaged in very close monitoring of the surviving sibling for evidence of any karyotypic abnormality. PMID- 10029351 TI - Characterization of the mitochondrial genome in childhood multiple sclerosis. III. Multiple sclerosis without optic neuritis and the non-LHON-associated genes. AB - The higher maternal transmission of multiple sclerosis in familial cases and the coincidence of a MS-like phenotype with mitochondrial point mutations in patients with Leber's hereditary optic neuropathy has inspired a detailed assessment of the mitochondrial genome as an etiological factor in the pathogenesis of MS. To further elucidate the contribution of maternally transmitted mutations to MS susceptibility, we sequenced five protein- and all RNA-coding genes of the mtDNA from thirteen children with MS and twenty unaffected individuals. After excluding several synonymous mutations and common polymorphisms, a total of ten ambiguous missense or protein synthesis mutations were selected and analysed. By defining minimal criteria for pathogenity--incidence, location and degree of evolutionary conservation--we conclude that sequence variations in COII, ATPase6 and 8, ND3, or ND4L subunits of oxidative phosphorylation as well as in rRNA and tRNA genes are unlikely to increase susceptibility for the development of MS. PMID- 10029350 TI - Characterization of the mitochondrial genome in childhood multiple sclerosis. II. Multiple sclerosis without optic neuritis and LHON-associated genes. AB - The occurrence of mitochondrial mutations with primary pathogenic significance for Leber's hereditary optic neuropathy in patients with a multiple sclerosis like phenotype and the preferential maternal transmission points to an involvement of the mitochondrial genome in conferring increased susceptibility to MS. To evaluate the link between MS and mtDNA variations we investigated a total of thirteen children with MS as well as twenty controls by sequencing eight mitochondrial encoded genes which are known to be the loci for LHON-associated mutations. Numerous synonymous nucleotide substitutions and common polymorphisms were excluded from comparative analyses. No primary LHON mutations were found. Secondary LHON mutations were identified more frequently in control subjects than in the children with MS. The remaining eight discrete missense mutations were chosen for further characterization. Only two of them were found in more than one patient. Our results suggest that nucleotide substitutions within the ND1, ND2, ND4, ND5, ND6, COI, COIII or cytochrome b genes of mtDNA do not contribute to the etiology of typical MS. However, the association of LHON mutations with visual impairment in MS as well as the relationship between phenotypic diversity in certain subgroups of patients with individual mtDNA genotypes merits further investigations. PMID- 10029352 TI - Infantile spasms associated with a histamine H1 antagonist. AB - Some anti-allergic agents act as histamine H1 antagonists and induce seizure discharges in epileptic patients. Of these agents, ketotifen has an especially potent effect. We have experienced 2 cases of 4-month-old boys who developed infantile spasms 8 to 10 days after ketotifen administration. They showed almost the same clinical course with regard to their age, the interval between ketotifen administration and the onset of seizures, their symptoms and EEG abnormalities. These cases suggest that the administration of ketotifen to young infants may be hazardous with regard to inducing infantile spasms. PMID- 10029353 TI - Juvenile form of dihydropteridine reductase deficiency in 2 Tunisian patients. AB - Two brothers are described who had juvenile-onset DHPR deficiency. Both were considered normal until six years of age when they developed a fluctuating and progressive encephalopathy combining mental retardation, epilepsy, pyramidal, cerebellar and extrapyramidal signs. PMID- 10029354 TI - Acquired and isolated asymmetrical palatal palsy. AB - Benign acquired and isolated asymmetrical palatal palsy is a rare condition in childhood. We report on three cases. Typical features include: sudden onset, abnormality of the palatal components of speech (rhinolalia), nasal escape of fluids from the ipsilateral nostril. It is supposed to be caused by viral infection, but attempts at viral isolation were unsuccessful. Complete spontaneous recovery is usual, taking a few weeks. Our paper seems to be the first report of magnetic resonance imaging of the brain in this condition. It did not disclose any abnormalities in the 2 cases in which it was performed. PMID- 10029355 TI - Dacrystic seizures reconsidered. AB - Ictal lachrymation has not been reported in children as a main seizure manifestation. We report an infant with tuberous sclerosis who presented with seizures characterised by lachrymation without apparent emotional change associated with a left posterior temporal epileptic focus. We discuss the pathophysiological implications, and propose a clinically orientated classification of crying seizures. PMID- 10029356 TI - Complete remission of a diffuse pontine glioma. AB - A patient is described in whom a large diffuse glioma of the pons extending into the midbrain was diagnosed at the age of 2 years. Biopsy showed a fibrillary astrocytoma. After shunting of a hydrocephalus, the clinical symptoms abated without conventional therapy. Repeated MRI studies showed a continuous decrease of the tumour which was no longer visible when the patient was 6.6 years old. In reviews on spontaneous remissions of oncologic disorders we were unable to find a case of a biologically benign brain stem tumour. There is one isolated report on a similar case, though without histologic documentation. PMID- 10029357 TI - Ornithine transcarbamylase deficiency: a case report. PMID- 10029358 TI - The case for treatment of dyspeptic patients infected with H. pylori. AB - H. pylori is probably the commonest bacterial infection worldwide and associated with a number of clinical outcomes including chronic active gastritis, peptic ulcer, gastric adenocarcinoma, gastric MALT lymphoma and possibly dyspepsia. Treatment to eradicate H. pylori infection has changed significantly the natural history of peptic ulcer disease and is now the recommended approach to patients with non-NSAID gastric and duodenal ulcers. Controversies remain as to whether H. pylori infection is a cause of dyspepsia and non-ulcer dyspepsia. However, results from several economic models evaluating a "test and treat" strategy have suggested that eradication of H. pylori infection as an initial choice is the most cost-effective approach and has a long-term benefit in a significant proportion of patients with dyspepsia. The conclusion of H. pylori as a group 1 human carcinogen by the IARC and the subsequent analyses have added further to the recommendation for eradication of the infection. PMID- 10029359 TI - H. pylori infection in non-ulcer patients--to treat or not to treat. The case against treatment. AB - Heretofore regarded as a strict pathogen, recent identification of multiple mutants of H. pylori, varying in pathogenicity, genomic composition, antigenic structure and other characteristics, has led to speculation that not all strains of the organism merit elimination. Affecting half the world's population, H. pylori appears to cause clinically significant disease in <20% of cases. The costs of eradicating harmless infection in over 2 billion people are prohibitive, particularly in countries lacking resources, and are questionable even in advanced countries where infection, gastritis and related diseases are declining as social conditions improve. Major controversies surround empiric eradication of helicobacter infection in patients with asymptomatic gastritis or non-specific dyspepsia. Apart from cost, and feasibility, there are concerns that widespread campaigns to eradicate H. pylori might cause major increases in esophageal reflux disease and esophageal adenocarcinoma, while causing some serious iatrogenic illness and increasing antibiotic resistance, with uncertain consequences to affected populations. PMID- 10029360 TI - Antimicrobial treatment of H. pylori infection--a pooled efficacy analysis of eradication therapies. AB - OBJECTIVE: To evaluate the clinical efficacy of available therapies directed towards Helicobacter pylori eradication. DESIGN: Pooled overall analyses of a limited number of drug combinations regardless of dosage, duration, formulation etc. SUBJECTS: Helicobacter pylori infected patients with or without complications. INTERVENTIONS: Efficacy data from all studies included in the analysis are transformed to or retained as intention to treat data. MAIN OUTCOME: Efficacy is presented as proportion of patients cured from the infection. Confidence intervals are enlarged by 1.5 due to the inferior strength of a pooled analysis. RESULTS: Dual therapies are ineffective. Triple therapies cure 70-90% of the patients. Well documented high efficacy is shown for a proton pump inhibitor plus two antimicrobials. Less studied but effective alternatives are ranitidine-bismuth plus two antimicrobials. CONCLUSION: A proton pump inhibitor plus two antimicrobials is the best validated highly effective type of eradication therapy. PMID- 10029361 TI - Is there a link between chronic Helicobacter pylori infection and coronary heart disease? AB - BACKGROUND: A number of epidemiological studies have reported on associations of coronary heart disease and raised levels of IgG serum antibodies to Helicobacter pylori. There is substantial uncertainty about the interpretation of these reports, however, as some authors have emphasised the most extreme findings to claim that a causal association exists, whereas others have reported the existence of no strong correlations. METHODS: A systematic review of the published literature was conducted. RESULTS: More than twenty relevant epidemiological reports were identified. There was a tendency towards larger odds ratios in smaller case-control studies that recruited controls opportunistically (e.g., hospital inpatients without heart disease) and that did not adjust for many confounders. Overall, the prospective studies reported no strong correlations between coronary heart disease and H. pylori infection. Even in a combined analysis, however, these studies were too small to be able to confirm or refute the existence of weak associations. CONCLUSION: Residual confounding by causal risk factors may well account for the weak associations that have been reported between coronary heart disease and H. pylori. PMID- 10029362 TI - Non-gastric effects of H. pylori infection: a literature review with respect to non gastric diseases which might be associated with H. pylori infection. AB - Helicobacter pylori (H. pylori) is the most common cause of peptic ulcers, and is considered as carcinogenic with respect to gastric cancer and MALT lymphoma. The role of H. pylori in other gastroduodenal diseases like atrophic gastritis and functional dyspepsia has been investigated in hundreds of works, but little is done about what role H. pylori may play in non gastric diseases. Gastro esophageal reflux disease does not seem to be related to H. pylori but Barrett's esophagus might be. Inflammatory bowel diseases tend to be reverse correlated with H. pylori. In coronary heart disease some studies have shown a connection, others not. Diabetes is not likely to be H. pylori-associated and nor do liver diseases with exception for cirrhosis, where a correlation is possible. Respiratory diseases are little examined but bronchiectasis might have a correlation with H. pylori. A small series of children, who had died in sudden infant death, showed a high rate of H. pylori infection. PMID- 10029363 TI - Scope of the problem of functional digestive disorders. AB - Functional dyspepsia and the irritable bowel syndrome (IBS) are amongst the most widely recognised functional gastrointestinal disorders. Symptom based diagnostic criteria have been developed and refined for the syndromes (the Rome criteria) and these are now widely applied in clinical research. Both functional dyspepsia and IBS are remarkably prevalent in the general population, affecting approximately 20% and 10% of persons, respectively. The prevalence is stable from year to year because the onset of these disorders is balanced by their disappearance in the population. Clinically useful predictors of the course of these disorders have not been identified. Approximately one third of persons with functional dyspepsia concurrently have IBS. In most studies from Western countries, it has been shown that only a minority with functional dyspepsia and IBS present for medical care; the factors that explain consultation behaviour remain inadequately defined although fear of serious disease and psychological distress may be important. The majority of patients diagnosed as having functional dyspepsia or IBS continue to have symptoms long term with a significant impact on quality of life. The indirect costs of the functional gastrointestinal disorders greatly outweigh the direct costs but overall these conditions are responsible for a major proportion of health care consumption. Rational management of the functional gastrointestinal disorders will only follow a better understanding of the natural history of these conditions. PMID- 10029364 TI - Imaging studies in dyspepsia. AB - Patients with functional dyspepsia have discomfort centred in the upper abdomen in the absence of oesophagitis, ulcer, cancer or other pathology which could have explained the dyspepsia. It is generally accepted that neither endoscopy, nor other imaging modalities give any positive findings supporting the diagnosis. However, recent investigations have shown that both endoscopic and ultrasonographic imaging show changes: erosive prepyloric changes (EPC) and accommodation abnormalities, respectively, in a high percentage of the patients. The diagnostic sensitivity and specificity of the changes are not yet known, but the fact that they are also seen in several other conditions characterised by dyspepsia, for instance in gallstone disease, may simply indicate that they are linked to epigastric discomfort in general, and not to a specific dyspeptic condition. Ultrasonographic imaging is a non-invasive, widely available, convenient, and reliable method for evaluation of gastric emptying, gastric motility, transpyloric flow and accommodation disturbances, which may play a crucial role in the pathogenesis of dyspepsia. PMID- 10029365 TI - Brain-gut interactions: implications for newer therapy. AB - Despite their high prevalence and significant economic impact on the healthcare system, functional GI disorders have evaded successful therapy. Conventional medical therapies are based on inadequate disease models, and the great majority of published treatment trials are flawed in their design, thus not permitting to draw any conclusions about true efficacy of any particular treatment. The past several years have seen the rapid evolution of a new, comprehensive disease model, based on alterations in brain-gut interactions. Even though the precise mechanisms and sites underlying these alterations remain incompletely understood, plausible targets for the development of effective pharmacologic treatment are receptors on peripheral terminals of visceral afferent nerves (opioids, serotonin), ion channels and receptors on dorsal horn neurons within the spinal cord (opioids, glutamate, CGRP, NK-1) and supraspinal targets in the brainstem, within the limbic system and in the prefrontal cortex (serotonin, catecholamines, dopamine, acetylcholine). Regardless of the primary pathophysiology underlying functional GI disorders (i.e. central vs. peripheral), different pharmacological strategies targeted at different sites in the periphery or within the central nervous system may be effective. PMID- 10029366 TI - Quality of life in different gastrointestinal conditions. AB - In recent years, there has been increasing interest in how gastrointestinal symptoms relate to and impact on patients' health-related quality of life. This is particularly the case for functional gastrointestinal disorders that are characterized by a lack of biological markers for disease activity. There is only a slight variation in the type of gastrointestinal symptoms reported with different gastrointestinal disorders, and patients with dyspepsia or irritable bowel syndrome, for example, often describe a variety of gastrointestinal symptoms with considerable overlap between them. The same pattern has been observed in patients with gastroesophageal reflux disease, even though heartburn and acid regurgitation are easier to distinguish from other gastrointestinal symptoms, particularly in patients in whom objective reflux is verified. Most aspects of health-related quality of life in patients with gastrointestinal disorders are compromised, irrespective of diagnosis. Patients with functional disorders seem, if anything, to display more emotional distress than those with organic disorders. Given the considerable overlap between different gastrointestinal symptom clusters, it is not surprising that these conditions have a similar impact in terms of perceived health status and quality of life. The key factors associated with the degree of perceived distress and dysfunction relate to disease severity and the presence of abdominal pain symptoms. PMID- 10029367 TI - Functional digestive disorders (FDD) in the year 2000--economic impact. AB - OBJECTIVE: The objective of this study is to quantify the future worldwide economic impact of functional gastrointestinal disease and to describe international differences that might exist between major industrialized countries. DESIGN: This study employs an econometric projection using data from the only known survey of national economic impact of functional gastrointestinal disease. Economic costs from this survey are combined with country specific population estimates, health care spending characteristics, and growth rates to estimate economic impact for major industrial countries. RESULTS: The estimated economic impact of functional gastrointestinal disease for eight major industrial countries is over 41 billion U.S. dollars annually. This estimate includes both direct and indirect costs of disease. CONCLUSION: The economic impact of functional gastrointestinal disease is large. Economic estimates are useful in policy decision making regarding the allocation of health care resources. PMID- 10029368 TI - Hepatitis C: controversies, strategies and challenges. AB - Risk factors for hepatitis C infection include I.V. drug use (42%); history of blood transfusion (6%); exposure to multiple heterosexual partners (6%); exposure to a household contact (3%); health care employment (2%); or hemodialysis (1%). Forty percent of patients have no identifiable risk factors. The HCV is a single stranded, positive-sense RNA virus. Six major genotypes have been identified; each contains a series of subtypes. In the U.S., prevalences are type 1 (74%); type 2 (15%); type 3 (6%); and type 4 (1%). Within an infected individual, HCV also exists as a spectrum of closely related genotypes referred to as a quasispecies, and more complex quasispecies correlate with longer duration of disease, higher levels of viremia, genotype 1 infection, and poorer response to interferon therapy. Diagnosis is made by measuring anti-HCV by EIA, with confirmation by RIBA or HCV RNA. Patients with chronic HCV infection, with or without aminotransferase elevation, have detectable serum RNA by PCR. Standard therapy is interferon alfa 2b (Intron A) at a dosage of 3 million units 3 times a week for 6 months. This results in a 40%-50% complete response at the end of treatment (normal aminotransferases and undetectable HCV RNA), but relapse occurs in 60%-80% of cases over the next six months. Longer (12 month to 18 month) courses are now widely advocated. Better patient selection, e.g., those with low serum HCV RNA levels and absence of cirrhosis, and increased duration of therapy may lead to better response rates. Combination therapy with other antiviral agents, such as ribavirin, has dramatically reduced relapse rates. PMID- 10029369 TI - The bioartificial liver: state-of-the-art. AB - The rationale for artificial liver support is based on the hypothesis that if essential liver functions can be restored during the critical phase of liver failure, it should be possible to improve the survival of patients with severe liver disease. In the case of bridge-to-transplantation, it should provide the patient sufficient metabolic support until a donor liver can be found and transplanted. Since the management of acute liver failure requires the replacement of the liver's myriad metabolic functions, the idea of a hybrid bioartificial liver (BAL) support system has been proposed. BAL systems incorporate a biological (hepatocytes) and a synthetic housing component (plastic housing shell and semipermeable membrane) coupled in such a way as to facilitate the delivery of essential liver functions. Of the several BAL designs that have been proposed, only the capillary hollow-fiber based systems have been rapidly developed for clinical trials. Capillary hollow-fiber based BAL devices are basically off-the-shelf artificial kidney membranes that have been modified for use as an artificial liver. However, most capillary hollow-fiber based BAL designs have inherent physical limitations of total diffusion surface area and capacity for hepatocyte mass. We have proposed a novel BAL design using microencapsulated hepatocytes to overcome these physical limitations. This new BAL design (UCLA-BAL) involves the direct hemoperfusion of a packed-bed column of microencapsulated porcine hepatocytes within an extracorporeal chamber. In extensive animal studies using a well-characterized animal model fulminant hepatic failure (FHF), we demonstrated that the UCLA-BAL system had superior diffusion surface area and a higher capacity for hepatocytes compared to conventional capillary hollow-fiber based BAL devices. UCLA-BAL treatment significantly (P<0.001), improved the survival rate of FHF animals and significantly (P<0.01) prolonged the survival time of similar animals with very severe liver injury. BAL treatment was convenient, easy to operate and well tolerated, and did not adversely affect the animal's hemodynamics during treatment. We therefore suggest that the UCLA-BAL is a significant improvement over conventional, first-generation, capillary hollow-fiber BAL systems. PMID- 10029370 TI - Pancreatic-biliary imaging and triage. AB - The pancreas and biliary tree (and their confluence at the papilla of Vater) are frequent sites for disease. In recent years there has been a proliferation of relevant technologies. Diagnostic methods include percutaneous ultrasound, standard CT scans, helical CT, magnetic resonance imaging, MRCP, endoscopic ultrasound, angiography, ERCP, laparoscopy, and laparoscopic ultrasound. Cytology and biopsy specimens can be taken in conjunction with many of these techniques. In addition to standard open surgical intervention, there are now many alternative therapeutic approaches wielded by endoscopists, interventional radiologists and laparoscopic surgeons. Novel chemotherapy and radiation oncology techniques and further dimensions. Many studies have attempted to evaluate the role of one particular modality, or to compare two diagnostic or therapeutic techniques. It is more important (and more difficult) to devise and test relevant management algorithms. These assessments are bedevilled by the problem of generalizability, since the results of many techniques are operator-dependent. This raises another issue-whether patients with these problems should be managed in regional specialty centers. Another complexity is that the management of a particular problem is influenced not only by the disease and its stage but also by the type of patient in whom it occurs (age, comorbidities, etc.). Multidisciplinary collaboration is a great challenge (12, 13). PMID- 10029371 TI - Radiation-induced enterocolitis: basic and applied science. AB - We adapted and introduced in our laboratory a simplified animal model of radiation-induced enterocolitis. After a shielding of the parenchymatous organs, our dose-response studies revealed that 20 Gy x-ray radiation resulted in about 20% mortality and reproducible lesions in the terminal ileum and proximal colon. These changes are optimal for pharmacologic studies since they may be decreased or aggravated by drugs. Sucralfate dose-dependently decreased the clinical signs of enterocolitis (e.g., lethargy, diarrhea) as well as the number and area of ileal and colonic erosions and ulcers. The wet weight of the ileum and colon were also decreased by sucralfate. bFGF at the small doses used exerted a beneficial effect only on a few of the parameters of enterocolitis. Thus sucralfate, and maybe bFGF, might decrease the severity and accelerate the healing of radiation induced enterocolitis. PMID- 10029372 TI - Medical therapy of inflammatory bowel disease for the 21st century. AB - Inflammatory bowel disease therapy can be considered in several subcategories, and this review is designed to provide selective updates for some of the most important therapeutic entities currently marketed or soon to be available for the medical management of IBD. Although conventional corticosteroids have been a major component of acute inflammatory bowel disease management, steroids have many serious disadvantages; and toxicity is heightened with chronic steroid therapy. Newer corticosteroids, particularly budesonide, may be less toxic than older agents such as prednisone. Budesonide may be used as an enema in active distal ulcerative colitis (UC) or as delayed release tablets in Crohn's disease (CD). However, budesonide is not completely free from steroid side effects, and may share in some of the toxicity of older corticosteroids, particularly when high dose budesonide is administered. Topical and oral aminosalicylates are widely utilized for the treatment of mild to moderate active UC and mild active CD, and they also are efficacious for maintenance of IBD remission. Recent data continue to support the concept that higher doses and prolonged use of mesalamine based drugs are therapeutically superior to lower doses and short term treatment. In addition, the combination of oral and rectal aminosalicylate formulations often succeeds in patients refractory to either used alone. The immunomodulatory drugs azathioprine and 6-mercaptopurine are particularly effective in treating both CD and UC, and methotrexate has also shown some promise in CD therapy. Immunosuppressive therapy for inflammatory bowel disease initially met with strong physician resistance. However, views have shifted in response to positive data on the utility of immunosuppressive agents in many cases of IBD. Although cyclosporine may be used as a 'rescue' medication in some severe IBD cases, it has been associated with severe toxic reactions. Possible candidates for cyclosporine treatment should be offered such therapy only in academic centers highly experienced with the nuances of this modality. Clinical trials of the newer entities IL-10, IL-11, tacrolimus, and anti-TNFalpha, have demonstrated variable efficacy in refractory IBD patients. Anti-TNFalpha has been very impressive, particularly in the presence of fistulizing Crohn's disease. Many physicians have utilized various antibiotics empirically as part of their 'general' management of IBD. Only metronidazole has been adequately studied in controlled CD trials, but other antibiotic studies are pending. Further exploration of antimicrobial treatment for IBD is clearly warranted. Many other investigational agents in disparate pharmaceutical categories have been employed in IBD therapy; and some of these also show varying degrees of promise, including the aloe vera derivative acemannan, several formulations of heparin, and both transdermal and intra-rectal nicotine. Despite the growing list of medications and formulations promoted for the treatment of IBD, no single drug or recognized combination has yet been confirmed as dependably clinically effective. Many additional investigations of IBD medical therapy are needed, including permutations of conventional medications, along with newer agents that may be more precisely targeted to specific aspects of IBD pathophysiology. All physicians who care for UC and CD patients enthusiastically await more optimal regimens for these challenging disorders. PMID- 10029373 TI - The diagnostic and prognostic value of tumor angiogenesis. AB - The "angiogenic switch" and tumor angiogenesis play a critical role in the growth and metastasis of solid tumors. Tumor angiogenesis is regulated by a balance of stimulators (e.g., VEGF, bFGF) and inhibitors of angiogenesis (e.g., angiostatin, endostatin, angiostatic steroids). Measuring angiogenesis (blood vessel density) and/or its main regulators such as VEGF and bFGF in solid tumors, or the levels of these growth factors in the serum or urine provides new and sensitive markers for tumor progression, metastasis and prognosis. PMID- 10029374 TI - Metastasis in colorectal cancer: what makes the tumor aggressive? AB - While local control of colorectal cancer can usually be obtained, distant spread is frequent and nearly always results in incurable disease and death. Therefore, the critical determinant of aggressiveness of colorectal cancers is the ability to disseminate widely. While the molecular biology of colorectal carcinogenesis is comparatively well understood, the mechanisms important in metastasis remain relatively cryptic. Conceptually, metastasis is a multistep process with a number of potential therapeutic targets. Critical steps include angiogenesis, local invasion, embolization to distant sites, and extravasation. Identification of high risk tumors may allow more judicious use of effective, but nonselective, cytotoxic adjuvant therapy. Specific inhibitors of particular steps of metastasis are already in various stages of testing. PMID- 10029375 TI - Colon cancer prevention by NSAIDs: what is the mechanism of action? AB - Colorectal cancer is second to lung cancer as the most common cause of cancer death in the United States; both environmental (diet, physical activity) and genetic (family history, mutations, polymorphisms) factors are related to colon cancer risk. Epidemiologic, animal model, and clinical studies all suggest that nonsteroidal anti-inflammatory drugs (NSAIDs) are potent preventive agents for colon cancer. Most epidemiologic studies (case control, and cohort) are consistent with a protective effect of regular, long-term use of aspirin use, although the prospective Physicians Health Study failed to find a significant protective effect. The entire class of NSAIDs appear to be effective in preventing carcinogen induced colon cancer in animal models. Clinical trials using the NSAID sulindac have shown dramatic regression of colonic adenomas in patients with Familial Polyposis. The biologic and biochemical mechanisms of the putative chemopreventive activity of the NSAIDs is under intense investigation. These drugs can induce cell cycle arrest and apoptosis in colon cancer cell lines through a mechanism that is fundamentally different from the apoptosis caused by cancer chemotherapeutic agents. Sulindac and its metabolites also appear to induce apoptosis in colonic adenomas in vivo. The clinically used NSAIDs are anti inflammatory due to their ability to decrease prostaglandin synthesis by inhibiting the cyclooxygenase (COX) enzymes. Cyclooxygenase inhibition, particularly COX 2 inhibition, is one putative biochemical target of the chemopreventive activity of NSAIDs. However, recent reports of chemopreventive activity of NSAID derivatives that no longer have COX inhibitory activity suggest that there are other biochemical targets as well. PMID- 10029376 TI - Flatus emission patterns and fibre intake. AB - Knowledge of the normal range of flatus emissions and their relationship to diet, particularly fibre, would be helpful in managing patients who complain of excessive flatus or abdominal distention. Sixty men and 60 women aged between 17 and 67 kept a three-day daily record, including one week-end day, of their flatus emissions, dietary fibre intake and beer consumption. Daily flatus emissions averaged 12.7 (range to 2-53) for men and 7.1 (range 1-32) for women. Fibre intake averaged 28+/-13 g for men and 24+/-3 g for women. Flatus emissions significantly correlated with dietary fibre intake (p<.001). There was a correlation between increased aroma of flatus emissions and beer intake in men and men recorded more aromatic flatus than women. This study of 120 normal individuals eating their choice of foods provides a basis to judge degrees of abnormality in patients complaining of excessive flatus. PMID- 10029377 TI - Diagnostic, pharmacological, surgical and behavioural developments in benign anorectal disease. AB - The investigation of benign anorectal disease has been transformed by new techniques of imaging such as anal endosonography and magnetic resonance imaging. This has led to more specific surgical treatments when structural damage is identified. It has also led to the identification of newly recognised pathologies, such as primary internal sphincter degeneration which causes passive faecal incontinence. A variety of new treatment modalities is also emerging. Pharmacological therapies are assuming great importance in relation to anal disease, with topical glyceryl trinitrate now the first treatment of choice for chronic anal fissure. For patients with intractable constipation behavioural techniques to modify pelvic floor and intestinal function are now the mainstay of therapy. New approaches to the surgical therapy of incontinence include the use of an artificial bowel sphincter, and the electrical stimulation of sacral nerves to modify pelvic floor function. PMID- 10029378 TI - Laparoscopic colorectal surgery in progress. AB - Nearly all standard colorectal operations have been attempted by the laparoscopic method. While bowel surgery is substantially more difficult it is proven feasible for most operations but its spread is slow. Less than 5% of all abdominal colorectal surgery is done laparoscopically a proportion which may rise to 20% in departments with a special interest. The complexity of the operation demands the learning of new skills which it will not be possible for all currently active colorectal surgeons to acquire. The learning phase is substantial, especially for resections, and yet the operation time remains about an hour longer than that of the open operation. Laparoscopic colorectal surgery is a fascinating subject because of its technical content, rapid change, and vitalisation of surgical thinking with profound repercussions on traditional operative technique. After seven years of breaking new ground it is time for the laparoscopic colorectal surgery to progress from a demonstration of what is possible to demonstrate when laparoscopy produces consistently better results at acceptable cost. PMID- 10029379 TI - Laparoscopic surgery for morbid obesity. AB - Morbid obesity, defined as a body mass index (BMI), i.e. weight (kg)/height (m2) over 36 for males and 38 for females, is a common condition and a threat for health, life and individual well being. Hitherto, surgery is the only effective treatment for weight reduction. Surgical methods can be malabsorptive, reducing the patients ability to absorb nutrients, or restrictive, reducing the capacity of food intake. Exclusively malabsorptive methods have been abandoned due to severe side effects. Restrictive methods, gastroplasties, reduces the compliance capacity of the stomach. Two types are performed laparoscopically, the vertical banded gastroplasty and the adjustable gastric banding. The proximal gastric by pass is also performed laparoscopically and is a combination of a restrictive proximal gastroplasty and a malabsorptive Roux-en-Y gastro-jejunal anastomosis. With laparoscopic adjustable gastric banding mean BMI was reduced from 41 kg/m2 to 33 kg/m2 (n = 43) after one year. Two years after surgery mean BMI was 30 kg/m2 (n = 16). The different operative techniques are further discussed in this paper. PMID- 10029380 TI - The impact of managed care on gastroenterology. AB - Managed care has emerged out o pressures to reduce the high cost of healthcare and has brought about unprecedented change and uncertainty for the specialist. To flourish in a managed care environment the subspecialist will need to rely on strategic planning. Four emerging approached to healthcare lend themselves to strategic planning. They are 1) practice-based clinical trials, 2) outcomes research, 3) clinical practice guidelines, and 4) systems-based disease management. This report explains how subspecialists in private practice can participate in and profit from each of these new approaches. PMID- 10029381 TI - Crohn's disease. PMID- 10029382 TI - Molecular genetics of Crohn's disease: recent advances. PMID- 10029383 TI - Genetic susceptibility in Crohn's disease--review of clinical studies. PMID- 10029384 TI - Cytokines and mucosal inflammatory response in Crohn's disease. PMID- 10029385 TI - Aminosalicylates for active disease and in the maintenance of remission in Crohn's disease. PMID- 10029386 TI - Immunosuppressive drugs in the treatment of Crohn's disease. PMID- 10029387 TI - Operations for Crohn's colitis: limited resection and preservation of anorectal function. PMID- 10029388 TI - The role of ansa-to-recurrent-laryngeal nerve anastomosis in operations for thyroid cancer. AB - OBJECTIVE: To study the recovery in phonation after reconstruction of the recurrent laryngeal nerve (RLN) in patients whose thyroid cancer was invading the nerve, and to evaluate the role of ansa cervicalis to RLN anastomosis (ARA) in operations for thyroid cancer. DESIGN: Retrospective study. SETTING: University hospital and private thyroid clinic hospital, Japan. SUBJECTS: 34 patients with thyroid cancer who underwent reconstruction of unilateral RLN and 331 consecutive patients operated on for thyroid cancer. INTERVENTIONS: Reconstruction was direct anastomosis (DA), free nerve grafting (FNG), vagus-RLN anastomosis (VRA) or ARA, including anastomosis behind the thyroid cartilage. MAIN OUTCOME MEASURES: Maximum phonation time (34 normal subjects and 26 patients with vocal cord paralysis served as controls), laryngoscopic examination, and the ratio of reconstruction in patients who needed resection of the RLN. RESULTS: The maximum phonation time started to increase rapidly 2-5 months postoperatively in most cases as the patients' voices recovered, and 12 months after reconstruction was significantly longer than in those patients with vocal cord paralysis (P < 0.0001). It was comparable to that of the normal subjects, although the reinnervated cords were fixed in the median. The number of reconstructions in the series of 331 patients increased from 18% to 82% after we started doing ARA with the meticulous technique of anastomosis inside the thyroid cartilage. CONCLUSIONS: ARA is as effective as DA or FNG in improving phonation in patients who need resection of a unilateral RLN. As ARA has several advantages over FNG it has a definite place in operations for thyroid cancer. PMID- 10029389 TI - Drainage systems in thyroid surgery: a randomised trial of passive and suction drainage. AB - OBJECTIVE: To investigate the effectiveness of high-vacuum and passive drainage systems after elective thyroid resection. DESIGN: Prospective randomised clinical study and multicentre postal survey. SETTING: Military hospital, Germany. PATIENTS: 80 patients, treated with passive closed drains (n = 40) or high-vacuum systems (n = 40). INTERVENTIONS: 1. Measuring the amount of blood collected during drainage and the extent of residual haematoma on ultrasonography. 2. Survey in Austria, Germany and Switzerland of annual number of bilateral thyroid resections, type of drainage used, and volume of postoperative drainage. RESULTS: 799 of the 1698 hospitals surveyed replied (47.2%). 785 (98.2%) of the 799 surgeons said that they used drainage systems of whom 766 (97.6%) used high vacuum systems. In the 40 patients in whom passive closed drainage was used, the median volume drained was 34 ml (range 0-175) compared with 115 ml (40-346) in the high vacuum group (p < 0.01). In the passive drainage group the extent of residual haematoma measured by us was 4.4 ml (range 0-21.7) compared with 5.3 ml (0.6-24.9) in the high vacuum group. CONCLUSIONS: The high-vacuum drainage that is most commonly used in Austria, Germany, and Switzerland results in increased blood loss with no reduction in the extent of residual wound haematoma and offers no additional advantage over passive drainage systems in thyroid surgery. PMID- 10029390 TI - Biliary-intestinal bypass in the treatment of obesity: long term follow up. AB - OBJECTIVE: To evaluate the long term outcome after biliary-intestinal bypass for morbid obesity. DESIGN: Retrospective study. SETTING: County hospital, Sweden. SUBJECTS: 120 consecutive patients operated on between 1977 and 1990. INTERVENTIONS: A variation of jejunoileal bypass in which the excluded bowel was anastomosed to the gallbladder. MAIN OUTCOME MEASURES: Weight, concentrations of blood lipids and glucose in blood, results of liver function tests, reversal rates, and complications. RESULTS: The mean body mass index was reduced by 39% (from 42 kg/m2 to 26 kg/m2), serum cholesterol and triglyceride concentrations by more than 30%, and fasting blood glucose concentrations by 1 1%. There were no cases of irreversible hepatic failure, diabetes, deaths related to the operation, or progressive renal failure. The incidence of renal calculi increased by a ratio 2.3. The reversal rate/year was 2% (n = 20). CONCLUSION: We conclude that biliary intestinal bypass may be used to treat cases of obesity associated with seriously high blood lipid concentrations and where gastric restrictive operations are less suitable. PMID- 10029391 TI - Modified mesh for hernia repair that is adapted to the physiology of the abdominal wall. AB - OBJECTIVE: To develop a new mesh for hernia repair that is adapted to the physiological forces. DESIGN: Animal experiment. SETTING: Surgical Department of the RWTH-Aachen. ANIMALS: Wistar rats MAIN OUTCOME MEASURES: Textile analysis, tensile strength, bending stiffness, histology and morphometry. RESULTS: After textile analysis of commercially available meshes in clinical use we defined the physiological forces and constructed a new mesh (Soft Hernia Mesh, SHM) based on a combination of non-absorbable polypropylene and absorbable polyglactin 910. The amount of non-absorbable material could be reduced to < 30% compared with Marlex while still guaranteeing the necessary pulling force of 16 N/cm. Improvements of the hosiery structure improved the symmetrical distribution of the retaining forces in all directions. Compared with the considerable restriction of the abdominal wall mobility by Prolene (polypropylene) and Mersilene (polyester) meshes there was no increase in the bending stiffness after the implantation of the new mesh. Histological examination showed a pronounced reduction of the inflammatory reaction in the tissues, and the collagen bundles were orientated merely around the mesh filaments instead of forming a scar plate that completely embedded the mesh. CONCLUSION: Different meshes caused specific histological reactions with changes of their mechanical properties after implantation in rodents. A new mesh with a reduced amount of polypropylene showed both less inflammation and less restriction in the mobility of the abdominal wall though it exceeded the required tensile strength of 16 N/cm. PMID- 10029393 TI - Shrinking of polypropylene mesh in vivo: an experimental study in dogs. AB - OBJECTIVE: To assess the extent of shrinkage of meshes used for hernia repair. DESIGN: Experimental study in dogs. SETTING: University hospital, Germany and University Research Centre, Moscow. ANIMALS: 10 dogs had monofilament polypropylene meshes that weighed 95 g/m2 (Marlex) or multifilament reduced polypropylene meshes combined with polyglactin 910 that weighed 55 g/m2 (Soft Hernia Mesh) implanted for either 3 or 6 months. MAIN OUTCOME MEASURES: Histological appearance and radiological assessment of the position and area of the mesh. RESULTS: After 4 weeks the area of mesh in the monofilament group was reduced from to 139 (11) to 75 (8) cm2 (54%) and that of the multifilament from 116 (18) to 77 (20) cm2 (66%). The multifilament mesh with the reduced amount of polypropylene showed less inflammatory response and less shrinkage. The mesh did not seem to have moved. CONCLUSION: Meshes that contain a lot of polypropylene shrink to about 30%-50% of their original size after 4 weeks, requiring an overlap of at least 3 cm if implanted subfascially. Reduction in the polypropylene content decreases both the inflammatory response and the shrinkage. Meshes with big pores are less likely to fold and improve compatibility. PMID- 10029392 TI - Role of simple V-Y advancement flap in the treatment of complicated pilonidal sinus. AB - OBJECTIVE: To evaluate our short term results of simple V-Y advancement flap for complicated pilonidal sinus. DESIGN: Prospective study. SETTING: Yuzuncu Yyl University hospital, Van, Turkey. SUBJECTS: 23 patients aged 19-47 (mean 31) years with complicated pilonidal sinus treated between October 1994 and December 1996, of whom 9 had had previous operations for pilonidal sinus. INTERVENTIONS: Bilateral V-Y-plasty to close the defect after wide excision (n = 7), and unilateral V-Y-plasty (n = 16) were performed under spinal anaesthesia. RESULTS: There were no complications during the operation. There were 4 minor complications (17%) consisted of seroma (n = 2) and severe wound pain, and wound infection (n = 1 each). All patients were discharged within 10 days of operation and returned to work within 3 weeks. The mean follow up was 18 months (range 10 25) and no recurrences have occurred so far. CONCLUSIONS: Simple V-Y advancement flap may prove to be useful in patients with recurrent and complicated pilonidal sinuses. PMID- 10029394 TI - An unusual case of isolated injury of the femoral vein after blunt trauma. PMID- 10029395 TI - Adrenal tuberculosis. PMID- 10029396 TI - Symptom perception and evaluation in childhood asthma. AB - BACKGROUND: Inaccuracies in symptom perception may contribute to morbidity and mortality in childhood asthma. OBJECTIVE: To systematically examine the accuracy of symptom perception on the part of children with asthma and their parents, as well as their interpretation and evaluation of the symptoms. METHOD: Twenty-eight patient/parent pairs from suburban and underserved urban pediatric populations participated in a 5-week protocol tracking subjective assessments of asthma severity (visual analog scales) and peak expiratory flow rates. Relationships between perceptual accuracy and demographic and disease factors were investigated. RESULTS: Adolescents were more accurate than school-aged children, more accurate children had better morbidity outcomes, and African American parents were more accurate than Caucasian parents. Socioeconomic status did not affect accuracy. Both children and parents missed early symptoms and waited too long prior to intervening in an exacerbation. CONCLUSIONS: There are multiple opportunities for error in symptom perception and evaluation. Identification of the source of error is critical to the effective utilization of education on self management. PMID- 10029397 TI - Test-retest reliability of symptom-limited cycle ergometer tests in patients with chronic obstructive pulmonary disease. AB - BACKGROUND: Symptom-limited exercise tests are widely used to evaluate the effects of pulmonary rehabilitation in patients with chronic obstructive pulmonary disease (COPD), but the reliability of these tests is not well established in COPD patients. OBJECTIVES: We compared test-retest reliability of two repeated symptom-limited exercise tests between COPD patients and healthy elderly subjects and between male and female patients. METHOD: Fifty-six COPD patients (40 men, 16 women) and 16 healthy subjects (6 men, 10 women) performed two symptom-limited exercise tests approximately 2 weeks apart. Measures of oxygen uptake (VO2), minute ventilation (VE), heart rate, and ratings of breathlessness and leg fatigue were obtained at peak exercise at each symptom limited exercise test. RESULTS: Repeated measures of peak exercise responses were stable for patients and healthy subjects and for male and female patients. Although mean percent error (absolute difference/mean) for peak exercise responses was low, some individuals' values exceeded 10%. There was no difference in the percent error between COPD patients and healthy subjects or between men and women with COPD. Test-retest reliability was lower for breathlessness ratings than for other peak exercise responses for all groups. CONCLUSIONS: Repeated symptom-limited exercise tests are reliable in COPD patients and healthy subjects. However, some individuals are less reliable, and these patients may require more than one exercise test to establish reliable performance. PMID- 10029398 TI - Psychometric properties of the functional performance inventory in patients with chronic obstructive pulmonary disease. AB - BACKGROUND: The Functional Performance Inventory (FPI) is a subjective measure of the performance dimension of functional status, based on an explicit analytical framework and the experiences of patients themselves. OBJECTIVES: To describe the conceptual foundation of the instrument, the procedures used to maximize content validity, and the results of the initial psychometric testing of the FPI in patients with chronic obstructive pulmonary disease (COPD). METHOD: Items and response structure for the instrument were drawn from the literature and qualitative interviews with 12 men and women with COPD. Twenty-four clinical and scientific experts participated in content validation. To assess the FPI's psychometric characteristics, 154 patients participated in a cross-sectional mail survey; 54 took part in a 2-week reproducibility assessment. Forty relatives were also included in validity testing. RESULTS: The instrument was internally consistent (alpha = .96) and reproducible (ICC = .85). Validity was evident in the significant (p < .001) correlations found between the FPI total score and the Functional Status Questionnaire (activities of daily living, r = .68; instrumental activities of daily living, r = .68), Duke Activity Status Index (r = .61), Bronchitis-Emphysema Symptom Checklist (r = -.59), Basic Need Satisfaction Inventory (r = .61), and Cantril's Ladder of Life Satisfaction (r = .63). The relationship between patient FPI score and relative perception of functioning, using the Katz Adjustment Scale for Relatives, was also significant (socially expected activities, r = .53; free-time activities, r = .49, p < .01). The instrument discriminated between patients with severe and moderate levels of perceived severity and activity limitation (t = 8.52, p <.001) and patients with FEV1 greater than and less than 1.0 liter (t = 4.25, p < .001). CONCLUSIONS: Results suggest that the FPI is a useful measure of functional performance in patients with COPD. Further development of the spiritual activities and work and school domains is in order, as is additional study of the instrument's responsiveness to change. PMID- 10029399 TI - Alternate child care, history of hospitalization, and preschool child behavior. AB - BACKGROUND: With more single mothers entering the workforce due to welfare reform efforts, more hospitalized children from single-parent families will have experienced alternate child care arrangements where routine care is provided by adults other than the child's mother. OBJECTIVES: To investigate with secondary analysis of data whether experience with alternate child care has a moderating effect on the relationship between hospitalization and behavior of preschool children living in female-headed single-parent families. METHOD: A sample of 60 preterm and 61 full-term children who were 3, 4, or 5 years old was recruited for the larger longitudinal study. Behavior problems were measured with the Child Behavior Checklist. History of hospitalization and alternate child care arrangements were measured with the Life History Calendar. RESULTS: Preschool children who experienced hospitalization without alternate child care experience had more somatic complaints, but those with both hospital and alternate child care experience had fewer aggressive behaviors than other children. For children with a history of hospitalization, aggressive behaviors decreased as the proportion of the child's life in alternate child care increased. CONCLUSIONS: Experience with alternate child care may ameliorate some of the negative effects of hospitalization, and potentially other novel and negative experiences, for preschool children. This could be due to child care providing positive experiences with separation from the mother, a peer group with which to talk about the novel experience, or actual instruction about the novel experience. PMID- 10029400 TI - The efficacy of developmentally sensitive interventions and sucrose for relieving procedural pain in very low birth weight neonates. AB - BACKGROUND: Procedural pain management for very low birth weight (VLBW) neonates has been minimal or nonexistent in most neonatal intensive care units (NICUs). OBJECTIVES: To compare the efficacy of developmentally sensitive behavioral interventions (nonnutritive sucking via a pacifier, positioning) and sucrose for relieving procedural pain in VLBW infants and to determine the influence of contextual factors (gestational age, postnatal age, birth weight, severity of illness, frequency of painful procedures) on pain response. METHOD: In a prospective randomized crossover trial, pain was assessed in 122 VLBW neonates using the Premature Infant Pain Profile following four randomly ordered interventions during consecutive routine heel lance procedures. RESULTS: Significant differences in pain existed among treatment interventions (F = 16.20, p < .0001). The pacifier with sucrose (F = 24.09, p < .0001) and pacifier with sterile water (F = 9.00, p = .003) significantly reduced pain. Prone positioning did not decrease pain (F = 2.24, p = .137). Frequency of painful procedures approached significance in influencing pain response (F = 3.59, p = .01). CONCLUSIONS: The most efficacious interventions for reducing pain from single painful events were the pacifier with sucrose and the pacifier with sterile water. Research on the efficacy and safety of implementing these interventions, alone and in combination, for repeated painful procedures is needed. In addition, research is needed on the influence of implementing these interventions on pain response and clinical outcomes (e.g., health status and neurodevelopmental status) in VLBW neonates in the NICU. PMID- 10029401 TI - Effects of distraction on children's pain and distress during medical procedures: a meta-analysis. AB - BACKGROUND: It is difficult to determine the usefulness of distraction to decrease children's distress behavior and pain during medical procedures because many studies use very small samples and report inconsistent findings. OBJECTIVES: To investigate the mean effect sizes across studies for the effects of distraction on young children's distress behavior and self-reported pain during medical procedures. METHOD: Hunter and Schmidt's (1990) procedures were used to analyze 16 studies (total n = 491) on children's distress behavior and 10 studies (total n = 535) on children's pain. RESULTS: For distress behavior, the mean effect size was 0.33 (+/-0.17), with 74% of the variance accounted for by sampling and measurement error. For pain, the mean effect size was 0.62 (+/-0.42) with 35% of the variance accounted for. Analysis of studies on pain that limited the sample to children 7 years of age or younger (total n = 286) increased the amount of explained variance to 60%. CONCLUSIONS: Distraction had a positive effect on children's distress behavior across the populations represented in this study. The effect of distraction on children's self-reported pain is influenced by moderator variables. Controlling for age and type of painful procedure significantly increased the amount of explained variance, but there are other unidentified moderators at work. PMID- 10029402 TI - Electronic publishing and nursing research. PMID- 10029403 TI - Mother-infant interaction: achieving synchrony. AB - BACKGROUND: Interventions that promote positive mother-infant interactions may reduce the risk of poor developmental outcomes for the child. OBJECTIVE: To examine the effect of infant communication education presented prenatally to first-time mothers on the quality of interaction that occurs between the mother infant dyad in the first 24 hours following birth. METHOD: Twenty-nine first-time mothers were randomly assigned to either an intervention or control group. The intervention group received education on infant behaviors, states, and communication cues. A specific mother-infant interaction was videotaped and scored using the Nursing Child Assessment Teaching Scale (NCATS). The scores between groups were compared to determine the effect of education on the interaction that occurred between the dyads. RESULTS: Significant intervention effect was found in the overall totals (t(27)= 1.69; p = .05) as well as the contingency scores related to sensitivity to cues (t(27)= 1.93; p = .05) and social-emotional growth-fostering behaviors (t(27)= 1.93; p = .05). CONCLUSION: A videotaped educational intervention on infant communication implemented prenatally resulted in significant differences between the intervention and control groups on NCATS scores (totals, sensitivity to cues, and social-emotional growth-fostering behaviors). The use of videotaped educational information facilitates very early mother-infant interaction. PMID- 10029404 TI - ras activity and cyclin D1 expression: an essential mechanism of mouse skin tumor development. AB - ras is a family of small GTP-binding proteins that transduce signals from tyrosine-kinase receptors to the nucleus and thus play a role in the regulation of cell proliferation and differentiation. Several lines of evidence have shown that the cell-cycle machinery, specifically the circuit cyclin D1/cyclin dependent kinase (cdk) 4 and 6-p16-pRb, lies downstream of ras. Point mutations that activate the ras protein and its downstream cascade have been observed in human and experimental tumors. In particular, ras mutations have been well characterized in the mouse skin two-stage carcinogenesis model, and a large body of literature has indicated that initiation with the genotoxic carcinogen 7,12 dimethylbenz[a]anthracene induces a specific point mutation in Ha-ras gene in this model. In the last few years, several studies have shown a correlation between ras activation and alterations in the expression of cyclin D1 as well as other cell cycle-regulated proteins, but the actual role of these alterations in tumor development had not been determined until a recent study provided genetic and biochemical evidence that cyclin D1 is a critical target of oncogenic ras in mouse skin carcinogenesis. Here we review these results, including the evidence that cyclin D1 has a role as a downstream mediator of ras activity during tumor development. We propose a model in which cyclin D1 has a unique growth-promoting role in tumor development but does not act as an oncogene independently of ras activity. PMID- 10029405 TI - Reversal of p53-induced cell-cycle arrest. AB - Activation of the tumor suppressor protein p53 can lead to arrest in both G1 and G2 stages of the cell cycle and, in some cells, to apoptotic cell death. In this study, we showed that the p53 response to a chemotherapeutic drug, actinomycin D, was reversible in both normal and tumor cells, even when a substantial proportion of tumor cells were undergoing apoptosis. Despite the clear reversibility of the p53-induced cell-cycle arrest after removal of actinomycin D, a substantial proportion of the cells arrested in G2 failed to resume normal cell-cycle progression and underwent another round of DNA synthesis. This endoreduplication probably reflects a function of the cyclin-dependent kinase inhibitor p21Waf1Cip1, which is expressed in response to p53. Our observation that this abnormal re-replication of DNA occurred in both transformed and untransformed cells after reversal of a p53 response may have implications for the eventual outcome of tumor therapies in which p53 is transiently expressed in a substantial number of normal as well as tumor cells. PMID- 10029406 TI - Differential regulation of p21 by p53 and Rb in cellular response to oxidative stress. AB - Oxidative stress to mammalian cells causes cellular damage and triggers inducible cellular responses leading to cell death by apoptosis. In this paper, we report that p53 was required for programmed cell death induced by oxidative stress in both mouse and human cells and that p53 transactivation was involved in induction of oxidative cell death. Furthermore, we show that p21 was highly responsive to oxidative stress in a p53-dependent manner and that ectopic expression of p21 could increase cellular susceptibility to oxidative stress in the absence of p53. However, p21 was not required for p53-directed oxidative cell death because mouse embryo fibroblasts MEFs lacking p21(p21-/- MEFs) were still susceptible to oxidative cell death. Interestingly, bax, a cell-death mediator regulated by p53, was overexpressed in p21-/- MEFs that underwent cell death by oxidative stress, suggesting a compensation for loss of p21 that may be responsible for the existence of cell-death responses in p21-knockout mouse fibroblasts. Finally, we provide evidence that the retinoblastoma gene product (Rb) is a negative regulator of p21 and a repressor of the cellular apoptotic process. Because p21 is regulated by p53 positively and by Rb negatively, p21 may be a link between p53 and Rb in determining cell fate after oxidative damage. PMID- 10029407 TI - Regulation of metastasis-related gene expression by p53: a potential clinical implication. AB - Tumor metastasis is the main cause of mortality and treatment failure in cancer patients. It is a complex biological process regulated by alternations in expression of many genes. The p53 tumor suppressor gene has been shown to regulate expression of some metastasis-related genes. p53 transcriptionally activates expression of the genes encoding epidermal growth factor receptor, matrix metalloproteinase (MMP)-2, cathepsin D, and thrombospondin-1 but represses expression of the genes encoding basic fibroblast growth factor and multidrug resistance-1. Decreased expression of E-cadherin is associated with p53 alternations. Because these p53-regulatory genes either promote or inhibit tumor metastasis, the net effect of p53 expression on tumor metastasis depends upon the pattern of expression of these genes in a particular tumor. Because radiotherapy has been shown to increase tumor metastasis in both animal and human studies and because p53 is activated by radiation or DNA-damaging reagents, here we propose the working hypothesis that p53 may promote tumor metastasis upon induction by local radiotherapy or chemotherapy in some tumor types. For patients whose tumors contain wild-type p53, MMP inhibitors might be given with or before radiotherapy or chemotherapy to prevent an increase in tumor metastasis. Special caution should be taken with patients with cancers such as nasopharyngeal carcinoma in which p53 mutation is infrequent and radiotherapy is the main choice of treatment. To test our hypothesis, three studies are proposed and could serve as an initial step in understanding the complex biological process following radiation-induced p53 activation and its roles in regulation of tumor metastasis. PMID- 10029408 TI - Differentially expressed transcripts in X-ray-induced lymphomas identified by dioxygenin-labeled differential display. AB - Differential display is an easily applied method for comparing gene expression in a variety of systems. We used a nonradioactive differential display technique to analyze X-ray-induced lymphomas derived from Emu-pim-1 transgenic and nontransgenic mice. Fragments of 11 differentially regulated genes were identified, three of which are novel sequences. One of the cloned fragments contained sequences of a mouse VL30 retroelement that was significantly overexpressed in a subset of lymphomas as compared with non-lymphomatous tissue. Interestingly, these lymphomas also displayed high levels of c-myc transcripts. An altered expression pattern of a glutathione S-transferase homologue was identified in several lymphomas. Moreover, a cytotoxic T-lymphocyte lipase appeared to be overexpressed specifically in lymphoma-containing spleen tissue, and the results suggest that it may be related to the endogenous immune response against lymphoma development. PMID- 10029409 TI - Alteration of G1 cell-cycle protein expression and induction of p53 but not p21/waf1 by the DNA-modifying carcinogen 2-acetylaminofluorene in growth stimulated hepatocytes in vitro. AB - 2-Acetylaminofluorene (AAF) is a potent tumor promoter in rat liver carcinogenesis models. In the resistant hepatocyte model, AAF is combined with a growth stimulus for efficient promotion of preneoplastic lesions. The promoting property of AAF in this model is closely associated with mito-inhibition of normal hepatocytes, an effect to which initiated cells are resistant. How AAF induces growth arrest is not known, but genotoxic as well as non-genotoxic effects have been implicated. To elucidate the mechanisms of AAF-induced mito inhibition, we studied the expression of the tumor suppressor protein p53 and the cyclin-dependent kinase (cdk) complexes mediating G1 progression and S-phase entry. Hepatocytes were isolated from male Fisher 344 rats fed either a control diet or a diet supplemented with 0.02% AAF for 1 wk and cultured in a defined serum-free medium containing epidermal growth factor, insulin, and dexamethasone. Thymidine labeling revealed a profound inhibition of DNA synthesis in AAF-exposed cells compared with control cells. The retinoblastoma protein did not become hyperphosphorylated in AAF-exposed cells. Thus, inhibition of G1 cyclin-cdk activity was implied as a cause of growth arrest. Indeed, G1 cell-cycle arrest was accompanied by reduced induction and nuclear accumulation of the cyclin D1 cdk4 complex and inhibited nuclear translocation of cdk2. Furthermore, the growth arrest was not mediated through p21/waf1 upregulation, although nuclear levels of p53 were increased. Thus, carcinogen-induced mito-inhibition may be effected by altered levels and localization of G1 cyclin-cdk complexes, independent of the upregulation of cdk inhibitory proteins. PMID- 10029411 TI - Accumulation of recombinant chromosomes and low fidelity of transmission of chromosome X DNA markers in gamma-ray-induced lymphomas lacking p53. AB - F1 offspring of male MSM male mice with a p53-deficient (knockout) allele and normal female BALB/c mice were backcrossed with MSM mice to produce N2 mice. Female F1 and N2 mice were irradiated with gamma-radiation, and thymic lymphomas were obtained from 69 F1 and 82 N2 mice heterozygous for X chromosome markers. Of these 151 mice, 91 carried a p53-deficient allele. These lymphomas were analyzed for allelic loss by using four marker loci distributed on X chromosome to assess the stability of the inactive X chromosome, which contributes little to cellular functions. Twenty lymphomas showed allelic loss of all four loci, suggesting loss of a whole inactive X chromosome due to mitotic nondisjunction, whereas 24 lost only a part of an X chromosome, as a result of somatic recombination. The p53 status of the lymphomas was determined by genotyping and allelic loss analysis: 53 had retained two wild-type p53 alleles, suggesting normal function; 69 had lost both alleles, indicating loss of function; and the remaining 29 had at least one wild-type p53 allele, so their p53 status was unclear. Compilation of these two data revealed one nondisjunction-type change and five recombination-type mutations on X chromosome in 53 lymphomas retaining functional p53. In contrast, 14 and 16 of these alterations, respectively, were observed in 69 lymphomas lacking p53 function. These results suggest that p53 loss significantly increases the accumulation of recombinant chromosomes and decreases the fidelity of mitotic chromosome transmission of the X chromosome in gamma-ray-induced lymphomas. PMID- 10029412 TI - Contribution of phosphatidylinositol 3-kinase to radiation resistance in human melanoma cells. AB - The activity of phosphatidylinositol 3-kinase (PI3K), a key component of multiple signal transduction pathways, was investigated in early- and late-stage melanoma cells that have varying degrees of radiation resistance. Analysis of PI3K biproducts (PI-3,4-P2 and PI-3,4,5-triphosphate) revealed a direct correlation between radiation resistance and levels of PI3K activity. Treating melanoma cells with wortmanin or LY294002, two different PI3K inhibitors, decreased PI3K activity and caused a dose-dependent decrease in resistance to ultraviolet radiation. Lower resistance to radiation elicited by LY294002 coincided with increased apoptosis. To further establish the role of PI3K in radiation resistance, we transfected early-stage melanoma cells with the cDNA of p85, the regulatory subunit of PI3K. Clones that constitutively overexpressed p85 exhibited a higher degree of PI-3,4-P2 synthesis and a corresponding increase in their resistance to ultraviolet radiation. The results of this study point to the role of PI3K and its biproducts in radiation resistance of human melanoma cells. PMID- 10029410 TI - A comparative analysis of allelic imbalance events in chemically induced rat mammary, colon, and bladder tumors. AB - In this paper, patterns of allelic imbalances (Als) in chemically induced rat mammary, colon, and bladder tumors from (Wistar Furth x Fischer 344)F1 rats are described and compared. Male F1 rats were administered azoxymethane (AOM), and colon tumors were collected at 58 wk after treatment. Female F1 rats were given either N-nitroso-N-methylurea (NMU) or N-butyl-(hydroxybutyl)-nitrosoamine (BBN), and mammary and bladder tumors were collected at 15 and 52 wk after treatment, respectively. DNA was extracted from a subset of 18 of the largest tumors from each group, and a genome scan was performed by using polymerase chain reaction and 90 polymorphic microsatellite markers. Als, such as loss of heterozygosity, gene duplication, and microsatellite instability, were observed at low frequencies in all of the tumor models. Thirty random Als were observed in the AOM-induced colon tumors but only four in the NMU-induced mammary tumors. In both these models, all the tumors were classified as adenocarcinomas, and most of the Als observed were confined to single tumors with atypical histopathology. In contrast, 27 random Als were identified in the BBN-induced bladder tumors. Als were observed in both transitional-cell carcinomas and papillomas, although most were in the carcinomas. Statistical analysis of the Al data revealed no significant nonrandom Als within or among the tumor models, although several of the infrequently observed Al events identified in the rat tumors may also be observed in the corresponding human tumor type. PMID- 10029413 TI - Interference of proteins involved in the cytoplasmic sequestration of p53 with human papillomavirus E6-mediated degradation. AB - The oncogenic human papillomaviruses (HPVs) are able to efficiently target p53 for degradation by the ubiquitin pathway. We previously demonstrated inefficient HPV E6-mediated degradation and resulting high steady-state levels of p53 in cell hybrids between a peripheral neuroepithelioma cell line and a cervical carcinoma cell line (HeLa). We now show that the p53 protein in these cell hybrids was cytoplasmically sequestered and exhibited sporadic punctate staining, which is characteristic of the p53 expression pattern observed in neuroblastic neuroblastoma (NB) cell lines, in which p53 is also sequestered. We hypothesized that the cytoplasmic sequestration of p53 in the cell hybrids might correlate with its inability to be rapidly degraded by HPV E6. Using NB cell lines as a model system to test this hypothesis, we demonstrated that the introduction of HPV E6 into two NB cell lines resulted in p53 insensitivity to HPV E6-mediated degradation. This was assessed by both pulse-chase analysis of p53 in metabolically labeled NB cells and western blotting. The enhanced stability of p53 was not due to a lack of HPV E6 expression or to a mutant conformation of the p53 protein. Our results therefore suggest that proteins involved in the cytoplasmic sequestration of p53 may also interfere with the ability of HPV E6 to target p53 for degradation. PMID- 10029414 TI - Optimal clip application and intraoperative angiography for intracranial aneurysms. AB - BACKGROUND: The actual incidence of residual aneurysm after clipping is unknown. The natural history of residual aneurysm can be regrowth and hemorrhage. Intraoperative angiography offers a cost-effective, safe interdiction to the problem of residual aneurysm and parent vessel stenosis. METHODS/RESULTS: Forty consecutive patients harboring 54 aneurysms underwent 42 operative procedures to clip 52 aneurysms, during which 220 intraoperative angiographic runs were performed. Ninety-three percent of the procedures were performed on patients with acute subarachnoid hemorrhage. There were 4 giant (>2.5 cm, 4/52 = 8%, all anterior circulation), 21 large (1.0-2.5 cm, 21/52 = 40%, 16/ 21 = 76% anterior circulation, 6/21 = 28% posterior circulation), and 27 small (<1.0 cm, 27/52-52%, 22/27 = 81% anterior circulation, 5/27 = 18% posterior circulation) aneurysms. Intraoperative angiography led to clip adjustment in 18/52 = 34% of aneurysms (4/18 = 22% for parent artery stenosis, 8/18 = 44% for residual aneurysm and 6/18 = 33% for both). Of the 18 adjustments made, 16 = 88% were made on giant or large aneurysms and two were small (one was a complex anterior communicating and one was a vertebral junction aneurysm). Follow-up angiography was performed on 26/42 = 62% of operative cases. Postoperative angiography confirmed intraoperative angiography in all cases. Two complications occurred during 220 angiographic runs: one embolic stroke and one incident of equipment failure. CONCLUSION: A grading scale was applied to test the relationship between anatomical site and size as they relate to the necessity for clip adjustment for complete aneurysm obliteration and/or parent artery compromise. Significance was related to site (basilar bifurcation, anterior communicating, middle cerebral bifurcation, and ophthalmic) and size (>1.0 cm), both as independent and codependent variables. An analysis of the cost-effectiveness of intraoperative angiography was demonstrated. PMID- 10029415 TI - Retrograde suction decompression of paraclinoid aneurysm--a revised technique. AB - BACKGROUND: Aneurysms of the ophthalmic segment of the carotid artery are difficult lesions to handle. Batjer and Samson described the technique of suction decompression of the aneurysm by inserting a needle and aspirating blood from the internal carotid artery in the neck. However, this method carries a risk of arterial dissection and distal embolization. METHOD: We describe a revised technique for suction decompression of paraclinoid aneurysms. The method makes use of the anatomical advantage of the carotid bifurcation. Instead of direct clamping of the internal carotid artery, we isolated the common and external carotid arteries and decompressed the aneurysm via the external carotid artery. We also saved the aspirated blood for autotransfusion. RESULTS: We have used this technique in two elderly patients with good results. CONCLUSION: This technique avoids dissection of the internal carotid artery and minimizes the risk of embolization. PMID- 10029416 TI - Neuropsychological evaluation and cerebral blood flow study of 30 patients with unruptured cerebral aneurysms before and after surgery. AB - BACKGROUND: We have recently had many opportunities to operate on patients who presented with no neurologic deficits and were incidentally detected to have unruptured cerebral aneurysms. Therefore, it is very important to know how craniotomy affects the normal brain when making decisions regarding surgery for asymptomatic cerebral diseases. METHODS: Thirty patients with unruptured cerebral aneurysms were evaluated. Aneurysm sites were as follows: internal carotid artery (ICA) (eight cases), anterior communicating artery (ACoA) (seven), middle cerebral artery (MCA) (five), basilar artery-superior cerebellar artery (BA-SCA) (two), and multiple aneurysms (three) [bilateral MCA: (two), ICA + Basilar top: (one)]. These patients underwent neuropsychological examinations [the Mini-Mental State (MMS) test, the "Kana-hiroi" test, and the "Maze" test] and single photon emission computed tomography (SPECT) before and after surgery. RESULTS: The details of the 17 cases whose Kana-hiroi tests deteriorated 1 month after surgery are as follows: ACoA: seven, MCA: five, ICA: three, BA: two. SPECT showed a decrease in CBF in nine cases (ACoA: six, ICA: two, MCA: one). There was a statistically significant difference (p<0.05) between patients with ACoA aneurysms and ICA aneurysms. Three months after operation, all of the patients with neuropsychological deterioration and four of the six low CBF patients recovered to preoperative levels. CONCLUSIONS: These results indicated that the operation for unruptured cerebral aneurysms is moderately safe and meaningful; such a study should be required to determine when those patients could return to normal life. PMID- 10029417 TI - Giant fusiform aneurysm of the basilar artery: consideration of its pathogenesis. AB - BACKGROUND: We tried to determine the pathogenesis of a fusiform aneurysm of the basilar artery based on the findings of two patients who had pontine infarctions due to thrombosis within the aneurysm. CASE REPORT: The patients were female, aged 75 and 62 years. At autopsy of the first case, the dilated basilar artery was filled with fresh and old thrombus. The wall was extremely thin on the left side, where a fresh red thrombus was evident, and thick on the right side, where an old white thrombus appeared. The thick wall had a thickened and hyalinized intima, and a deposition of atheromatous plaque disrupted both the internal elastic lamina and muscle layer. The left vertebral artery was atherosclerotic and its lumen was severely compromised, but the right vertebral artery was hypoplastic. On angiogram of the second case, the dilated basilar artery presumably was filled with thrombus on the left side, contralateral to the dilated and tortuous vertebral artery. The left vertebral artery was hypoplastic. CONCLUSION: Atherosclerosis may be the essential factor in the pathogenesis of a fusiform aneurysm of the basilar artery in elderly patients. The disrupted internal elastic lamina and muscle layer may be susceptible to mechanical injury by hemodynamic strain, causing progressive attenuation of the arterial wall. Stenosis of the vertebral artery on the dominant side probably produces a jet stream within the basilar artery on the stenotic side and a stagnant zone on the opposite side, promoting the initial thrombus formation. PMID- 10029418 TI - Posterior inferior cerebellar artery aneurysms associated with posterior fossa arteriovenous malformation: report of five cases and literature review. AB - BACKGROUND: The association of posterior inferior cerebellar artery (PICA) aneurysms with posterior fossa arteriovenous malformation (AVM) is uncommon. Over the past 3 years, five patients with this condition were treated at this institution. A review of the clinical history of these and other reported cases has illuminated common threads in the presentation, treatment, and outcome of these lesions. METHODS: The findings of 27 patients (5 from our institution and 22 from the medical literature) with PICA aneurysms associated with AVMs were reviewed. RESULTS: Eighty-four percent of individuals presented with sub arachnoid hemorrhage (SAH); 89% of these episodes resulted from aneurysm rupture documented by either intraoperative inspection or autopsy. All aneurysms were located on a feeding artery to the AVM, and 81% originated from distal portions of PICA. The majority of patients presented with Hunt & Hess grade I SAH; all patients who presented with hemorrhage were treated surgically. Surgical strategy was directed both to secure the aneurysm and to resect the AVM during the course of a single procedure. Although four individuals either died on admission or in the perioperative period, overall outcome was excellent or good in 82% of patients. CONCLUSIONS: PICA aneurysms associated with AVMs most often involve the distal segments of the artery. Patients usually present with SAH secondary to aneurysmal rupture. Surgical clipping of the aneurysm and excision of the AVM is possible in a single procedure with minimal morbidity. Overall prognosis is favorable in 80% of the cases. PMID- 10029419 TI - Radical surgery of a giant Galen's vein aneurysm using total circulatory arrest: case report. AB - BACKGROUND: Arteriovenous malformations of Galen's vein are a rare type of vascular anomaly. The complex anatomy of these lesions creates an extremely difficult management dilemma. We report successful surgical treatment of a 7-year old patient with a Galen's vein aneurysm. METHODS AND RESULTS: A 7-year-old patient with slowly progressing gait disturbance, emotional instability, and strange behaviour is presented. A computed tomography scan revealed a high density mass in the pineal region and cerebral angiography showed an aneurysm of Galen's vein. We decided to perform surgical excision of the aneurysm. The operation was performed under hypothermic circulatory arrest with barbiturate cerebral protection. The patient had no signs of postoperative ischemic deficits, hemorrhage, or neurologic deterioration. CONCLUSIONS: Various techniques have been described for the obliteration of Galen's vein aneurysms, including direct surgical approach, staged operation, and transarterial, transvenous or transtorcular embolization. We present this patient to illustrate the use of hypothermic circulatory arrest and barbiturate cerebral protection for successful surgical excision of this complex vascular lesion. The combination of these techniques allowed us, in this case, to operate with reasonable safety on otherwise, difficult to treat aneurysm of Galen's vein. PMID- 10029420 TI - Evaluation of neuronal loss in adult moyamoya disease by 123I-iomazenil SPECT. AB - BACKGROUND: Central benzodiazepine (BZD) receptor imaging is effective to evaluate neuron density in the pathological brain cortex. This study used BZD receptor imaging to evaluate neuronal damage in adult ischemic moyamoya disease. METHODS: Single photon emission computed tomography and a novel tracer, 123I iomazenil, were used to measure BZD receptor density in the brain. Evaluation of early and late images was performed in three asymptomatic, unoperated patients, and six mildly symptomatic, operated patients. RESULTS: Uptakes in the frontal, parietal, and occipital lobes of symptomatic patients were significantly lower (p<0.05) than those of asymptomatic patients. The late image/ early image count ratios (L/E ratios) of asymptomatic patients were relatively constant (mean, 0.571; range, 0.550-0.581) in all regions of interest. In contrast, the L/E ratios of symptomatic patients were not uniform. CONCLUSIONS: The neuron density was preserved in adult asymptomatic patients despite harboring moyamoya disease. In contrast, the neuronal density was decreased in symptomatic patients even though their symptoms were mild and they had undergone revascularization. PMID- 10029421 TI - Tentorial dural arteriovenous fistula obliterated using the petrosal approach. AB - BACKGROUND: Tentorial dural arteriovenous fistulas (AVFs) are uncommon lesions usually treated surgically using a subtemporal exposure with division of the tentorium. This exposure requires significant retraction of the temporal lobe and has the possibility of significant arterialized venous bleeding if a draining vein is accidentally cut during division of the tentorium. Skull base surgical techniques may provide alternate approaches for the surgical treatment of tentorial dural AVFs. METHODS: A tentorial dural arteriovenous fistula supplied by the tentorial artery and drained by the petrosal vein was exposed and obliterated using the petrosal (subtemporal-presigmoid) approach. RESULTS: The petrosal approach allowed the exposure and division of the superior petrosal sinus and tentorium with direct visualization of the supratentorial and the infratentorial compartments, avoiding accidental damage to the draining veins. The dural fistula was easily obliterated after its venous drainage was interrupted and the tentorial artery occluded. CONCLUSIONS: Tentorial dural AVFs can be safely treated with interruption of the venous drainage. The exposure can be enhanced with a petrosal approach, decreasing the possibility of uncontrolled bleeding during the procedure. PMID- 10029422 TI - Vertebral arteriovenous fistula that developed in the same place as a previous ruptured aneurysm: a case report. AB - BACKGROUND: Aneurysms of the extracranial vertebral artery (VA) and vertebral arteriovenous fistulas (VAVFs) are relatively rare diseases. The most frequent cause of both diseases is trauma. Atraumatic lesions are less common. Presented here is a case of atraumatic AVF of the extracranial VA that developed in the same location as a previous ruptured aneurysm of the ipsilateral VA that was originally treated by proximal occlusion 11 years earlier. METHODS: A 40-year-old woman presented with a massive hematoma in the upper posterior neck region caused by the rupture of an extracranial VA aneurysm. Proximal occlusion of the VA was performed by use of a detachable balloon. She enjoyed good health for 11 years, then she noticed a pulsatile bruit. Angiograms revealed an AVF between the left VA that was fed by collateral circulation and the paravertebral venous plexus. Incidentally found were soft tissue masses in the left retroauricular and the right suboccipital regions. Also, skull X-ray films showed multiple bony defects. Biopsy of the subcutaneous mass was performed in the hope of obtaining clues as to which pathological processes had weakened the artery. RESULTS: As direct transarterial access to the fistula was out of the question, the fistulous compartment of the paravertebral venous plexus was tightly packed with multiple platinum coils effected by the transfemoral approach. A histological examination of the specimen revealed features of a neurofibroma, and a diagnosis of neurofibromatosis Type 1 was established. CONCLUSIONS: In this case, transvenous embolization of the VAVF was successfully performed. The fragility of the arterial wall, related to neurofibromatosis Type 1, was considered to contribute to the development of the aneurysm and AVF. PMID- 10029423 TI - Development of a dural arteriovenous fistula around the jugular valve after transvenous embolization of cavernous dural arteriovenous fistula. AB - BACKGROUND: Endovascular therapy for dural arteriovenous fistulas (DAVFs) is not without any risks, although it has been generally accepted to be a safe procedure. In this paper, we report a very rare complication: metachronous DAVF around a jugular valve 4 months after transvenous embolization. CASE DESCRIPTION: A 43-year-old woman presented with left proptosis, chemosis, and double vision. Cerebral angiography demonstrated a left cavernous DAVF. The patient's symptoms resolved almost completely after embolization with platinum coils via the superior ophthalmic vein. Four months later, angiography revealed a metachronous DAVF around a jugular valve. CONCLUSION: To our knowledge, only four such cases have been reported in the literature. Careful follow-up of patients treated with transvenous embolization and accumulation of such cases are needed to understand the pathogenesis of multiple DAVFs. PMID- 10029424 TI - Third ventricular lesion masquerading as suprasellar disease. AB - We discuss the case of a patient who presented with a bitemporal visual field disturbance thought to arise from chiasmatic compression secondary to a suprasellar mass. The patient was ultimately diagnosed with medulloblastoma with diffuse intraventricular disease. Careful review of magnetic resonance (MR) findings in this case demonstrate the apparent suprasellar mass to be within the suprachiasmatic recess of the third ventricle. The role of MR imaging in distinguishing between suprasellar disease involving the third ventricle and primary third ventricular lesions is discussed. PMID- 10029425 TI - Akinetic mutism after fourth ventricle choroid plexus papilloma: treatment with a dopamine agonist. AB - BACKGROUND: Akinetic mutism is a behavioral state wherein a patient seems to be awake but does not move or speak. Several patients are reported to have developed mutism after posterior fossa surgery. We present a patient who developed akinetic mutism after total excision of a choroid plexus papilloma of the fourth ventricle, and who was treated with bromocriptine. CASE DESCRIPTION: An 18-year old woman was admitted with akinetic mutism, which had developed 6 days after posterior fossa surgery. She had had no neurologic deficit in the first 5 days after surgery and could communicate with her family. Despite antioedematous therapy and daily lumbar punctures to drain cerebrospinal fluid, there was no clinical improvement after she entered the akinetic mute state. Brain magnetic resonance revealed ventriculomegaly; brain single photon emission computed tomography revealed bilateral reduction of perfusion in the frontal region. Because daily lumbar drainage did not result in clinical improvement, shunt placement was not considered. Bromocriptine therapy was begun at a dose of 2x2.5 mg; 24 hours later, the patient started to speak and move her upper extremities. Further improvement occurred over the following week when the dose was increased to 3x2.5 mg. Bromocriptine was replaced with a placebo to determine whether the neurologic improvement was caused by the medicine. The patient's neurologic status deteriorated progressively; therefore, bromocriptine was restarted and she was discharged from the hospital. During the 6 months of follow-up, the patient has remained in good health. CONCLUSIONS: The etiology of akinetic mutism is not clear. Monoaminergic pathways, particularly dopaminergic cell groups, are most probably involved in this syndrome, because bromocriptine has a dramatic effect on these patients, as demonstrated in our case. PMID- 10029426 TI - Solitary sarcoid granuloma of the cerebellopontine angle: a case report. AB - BACKGROUND: Sarcoidosis involves the nervous system about 5% of the time and usually manifests as a granulomatous inflammation of the basal meninges and hypothalamus. Cases which are strictly isolated to the central nervous system occur infrequently; rarely, they may present as an intracranial mass. METHODS: We present the case of a solitary sarcoid granuloma at the cerebellopontine angle in a 42-year-old female who presented with headache, facial numbness, and hearing loss. RESULTS: A suboccipital craniectomy was performed and the lesion was noted to be grossly adherent to the lower cranial nerves and skull base. The lesion was misdiagnosed as a meningioma with preoperative magnetic resonance imaging and intraoperative histology, and perhaps additional morbidity resulted. CONCLUSION: We present this case in order to demonstrate the importance of differentiating these dural-based lesions and propose that cases of neurosarcoidosis presenting as a solitary granuloma be treated with surgical debulking and immunosuppression. PMID- 10029427 TI - Functional outcome and the effect of cranioplasty after retromastoid craniectomy for microvascular decompression. AB - BACKGROUND: While the efficacy of retromastoid craniectomy for microvascular decompression for hyperactive cranial nerve syndromes is well established, there is no real information regarding the functional outcome of these operations. The purpose of this retrospective questionnaire study is to assess functional outcome regarding presence and duration of postoperative headache, incisional pain, and the time to return to normal activity in patients undergoing retromastoid craniectomy for microvascular decompression. The effect of closure with bone chips or cranioplasty in the defect upon these functional outcomes was studied, as was the influence of the particular nerve that was the object of decompression. METHODS: Four-hundred and ninety-five consecutive patients were contacted and 320 (65%) returned questionnaires with enough information to be suitable for analysis. RESULTS: The incidence of postoperative headache was initially 60.1%, dropping to 28.8% at 1 month and 16.8% at 6 months. Incisional pain likewise declined with time, noted in 25.8% at 1 month and only 13.1% at 6 months. Use of a cranioplasty made no significant difference in influencing either postoperative headache or incisional pain, nor was the nature of the procedure a significant factor. CONCLUSION: Twenty-five percent of patients resumed normal activity by 3 weeks, 50% by 1 month, and 90% by 3 months. Overall, 98% of patients responding reported returning to normal activity. Therefore, although there is an incidence of postoperative headache and incisional pain, these decrease with time and do not seem to interfere with the return to normal activity, nor are they affected by placement of a cranioplasty or the nature of the operation. PMID- 10029428 TI - Facial canal decompression leads to recovery of combined facial nerve paresis and trigeminal sensory neuropathy: case report. AB - BACKGROUND: Trigeminal sensory neuropathy is often associated with facial idiopathic nerve paralysis (Bell's palsy). Although a cranial nerve viral polyneuropathy has been proposed as the usual cause, in many instances the etiology remains unclear. This case report of recovery of both trigeminal and facial neuropathy after surgical decompression of the facial nerve suggests an anatomic link. METHODS: A case of a 39-year-old woman presenting with recurrent unilateral facial paralysis is summarized. Her fifth episode, which did not spontaneously recover, was associated with retroorbital and maxillary pain as well as sensory loss in the trigeminal distribution. RESULTS: A middle cranial fossa approach for decompression of the lateral internal auditory canal, labyrinthine segment of the facial nerve and the geniculate ganglion was performed. The patient's pain and numbness resolved immediately postoperatively, and the facial paralysis improved markedly. CONCLUSION: This result implicates a trigeminal-facial reflex as hypothesized by others. It suggests that decompression of the facial nerve can lead to improvement in motor and sensory function as well as relief of pain in some patients with combined trigeminal and facial nerve dysfunction. PMID- 10029429 TI - Presurgical contribution of quantitative stereotactic positron emission tomography in temporo limbic epilepsy. AB - BACKGROUND: We quantified the interictal metabolic changes associated with temporal lobe epilepsy by using an accurate stereotactic method. METHODS: We selected 16 patients who had proven unilateral focal or regional temporal onset defined by SEEG criteria. Each patient underwent stereotactic MRI and stereotactic [18 fluoro] fluorodeoxyglucose positron emission tomography (PET). RESULTS: Asymmetries (mean, +/- SD) were found in mesio-temporal structures: amygdala (-0.033+/-0.027, p = 0.0002), hippocampus (-0.035+/-0.032, p = 0.0006), and superior temporal gyrus (-0.036+/-0.032, p = 0.0004). Four of the sixteen patients had previously had unlocalized qualitative nonstereotactic PET analysis. CONCLUSIONS: The quantitative stereotactical PET method allows a higher resolution study of mesio-temporal structures. PMID- 10029430 TI - Neurofibromatosis type 1 peripheral nerve tumors: aberrant activation of the Ras pathway. AB - BACKGROUND: Neurofibromatosis Type 1 (NF1) is an autosomal dominant transmitted cancer predisposing syndrome, with peripheral nerve tumors being a prominent feature. The NF1 gene encodes a large cytoplasmic protein called neurofibromin, which is a major negative regulator of Ras, a key protein in a major signal transduction pathway. It is hypothesized, based on data from neurogenic sarcoma cell lines, that loss of neurofibromin leads to increased levels of activated Ras GTP, and subsequent uncontrolled mitogenic signals to the nucleus. However, it is not known whether aberrant activity of the Ras pathway is also a prevalent molecular pathogenetic mechanism in actual peripheral nerve tumors. METHODS: To investigate whether aberrant Ras activity was present, and varied with increased tumorigenic potential in peripheral nerve tumors, we have recently developed and published an enzymatic luciferase-based assay that allows measurement of Ras activity in tissues for the first time. RESULTS AND CONCLUSIONS: Neurofibromin, the gene product of the NF1 gene, was not expressed in the NF1 tumors. Levels of activated Ras-GTP in NF1 neurogenic sarcomas and NF1 plexiform neurofibromas were approximately 15 and 5 times higher, respectively, compared with non-NF1 schwannomas, supporting the hypothesis that aberrant activity of this key signaling pathway is important in the pathogenesis of these tumors. In this article we review this data, the molecular genetics of NF1, and the current knowledge of the role of neurofibromin in cellular control. Our understanding of the molecular pathogenic mechanisms of NF1 tumors should be transferable to sporadic peripheral nerve tumors, and allow development of biological therapies directed against relevant targets such as Ras. PMID- 10029431 TI - Brain abscess caused by Streptococcus intermedius: two case reports. AB - BACKGROUND: Although Streptococcus intermedius has been recognized as an important pathogen for abscess formation outside the central nervous System, the Streptococcus milleri group, of which it is a member, has not been recognized as a specific pathogen for brain abscess, often thought to be caused by Streptococcus viridans, which includes other streptococcal species. CASE DESCRIPTION: Two cases of brain abscess in the left frontal lobe caused by S. intermedius, which responded well to antimicrobial treatment combined with needle aspiration, are presented. In the first patient, the predisposing disease was paranasal sinusitis of the frontal and ethmoid sinuses. In the second patient, the source of the pathogen was not detected despite extensive examination. The patients underwent aspiration of pus under ultrasound guidance in the first patient, and via a computed tomography-guided stereotactic procedure in the second patient. They subsequently received appropriate antimicrobial therapy against S. intermedius isolated from the pus culture. Both patients were discharged without any neurological deficits. CONCLUSION: It is important to recognize S. intermedius as a pathogen of brain abscess, and to be aware of its predisposing factors, i.e., mucosal disturbance and liver abscess. PMID- 10029432 TI - On the mechanism of transient postoperative deficit of cranial nerves. AB - BACKGROUND: Transient cranial nerve deficit is a common postoperative complication after surgery at the cranial base. In this type of surgery, the cranial nerves are often not macroscopically damaged or transected, but more or less manipulated during surgery. In this article, the cellular mechanisms of postoperative cranial nerve deficit are reviewed. METHODS: Experimental and clinical papers concerning cranial and peripheral nerve damage during surgery were critically reviewed. RESULTS: There are definite differences in the anatomical and histological structure between peripheral and intracranial nerves, which make the latter much more prone to intraoperative damage. Several pathological mechanisms are responsible for postoperative deficit, such as segmental demyelination of the nerve, comprised microcirculation within the nerve, postoperative edema, and "synaptic stripping" around the cell bodies of the affected neurons, which can be regarded as a regenerative response of the nervous system. CONCLUSIONS: Several cellular mechanisms are responsible for postoperative cranial nerve deficit after skull base surgery. Understanding these mechanisms is important for all surgeons involved in the treatment of skull base lesions. PMID- 10029433 TI - The New England Journal of Medicine report on unruptured intracranial aneurysms: a critique. PMID- 10029434 TI - Preventing complications in spine surgery. PMID- 10029435 TI - Acute spinal cord injuries: a search for functional improvement. PMID- 10029436 TI - Understanding the pathogenesis of primary peritoneal carcinoma: involvement of the BRCA1 and p53 genes. PMID- 10029437 TI - Some thoughts about the past and future of pathology workforce. AB - Comprehensive information on pathology workforce is currently not available. Prudent planning for pathology Graduate Medical Education (GME) requires more timely data than presently exist. In addition, we lack understanding of workforce kinetics in academic pathology which often serves as a buffer in times of surplus. Although the heads of community hospital and private laboratory groups control the majority of decisions regarding pathology workforce, a database of these decision-makers does not exist. However, information from the most recent published sources strongly suggests that a significant surplus already exists. Furthermore, this position is supported by earlier unpublished work from the 1994 1995 Conjoint Committee on Pathology Enhancement (CCOPE) surveys. PMID- 10029438 TI - Immunohistochemical evaluation of K-ras, p53, and HER-2/neu expression in hyperplastic, dysplastic, and carcinomatous lesions of the pancreas: evidence for multistep carcinogenesis. AB - The pathobiology of precursor lesions leading to invasive pancreatic adenocarcinoma remains a controversial area, but knowledge of the mechanisms of tumorigenesis may lead to possibly earlier detection, prevention, and treatment in the future. We hypothesize that ductal hyperplasia and dysplasia of the pancreas represent precursor lesions and are part of a continuous developmental spectrum evolving into ductal adenocarcinoma of the pancreas. To further define this sequence, we studied the immunohistochemical markers HER-2/neu, K-ras, and p53 in 15 adenocarcinomas and 15 nonmalignant specimens of the pancreas. The 15 nonmalignant specimens of the pancreas included both normal pancreas and chronic pancreatitis. Overall, HER-2/neu was positive in normal ducts, ductal hyperplasia, dysplasia, and carcinoma cells in 0 of 30, 11 of 20 (55%), 10 of 15 (67%), and 12 of 15 (80%), respectively, with progressive increase in the intensity of staining; p53 was positive in 1 of 30 (3%), 0 of 20, 3 of 15 (20%), and 13 of 15 (80%), respectively, and K-ras was positive in 1 of 30 (3%), 6 of 20 (30%), 11 of 15 (73%), and 8 of 15% (53%), respectively. These data support the hypothesis that ductal hyperplasia and dysplasia of the pancreas represent precursor lesions, and, in a fashion similar to that in colorectal tumorigenesis, pancreatic cancer seems to accumulate progressive genetic alterations. PMID- 10029439 TI - Analysis of clonality of atypical cutaneous lymphoid infiltrates associated with drug therapy by PCR/DGGE. AB - Atypical lymphocytic infiltrates that mimic cutaneous lymphoma (ie, pseudolymphoma) are often observed in skin biopsy specimens from patients with altered immune function. The latter may reflect systemic immune dysregulatory states such as collagen vascular disease or human immunodeficiency virus infection. Among the iatrogenic causes are drug therapy with agents that abrogate lymphocyte function. These drugs encompass the anticonvulsants, antidepressants, phenothiazines, calcium channel blockers, and angiotensin-converting enzyme inhibitors. The appellation of lymphomatoid hypersensitivity reaction has been applied to cases of drug-associated pseudolymphoma. Pathologically and clinically, the distinction of such cases from cutaneous lymphoma is difficult. We employed the polymerase chain reaction (PCR) on archival material of proven drug-associated lymphomatoid hypersensitivity reactions both to explore its utility as an adjunct in diagnosis and to investigate the genotypic aberrations induced by drug therapy. Formalin-fixed, paraffin-embedded biopsy specimens from seven cutaneous T-cell lymphomas (CTCL), one nodal T-cell lymphoma, two cutaneous B-cell lymphomas, three typical hypersensitivity reactions, one tonsil, and 14 lymphomatoid hypersensitivity reactions were studied. Control cases for which DNA derived from fresh tissue was used include the Jurkat T-cell tumor line, placenta, one nodal B-cell lymphoma, and one case of reactive lymph node hyperplasia. DNA was obtained and purified by standard methods, then amplified with oligonucleotide primers specific for the T-cell receptor gamma locus and the immunoglobulin heavy chain genes. T-cell amplicons were analyzed by denaturing gradient gel electrophoresis (DGGE) and B-cell amplicons by either nondenaturing polyacrylamide or agarose gel electrophoresis. The nodal and Jurkat T-cell lymphomas, six of seven CTCL, one cutaneous B-cell lymphoma, and 2 of 14 lymphomatoid hypersensitivity reactions showed dominant ("monoclonal") T-cell gene rearrangement patterns, and the remainder of cases were polyclonal. A causal relationship between drug therapy and skin eruption was ascertained in the two patients showing T-cell rearrangements, and both experienced complete and sustained lesional resolution on discontinuation of the implicated drug. The only immunoglobulin heavy chain gene rearrangements detected by PCR were in two of the three B-cell lymphomas. We conclude that PCR/DGGE is a powerful method for assaying T-cell clonality in archival tissue and can aid in the discrimination of reactive from malignant cutaneous infiltrates with appropriate clinicopathologic correlation. Recognition that a monoclonal TCRgamma rearrangement can be observed in cases of drug-associated lymphomatoid hypersensitivity may help in avoiding a misdiagnosis of malignant lymphoma. PMID- 10029440 TI - Interphase cytogenetics of chromosomes 11 and 17 in fine needle aspirates of breast cancer. AB - The aims of this investigation were to compare quantitative with qualitative analysis of fluorescent in situ hybridization (FISH) centromere signals in interphase breast cancer cell nuclei and to evaluate the possible clinical utility of detecting numerical abnormalities of chromosomes 11 and 17 by FISH in the preoperative prediction of breast cancer histological grade. Commercial digoxigenin-labeled centromere probes to chromosomes 11 and 17 were hybridized to 69 malignant aspirates with histological follow-up. Aspirates were categorized as disomic or aneusomic for chromosomes 11 and 17 qualitatively; a subset of aspirates was also analyzed quantitatively. The quantitative and qualitative approaches resulted in almost identical categorisation. There was a significant association between the qualitative categorization of aspirates as aneusomic or disomic, the histological grade of the excised tumours (P = .0695, n = 69), and the cytological grade of the clinical aspirates (P = .006, n = 35). Although histological grade III tumors were almost invariably polysomic for one or both chromosomes, polysomy was also detected in grade I and II tumors. Qualitative FISH analysis was shown to be more sensitive than cytological grading in predicting histological grade III but was of lower specificity and was therefore not clinically useful. PMID- 10029441 TI - Proliferative pattern of exophytic and superficially invasive and noninvasive low grade urothelial carcinomas. AB - In urothelial low-grade carcinomas of the bladder stage pT1, prognosis in general is good. In a subset of these tumors infiltrating beyond the lamina muscularis mucosae, prognosis clearly worsens. Unfortunately, evaluation of the lamina muscularis mucosae often is very difficult or even impossible because of its incomplete extension. In an immunohistochemical study on 131 pTa and pT1 urothelial tumors without provable lamina muscularis mucosae, we evaluated the proliferative activity with the monoclonal antibody MIB-1 and the expression pattern of cytokeratins of high molecular weight with the monoclonal antibody 34betaE12. The highest proliferative indices were found in tumors with a diffuse expression pattern of MIB-1 and 34betaE12. A preliminary analysis of follow-up data showed that 70.6% of the pT1 GIb-GIa tumors that recurred showed a diffuse expression pattern for both markers. Whether these patients are candidates for a doser follow-up or even for a more radical therapy has to be subject to further follow-up studies. PMID- 10029442 TI - Altered surface and cyst epithelium of ovaries removed prophylactically from women with a family history of ovarian cancer. AB - Despite intensive investigation, the nature of epithelial ovarian cancer precursors remains controversial. Because women with a strong family history of ovarian cancer have a high probability of developing ovarian cancer themselves, ovaries removed prophylactically from such patients provide an opportunity to identify early neoplastic changes. Ovaries removed from 64 consecutive patients undergoing prophylactic oophorectomy and from 30 women with normal ovaries and no known family history of ovarian cancer were examined by light microscopy for a number of histopathologic features and by image cytometry for abnormalities of the cyst and surface epithelium. All analyses were performed without knowledge of the family history. Seven benign, but no tumors of low malignant potential or malignant epithelial tumors were found in the prophylactic oophorectomy group. There were more cortical inclusion cysts in the prophylactically removed than controls ovaries (P = .016), but no other architectural features differed between the two groups. No abnormalities were found in the surface or cyst epithelium in either group by light microscopy. In contrast, image analysis identified differences in the nuclei between the two groups, indicating that those from the surface epithelium of prophylactically removed ovaries were larger and contained more heterogeneously dense chromatin than those of controls, and that nuclei of the cyst epithelium had more irregular outlines. Ovarian epithelium from prophylactically removed ovaries exhibit abnormalities that are only identified by image analysis, and which might represent early preneoplastic changes. Such ovaries may be useful for identifying early molecular changes in ovarian cancer. PMID- 10029443 TI - Alveolar adenoma: a histochemical, immunohistochemical, and ultrastructural analysis of 17 cases. AB - Alveolar adenoma of lung is a rare benign neoplasm of uncertain histogenesis. Its rarity hampers characterization of its epithelial and mesenchymal elements. Clinical and histopathologic features of 17 alveolar adenomas were reviewed. Histochemistry was performed on 10 cases, ultrastructural analysis on two, and immunohistochemistry on six cases for pneumocyte markers, thyroid transcription factor (TTF-1), surfactant protein markers pro-SP-B and pro-SP-C, and the Clara cell marker, CC10. Immunohistochemistry was performed in nine cases for desmin, smooth muscle actin, muscle-specific actin, cytokeratin, proliferating cell nuclear antigen (PCNA), factor VIII, and carcinoembryonic antigen. The mean age was 53 years. Seven cases occurred in men, and nine occurred in women. The age and sex were not known for one patient. The tumors were coin lesions on chest radiographs in asymptomatic patients except for one (cough). The mean size was 2.2 cm. The tumors were well demarcated with multiple cystic spaces containing granular material. Mostly type 2 pneumocytes lined the cystic spaces with fewer type 1 cells and no Clara cells. This was confirmed by staining for TTF-1, pro-SP B, and pro-SP-C and by ultrastructure. CC10 was negative in all cases. The stroma varied from prominent spindle cells with a myxoid matrix to thin alveolar septa. The interstitial spindle cells resembled fibroblasts by immunohistochemistry and ultrastructure. Follow-up data available in five cases showed no recurrence at 2, 2, 5, 8, and 13 years. In summary, alveolar adenoma is a benign neoplasm consisting of an intimate admixture of alveolar epithelial and septal mesenchymal tissue. Most of the epithelial cells are type 2 pneumocytes, and the interstitial stromal cells are fibroblasts or fibroblast-like cells. Recognition of its characteristic morphological appearance allows for its distinction from other benign lesions of the lung. PMID- 10029445 TI - Rarity of genomic instability in pathogenesis of systemic anaplastic large cell lymphoma (ALCL) in immunocompetent patients. AB - Microsatellite instability (MSI) is a recently described type of genetic alteration resulting from defects in the DNA mismatch repair genes that appears to play an integral role in neoplastic transformation. MSI has been described in a wide variety of malignancies; however, data regarding the role of MSI in the pathogenesis of non-Hodgkin's lymphoma (NHL) are limited. MSI appears to be important in some T-cell lymphomas, including ALCL arising in immunocompromised patients. In addition, MSI has recently been identified in CD30+ cutaneous lymphoproliferative processes and lymphoblastic lymphoma. In this study, we have analyzed five well-characterized cases of systemic T-cell ALCL arising in immunocompetent patients for the presence of MSI. Genomic DNA isolated from paired normal and tumor tissue was analyzed at seven microsatellite loci by polymerase chain reaction. We were unable to identify MSI or loss of heterozygosity (LOH) in our cases, suggesting that abnormalities in the DNA mismatch repair system do not play a major role in the pathogenesis of most systemic ALCL. Our data provide additional molecular evidence that the various subgroups of lymphoma with ALCL morphology are biologically distinct processes. PMID- 10029444 TI - Decreased immunoexpression of prostate inhibin peptide in prostatic carcinoma: a study with monoclonal antibody. AB - Prostate inhibin peptide (PIP) is a follicle-stimulating hormone (FSH) regulating peptide produced by the prostate. The mechanism of its endocrine role in regulating prostate growth is believed to be androgen-independent but FSH dependent. Previous studies using polyclonal antibody proposed PIP as a prostatic specific marker in cancer diagnosis. However, the recently available monoclonal antibody has not yet been evaluated. Paraffin sections of 72 prostatectomy specimens for prostate cancer with or without hormonal blockage therapy and 10 nonneoplastic prostate tissues from autopsy were stained by using PIP monoclonal antibody (clone: 4A6A6) with the avidin-biotin complex method. PIP reactivity was semiquantitatively estimated in prostatic carcinoma (PCA), prostatic intraepithelial neoplasia (PIN), benign prostatic hyperplasia (BPH) and normal tissue in each case when ever present. Statistical analyses were performed accordingly. PIP expression is predominantly cytoplasmic. Urothelium, seminal vesicles, inflamed prostatic glands, basal cells, and squamous metaplasia were negative for PIP. Average percentage of cells expressing PIP was significantly decreased in PIN (40%) and PCA (14%) when compared with BPH (81%) and normal tissue (68%). There was no correlation of tumor PIP level with patient's age, tumor size, Gleason score, tumor stage, or the usage of preoperative hormonal blockage therapy. PIP monoclonal antibody should be used with caution as a prostate-specific marker in surgical pathology. The mechanism for this alteration and the effect of PIP on prostatic tumor growth, particularly in patients under a variety of hormonal therapies, needs further study. PMID- 10029446 TI - Mediastinal B-cell lymphoma: a study of its histomorphologic spectrum based on 109 cases. AB - Mediastinal B-cell lymphoma (MBL) is a distinct variant of aggressive non Hodgkin's lymphoma with characteristic clinical and biological features but less well-defined histomorphology. We reevaluated 124 biopsy specimens from 109 MBL patients of an Italian/French/German retrospective clinical study. MBL was primarily diagnosed on clinical and histological grounds in conjunction with the detection of CD20 expression by immunohistology. Cytologically, MBL features limited intralesional but considerable interindividual cytological diversity, ranging from medium-sized to very large, atypical cells. Sclerosis and necrosis are restricted to extrathymic and extranodal sites of involvement, predominantly the lung, as is angioinvasion, which predominantly affects larger vessels. The medium-sized and the large cell variants resemble marginal zone lymphoma variants, whereas the very large cell variant of MBL has not so far been found to have any extramediastinal counterpart. We conclude that MBL displays a broad morphological spectrum covering more than is implied by the term "diffuse large cell lymphoma." Because statistical analysis of cytological and histological criteria failed to correlate with prognosis in this comprehensive group of patients, we think it inadvisable further to subclassify MBL. PMID- 10029447 TI - Mast cells are augmented in deep vein thrombosis and express a profibrinolytic phenotype. AB - A number of recent data suggest that mast cells (MC) and their products are involved in the pathophysiology of thrombosis. In the current study, we have evaluated the number, distribution, and phenotype of MC in patients with deep vein thrombosis of the lower limb (DVT) (n = 15). Contralateral nonthrombosed limb veins served as control (CO). MC were examined by Giemsa staining and by immunohistochemistry using antibodies against tryptase, chymase, tissue-type plasminogen activator (tPA), urokinase (uPA), urokinase receptor (uPAR), and plasminogen activator inhibitors (PAI-1, PAI-2). We found an increase in the number of tryptase-positive MC in DVT compared with CO (DVT: 9.1+/-1.0 v CO: 4.7+/-0.6 MC/mm2, P < .05). Most of these MC appeared to accumulate in the adventitia of the thrombosed veins, in vicinity of the vasa vasorum. In both DVT and CO, MC reacted with monoclonal antibodies to c-kit, tryptase, and chymase. MC also stained positive for tPA and urokinase receptor, but did not express detectable PAI-1 or PAI-2. As compared with CO, a decreased proportion of MC in DVT was found to stain positive for chymase and tPA. Together, our results show that MC increase in number in DVT and express a profibrinolytic phenotype. We hypothesize that MC and MC-derived profibrinolytic molecules play a role in the pathophysiology of DVT. PMID- 10029448 TI - Role of transforming growth factor-beta1 and decorin in development of central fibrosis in pulmonary adenocarcinoma. AB - Transforming growth factor-beta1 (TGF-beta1) is known as the growth factor that stimulates the synthesis of extracellular matrix. Recently, TGF-beta has been found to control the growth of cancer cells. Small chondroitin-dermatan sulfate (decorin) is an abundant extracellular matrix component. TGF-beta1 stimulates the synthesis of decorin, and decorin is considered to bind TGF-beta1. The activity of decorin in neutralizing TGF-beta1 activity suggests that decorin serves as a negative-feedback regulator of TGF-beta1 activity. To investigate the role and relationship of TGF-beta1 and decorin in the formation of central fibrosis in pulmonary adenocarcinoma, we performed an immunohistochemical study of TGF-beta1 and decorin in 61 cases of T1 pulmonary adenocarcinoma. Positive stainings for TGF-beta1 were shown in 40 cases and negative in 21 cases. Twenty-seven of 32 cases with central fibrosis were positive for TGF-beta1. Positive staining for TGF-beta1 was significantly related to the appearance of central fibrosis in pulmonary adenocarcinoma. When central fibrosis was composed of proliferative connective tissue with loose staining for decorin, cancer cells showed intense staining for TGF-beta1. When central fibrosis was composed of old fibrotic tissue with dense staining for decorin, cancer cells showed weak staining for TGF-beta1. Our results suggest that TGF-beta1 has an important role in the formation of central fibrosis in pulmonary adenocarcinoma, and decorin may play a role as a negative feedback regulator in the production of TGF-beta1 in pulmonary adenocarcinoma. PMID- 10029449 TI - Microcalcifications in the anterior pituitary gland of the fetus and the newborn: a histochemical and immunohistochemical study. AB - Calcified concretions are a normal and constant finding in the anterior pituitary gland of fetuses and newborns. Their light and electron microscopic characteristics have been recently reported by the authors. In this study, undecalcified and decalcified sections from 20 neonatal and 60 fetal anterior pituitary glands were studied by histochemical and immunohistochemical methods to further clarify their nature and mechanism of formation. All the glands revealed homogeneous and/or laminar calcifications located either within the interstitium or follicular structures. They were composed of a diastase-resistant periodic acid-Schiff-positive carbohydrate-rich matrix. The Feulgen method for DNA was negative. Their core frequently reacted to Alcian blue and epithelial membrane antigen (EMA). EMA also stained the apical membranes of adjacent epithelial cells. Other immunostains (vimentin, keratin, and pituitary hormones) were negative. The positive staining for Alcian blue and EMA and the negative staining with the Feulgen method for DNA suggest that the core of the calcifications consists of acidic mucosubstances and EMA-positive proteinaceous material previously secreted by viable pituitary cells. The EMA-negative periphery of the concretions probably develops from further extracellular peripheral mineralization that leads to larger, sometimes laminated psammoma bodies. The occurrence of pituitary calcifications in states of adult physiological and pathological hyperprolactinemia suggests that the marked proliferation of lactotrophs occurring during the fetal life play an important role in the pathogenesis of the fetal and neonatal concretions. PMID- 10029450 TI - Incidence of loss of heterozygosity at p53 and BRCA1 loci in serous surface carcinoma. AB - Serous surface carcinoma (SSC) is a neoplasm histologically indistinguishable from typical serous carcinomas that arise from the ovary but has a distinct clinical presentation. It is characterized by widespread peritoneal dissemination at presentation, but the ovaries are grossly normal in size and shape. If the carcinoma involves the ovaries microscopically, the tumor is confined to the surface or is minimally invasive. The recognition of this entity is important, because in some studies it appears to have a poorer prognosis than stage-matched serous cancers of the ovary. Loss of heterozygosity (LOH) of the p53 (17p) and BRCA1 (17q) tumor suppressor genes has been frequently identified in sporadic ovarian carcinomas. Although 17p LOH is correlated with common p53 gene mutations, inactivating mutations of the BRCA1 gene are uncommon in sporadic ovarian cases. In contrast, germline BRCA1 mutations are responsible for some hereditary forms of ovarian cancer, where it has been suggested that germline BRCA1 mutations confer a more favorable prognosis. In this study, 12 sporadic SSC were assessed for the presence of allelic deletions on the p53 and BRCA1 gene loci. DNA from both tumor and normal cells was obtained for LOH studies using tissue microdissection. Polymerase chain reaction (PCR) amplification was performed with the polymorphic DNA markers TP53 (17p13.1/p53 gene) and D17S579 (17q/BRCA1 gene). LOH in the p53 and BRCA1 loci was detected in 62.5% and 66.6% of the cases, respectively. In 50% of tumors informative for both markers, it is possible that an entire chromosome may be lost. In conclusion, we have shown that LOH of the p53 and BRCA1 loci is a frequent event in sporadic SSC, similar to what has been described in the usual form of serous ovarian carcinoma. Mutational analysis will be necessary to determine the exact role of these genes in this group of tumors. PMID- 10029451 TI - Expression of proopiomelanocortin (POMC)-derived melanocyte-stimulating hormone (MSH) and adrenocorticotropic hormone (ACTH) peptides in skin of basal cell carcinoma patients. AB - We proposed that local expression and production of proopiomelanocortin (POMC) peptides may play a role in human skin physiology and pathology, including the development and progression of skin cancers. Reverse transcription polymerase chain reaction (RT-PCR) and Northern blotting hybridization techniques were used to study gene expression. Reversed-phase (RP) high-pressure liquid chromatography (HPLC) separation with subsequent radioimmunoassays were used to identify alpha melanocyte-stimulating hormone (alpha-MSH) and adrenocorticotropic hormone (ACTH) peptides. Immunocytochemistry (IHC) was used to localize ACTH, alpha-MSH, and beta-MSH antigens in skin. RT-PCR, RP-HPLC, and IHC analyses documented the expression of POMC mRNA and production of ACTH and alpha-MSH peptides in lesional and perilesional skin of basal cell carcinoma (BCC) patients and in cultured keratinocytes, which was accompanied by the expression of the MC1-R gene encoding the receptor activated by MSH and ACTH. Thirty specimens were analyzed by IHC. Immunoreactive alpha-MSH, beta-MSH, and ACTH were detected, in 21 of 21, in 11 of 20, and in 6 of 8 of lesional skin, and in 6 of 6, in 5 of 7, and in 6 of 8 perilesional skin specimens analyzed, respectively. Antigen distribution was heterogenous and present in BCC, epidermis, hair follicles, dermal mononuclear cells, and extracellular matrix. We conclude that messenger RNA for POMC, MC1-R, and the peptides MSH and ACTH are produced in skin of BCC patients. Because keratinocytes are a target for MSH and ACTH bioregulation, the production of these peptides is stimulated by UVB, and the peptides can act as immunosupressors, we suggest that MSH and ACTH may facilitate development of BCC. PMID- 10029453 TI - Reverse transcriptase polymerase chain reaction as a reliable method to detect epidermal growth factor receptor exon 2-7 gene deletion in human glioblastomas. AB - Epidermal growth factor receptor (EGFR) gene amplification has been reported to occur in diverse carcinoma types such as lung, ovarian, and breast carcinomas and in glioblastomas. A 801-bp in-frame deletion close to the aminoterminus of the receptor protein has been found to occur more or less frequently within at least three of these tumor entities. We studied EGFR gene alterations using the polymerase chain reaction and EGFR gene expression of 65 astrocytic tumors (51 glioblastomas World Health Organization [WHO] IV, five anaplastic astrocytomas WHO III, and nine astrocytomas WHO II). EGFR gene amplification, as determined by Southern blotting using a full-length cDNA probe, was observed in 22 of 51 glioblastomas (43%) but in none of the grade II astrocytomas. Two of five anaplastic astrocytomas at WHO III showed a considerable degree of EGFR amplification but, according to the neuroradiological data, these two tumors had to be considered as glioblastomas. The most frequently found genetic alteration was the 801-bp deletion near the receptor aminoterminus comprising a complete loss of exon 2 to exon 7 (del2-7). We showed that RT-PCR is superior to Southern blot analysis in detection of this type of deletion and can be assigned to 9 of 38 (24%) glioblastomas examined. Expression of a EGF receptor protein was enhanced in most of the tumors with gene amplification. However, 5 of 18 tumors that express a receptor protein in the absence of EGFR gene amplification also showed elevated levels of EGFR gene expression. In addition to the full-length receptor protein, a signal in the 140-kDa range was observed in 17 of 35 glioblastomas (49%). This fragment may correspond to the truncated de12-7 receptor protein or might be due to proteolysis of the full-length receptor protein. PMID- 10029452 TI - Primary undifferentiated small cell carcinoma of the esophagus. AB - We histologically examined undifferentiated small cell carcinoma of the esophagus from 21 patients and used immunohistochemical methods for detection of chromogranin A and p53, bcl-2, and Rb oncoproteins. Nine (43%) of the 21 carcinomas consisted solely of undifferentiated cells, but heterogeneous components of in situ or invasive squamous cell carcinoma or mucoepidermoid carcinoma were observed in the other 12 (57%) tumors. Squamous cell carcinoma in situ was observed in the mucosa adjacent to the main tumor in 7 (50%) of the 14 resected esophageal specimens. An admixture of invasive squamous cell carcinoma and undifferentiated carcinoma was observed in 4 (19%) of the 21 tumors, and mucoepidermoid carcinoma was noted in one case. Chromogranin A staining yielded a positive reaction in two (10%) undifferentiated components but was negative in all heterogeneous components. Multiple sites of p53 immunopositivity were seen in the undifferentiated component of 17 (81%) of the 21 tumors, as well as in the in situ or invasive squamous cell carcinoma or mucoepidermoid carcinoma components of 9 (75%) of 12 tumors. Seven (33%) of the 21 tumors showed positive bcl-2 immunoreactivity in the small cell component, but all of the heterogeneous components were negative. Rb protein immunoreactivity was observed in the small cell component of one (5%) case and in 9 (75%) of the 12 heterogeneous components. Six (86%) of the seven in situ squamous cell carcinoma components were positive for Rb protein. Eighteen (86%) of the 21 patients died within 24 months of diagnosis. Two patients (10%) who survived for more than 24 months had received chemotherapy. PMID- 10029454 TI - The expression of TIA-1+ cytolytic-type granules and other cytolytic lymphocyte associated markers in CD30+ anaplastic large cell lymphomas (ALCL): correlation with morphology, immunophenotype, ultrastructure, and clinical features. AB - Anaplastic large cell lymphomas (ALCL) are a heterogeneous group of CD30+ large cell lymphomas; the most characteristic type have a T or null cell phenotype, often express epithelial membrane antigen (EMA) and cytolytic lymphocyte markers, and often possess a nonrandom t(2;5)(p23;q35) chromosomal translocation. We studied 22 (19 T, 1 null, 2 B cell) ALCL, including four primary cutaneous ALCL (PC-ALCL), for the expression of TIA-1, the cytotoxic T lymphocyte (CTL) or natural killer (NK) cell-associated antigens CD4, CD8, betaF1, TCRdelta1, CD56, and CD57, the ALCL-associated antigens p80 and EMA, and the Hodgkin's disease associated marker CD15 to better define the relationship of these markers to histological subtype, primary site, and patient clinical characteristics. TIA-1 expression was seen in 12 of 20 (60%) T or null cell ALCLs with a cytoplasmic, granular distribution. Ultrastructural studies showed cytotoxic-type granules (dense core, multivesicular, and intermediate types) with TIA-1 localized to granules on immunogold labeling. TIA-1 staining strongly correlated with young patient age (< or = 32 years, P < .05) and EMA expression (P < .05). Excluding the four PC-ALCL cases, TIA-1 staining also correlated with p80 expression (P < .05) in all of the T cell cases. Three CD15+ cases were TIA-1-. TIA-1 expression in T or null cell ALCL was seen in all morphological subtypes (2 of 2 small cell variant, 3 of 4 monomorphic variant, and 7 of 14 pleomorphic variant) and primary tumor sites (6 of 14 nodal, 2 of 4 primary cutaneous, 2 of 2 bone, and 2 of 2 soft tissue). TIA-1+ granules were seen in all subsets: 5 of 6 CD4+, 1 of 2 CD8+, 4 of 8 CD56+, and 1 of 2 CD57+ ALCL. Of note, 4 of 10 T or null cell ALCL expressed gammadelta T-cell receptors (TCR), whereas only 1 of 10 T or null cell ALCL was alphabeta TCR+; TCR were not detected in five cases. TIA-1 was expressed by 3 of 4 gammadelta TCR+ ALCL and 1 of 1 alphabeta TCR+ ALCL. These data support a cytotoxic lymphocyte phenotype in most T or null cell ALCL and suggest that some T cell ALCL are derived from cytolytic CD4+ T cells, gammadelta T cells, or NK-like (CD56+ or CD57+) T cells. PMID- 10029455 TI - Multiple oncocytic cysts with tyrosine-crystalloids in the parotid gland. AB - A case of multiple oncocytic cysts with intraluminal tyrosine-rich crystalloids involving the parotid gland is described. The microscopic and ultrastructural findings are presented. PMID- 10029456 TI - Detection of EWS-WT1 fusion mRNA in ascites of a patient with desmoplastic small round cell tumor by RT-PCR. AB - Desmoplastic small round cell tumor (DSRCT) is a rare, aggressive malignancy characterized cytogenetically by a unique translocation of chromosomes 11 and 22 [t(11:22)(p13:ql2)], resulting in fusion of the EWS and WT1 genes. The presence of a unique fusion mRNA in DSRCT allows disease detection and diagnosis by reverse transcription polymerase chain reaction (RT-PCR), as previously described in fixed paraffin-embedded material. In this report, EWS WT1 fusion mRNA was detected in ascites from a patient with DSRCT by RT-PCR. RT-PCR results confirmed the diagnoses of DSRCT and of malignant ascites at the molecular level. RT-PCR assays for specific molecular markers, such as EWS-WT1 fusion mRNA, are potentially powerful methods that can complement routine histological, cytological, and/or immunohistologic assays. PMID- 10029457 TI - Ovarian strumal carcinoid with severe constipation: immunohistochemical and mRNA analyses of peptide YY. AB - Functioning ovarian carcinoid tumors are well known to cause carcinoid syndrome. Recently, strumal and trabecular ovarian carcinoid tumors are reported to cause severe constipation possibly because of tumor-producing peptide YY (PYY). We studied a case of primary ovarian strumal carcinoid who had had severe constipation until the tumor was removed by surgical operation. Immunohistochemically, many tumor cells were strongly positive for PYY. By Northern blot and reverse transcription polymerase chain reaction analyses, PYY mRNA was expressed in a complete form as detected in normal human colon mucosa. From these findings, an ovarian strumal carcinoid is strongly suggested to express complete PYY mRNA and therefore complete PYY protein that results in severe constipation. PMID- 10029458 TI - Parvovirus B19 in fetal hydrops. PMID- 10029459 TI - A trichilemmal carcinoma arising from a proliferating trichilemmal cyst: a response. PMID- 10029460 TI - Glass-ionomer restoratives: a systematic review of a secondary caries treatment effect. AB - It is generally accepted that glass ionomers inhibit secondary caries in vivo, and data from in vitro studies support this effect. The aim of this review was a systematic assessment, from the literature, of clinical evidence for the ability of glass-ionomer restoratives to inhibit secondary caries at the restoration margin. Inclusion and exclusion criteria for selection of the review papers were established prior to commencement of the literature search. Papers which conformed to these criteria, and reported on secondary caries as an outcome, were selected (N = 52). Primary and secondary lists of systematic criteria for use in the assessment of the papers were drawn up. The primary list of 14 criteria was applied to each paper. No paper fulfilled all these criteria, necessitating the use of the secondary measures: (i) a prospective study and (ii) use of an appropriate control. This yielded 28 papers. Tabulation of these papers by occurrence of secondary caries in the glass-ionomer or control groups demonstrated an even distribution between positive and negative outcomes. Valid evidence is considered to be best obtained from randomized, controlled studies of sufficient sample size. No conclusive evidence for or against a treatment effect of inhibition of secondary caries by the glass-ionomer restoratives was obtained from the systematic review. There is a need for appraisal of the methods currently adopted for the clinical evaluation of glass-ionomer restorative materials, and for further development of the methodology to support future systematic reviews. PMID- 10029461 TI - Non-steroidal anti-inflammatory drugs for altering periodontal bone loss. PMID- 10029462 TI - A cross-cultural study of oral health values. AB - The Oral Health Impact Profile (OHIP) is a measure of oral-health-related quality of life developed in Australia but being used increasingly in other populations. In view of the culturally specific nature of peoples' perceptions of health, if we are to make between-population comparisons of oral-health-related quality of life, cross-cultural equivalency of the relevant instruments needs to be verified. A study was therefore undertaken to compare item weights generated by an Australian sample with those generated by a sample of English-speaking Canadians and another of French-speaking Canadians. In addition, within-group comparisons by age were performed. The items and subscales used for the 2 Canadian samples were identical to those developed in Australia, although a formal French translation was used for the French-speaking sample. The method used for the generation of weights was Thurstone's paired-comparison technique, based on the judgments of convenience samples of subjects drawn from each of the three cultural settings. Comparisons were made by means of intra-subscale weight rankings and magnitude. Spearman's rank correlations of r> or =0.6 were found for 16/21 between-group comparisons and for 12/21, 19/21, and 8/21 within-group comparisons made by age in Australia, Ontario, and Quebec, respectively. Comparisons of the magnitudes of weights found that, even when items were ranked similarly, magnitudes could be quite different. These results suggest a reasonable degree of cross-cultural consistency, and hence validity, for the OHIP. PMID- 10029463 TI - Clinical predictability of temporomandibular joint disc displacement. AB - Single items from a typical clinical examination have proved disappointing in their predictive value for temporomandibular joint (TMJ) disc displacement. Only one criterion (the 12 o'clock) is used to diagnose normal disc position. According to this criterion, the posterior band of the disc should be located at the top of the condyle, at the 12 o'clock position. The purpose of this study was to determine which signs and symptoms provide a valid prediction of the condition of the joint based on 4 magnetic resonance imaging (MRI) criteria used to define normal disc position. Sagittal MRI and clinical findings of 137 temporomandibular disorder patients and 23 normal asymptomatic volunteers were used. Three calibrated and blinded observers interpreted the images. Disc position with the mouth closed was evaluated based on 4 MRI criteria: 12, 11, 10 o'clock, and the intermediate zone. Disc position with the mouth open was determined based on one criterion. It was considered normal if the intermediate zone of the disc was located between the condyle and the articular eminence. Joints were classified as normal or as having disc displacement with or without reduction. The sensitivity and specificity of multiple clinical parameters for predicting the condition of the joint established by each of these 4 gold-standard MRI criteria were then determined. Regarding disc displacement with reduction, significant differences were observed in the sensitivity and specificity of all of the clinical parameters used to predict the imaging diagnosis established by each of the criteria. Concerning disc displacement without reduction, no significant differences were observed. The intermediate zone criterion was the criterion that most accurately reflected the condition of the joint. The clinical predictability of the disorder diagnosed according to this criterion suggests that clinical findings alone are too often nonspecific as predictors of the imaging stage of disc displacement. However, we found that combining the most sensitive clinical items to predict the disorder and using an overall criterion for positivity to interpret the results led to an impressive increase in the specificity of the combination, enabling false-positive diagnoses to be excluded. PMID- 10029464 TI - Adjusting estimates of alveolar bone loss for missing observations: developing and testing a general model. AB - The occurrence of missing teeth is a vexing and growing problem in epidemiological studies of dental disease. The number of units of measurement (i.e., teeth/tooth sites) varies between persons and may affect summary statistics in descriptive studies as well as in analytical studies. The purpose of the present study was to develop a general model to adjust summary statistics for missing teeth. The proposed method was applied to alveolar bone loss in current smokers, former smokers, and non-smokers, from 45 to 64 years of age (n = 812). Alveolar bone loss was measured on bitewing radiographs. The adjustment method was based on the assumption that the probability of losing a tooth was an increasing function of alveolar bone loss. The main finding of the present study was that mean alveolar bone loss increased after adjustment for the number of missing teeth. This increase was larger for current smokers than for non-smokers, indicating that the effects of smoking were slightly underestimated when missing sites were ignored. Further research is required for the model to be applied to other data, estimating different types of dental disease with various degrees of disease prevalence and various numbers of missing teeth, and for validating the adjustment method by means of longitudinal data. PMID- 10029465 TI - Prenatal development of the alveolar bone of human deciduous incisors and canines. AB - The formation of the human alveolar process around the incisors and canines is a hitherto unreported aspect of fetal oral development. The question is how, where, and when the alveolar process is formed. The purpose of this study was to elucidate the questions where and when and hence to analyze the pattern of formation of the alveolar bone around developing human deciduous canine and incisor teeth. The study was conducted with material selected from a sample of 61 normal human fetuses, legally or spontaneously aborted. Fertilization ages ranged from 9 to 22 weeks, crown-rump Length from 25 to 205 mm, and foot length from 4 to 34 mm. From this material, 7 maxillae and 10 mandibles were selected for the study according to developmental stages of the canines and incisors and according to the orientation of the histological sections. The skeletal investigation consisted of macroscopic and microscopic analysis of the mandibles and maxillae. The investigations revealed the absence of bone between the central and lateral incisors in the mandibles and maxillae of fetuses below the ages of 21 and 22 weeks, respectively. In three specimens, alveolar bone between the central and lateral incisors was recorded (21, 21, and 22 weeks of fertilization). Absence of bone labial to the canine was recorded in all fetuses investigated. In all other regions, alveolar bone occurred as a regular finding. The present study has shown that alveolar bone formation is strictly coordinated with tooth formation. Alveolar bone occurs later in the area labial to the canine and in the region between the central and lateral incisors than it does in other areas associated with the incisor/canine regions. Knowledge of this pattern in the formation of the alveolar process seems to be of importance for a future elucidation of how the alveolar process is initially formed. PMID- 10029466 TI - Temporal and spatial expression of c-jun and jun-B proto-oncogenes in pulp cells involved with reparative dentinogenesis after cavity preparation of rat molars. AB - c-jun and jun-B are nuclear proto-oncogenes induced by growth factors such as bone morphogenetic proteins (BMPs). These gene products enhance the expression of many genes, including osteocalcin and collagen types, indicating that c-jun and jun-B play important roles in the cell differentiation process. It is also known that BMPs affect the differentiation of pulp cells to odontoblast-like cells during reparative dentinogenesis, but little is known about the transcriptional regulation of genes in cells associated with reparative dentinogenesis. In this study, we examined the expression of c-jun and jun-B in pulp cells during reparative dentinogenesis after cavity preparation of rat molars by in situ hybridization. In rat tooth germs, c-jun and jun-B were co-expressed in the odontoblastic lineage. In rat adult molars, c-jun was expressed in the odontoblast layer, but the jun-B expression was absent in all pulp cells. After cavity preparation, we found that c-jun and jun-B were coexpressed in pulp cells underneath cavities. During the early phase of reparative dentinogenesis, levels of c-jun and jun-B greatly increased in pulp cells within and around the reparative dentin matrix formed adjacent to the cavity floor. Fourteen days after cavity preparation, c-jun and jun-B were expressed only in pulp cells lining the irregular surface of the thick reparative dentin. These results suggest that c jun and jun-B may play important roles both in physiological and in reparative dentinogenesis; in particular, the limited distribution of the jun-B expression suggests a specific role of jun-B only in cells involved with the active formation of the dentin matrix during primary and reparative dentinogenesis. PMID- 10029467 TI - Production of matrix-degrading enzymes and inhibition of osteoclast-like cell differentiation by fibroblast-like cells from the periodontal ligament of human primary teeth. AB - Clinically, the most apparent difference between the primary and permanent dentitions is the physiologic loss of the primary tooth by root resorption. Root resorption is associated with loss of integrity of the periodontal ligament (PDL), followed by recruitment of resorptive cells that remove root structure. We therefore cultured primary dentition PDL fibroblasts (PPDL cells) to investigate in vitro their production of matrix metalloproteinases (MMPs) and tissue inhibitors of MMP (TIMPs), and the effects of soluble factors produced by these cells on osteoclast-like cell differentiation. These studies demonstrate that PPDL cells in vitro have a heterogeneous morphology, and they constitutively synthesize 92-kDa gelatinase, 72-kDa gelatinase, and 53/57-kDa procollagenase as well as TIMP-1, -2, and a third inhibitor of matrix metalloproteinase, as determined by substrate gel zymography and immunoblot analysis. Compared with PDL cells from the permanent dentition, PPDL cells generally produced a greater amount of collagenase but similar amounts of the gelatinases and inhibitors. PPDL cells were treated with pro-inflammatory cytokines to determine their effect on the expression of matrix-degrading enzymes and inhibitors. Interleukin-1alpha and tumor necrosis factor-alpha enhanced the constitutive expression of proteinases but not that of inhibitors in PPDL cells. Conditioned media from PPDL cell lines inhibited the differentiation of osteoclast-like cells in mouse bone marrow cultures. These findings indicate that PPDL cells may modulate the cascade of root resorption both by their regulated production of proteinases and inhibitors and by synthesis of unknown soluble factor(s) that may regulate osteoclast development. PMID- 10029468 TI - Construction and characterization of human salivary histatin-5 multimers. AB - Human salivary histatin-5 (Hsn-5), a 24-amino acid polypeptide, is a potent candidacidal molecule. In this study, we have explored the following two hypotheses: More potent Hsn molecules may be achieved by duplication of the functional domain of Hsn-5 (C16, residues 9-24 of Hsn-5), and Hsn may act like other cationic peptides which aggregate and form channels across the target membrane. A PCR-based gene splicing by overlap extension (SOE) method was used to construct the DNA fragments encoding the following fusion molecules: Hsn-5--Hsn 5, Hsn-5--C16, and C16--C16. These constructs were expressed in E. coli, the proteins produced were purified, and their anticandidal activities as well as secondary structures were determined. Contrary to our hypotheses, results showed that none of the multimers possessed increased candidacidal activity. Specifically, C16--C16 and Hsn-5--C16 displayed candidacidal activity comparable with that of Hsn-5, while Hsn-5--Hsn-5 possessed significantly decreased candidacidal activity, yet all molecules retained an alpha-helical structure in a hydrophobic environment. Additionally, the circular dichroism data showed that Hsn-5 in an alpha-helical conformation does not aggregate in a hydrophobic environment, not even at 14- to 18-fold its physiological concentration. Our results suggest that the development of enhanced Hsn-5 molecules may not be achieved by duplication of its functional domain, and that Hsns may not act like other antimicrobial cationic peptides which aggregate and form channels across the target membrane. PMID- 10029469 TI - Regional measurement of resin-dentin bonding as an array. AB - During the development of the microtensile bond-testing method, large variations in bond strengths were noted among serial sections. The reason for these variations is unknown. The purpose of this work was to determine the consistency of resin-dentin bond strengths across the occlusal surface of coronal dentin by dividing composite resin buildups into an array of 1x1 mm beams, the top half consisting of composite resin, and the bottom half consisting of dentin. Extracted human third molars had the occlusal enamel removed as a single section by means of a diamond saw. Resin composite buildups were made after the dentin was bonded with either One-Step or MacBond. After being stored in 37 degrees C water for 1 day, the teeth were vertically sectioned at 1-mm increments into slabs of bonded teeth. Each slab was further subdivided by vertical sections into 1x1x8 mm beams. Each beam was assigned an x-y coordinate and tested for tensile bond strength. Two different clinicians (A and B) performed the same procedures using One-Step in a parallel study. Using One-Step, clinician A obtained a large number of zero bonds in superficial dentin but fewer in deep dentin. This resulted in a very large standard deviation in bond strengths (mean +/- SD of 22+/-20 MPa in superficial dentin and 27+/-14 MPa in deep dentin). Clinician B obtained much higher (p<0.001) and more uniform bond strengths with One-Step (56+/-13 MPa in superficial dentin and 57+/-12 MPa in deep dentin). With MacBond, there were no zero bonds and hence less variation, with a mean of 41+/-13 MPa in superficial dentin and 27+/-12 MPa (x +/- SD) in deep dentin. When pairs of Z100 resin composite cylinders were bonded together with One-Step and then sectioned into an array, there was little variation in regional bond strength (37 +/-1 MPa). Dividing bonded resin composite buildups into an array of 20 to 30 1x1x8 mm beams allows for the evaluation of uniformity of resin-dentin bonds. The method used in this study detected local regional differences in resin-dentin bond strengths. The largest differences were shown to be related to technique rather than to material. The results indicate that resin-dentin bonds may not be as homogenous as was previously thought. PMID- 10029470 TI - Ceramic whisker reinforcement of dental resin composites. AB - Resin composites currently available are not suitable for use as large stress bearing posterior restorations involving cusps due to their tendencies toward excessive fracture and wear. The glass fillers in composites provide only limited reinforcement because of the brittleness and low strength of glass. The aim of the present study was to reinforce dental resins with ceramic single-crystalline whiskers of elongated shapes that possess extremely high strength. A novel method was developed that consisted of fusing silicate glass particles onto the surfaces of individual whiskers for a two-fold benefit: (1) to facilitate silanization regardless of whisker composition; and (2) to enhance whisker retention in the matrix by providing rougher whisker surfaces. Silicon nitride whiskers, with an average diameter of 0.4 microm and length of 5 microm, were coated by the fusion of silica particles 0.04 microm in size to the whisker surface at temperatures ranging from 650 degrees C to 1000 degrees C. The coated whiskers were silanized and manually blended with resins by spatulation. Flexural, fracture toughness, and indentation tests were carried out for evaluation of the properties of the whisker-reinforced composites in comparison with conventional composites. A two fold increase in strength and toughness was achieved in the whisker-reinforced composite, together with a substantially enhanced resistance to contact damage and microcracking. The highest flexural strength (195+/-8 MPa) and fracture toughness (2.1+/-0.3 MPa x m(1/2)) occurred in a composite reinforced with a whisker-silica mixture at whisker:silica mass ratio of 2:1 fused at 800 degrees C. To conclude, the strength, toughness, and contact damage resistance of dental resin composites can be substantially improved by reinforcement with fillers of ceramic whiskers fused with silica glass particles. PMID- 10029471 TI - The influence of antagonist standardization on wear. AB - For differences among materials to be easily detected, low variation in in vitro wear tests is desirable. The working hypothesis of this paper was that antagonists standardized for shape and size and according to materials would show mean values similar to those found in natural, non-standardized cusps, and that standardization would lead to a reduction in mean variation. First, the shapes and sizes of palatal cusps of non-erupted human upper third molars were measured. The cusp cupola was best described by the formula y = 0.001 x2 and was symmetrical around the axis of rotation. Up to 200 microm of the y-axis, this parabola corresponded best to a ball radius of 0.6 mm. Based on this information, standardized antagonists were fabricated from both human enamel and steatite. Wear in the occlusal contact area and the wear of opposing conventional ceramic and fine hybrid composite, respectively, were quantified in a computerized chewing simulator. As a control, natural human enamel cusps were used. Standardization of enamel cusps did not reduce the variation of the resulting wear compared with that of non-standardized enamel antagonists. Furthermore, standardization led to significantly different results both in the antagonists and in the opposing restorative materials. Thus, natural enamel antagonists are preferable for the simulation of wear in the occlusal contact area. PMID- 10029472 TI - Elemental analysis and clinical implications of calcification deposits associated with silicone breast implants. AB - Calcification of the fibrous capsule surrounding silicone breast implants is a well-recognized occurrence that increases with time following implantation. These mineralized deposits potentially confound mammographic breast cancer surveillance already made difficult by the obscuring effects of silicone breast implants. The authors performed elemental analysis of silicone breast implant-associated calcifications to define better their chemical composition as related to mammographic and clinical significance. Electron probe microanalysis and infrared spectroscopy revealed all of the calcification deposits to be calcium complexed with tribasic phosphate. No evidence of calcium oxalate, calcium carbonate, silicone, or talc was observed. Caution must be employed in interpreting mammograms in women with silicone breast implants as well as those who have had their silicone breast implants removed. High-density mammographic calcifications indicative of calcium phosphate associated with a silicone breast implant may represent an accepted consequence of implantation or nearby carcinoma. We recommend baseline mammography on women who have had their silicone breast implants removed to prevent unnecessary fine-needle aspiration or tissue biopsy of retained breast capsule calcifications during subsequent routine surveillance for carcinoma. PMID- 10029473 TI - Reconstruction of the proximal interphalangeal joint collateral ligaments using the Mitek Micro Arc Anchor: an in vitro biomechanical assessment. AB - Proximal interphalangeal joint (PIP) collateral ligament injuries are common and sometimes result in painful, stiff fingers. A number of techniques have been utilized in the past to reconstruct complete collateral ligament injuries. Recently, bone anchor systems have been described that allow collateral ligament reconstruction without the necessity of pull-out wires and other more cumbersome methods to reconstruct these ligaments. The Mitek bone anchor system has been used successfully in a variety of anatomic locations throughout the body to reattach soft tissues to bone. The current study was conducted to evaluate the biomechanical effects of the use of the Mitek Micro Arc Anchor in collateral ligament injuries of the PIP joint. In cadaveric PIP joints, the collateral ligament was isolated and then transsected in its mid substance. The authors compared suturing the ligament alone in standard fashion to repair of the ligament using a bone anchor inserted in the base of the middle phalanx. The joints were stressed to failure, with a lateral load applied at the distal end of the middle phalanx on a materials testing machine. The mean tensile failure loads of the two groups were the following: Mitek anchor, 16.4 +/- 3.7 N; suture repair, 19.3 +/- 7.6 N. The authors found no significant difference in the force required for failure of the repair or in the pattern of failure in the two groups. The Mitek Micro Arc Anchor appears to be adequate biomechanically to reconstruct the collateral ligaments of the finger PIP joint. PMID- 10029474 TI - Full-thickness skin graft from the ulnar aspect of the wrist to cover defects on the hand and digits. AB - Skin defects on the volar surface of the hand and digits are commonly treated with skin grafts. Many donor sites capable of providing adequate skin have already been reported. Ideal conditions for the donor site depend on skin color, texture, durability, and size. The authors describe the use of a new donor site for harvesting skin grafts to repair relatively small skin defects on the hand and digits. They used full-thickness skin grafts from the ulnar aspect of the wrist to reconstruct burn contractures and syndactyly in 20 patients. Their grafts provided an ideal color and texture match, and normal function of the hand and digits was restored. The donor site was closed directly, and the resulting scar was inconspicuous. PMID- 10029475 TI - Serratus anterior-rib composite flap: anatomic studies and clinical application to hand reconstruction. AB - Because of its relative ease of dissection, increased length of the vascular pedicle, and excellent diameter for anastomosis, the serratus anterior-rib composite flap has been used to reconstruct bony and soft-tissue defects in the face and lower extremities. However, no data are available on optimal rib level or harvest location. The authors report the results of the vascular anatomy of this flap in 6 fresh cadavers and 2 clinical patients using this flap to reconstruct a defect in the hand. Arteriograms were performed through the thoracodorsal artery, and microscopic dissections were done at the rib periosteum. The sixth through the ninth ribs showed consistent filling of their respective intercostal vessels. The rib segments near the anterior axillary line had the most abundant communicating vessels between the serratus and the periosteum. In two patients, the serratus-rib composite free flap provided excellent bone and muscle length for reconstructing the first metacarpal defect. PMID- 10029476 TI - The extended deep inferior epigastric flap: a case series. AB - The extended deep inferior epigastric flap is a reliable flap that has been found to be useful in covering difficult wounds in the lower torso, groin, perineum, and thigh regions. The author addresses the indications and outcomes in a series of 7 patients. PMID- 10029477 TI - Submucous cleft palate: a 10-year series. AB - Twenty-nine consecutive patients with submucous cleft palate were treated at the University of Florida during the 10-year period from 1986 to 1996. Twenty-seven patients were available for speech follow-up. The evaluation of these patients and rationale for treatment are discussed. The largest subgroup of patients were treated with the Furlow Z-plasty palatoplasty, which yielded a successful outcome in 15 of 18 patients, or 83%. The overall success rate was 96%. The Furlow Z plasty palatoplasty was noted to have a very high rate of success for patients with velopharyngeal gaps of 8 mm or less, and less likelihood of success when the velopharyngeal gap exceeded 8 mm. PMID- 10029478 TI - Augmentation of the nasal floor with Surgicel in primary lip repair: a prospective study showing no efficacy. AB - The symmetry of the alar base and the nasal floor is very important in achieving a satisfactory result in primary lip and nasal reconstruction during cleft lip repair. The skeletal base of the nasal pyramid is usually hypoplastic even in incomplete clefts. A periosteal pocket filled with Surgicel can facilitate blood clot formation and can theoretically stimulate bone formation, thereby improving the asymmetry of the bone base. To test this hypothesis, a prospective study was performed in 64 primary lip repairs by comparing the effect of subperiosteal nasal floor augmentation with Surgicel. From February 1989 to June 1993, 64 patients with incomplete cleft lips (excluding occult cleft lip and complete clefts with Simonart's band) were operated by the same surgeon. The patients were divided randomly into two groups. One group had subperiosteal nasal floor augmentation with Surgicel and the other group did not. The lip repair was a rotation-advancement cheiloplasty with primary closed rhinoplasty of the tip and ala. In the first group, a subperiosteal pocket was created under the cleft alar base and the nasal floor. The pocket was filled with Surgicel up the point where the level of the alar base and the nasal floor was symmetrical with the noncleft side. The control group underwent a similar procedure, less the creation of the subperiosteal pocket and the use of Surgicel. All patients were followed for at least 3 years and their photographs were used to compare and analyze the results of their nasal correction. Critical attention was paid to the symmetry of their nasal floor and alar base. The results were evaluated by at least two plastic surgeons for consistency. The data indicate that the control group showed a higher number of subjects with asymmetry (10 of 32) compared with the study group (8 of 32). However, there was no statistical significance to the findings. Two patients in the study group who received Surgicel developed hypertrophic lip scars. This study, although unable to determine statistically the contributory affect of Surgicel in primary nasal reconstruction, does show a possible benefit from the use of osteogenic materials in the primary management of the deficient nasal floor. Hypertrophic scars developed by 2 patients in the study group may point to a possible soft-tissue reaction to the use of Surgicel in primary lip and nasal repair. PMID- 10029479 TI - Pierre Robin syndrome: mandibular growth during the first year of life. AB - Micrognathia and glossoptosis may cause severe respiratory and feeding difficulties in newborns with Pierre Robin syndrome. The growth of the mandible is alleged to more or less "catch up" during the first year of life. We could not objectify such a catch-up growth using the noninvasive and harmless measurement of the jaw index. The jaw index is defined as alveolar overjet x maxillary arch/mandibular arch. The alveolar overjet is the frontodorsal distance between the most anterior points of the upper and lower alveolar arches, whereas the maxillary arch is measured from the left tragus to the right tragus via the subnasal point, and the mandibular arch is measured from the left to the right tragus via the pogonion point. The growth of the mandible in 7 Pierre Robin patients was found to be proportionately similar to that observed in healthy control subjects age 0 months (N = 100), 6 months (N = 42), and 1 year (N = 32). PMID- 10029480 TI - The effect of onlay Medpor implants on mandibular growth in young rabbits: an experimental study. AB - Medpor implants were placed on the periosteum of the mandible in infant rabbits to study their effects on growth. Three months later radiological and histopathological studies were performed in situ and after removal of the mandible. The authors demonstrate that implants did not affect normal development of the mandible; however, there was a decrease in bone thickness and a mononuclear cell reaction was caused where the implant came in contact with the bone. PMID- 10029481 TI - Prospective comparison of axial computed tomography and standard and panoramic radiographs in the diagnosis of mandibular fractures. AB - Objective data comparing sensitivity and accuracy between traditional and computed imaging techniques used for diagnosing mandibular fractures is sparse. To address the paucity of information the authors studied prospectively 33 mandibular fractures in 21 consecutive patients with standard mandibular series, panoramic tomography, axial computed tomography (CT), and coronal CT. Differences in diagnostic accuracy and sensitivity as compiled by four blinded reviewers were calculated. Although overall sensitivities of mandibular fracture detection were not statistically significant between the imaging studies, a distinction between the four methods did exist. Coronal CT was the most accurate imaging method, followed by mandibular series, panoramic topography, and axial CT. Excluding technically inadequate studies, panoramic tomography was 100% accurate and sensitive. Diagnostic accuracy and sensitivity did not correlate measurably with reviewers' impressions of the quality of a particular exam. Axial CT detected significantly fewer angle fractures than standard radiographs (60% vs. 98%, p = 0.006) and coronal CT (60% vs. 100%, p = 0.008). False-positives were unusual except for plain mandibular radiographs. The clear definition of both coronal and axial CT scans made their analysis simpler than the plain radiographs. Lack of fracture displacement was the single most important factor in missed fractures with all modalities. Despite reviewer concerns about the quality of the plain mandibular series, the high accuracy and sensitivity of this imaging technique and applicability in all patients, coupled with its low cost, make it an excellent screening exam for all patients with suspected mandibular fractures. In clinically stable and cooperative patients with mandibular trauma, panoramic radiography and coronal CT are recommended to confirm clinical suspicions when the mandibular series is equivocal. To supplement the mandibular series in the uncooperative or multisystem trauma patient, axial CT scans have not been beneficial. These diagnostic modalities do not obviate the need for a careful physical exam. PMID- 10029482 TI - Salvage of the lower leg using a reversed long free fibular flap. AB - The advantages of end-to-side anastomoses have been well documented in microvascular surgery. The vessels of the fibular flap do not usually permit end to-side anastomosis to recipient vessels in the proximal part of the lower leg because the pedicle length of the free fibular flap is usually too short. Therefore, vein grafts are used to elongate the vessels. If a harvested long free fibular flap that is used to bridge a massive defect of the tibia is reversed and placed into the medullary cavity of the tibia, the flap vessels can be anastomosed, using the end-to-side technique, to the recipient vessels without vein grafts in the distal part of the lower leg. Thus, the flap artery (the peroneal artery) fills in a retrograde fashion. The patient reported was reconstructed with a reversed long free fibular flap. The postoperative period was uneventful. The patient can stand and walk with a protective shoe 2 years postoperatively. PMID- 10029483 TI - Omental transfer to the brain: an experimental study in hydrocephalic rabbits. AB - Hydrocephalus is a common and potentially lethal condition in children that results from an imbalance between absorption and production of cerebral spinal fluid (CSF). Silastic shunts are inserted to drain excess CSF, but they are prone to a number of problems, and at times may be unreliable and ineffective. This study examines the physiological basis of a pedicled omental transfer to the brain as a functional conduit for CSF in an experimentally induced hydrocephalic rabbit model. The ability of the omentum to transport CSF from the subarachnoid space was tested using radioactive tracer substances: radio-iodinated serum albumin (125I-RISA), chromium 51-ethylenediaminetetraacetate (51Cr-EDTA), and technetium 99m (99mTc) glucoheptonate. Immediate ability of exteriorized omentum to transport artificial CSF, as well as transposed omental transport of subarachnoid CSF at 1 month, were examined. Nuclear scan measurements were correlated with clinical observation and a double-blind histological analysis with trichrome and hematoxylin-eosin stain. Exteriorized omentum rapidly absorbed 99mTc glucoheptonate-labeled artificial CSF, with a rapid appearance in the systemic circulatory and urinary systems. Transposed omentum to the brain in animals with artificially created hydrocephalus showed evidence of CSF-labeled 125I-RISA and 51Cr-EDTA absorption in those animals demonstrating histologically viable omentum. PMID- 10029484 TI - Dexamethasone increases survival and attenuates induction of inducible nitric oxide synthase in experimental skin flaps. AB - The molecule nitric oxide synthesized by the enzyme nitric oxide synthase (NOS) has been shown to be of major physiological and pathophysiological importance in the body. During ischemia and reperfusion, induction of free ionic calcium (Ca2+) independent inducible NOS (iNOS) is thought to result in an overproduction of NO, leading to tissue damage. The glucocorticoid dexamethasone is known to inhibit the induction of iNOS, and the aim of the current study was to determine the effect of dexamethasone on viability and NOS activity in an ischemic flap model on the dorsum of the rat. Vehicle (N = 20) or dexamethasone (N = 20) was administered 3 hours prior to operation. The surviving area was measured and the flaps were removed after 24 hours for 10 rats in each group and after 48 hours for the remaining 10 rats in each group. Treatment with dexamethasone resulted in an improved flap viability at both 24 hours (p < 0.001) and 48 hours (p < 0.01), and a reduced induction of Ca2+-independent NOS activity in the proximal part of the flaps at 24 hours (p < 0.001). In the current study the authors show that dexamethasone attenuates the induction of Ca2+-independent NOS and increases survival in experimental skin flaps. PMID- 10029485 TI - A new flap model in the rat: the pectoral skin flap. AB - The purpose of this study was to describe a new axial-pattern experimental flap model in the rat. Wistar rats weighing 200 to 250 g were used in the experiment. In 15 rats, the superficial anatomy of the ventral thoracic region was studied by anatomic dissection, dye injection, and microangiography, using 5 rats in each group. The anatomic studies revealed that the ventral thoracic skin derives its principal blood supply from the long thoracic artery--a branch of the common thoracic artery. Based on these anatomic studies, the pectoral skin flap model, pedicled on the long thoracic vessels, was created in the rat. The flap is bounded medially by the midsternal line, laterally by the anterior axillary line, and superiorly and inferiorly by transverse lines passing at the level of the suprasternal notch and the xyphoid process respectively. In 5 animals, bilateral flaps (N = 10) were raised and replaced in situ. In 15 animals, oversized flaps were created by extending the flap for both a greater width (N = 10) and length (N = 10). Although all the flaps limited to the cutaneous territory as described were found to survive totally, oversized flaps underwent partial necrosis distally. The authors conclude that the pectoral flap is a simple and reliable skin flap model for future biological and pharmacological study because it is very easy to raise, has a consistent vascular pedicle, and has well-defined borders with consistent landmarks. PMID- 10029486 TI - Striae distensae of augmented breasts after oral contraceptive therapy. AB - A case of striae distensae (SD) of bilateral augmented breasts following oral contraceptive therapy is presented. Striae maturation and the prevention of additional skin marks was achieved with immediate cessation of oral contraceptive pill therapy and long-term daily topical application of tretinoin cream. It is suggested that patients who are candidates for breast augmentation surgery should be informed of the possible risk of developing SD if they are taking or planning to take the contraceptive pill. PMID- 10029487 TI - Long-term follow-up of a sponge breast implant and review of the literature. AB - A case of a woman who underwent removal of a breast implant consistent with a polyvinyl sponge contained within a polyethylene bag is described. The use of the polyvinyl alcohol sponge as a breast implant virtually ceased in the mid 1960s with the introduction of silicone gel breast prostheses. However, it is still possible that the plastic surgeon may encounter a patient with one of these sponge implants in place. Thus, it is important for the plastic surgeon to be aware of their existence, natural history, and potential late complications. In addition, since the removal of silicone from general use for augmentation mammaplasty, there have been intense efforts to identify new filler materials for use in breast implants. Polyvinyl alcohol has been considered a possible material. There is a paucity of information in the recent literature pertaining to the characteristics and use of polyvinyl alcohol sponge implants. Therefore, this report describes a patient treated 38 years following placement of this type of implant and reviews the literature. PMID- 10029488 TI - Cartilaginous metaplasia in the capsule of a Dacron-backed silicone gel breast prosthesis. AB - Capsular metaplastic changes described as "synovial metaplasia" have been reported in association with silicone gel breast prostheses. Initially this finding was thought to be more common with textured implants. Recent studies have shown no relation between implant shell type (textured vs. smooth). The incidence of this metaplasia has been shown to decrease with the age of the implant, suggesting that it is a transitional finding in capsular maturation. The metaplastic cells in the synovial metaplasia may have secretory characteristics, but the exact etiology and function of the metaplasia are not yet fully understood. Experimentally, a similar connective tissue reaction has been induced by repeated injections of air to produce the so-called "air pouch." The current study describes cartilaginous metaplasia in the capsule surrounding a silicone filled, Cronin-type, Dacron-backed breast prosthesis. At 26 years after bilateral breast augmentation, this patient presented with breast pain and firmness. During surgical removal the implants were intact but the capsules were densely hyalinized, irregularly calcified, and on one side there was cartilaginous metaplasia within the connective tissue of the capsule. This had occurred independently of calcification. This was believed to be an unusual tissue response. Review of the English literature failed to identify a comparable case. PMID- 10029489 TI - Repair of a large "coup de sabre" with soft-tissue expansion and artificial bone graft. AB - The authors present a case of a "coup de sabre"--a linear form of scleroderma--in an 18-year-old woman treated by means of an expanded forehead and scalp flap, a hydroxyapatite implant, and an autologous iliac bone graft. Hydroxyapatite was implanted to augment a depressive bony deformity. The nasal deformity was repaired with an expanded forehead flap and an autologous iliac bone graft. This is the first reported case in which a deformity of scleroderma was treated with a combination of an expanded skin flap and a hydroxyapatite implant. PMID- 10029490 TI - Endoscopically assisted removal of unilateral coronoid process hyperplasia. AB - Coronoid process hyperplasia (CPH) is an uncommon disorder characterized by an enlarged coronoid process impinging against the posterior aspect of the zygomatic arch. Young male adults are usually affected, presenting with limited mouth opening, which is typically painless and progressive in nature. The diagnosis of true CPH is established by the findings of (1) uniform coronoid enlargement on radiographic examination and (2) normal bone structure on histopathological examination (i.e., the specimen should be free of any neoplastic growth, such as the previously reported cases of coronoid osteomas, osteochondromas, or exostoses). The treatment is mainly surgical, by means of a coronoidectomy. An intraoral approach is mostly preferred for this procedure to avoid an external scar. However, to avoid the drawbacks of this approach, such as limited exposure and the risk of hematoma and subsequent fibrosis, an extraoral approach may be indicated. This report describes a case of true unilateral CPH in a 17-year-old boy who presented with progressive limited mouth opening in the absence of any pain. Computed tomography (CT) demonstrated a uniformly enlarged right coronoid process. A coronoidectomy was performed with the aid of endoscopic systems, approaching via two short incisions in the temporal scalp. Histopathological examination of the specimen demonstrated essentially a normal bony structure with no evidence of a neoplasm. The authors present the endoscopically assisted technique of coronoid process excision as an alternative method of surgical treatment of CPH and any mass of the coronoid process in general. With this method, the incision is much shorter than a conventional coronal incision and thus morbidity is diminished considerably. PMID- 10029491 TI - Acral dermatofibrosarcoma protuberans with metastases. AB - Dermatofibrosarcoma protuberans (DFSP) is an uncommon cutaneous tumor that occurs rarely on the extremities. This tumor has a particular propensity for local recurrence following seemingly adequate excision. Metastases are rare, and usually follow repeated local recurrences. On rare occasions, fibrosarcomatous change may arise in a DFSP, and appears to affect adversely the prognosis. The adequacy of the initial resection is the most important prognostic factor; however, suggested margins vary between 1.5 and 5 cm. The ideal margin of resection on the foot is unknown. We report a patient with recurrent, acral DFSP with fibrosarcomatous change and pulmonary parenchymal metastases in a 48-year old black male. PMID- 10029492 TI - A new multiangle goniometer. AB - A goniometer that measures simultaneously the angles of the metacarpophalangeal, proximal interphalangeal, and distal interphalangeal joints is presented. This allows faster measurement of these angles, encouraging and simplifying accurate records of patient hand movements. The individual angles can be recorded or traced on a chart, providing a visual record. PMID- 10029493 TI - Re: Sentinel lymph node mapping in melanoma of the ear. PMID- 10029494 TI - Complex volar dislocation of the metacarpophalangeal joint of the thumb. PMID- 10029495 TI - Recurrent dermatofibrosarcoma protuberans with total fibrosarcomatous change. PMID- 10029496 TI - Nuisance nonhealing ulcer of the foot: verruca plantaris. PMID- 10029497 TI - Cost functions for dialysis facilities and the quality of dialysis. PMID- 10029498 TI - Practice patterns, case mix, Medicare payment policy, and dialysis facility costs. AB - OBJECTIVE: To evaluate the effects of case mix, practice patterns, features of the payment system, and facility characteristics on the cost of dialysis. DATA SOURCES/STUDY SETTING: The nationally representative sample of dialysis units in the 1991 U.S. Renal Data System's Case Mix Adequacy (CMA) Study. The CMA data were merged with data from Medicare Cost Reports, HCFA facility surveys, and HCFA's end-stage renal disease patient registry. STUDY DESIGN: We estimated a statistical cost function to examine the determinants of costs at the dialysis unit level. PRINCIPAL FINDINGS: The relationship between case mix and costs was generally weak. However, dialysis practices (type of dialysis membrane, membrane reuse policy, and treatment duration) did have a significant effect on costs. Further, facilities whose payment was constrained by HCFA's ceiling on the adjustment for area wage rates incurred higher costs than unconstrained facilities. The costs of hospital-based units were considerably higher than those of freestanding units. Among chain units, only members of one of the largest national chains exhibited significant cost savings relative to independent facilities. CONCLUSIONS: Little evidence showed that adjusting dialysis payment to account for differences in case mix across facilities would be necessary to ensure access to care for high-cost patients or to reimburse facilities equitably for their costs. However, current efforts to increase dose of dialysis may require higher payments. Longer treatments appear to be the most economical method of increasing the dose of dialysis. Switching to more expensive types of dialysis membranes was a more costly means of increasing dose and hence must be justified by benefits beyond those of higher dose. Reusing membranes saved money, but the savings were insufficient to offset the costs associated with using more expensive membranes. Most, but not all, of the higher costs observed in hospital based units appear to reflect overhead cost allocation rather than a difference in real resources devoted to treatment. The economies experienced by the largest chains may provide an explanation for their recent growth in market share. The heterogeneity of results by chain size implies that characterizing units using a simple chain status indicator variable is inadequate. Cost differences by facility type and the effects of the ongoing growth of large chains are worthy of continued monitoring to inform both payment policy and antitrust enforcement. PMID- 10029499 TI - Can restrictions on reimbursement for anti-ulcer drugs decrease Medicaid pharmacy costs without increasing hospitalizations? AB - OBJECTIVE: To examine the impact of a policy restricting reimbursement for Medicaid anti-ulcer drugs on anti-ulcer drug use and peptic-related hospitalizations. DATA SOURCES/STUDY SETTING: In addition to U.S. Census Bureau data, all of the following from Florida: Medicaid anti-ulcer drug claims data, 1989-1993; Medicaid eligibility data, 1989-1993; and acute care nonfederal hospital discharge abstract data (Medicaid and non-Medicaid), 1989-1993. STUDY DESIGN: In this observational study, a Poisson multiple regression model was used to compare changes, after policy implementation, in Medicaid reimbursement for prescription anti-ulcer drugs as well as hospitalization rates between pre- and post-implementation periods in Medicaid versus non-Medicaid patients hospitalized with peptic ulcer disease. PRINCIPAL FINDINGS: Following policy implementation, the rate of Medicaid reimbursement for anti-ulcer drugs decreased 33 percent (p < .001). No associated increase occurred in the rate of Medicaid peptic-related hospitalizations. CONCLUSIONS: Florida's policy restricting Medicaid reimbursement for anti-ulcer drugs was associated with a substantial reduction in outpatient anti-ulcer drug utilization without any significant increase in the rate of hospitalization for peptic-related conditions. PMID- 10029501 TI - Making Medicaid managed care research relevant. AB - OBJECTIVE: To help researchers better understand Medicaid managed care and the kinds of research studies that will be both feasible and of value to policymakers and program staff. The article builds on our experience researching Medicaid managed care to provide insight for researchers who want to be policy relevant. PRINCIPAL FINDINGS: We draw four lessons from our work on Medicaid managed care in seven states. First, these are complex programs that differ substantially across states. Second, each program faces common challenges and issues. The need to address common design elements involving program eligibility, managed care and provider contracting, beneficiary enrollment, education, marketing, and administration and oversight provides a vehicle that researchers can use to help understand states and to provide them with relevant insight. Third, well-designed case studies can provide invaluable descriptive insights. Such case studies suggest that providing effective descriptions of state programs and experience, monitoring information on program performance and tradeoffs, and insight on implementation and design are all valuable products of such studies that have considerable potential to be converted into policy-actionable advice. And fourth, some questions demand impact studies but the structure of Medicaid managed care poses major barriers to such studies. CONCLUSIONS: Many challenges confront researchers seeking to develop policy-relevant research on managed care. Researchers need to confront these challenges in turn by developing second-best approaches that will provide timely insight into important questions in a relatively defensible and rigorous way in the face of many constraints. If researchers do not, others will, and researchers may find their contributions limited in important areas for policy debate. PMID- 10029500 TI - Incidence and duration of hospitalizations among persons with AIDS: an event history approach. AB - OBJECTIVE: To analyze hospitalization patterns of persons with AIDS (PWAs) in a multi-state/multi-episode continuous time duration framework. DATA SOURCES: PWAs on Medicaid identified through a match between the state's AIDS Registry and Medicaid eligibility files; hospital admission and discharge dates identified through Medicaid claims. STUDY DESIGN: Using a Weibull event history framework, we model the hazard of transition between hospitalized and community spells, incorporating the competing risk of death in each of these states. Simulations are used to translate these parameters into readily interpretable estimates of length of stay, the probability that a hospitalization will end in death, and the probability that a nonhospitalized person will be hospitalized within 90 days. PRINCIPAL FINDINGS: In multivariate analyses, participation in a Medicaid waiver program offering case management and home care was associated with hospital stays 1.3 days shorter than for nonparticipants. African American race and Hispanic ethnicity were associated with hospital stays 1.2 days and 1.0 day longer than for non-Hispanic whites; African Americans also experienced more frequent hospital admissions. Residents of the high-HIV-prevalence area of the state had more frequent admissions and stays two days longer than those residing elsewhere in the state. Older PWAs experienced less frequent hospital admissions but longer stays, with hospitalizations of 55-year-olds lasting 8.25 days longer than those of 25-year-olds. CONCLUSIONS: Much socioeconomic and geographic variability exists both in the incidence and in the duration of hospitalization among persons with AIDS in New Jersey. Event history analysis provides a useful statistical framework for analysis of these variations, deals appropriately with data in which duration of observation varies from individual to individual, and permits the competing risk of death to be incorporated into the model. Transition models of this type have broad applicability in modeling the risk and duration of hospitalization in chronic illnesses. PMID- 10029502 TI - Excess capacity: markets regulation, and values. AB - OBJECTIVE: To examine the conceptual bases for the conflicting views of excess capacity in healthcare markets and their application in the context of today's turbulent environment. STUDY SETTING: The policy and research literature of the past three decades. STUDY DESIGN: The theoretical perspectives of alternative economic schools of thought are used to support different policy positions with regard to excess capacity. Changes in these policy positions over time are linked to changes in the economic and political environment of the period. The social values implied by this history are articulated. DATA COLLECTION: Standard library search procedures are used to identify relevant literature. PRINCIPAL FINDINGS: Alternative policy views of excess capacity in healthcare markets rely on differing theoretical foundations. Changes in the context in which policy decisions are made over time affect the dominant theoretical framework and, therefore, the dominant policy view of excess capacity. CONCLUSIONS: In the 1990s, multiple perspectives of optimal capacity still exist. However, our evolving history suggests a set of persistent values that should guide future policy in this area. PMID- 10029503 TI - Commentary: excess capacity, a commentary on markets, regulation, and values. PMID- 10029504 TI - A taxonomy of health networks and systems: bringing order out of chaos. AB - OBJECTIVE: To use existing theory and data for empirical development of a taxonomy that identifies clusters of organizations sharing common strategic/structural features. DATA SOURCES: Data from the 1994 and 1995 American Hospital Association Annual Surveys, which provide extensive data on hospital involvement in hospital-led health networks and systems. STUDY DESIGN: Theories of organization behavior and industrial organization economics were used to identify three strategic/structural dimensions: differentiation, which refers to the number of different products/services along a healthcare continuum; integration, which refers to mechanisms used to achieve unity of effort across organizational components; and centralization, which relates to the extent to which activities take place at centralized versus dispersed locations. These dimensions were applied to three components of the health service/product continuum: hospital services, physician arrangements, and provider-based insurance activities. DATA EXTRACTION METHODS: We identified 295 health systems and 274 health networks across the United States in 1994, and 297 health systems and 306 health networks in 1995 using AHA data. Empirical measures aggregated individual hospital data to the health network and system level. PRINCIPAL FINDINGS: We identified a reliable, internally valid, and stable four-cluster solution for health networks and a five-cluster solution for health systems. We found that differentiation and centralization were particularly important in distinguishing unique clusters of organizations. High differentiation typically occurred with low centralization, which suggests that a broader scope of activity is more difficult to centrally coordinate. Integration was also important, but we found that health networks and systems typically engaged in both ownership-based and contractual-based integration or they were not integrated at all. CONCLUSIONS: Overall, we were able to classify approximately 70 percent of hospital-led health networks and 90 percent of hospital-led health systems into well-defined organizational clusters. Given the widespread perception that organizational change in healthcare has been chaotic, our research suggests that important and meaningful similarities exist across many evolving organizations. The resulting taxonomy provides a new lexicon for researchers, policymakers, and healthcare executives for characterizing key strategic and structural features of evolving organizations. The taxonomy also provides a framework for future inquiry about the relationships between organizational strategy, structure, and performance, and for assessing policy issues, such as Medicare Provider Sponsored Organizations, antitrust, and insurance regulation. PMID- 10029505 TI - Commentary: on "a taxonomy of healthcare networks and systems: bringing order out of chaos". PMID- 10029506 TI - Risk-adjusted capitation based on the Diagnostic Cost Group Model: an empirical evaluation with health survey information. AB - OBJECTIVE: To evaluate the predictive accuracy of the Diagnostic Cost Group (DCG) model using health survey information. DATA SOURCES/STUDY SETTING: Longitudinal data collected for a sample of members of a Dutch sickness fund. In the Netherlands the sickness funds provide compulsory health insurance coverage for the 60 percent of the population in the lowest income brackets. STUDY DESIGN: A demographic model and DCG capitation models are estimated by means of ordinary least squares, with an individual's annual healthcare expenditures in 1994 as the dependent variable. For subgroups based on health survey information, costs predicted by the models are compared with actual costs. Using stepwise regression procedures a subset of relevant survey variables that could improve the predictive accuracy of the three-year DCG model was identified. Capitation models were extended with these variables. DATA COLLECTION/EXTRACTION METHODS: For the empirical analysis, panel data of sickness fund members were used that contained demographic information, annual healthcare expenditures, and diagnostic information from hospitalizations for each member. In 1993, a mailed health survey was conducted among a random sample of 15,000 persons in the panel data set, with a 70 percent response rate. PRINCIPAL FINDINGS: The predictive accuracy of the demographic model improves when it is extended with diagnostic information from prior hospitalizations (DCGs). A subset of survey variables further improves the predictive accuracy of the DCG capitation models. The predictable profits and losses based on survey information for the DCG models are smaller than for the demographic model. Most persons with predictable losses based on health survey information were not hospitalized in the preceding year. CONCLUSIONS: The use of diagnostic information from prior hospitalizations is a promising option for improving the demographic capitation payment formula. This study suggests that diagnostic information from outpatient utilization is complementary to DCGs in predicting future costs. PMID- 10029507 TI - Commentary: improving risk-adjustment models for capitation payment and global budgeting. PMID- 10029508 TI - Organizational and environmental factors associated with nursing home participation in managed care. AB - OBJECTIVE: To develop and test a model, based on resource dependence theory, that identifies the organizational and environmental characteristics associated with nursing home participation in managed care. DATA SOURCES AND STUDY SETTING: Data for statistical analysis derived from a survey of Directors of Nursing in a sample of nursing homes in eight states (n = 308). These data were merged with data from the On-line Survey Certification and Reporting System, the Medicare Managed Care State/County Data File, and the 1995 Area Resource File. STUDY DESIGN: Since the dependent variable is dichotomous, the logistic procedure was used to fit the regression. The analysis was weighted using SUDAAN. FINDINGS: Participation in a provider network, higher proportions of resident care covered by Medicare, providing IV therapy, greater availability of RNs and physical therapists, and Medicare HMO market penetration are associated with a greater likelihood of having a managed care contract. CONCLUSION: As more Medicare recipients enroll in HMOs, nursing home involvement in managed care is likely to increase. Interorganizational linkages enhance the likelihood of managed care participation. Nursing homes interested in managed care should consider upgrading staffing and providing at least some subacute services. PMID- 10029509 TI - Guest editorial: health surveillance in Canada. PMID- 10029510 TI - Perspectives on epidemiologic surveillance in the 21st century. AB - This paper describes the importance of epidemiologic surveillance as a systematic, ongoing and population-based system for early warning and program development in the 21st century. Such a system routinely collects data on three classes of indicators (health outcomes, risk factors and intervention strategies) to set up both an early warning system (to identify associations and make predictions on health outcomes) and a program development system (to assess the need for intervention strategies, to plan and implement such strategies and to assess their effectiveness). A comprehensive surveillance system must be systematic (evidence-based selection of indicators, not hypothesis-driven), ongoing (continuous data collection, including repeated surveys) and population based (whole population, or representative samples of the population). Such a system need not be developed from scratch, but can be based on linkage of existing databases and collection of additional information for identified data gaps. The initial steps for selecting indicators and creating a prototype framework for a comprehensive surveillance system are proposed to stimulate further discussion. It is suggested that surveillance systems should be more widely used in public health. PMID- 10029511 TI - Suicide in the Northwest Territories: A descriptive review. AB - The incidence of suicide among the populations of the Northwest Territories (NWT) is notably higher than in the rest of Canada. A comparison of three five-year time periods between 1982 and 1996 reveals an increasing incidence rate, particularly for Nunavat, the eastern half of the NWT, occupied primarily by Inuit people. This is largely attributable to a rising use of hanging as opposed to other methods of suicide. A coroner's record review of suicides occurring between 1994 and 1996 demonstrates the preponderance of young males and of Inuit among those who committed suicide, the majority of whom committed suicide in familiar settings, usually their own homes, and often while others were on the premises. Thirty-six percent of those who committed suicide had experienced a recent family or relationship breakup, and twenty-one percent were facing criminal proceedings. Understanding the impact of these and other reported circumstances on the imminent risk of suicide requires further investigation. PMID- 10029512 TI - Monograph series on aging-related diseases: XI. Glaucoma. AB - In Canada, glaucoma is the second leading cause of blindness in people aged 50 and over, with primary open-angle glaucoma (POAG) accounting for 90% of all cases. Prevalence of POAG increases with age, and the condition is found more commonly among blacks than whites. Elevated intraocular pressure is an important risk factor for the disease; however, its positive predictive value for the presence of disease is poor. Prevalence of primary angle-closure glaucoma also increases with age, occurs more frequently among the Inuit and Asians, and has been reported to be more common among women. There are various diagnostic methods used to determine the presence or absence of glaucoma, but none can effectively identify the disease in its early stages unless routine screening is conducted. Current treatment of glaucoma is aimed at lowering intraocular pressure, which usually, but not always, stops disease progression. PMID- 10029513 TI - Critical appraisal of the health research literature: prevalence or incidence of a health problem. AB - This article identifies and discusses criteria that can be used by health professionals to critically appraise research articles that estimate the prevalence or incidence of a disease or health problem. These guidelines will help determine the validity and usefulness of such community assessment studies. The criteria relate to the validity of the study methods (design, sampling frame, sample size, outcome measures, measurement and response rate), interpretation of the results and applicability of the findings. The research question "What is the prevalence of dementia in Canada?" is used as an example for this paper. PMID- 10029514 TI - Surveillance of drug overdose deaths using medical examiner data. AB - This paper describes the epidemiology of drug overdose deaths investigated by the medical examiner in one of the cities participating in the Canadian Community Epidemiology Network on Drug Use and assesses the quality of the information obtained from medical examiner charts with respect to drug overdose deaths, for surveillance purposes. Information was abstracted from medical examiner charts of all deaths involving drugs from 1993 to 1995 in Halifax, Nova Scotia. During these three years, 636 deaths from all causes were investigated by the medical examiner. Of the 42 overdose deaths, 47.6% were suicides. Ethanol was detected in 47.8% of overdose deaths, and 61.9% of all overdose deaths involved psychotropic medications. Two deaths were attributed to an illicit drug (cocaine). An independent review performed by a toxicologist and a medical examiner revealed poor overall agreement concerning overdose as a cause of death (Kappa coefficient: 0.27). In conclusion, the average crude mortality rate due to drug overdose in Halifax from 1993 to 1995 was 4.1 deaths per 100,000 population. Potential threats to the quality of data were the lack of standardization concerning toxicological testing and the definition of drug overdose. PMID- 10029515 TI - Multiple types of association of photosystem II and its light-harvesting antenna in partially solubilized photosystem II membranes. AB - Photosystem II is a multisubunit pigment-protein complex embedded in the thylakoid membranes of chloroplasts. It utilizes light for photochemical energy conversion, and is heavily involved in the regulation of the energy flow. We investigated the structural organization of photosystem II and its associated light-harvesting antenna by electron microscopy, multivariate statistical analysis, and classification procedures on partially solubilized photosystem II membranes from spinach. Observation by electron microscopy shortly after a mild disruption of freshly prepared membranes with the detergent n-dodecyl-alpha,D maltoside revealed the presence of several large supramolecular complexes. In addition to the previously reported supercomplexes [Boekema, E. J., van Roon, H., and Dekker, J. P. (1998) FEBS Lett. 424, 95-99], we observed complexes with the major trimeric chlorophyll a/b protein (LHCII) in a third, L-type of binding position (C2S2M0-2L1-2), and two different types of megacomplexes, both identified as dimeric associations of supercomplexes with LHCII in two types of binding sites (C4S4M2-4). We conclude that the association of photosystem II and its associated light-harvesting antenna is intrinsically heterogeneous, and that the minor CP26 and CP24 proteins play a crucial role in the supramolecular organization of the complete photosystem. We suggest that different types of organization form the structural basis for photosystem II to specifically react to changing light and stress conditions, by providing different routes of excitation energy transfer. PMID- 10029516 TI - Multiple activation steps of the N-formyl peptide receptor. AB - The human N-formyl peptide receptor (FPR) is representative of a growing family of G protein-coupled receptors (GPCR) that respond to chemokines and chemoattractants. Despite the importance of this receptor class to immune function, relatively little is known about the molecular mechanisms involved in their activation. To reveal steps required for the activation of GPCR receptors, we utilized mutants of the FPR which have previously been shown to be incapable of binding and activating G proteins. For this study, the FPR mutants were expressed in human myeloid U937 cells and characterized for functions in addition to G protein coupling, such as receptor phosphorylation and ligand-induced receptor internalization. The results demonstrated that one of the mutants, R123G, though being unable to activate G protein, was capable of undergoing ligand-induced phosphorylation as well as internalization. Receptor internalization was monitored by following the fate of the ligand as well as by directly monitoring the fate of the receptor. The results with the R123G mutant were in contrast to those obtained for mutants D71A and R309G/E310A/R311G which, though being expressed at the cell surface and binding ligand, were incapable of being phosphorylated or internalized upon agonist stimulation. These results suggest that following ligand binding at least two "steps" are required for full activation of the wild-type FPR. That these observations may be of more general importance in GPCR-mediated signaling is suggested by the highly conserved nature of the mutants studied: D71, R123, and the site represented by amino acids 309 311 are very highly conserved throughout the entire superfamily of G protein coupled receptors. Models of receptor activation based on the observed results are discussed. PMID- 10029517 TI - Structural elements and limited proteolysis of CD39 influence ATP diphosphohydrolase activity. AB - CD39, the mammalian ATP diphosphohydrolase (ATPDase), is thought to contain two transmembrane domains and five "apyrase conserved regions" (ACR) within a large extracellular region. To study the structure of this ectoenzyme, human CD39 was modified by directed mutations within these ACRs or by sequential deletions at both termini. ATPDase activity was well preserved with FLAG tagging, followed by the removal of either of the demonstrated C- or N-transmembrane regions. However, deletions within ACR-1 (aa 54-61) or -4 (aa 212-220), as well as truncation mutants that included ACR-1, -4, or -5 (aa 447-454), resulted in substantive loss of biochemical activity. Intact ACR-1, -4, and -5 within CD39 are therefore required for maintenance of biochemical activity. Native and mutant forms of CD39 lacking TMR were observed to undergo multimerization, associated with the formation of intermolecular disulfide bonds. Limited tryptic cleavage of intact CD39 resulted in two noncovalently membrane-associated fragments (56 and 27 kDa) that substantially augmented ATPDase activity. Glycosylation variation accounted for minor heterogeneity in native and mutant forms of CD39 but did not influence ATPDase function. Enzymatic activity of ATPDase may be influenced by certain posttranslational modifications that are relevant to vascular inflammation. PMID- 10029518 TI - Kinetic characterization of CheY phosphorylation reactions: comparison of P-CheA and small-molecule phosphodonors. AB - In the chemotaxis system of Escherichia coli, phosphorylation of the CheY protein plays an important role in regulating the swimming pattern of the cell. In vitro, CheY can be phosphorylated either by phosphotransfer from phospho-CheA or by acquiring a phosphoryl group from any of a variety of small, high-energy phosphodonor molecules such as acetyl phosphate. Previous work explored the rapid kinetics of CheY phosphorylation by CheA. Here we extend that work and examine the kinetics of CheY phosphorylation by several small-molecule phosphodonors, including acetyl phosphate, benzoyl phosphate, carbamoyl phosphate, 2 methoxybenzoyl phosphate, and phosphoramidate. Our results indicate that these phosphodonors bind to CheY with relatively low affinity (Ks values ranging from 10 to 600 mM) and that the rate constant (kphos) for phosphotransfer at saturating phosphodonor concentrations is relatively slow (values ranging from 0.05 to 0.5 s-1). By contrast, under identical conditions, phosphorylation of CheY by phospho-CheA occurs much more rapidly (kphos approximately 800 s-1) and reflects CheY binding to phospho-CheA considerably more tightly (Ks approximately 60 microM) than it does to the small-molecule phosphodonors. In comparing CheA mediated phosphorylation of CheY to small-molecule-mediated phosphorylation of CheY, the large difference in kphos values suggests that phospho-CheA makes significant contributions to the catalysis of CheY phosphorylation. The effects of pH and ionic strength on CheY phosphorylation kinetics were also investigated. For CheA-->CheY phosphotransfer, increasing ionic strength resulted in increased Ks values while kphos was unaffected. For CheY phosphorylation by small-molecule phosphodonors, increasing ionic strength resulted in decreasing Ks values and increasing kphos values. The significance of these effects is discussed in relation to the catalytic mechanism of CheY phosphorylation by phospho-CheA and small-molecule phosphodonors. PMID- 10029519 TI - Comparative analysis of the efficacy of A1 adenosine receptor activation of Gi/o alpha G proteins following coexpression of receptor and G protein and expression of A1 adenosine receptor-Gi/o alpha fusion proteins. AB - HEK293T cells were transiently transfected to express either the human A1 adenosine receptor together with pertussis toxin-resistant cysteine-to-glycine forms of the alpha subunits of Gi1 (C351G), Gi2 (C352G), and Gi3 (C351G) and wild type Go1alpha or fusion proteins comprising the A1 adenosine receptor and these Gi/o G proteins to compare A1 adenosine receptor agonist-mediated activation of these Gi family G proteins upon coexpression of individual Gi/o G proteins and receptor versus expression as receptor-G protein fusion proteins. Addition of the adenosine receptor agonist 5'-N-ethylcarboxamidoadenosine (NECA) to membranes of pertussis toxin-treated cells resulted in a concentration-dependent stimulation of [35S]GTPgammaS binding with comparable amounts of NECA required to produce half-maximal stimulation following transfection of A1 adenosine receptor and Gi/o G proteins either as fusion proteins or as separate polypeptides. However, the magnitude of agonist-mediated activation of GTPgammaS binding was greatly enhanced by expressing the A1 adenosine receptor and Gi family G proteins from chimaeric open reading frames. This observation was consistent following the study of more than 40 agonists. No preferential activation of any G protein was observed with more than 40 A1 receptor agonists following cotransfection of receptor with G protein or transfection of receptor-G protein fusion proteins. These studies demonstrate the utility of using fusion proteins to study receptor G protein interaction, show that the A1 adenosine receptor couples equally well to the Gi/o G proteins Gi1alpha, G i2alpha, Gi3alpha, and Go1alpha, and demonstrate that for a range of agonists there is no selectivity for activation of any particular A1 adenosine receptor-Gi/o G protein combination. PMID- 10029520 TI - Role of mitogen-activated protein kinases in S-nitrosoglutathione-induced macrophage apoptosis. AB - The inflammatory mediator nitric oxide (NO*) promotes apoptotic cell death based on morphological evidence, accumulation of the tumor suppressor p53, caspase-3 activation, and DNA fragmentation in RAW 264.7 macrophages. Since nitrosothiols may actually be the predominant form of biologically active NO* in vivo, we used S-nitrosoglutathione (GSNO) to study activation of extracellular signal-regulated protein kinases1/2 (ERK1/2), c-Jun N-terminal kinases/stress-activated protein kinases (JNK1/2), and p38 kinases. Moreover, we determined the role of mitogen activated protein kinase signaling in the apoptotic transducing ability of GSNO. ERK1/2 became activated in response to GSNO after 4 h and remained active for the next 20 h. Blocking the ERK1/2 pathway by the mitogen-activated protein kinase kinase inhibitor PD 98059 enhanced GSNO-elicited apoptosis. p38 was activated as well, but inhibition of p38 with SB 203580 left apoptosis unaltered. Activation of JNK1/2 by GSNO showed maximal kinase activities between 2 and 8 h. Attenuating JNK1/2 by antisense-depletion eliminated the pro-apoptotic action of low GSNO concentrations (250 microM), whereas apoptosis proceeded independently of JNK1/2 at higher doses of the NO donor (500 microM). Decreased apoptosis by JNK1/2 depletion prevented p53 accumulation after the addition of GSNO, which positions JNK1/2 upstream of the p53 response at low agonist concentrations. In line, JNK1/2 activation proceeded unaltered in p53-antisense transfected macrophages. However, with higher GSNO concentrations apoptotic transducing pathways, including p53 accumulation, were JNK1/2 unrelated. The regulation of mitogen activated protein kinases by GSNO may help to define cell protective and destructive actions of reactive nitrogen species. PMID- 10029521 TI - Effects of site-directed mutagenesis of protolytic residues in subunit I of Bacillus subtilis aa3-600 quinol oxidase. Role of lysine 304 in proton translocation. AB - Various protolytic residues in subunit I of aa3-600 quinol oxidase of the aerobic Gram-positive Bacillus subtilis were mutagenized to nonpolar residues. Two of the mutations, Y284F and K304L, impaired the bioenergetic function of the microorganism. The Y284F mutation suppressed the electron-transfer activity of quinol oxidase and altered its interaction with CO and H2O2, thus showing destruction of the binuclear domain as observed for the bo3 quinol oxidase of Escherichia coli. The K304L mutation did not alter significantly the redox activity of the oxidase and its interaction with CO and H2O2 but suppressed the proton pumping activity of the enzyme. These results show that the K304 residue, which is invariantly conserved (as K or R) in practically all the sequences of the heme-copper oxidases so far available (around 100), is essential for the proton pumping activity of the oxidase. PMID- 10029522 TI - Kinetic mechanism of Tritrichomonas foetus inosine 5'-monophosphate dehydrogenase. AB - IMP dehydrogenase (IMPDH) catalyzes the oxidation of IMP to XMP with conversion of NAD+ to NADH. This reaction is the rate-limiting step in de novo guanine nucleotide biosynthesis. IMPDH is a target for antitumor, antiviral, and immunosuppressive chemotherapy. We have determined the complete kinetic mechanism for IMPDH from Tritrichomonas foetus using ligand binding, isotope effect, pre steady-state kinetic, and rapid quench kinetic experiments. Both substrates bind to the free enzyme, which suggests a random mechanism. IMP binds to the enzyme in two steps. Two steps are also involved when IMP binds to a mutant IMPDH in which the active site Cys is substituted with a Ser. This observation suggests that this second step may be a conformational change of the enzyme. No Vm isotope effect is observed when [2-2H]IMP is the substrate which indicates that hydride transfer is not rate-limiting. This result is confirmed by the observation of a pre-steady-state burst of NADH production when monitored by absorbance. However, when NADH production was monitored by fluorescence, the rate constant for the exponential phase is 5-10-fold lower than when measured by absorbance. This observation suggests that the fluorescence of enzyme-bound NADH is quenched and that this transient represents NADH release from the enzyme. The time-dependent formation and decay of [14C]E-XMP intermediates was monitored using rapid quench kinetics. These experiments indicate that both NADH release and E-XMP hydrolysis are rate-limiting and suggest that NADH release precedes hydrolysis of E-XMP. PMID- 10029523 TI - Observation of a novel transient ferryl complex with reduced CuB in cytochrome c oxidase. AB - The reaction between mixed-valence (MV) cytochrome c oxidase from beef heart with H2O2 was investigated using the flow-flash technique with a high concentration of H2O2 (1 M) to ensure a fast bimolecular interaction with the enzyme. Under anaerobic conditions the reaction exhibits 3 apparent phases. The first phase (tau congruent with 25 micros) results from the binding of one molecule of H2O2 to reduced heme a3 and the formation of an intermediate which is heme a3 oxoferryl (Fe4+=O2-) with reduced CuB (plus water). During the second phase (tau congruent with 90 micros), the electron transfer from CuB+ to the heme oxoferryl takes place, yielding the oxidized form of cytochrome oxidase (heme a3 Fe3+ and CuB2+, plus hydroxide). During the third phase (tau congruent with 4 ms), an additional molecule of H2O2 binds to the oxidized form of the enzyme and forms compound P, similar to the product observed upon the reaction of the mixed valence (i.e., two-electron reduced) form of the enzyme with dioxygen. Thus, within about 30 ms the reaction of the mixed-valence form of the enzyme with H2O2 yields the same compound P as does the reaction with dioxygen, as indicated by the final absorbance at 436 nm, which is the same in both cases. This experimental approach allows the investigation of the form of cytochrome c oxidase which has the heme a3 oxoferryl intermediate but with reduced CuB. This state of the enzyme cannot be obtained from the reaction with dioxygen and is potentially useful to address questions concerning the role of the redox state in CuB in the proton pumping mechanism. PMID- 10029524 TI - Electrospray ionization mass spectrometric analysis of intact cytochrome P450: identification of tienilic acid adducts to P450 2C9. AB - A general scheme for the purification of baculovirus-expressed cytochrome P450s (P450s) from the crude insect cell pastes has been designed which renders the P450s suitable for analysis by high-performance liquid chromatography (HPLC) electrospray ionization mass spectrometry (ESI-MS). An HPLC/ESI-MS procedure has been developed to analyze small amounts of intact purified P450 (P450s cam-HT, 1A1, 1A2, 2A6, 2B1, 2C9, 2C9 C175R, 3A4, 3A4-HT) and rat NADPH cytochrome P450 reductase (P450 reductase). The experimentally determined and predicted (based on the amino acid sequences) molecular masses (MMs) of the various proteins had identical rank orders. For each individual protein, the difference between the experimentally determined (+/-SD, based on experiments performed on at least 3 different days) and predicted MMs ranged from 0.002 to 0.035%. Each experimentally determined MM had a standard deviation of less than 0.09% (based on the charge state distribution). Application of this HPLC/ESI-MS technique made the detection of the covalent modification to P450 2C9 following mechanism-based inactivation by tienilic acid possible. In the absence of glutathione, three P450 2C9 species were detected that produced ESI mass spectra corresponding to native P450 2C9 and both a monoadduct and a diadduct of tienilic acid to P450 2C9. In the presence of glutathione, only native P450 2C9 and the monoadduct were detected. Based on the observed mass shifts for the P450 2C9/tienilic acid adducts, a mechanism for the inactivation of P450 2C9 by tienilic acid is proposed. PMID- 10029525 TI - Tertiary contacts of helix V in the lactose permease determined by site-directed chemical cross-linking in situ. AB - The six N-terminal transmembrane helices (N6) and the six C-terminal transmembrane helices (C6) in lactose permease, each containing a single Cys residue, were coexpressed, and cross-linking was studied. The proximity of paired Cys residues in helices V and VII, VIII, or X was studied by thiol-specific chemical cross-linking. The results demonstrate that Cys residues in the periplasmic half of helix V cross-link with Cys residues in the periplasmic half of helix VII. In contrast, no cross-linking is evident with paired Cys residues in the cytoplasmic halves of helices V and VII. Moreover, Cys residues on one entire face of helix V cross-link with Cys residues on one face of helix VIII. Finally, paired Cys residues at the cytoplasmic ends of helices V and X cross link, but no cross-linking is observed when paired Cys residues are placed at the periplasmic ends of the two helices. Taken together, the results indicate that the periplasmic halves of helices V and VII are in close proximity and that the two helices tilt away from one another toward the cytoplasmic side of the membrane. Furthermore, helices V and VIII are in close proximity throughout their lengths and do not tilt appreciably with respect to one another, and helices V and X are in close proximity at the cytoplasmic but not at the periplasmic face of the membrane. PMID- 10029526 TI - Phenylalanine dehydrogenase from Rhodococcus sp. M4: high-resolution X-ray analyses of inhibitory ternary complexes reveal key features in the oxidative deamination mechanism. AB - The molecular structures of recombinant L-phenylalanine dehydrogenase from Rhodococcus sp. M4 in two different inhibitory ternary complexes have been determined by X-ray crystallographic analyses to high resolution. Both structures show that L-phenylalanine dehydrogenase is a homodimeric enzyme with each monomer composed of distinct globular N- and C-terminal domains separated by a deep cleft containing the active site. The N-terminal domain binds the amino acid substrate and contributes to the interactions at the subunit:subunit interface. The C terminal domain contains a typical Rossmann fold and orients the dinucleotide. The dimer has overall dimensions of approximately 82 A x 75 A x 75 A, with roughly 50 A separating the two active sites. The structures described here, namely the enzyme.NAD+.phenylpyruvate, and enzyme. NAD+.beta-phenylpropionate species, represent the first models for any amino acid dehydrogenase in a ternary complex. By analysis of the active-site interactions in these models, along with the currently available kinetic data, a detailed chemical mechanism has been proposed. This mechanism differs from those proposed to date in that it accounts for the inability of the amino acid dehydrogenases, in general, to function as hydroxy acid dehydrogenases. PMID- 10029527 TI - Solution structure of a sweet protein single-chain monellin determined by nuclear magnetic resonance and dynamical simulated annealing calculations. AB - Single-chain monellin (SCM), which is an engineered 94-residue polypeptide, has proven to be as sweet as native two-chain monellin. SCM is more stable than the native monellin for both heat and acidic environments. Data from gel filtration HPLC and NMR indicate that the SCM exists as a monomer in aqueous solution. The solution structure of SCM has been determined by nuclear magnetic resonance (NMR) spectroscopy and dynamical simulated annealing calculations. A stable alpha-helix spanning residues Phe11-Ile26 and an antiparallel beta-sheet formed by residues 2 5, 36-38, 41-47, 54-64, 69-75, and 83-88 have been identified. The sheet was well defined by backbone-backbone NOEs, and the corresponding beta-strands were further confirmed by hydrogen bond networks based on amide hydrogen exchange data. Strands beta2 and beta3 are connected by a small bulge comprising residues Ile38-Cys41. A total of 993 distance and 56 dihedral angle restraints were used for simulated annealing calculations. The final simulated annealing structures (k) converged well with a root-mean-square deviation (rmsd) between backbone atoms of 0.49 A for secondary structural regions and 0.70 A for backbone atoms excluding two loop regions. The average restraint energy-minimized (REM) structure exhibited root-mean-square deviations of 1.19 A for backbone atoms and 0.85 A for backbone atoms excluding two loop regions with respect to 20 k structures. The solution structure of SCM revealed that the long alpha-helix was folded into the concave side of a six-stranded antiparallel beta-sheet. The side chains of Tyr63 and Asp66 which are common to all sweet peptides showed an opposite orientation relative to H1 helix, and they were all solvent-exposed. Residues at the proposed dimeric interface in the X-ray structure were observed to be mostly solvent-exposed and demonstrated high degrees of flexibility. PMID- 10029528 TI - Carbamoyl phosphate synthetase: closure of the B-domain as a result of nucleotide binding. AB - Carbamoyl phosphate synthetase (CPS) catalyzes the production of carbamoyl phosphate which is subsequently employed in the metabolic pathways responsible for the synthesis of pyrimidine nucleotides or arginine. The catalytic mechanism of the enzyme occurs through three highly reactive intermediates: carboxyphosphate, ammonia, and carbamate. As isolated from Escherichia coli, CPS is an alpha, beta-heterodimeric protein with its three active sites separated by nearly 100 A. In addition, there are separate binding sites for the allosteric regulators, ornithine, and UMP. Given the sizable distances between the three active sites and the allosteric-binding pockets, it has been postulated that domain movements play key roles for intramolecular communication. Here we describe the structure of CPS from E. coli where, indeed, such a domain movement has occurred in response to nucleotide binding. Specifically, the protein was crystallized in the presence of a nonhydrolyzable analogue, AMPPNP, and its structure determined to 2.1 A resolution by X-ray crystallographic analysis. The B-domain of the carbamoyl phosphate synthetic component of the large subunit closes down over the active-site pocket such that some atoms move by more than 7 A relative to that observed in the original structure. The trigger for this movement resides in the hydrogen-bonding interactions between two backbone amide groups (Gly 721 and Gly 722) and the beta- and gamma-phosphate groups of the nucleotide triphosphate. Gly 721 and Gly 722 are located in a Type III' reverse turn, and this type of secondary structural motif is also observed in D-alanine:D alanine ligase and glutathione synthetase, both of which belong to the "ATP grasp" superfamily of proteins. Details concerning the geometries of the two active sites contained within the large subunit of CPS are described. PMID- 10029529 TI - Determinants of ligand binding to cAMP-dependent protein kinase. AB - Protein kinases are essential for the regulation of cellular growth and metabolism. Since their dysfunction leads to debilitating diseases, they represent key targets for pharmaceutical research. The rational design of kinase inhibitors requires an understanding of the determinants of ligand binding to these proteins. In the present study, a theoretical model based on continuum electrostatics and a surface-area-dependent nonpolar term is used to calculate binding affinities of balanol derivatives, H-series inhibitors, and ATP analogues toward the catalytic subunit of cAMP-dependent protein kinase (cAPK or protein kinase A). The calculations reproduce most of the experimental trends and provide insight into the driving forces responsible for binding. Nonpolar interactions are found to govern protein-ligand affinity. Hydrogen bonds represent a negligible contribution, because hydrogen bond formation in the complex requires the desolvation of the interacting partners. However, the binding affinity is decreased if hydrogen-bonding groups of the ligand remain unsatisfied in the complex. The disposition of hydrogen-bonding groups in the ligand is therefore crucial for binding specificity. These observations should be valuable guides in the design of potent and specific kinase inhibitors. PMID- 10029530 TI - Crystal structure of the potent natural product inhibitor balanol in complex with the catalytic subunit of cAMP-dependent protein kinase. AB - Endogenous protein kinase inhibitors are essential for a wide range of physiological functions. These endogenous inhibitors may mimic peptide substrates as in the case of the heat-stable protein kinase inhibitor (PKI), or they may mimic nucleotide triphosphates. Natural product inhibitors, endogenous to the unique organisms producing them, can be potent exogenous inhibitors against foreign protein kinases. Balanol is a natural product inhibitor exhibiting low nanomolar Ki values against serine and threonine specific kinases, while being ineffective against protein tyrosine kinases. To elucidate balanol's specific inhibitory effects and provide a basis for understanding inhibition-regulated biological processes, a 2.1 A resolution crystal structure of balanol in complex with cAMP-dependent protein kinase (cAPK) was determined. The structure reveals conserved binding regions and displays extensive complementary interactions between balanol and conserved cAPK residues. This report describes the structure of a protein kinase crystallized with a natural ATP mimetic in the absence of metal ions and peptide inhibitor. PMID- 10029531 TI - Human cathepsin V functional expression, tissue distribution, electrostatic surface potential, enzymatic characterization, and chromosomal localization. AB - Cathepsin V, a thymus and testis-specific human cysteine protease, was expressed in Pichia pastoris, and its physicokinetic properties were determined. Recombinant procathepsin V is autocatalytically activated at acidic pH and is effectively inhibited by various cysteine protease class-specific inhibitors. The S2P2 subsite specificity of cathepsin V was found to be intermediate between those of cathepsins S and L. The substrate binding pocket, S2, accepted both aromatic and nonaromatic hydrophobic residues, whereas cathepsins L and S preferred either an aromatic or nonaromatic hydrophobic residue, respectively. In contrast to cathepsin L, but similar to cathepsin S, cathepsin V exhibited only a very weak collagenolytic activity. Furthermore, cathepsin V was determined to be significantly more stable at mildly acidic and neutral pH than cathepsin L, but distinctly less stable than cathepsin S. A homology structure model of cathepsin V revealed completely different electrostatic potentials on the molecular surface when compared with human cathepsin L. The model-based electrostatic potential of human cathepsin V was neutral to weakly positive at and in the vicinity of the active site cleft, whereas that of cathepsin L was negative over extended regions of the surface. Surprisingly, the electrostatic potential of the human cathepsin V model structure resembled that of the model structure of mouse cathepsin L. These differences in the electrostatic potential at the molecular surfaces provide a reactivity determinant that may be the source of differences in substrate selectivity and pH stability. Cathepsin V was mapped to the chromosomal region 9q22.2, a site adjacent to the cathepsin L locus. The high sequence identity and the overlapping chromosomal gene loci suggest that both proteases evolved from an ancestral cathepsin L-like precursor by gene duplication. PMID- 10029532 TI - Conserved residues and their role in the structure, function, and stability of acyl-coenzyme A binding protein. AB - In the family of acyl-coenzyme A binding proteins, a subset of 26 sequence sites are identical in all eukaryotes and conserved throughout evolution of the eukaryotic kingdoms. In the context of the bovine protein, the importance of these 26 sequence positions for structure, function, stability, and folding has been analyzed using single-site mutations. A total of 28 mutant proteins were analyzed which covered 17 conserved sequence positions and three nonconserved positions. As a first step, the influence of the mutations on the protein folding reaction has been probed, revealing a folding nucleus of eight hydrophobic residues formed between the N- and C-terminal helices [Kragelund, B. B., et al. (1999) Nat. Struct. Biol. (In press)]. To fully analyze the role of the conserved residues, the function and the stability have been measured for the same set of mutant proteins. Effects on function were measured by the extent of binding of the ligand dodecanoyl-CoA using isothermal titration calorimetry, and effects on protein stability were measured with chemical denaturation followed by intrinsic tryptophan and tyrosine fluorescence. The sequence sites that have been conserved for direct functional purposes have been identified. These are Phe5, Tyr28, Tyr31, Lys32, Lys54, and Tyr73. Binding site residues are mainly polar or charged residues, and together, four of these contribute approximately 8 kcal mol-1 of the total free energy of binding of 11 kcal mol-1. The sequence sites conserved for stability of the structure have likewise been identified and are Phe5, Ala9, Val12, Leu15, Leu25, Tyr28, Lys32, Gln33, Tyr73, Val77, and Leu80. Essentially, all of the conserved residues that maintain the stability are hydrophobic residues at the interface of the helices. Only one conserved polar residue, Gln33, is involved in stability. The results indicate that conservation of residues in homologous proteins may result from a summed optimization of an effective folding reaction, a stable native protein, and a fully active binding site. This is important in protein design strategies, where optimization of one of these parameters, typically function or stability, may influence any of the others markedly. PMID- 10029533 TI - Electrostatic mutations in iberiotoxin as a unique tool for probing the electrostatic structure of the maxi-K channel outer vestibule. AB - Iberiotoxin (IbTX or alpha-KTx 1.3), a selective, high-affinity blocker of the large-conductance, calcium-activated (maxi-K) channel, exhibits a unique, asymmetric distribution of charge. To test how these charges control kinetics of IbTX binding, we generated five mutants at two positions, K27 and R34, that are highly conserved among other isotoxins. The dissociation and association rate constants, koff and kon, were determined from toxin-blocked and -unblocked durations of single maxi-K channels incorporated into planar lipid bilayers. Equilibrium dissociation constant (Kd) values were calculated from koff/kon. The IbTX mutants K27N, K27Q, and R34N caused large increases in Kd values compared to wild-type, suggesting that the IbTX interaction surface encompasses these residues. A well-established pore-blocking mechanism for IbTX predicts a voltage dependence of toxin-blocked times following occupancy of a potassium binding site in the channel pore. Time constants for block by K27R were approximately 5-fold slower at -20 mV versus +40 mV, while neutralization of K27 relieved the voltage dependence of block. This suggests that K27 in IbTX interacts with a potassium binding site in the pore. Neutralized mutants of K27 and R34, with zero net charge, displayed toxin association rate constants approximately 10-fold slower than wild-type. Association rates for R34N diminished approximately 19-fold when external potassium was increased from 30 to 300 mM. These findings suggest that simple net charge and diffusional processes do not control ingress of IbTX into the channel vestibule. PMID- 10029534 TI - Xylan binding subsite mapping in the xylanase from Penicillium simplicissimum using xylooligosaccharides as cryo-protectant. AB - Following a recent low-temperature crystal structure analysis of the native xylanase from Penicillium simplicissimum [Schmidt et al. (1998) Protein Sci. 7, 2081-2088], where an array of glycerol molecules, diffused into the crystal during soaking in a cryoprotectant, was observed within the active-site cleft, we utilized monomeric xylose as well as a variety of linear (Xn, n = 2 to 5) and branched xylooligomers at high concentrations (typically 20% w/v) as cryoprotectant for low-temperature crystallographic experiments. Binding of the glycosidic moiety (or its hydrolysis products) to the enzyme's active-site cleft was observed after as little as 30 s soaking of a native enzyme crystal. The use of a substrate or substrate analogue as cryoprotectant therefore suggests itself as a simple and widely applicable alternative to the use of crystallographic flow cells for substrate-saturation experiments. Short-chain xylooligomers, i.e., xylobiose (X2) and xylotriose (X3), were found to bind to the active-site cleft with its reducing end hydrogen-bonded to the catalytic acid-base catalyst Glu132. Xylotetraose (X4) and -pentaose (X5) had apparently been cleaved during the soaking time into a xylotriose plus a monomeric (X4) or dimeric (X5) sugar. While the trimeric hydrolysis product was always found to bind in the same way as xylotriose, the monomer or dimer yielded only weak and diffuse electron density within the xylan-binding cleft, at the opposite side of the active center. This suggests that the two catalytic residues divide the binding cleft into a "substrate recognition area" (from the active site toward the nonreducing end of a bound xylan chain), with strong and specific xylan binding and a "product release area" with considerably weaker and less specific binding. The size of the substrate recognition area (3-4 subsites for sugar rings) explains enzyme kinetic data, according to which short oligomers (X2 and X3) bind to the enzyme without being hydrolyzed. PMID- 10029535 TI - Structure of Thermus thermophilus HB8 aspartate aminotransferase and its complex with maleate. AB - The three-dimensional structures of pyridoxal 5'-phosphate-type aspartate aminotransferase (AspAT) from Thermus thermophilus HB8 and pyridoxamine 5' phosphate type one in complex with maleate have been determined by X-ray crystallography at 1.8 and 2.6 A resolution, respectively. The enzyme is a homodimer, and the polypeptide chain of the subunit is folded into one arm, one small domain, and one large domain. AspATs from many species were classified into aminotransferase subgroups Ia and Ib. The enzyme belongs to subgroup Ib, its sequence being less than 16% identical to the primary sequences of Escherichia coli, pig cytosolic, and chicken mitochondrial AspATs, which belong to subgroup Ia whose sequences are more than 40% identical and whose three-dimensional structures are quite similar with the active site residues almost completely conserved. The first X-ray analysis of AspAT subgroup Ib indicated that the overall and the active site structures are essentially conserved between the AspATs of subgroup Ia and the enzyme of subgroup Ib, but there are two distinct differences between them. (1) In AspAT subgroup Ia, substrate (or inhibitor) binding induces a large movement of the small domain as a whole to close the active site. However, in the enzyme of subgroup Ib, only the N-terminal region (Lys13-Val30) of the small domain approaches the active site to interact with the maleate. (2) In AspAT subgroup Ia, Arg292 recognizes the side chain carboxylate of the substrate; however, residue 292 of the enzyme in subgroup Ib is not Arg, and in place of Arg292, Lys109 forms a salt bridge with the side chain carboxylate. The thermostability of the enzyme is attained at least in part by the high content of Pro residues in the beta-turns and the marked increase in the number of salt bridges on the molecular surface compared with the mesophilic AspAT. PMID- 10029536 TI - Crystal structure of an inactive duck delta II crystallin mutant with bound argininosuccinate. AB - Delta-crystallin, the major soluble protein component of avian and reptilian eye lenses, is highly homologous to the urea cycle enzyme, argininosuccinate lyase (ASL). In duck lenses, there are two highly homologous delta crystallins, delta I and delta II, that are 94% identical in amino acid sequence. While delta II crystallin has been shown to exhibit ASL activity in vitro, delta I is enzymatically inactive. The X-ray structure of a His to Asn mutant of duck delta II crystallin (H162N) with bound argininosuccinate has been determined to 2.3 A resolution using the molecular replacement technique. The overall fold of the protein is similar to other members of the superfamily to which this protein belongs, with the active site located in a cleft formed by three different monomers in the tetramer. The active site of the H162N mutant structure reveals that the side chain of Glu 296 has a different orientation relative to the homologous residue in the H91N mutant structure [Abu-Abed et al. (1997) Biochemistry 36, 14012-14022]. This shift results in the loss of the hydrogen bond between His 162 and Glu 296 seen in the H91N and turkey delta I crystallin structures; this H-bond is believed to be crucial for the catalytic mechanism of ASL/delta II crystallin. Argininosuccinate was found to be bound to residues in each of the three monomers that form the active site. The fumarate moiety is oriented toward active site residues His 162 and Glu 296 and other residues that are part of two of the three highly conserved regions of amino acid sequence in the superfamily, while the arginine moiety of the substrate is oriented toward residues which belong to either domain 1 or domain 2. The analysis of the structure reveals that significant conformational changes occur on substrate binding. The comparison of this structure with the inactive turkey delta I crystallin reveals that the conformation of domain 1 is crucial for substrate affinity and that the delta I protein is almost certainly inactive because it can no longer bind the substrate. PMID- 10029537 TI - Mutational analysis of amino acid residues involved in argininosuccinate lyase activity in duck delta II crystallin. AB - Delta-crystallins are the major structural eye lens proteins of most birds and reptiles and are direct homologues of the urea cycle enzyme argininosuccinate lyase. There are two isoforms of delta-crystallin, delta Iota and delta IotaIota, but only delta IotaIota crystallin exhibits argininosuccinate lyase (ASL) activity. At the onset of this study, the structure of argininosuccinate lyase/delta IotaIota crystallin with bound inhibitor or substrate analogue was not available. Biochemical and X-ray crystallographic studies had suggested that H162 may function as the catalytic base in the argininosuccinate lyase/delta IotaIota crystallin reaction mechanism, either directly or indirectly through the activation of a water molecule. The identity of the catalytic acid was unknown. In this study, the argininosuccinate substrate was modeled into the active site of duck delta IotaIota crystallin, using the coordinates of an inhibitor-bound Escherichia coli fumarase C structure to orient the fumarate moiety of the substrate. The model served as a means of identifying active site residues which are positioned to potentially participate in substrate binding and/or catalysis. On the basis of the results of the modeling, site-directed mutagenesis was performed on several amino acids, and the kinetic and thermodynamic properties of each mutant were determined. Kinetic studies reveal that five residues, R115, N116, T161, S283, and E296, are essential for catalytic activity. Determination of the free energy of unfolding/refolding of wild-type and mutant delta II crystallins revealed that all constructs exhibit similar thermodynamic stabilities. During the course of this work, the structure of an inactive delta IotaIota crystallin mutant with bound substrate was solved [Vallee et al. (1999) Biochemistry 38, 2425-2434], which has allowed the kinetic data to be interpreted on a structural basis. PMID- 10029538 TI - Relationship between phospholamban and nucleotide activation of cardiac sarcoplasmic reticulum Ca2+ adenosinetriphosphatase. AB - A strong connection with nucleotide activation of Ca2+ATPase and phospholamban inhibition has been found. Phospholamban decreases the number of activatable Ca2+ATPase without affecting substrate affinity or the ability of nucleotide to serve its dual modulatory roles, i.e., catalytic and regulatory. Low concentrations of certain nucleotide mimetics, quercetin, tannin, and ellagic acid, with structural similarity to adenine can unmask phospholamban's inhibitory effect while concurrently acting as competitive inhibitors of nucleotide binding. Micromolar concentrations of tannin (EC50 approximately 0.3 microM) and ellagic acid (EC50 approximately 3 microM) stimulated Ca2+ uptake and calcium-activated ATP hydrolysis at submicromolar Ca2+ in isolated cardiac sarcoplasmic reticulum (SR). Stimulation of Ca2+ATPase was followed by pronounced inhibiton at only slightly higher tannin concentrations (IC50 approximately 3 microM), whereas inhibitory effects by ellagic acid were observed at much greater concentrations (IC50 > 300 microM) than the EC50. A complex relationship between compound, SR protein, and MgATP concentration is a major determining factor in the observed effects. Stimulation was only observed under conditions of phospholamban regulation, while the inhibitory effects were observed in cardiac SR at micromolar Ca2+ and in skeletal muscle SR, which lacks phospholamban. Maximal stimulation of Ca2+ATPase was identical to that observed with the anti phospholamban monoclonal antibody 1D11. Both compounds appear to relieve the Ca2+ATPase from phospholamban inhibition, thereby increasing the calcium sensitivity of the Ca2+ATPase like that observed with phosphorylation of phospholamban or treatment with monoclonal antibody 1D11. Tannin, even under stimulatory conditions, is a competitive inhibitor of MgATP with a linear Dixon plot. The subsequent inhibitory action of higher tannin concentrations results from competition of tannin with the nucleotide binding site of the Ca2+ATPase. In contrast, ellagic acid produced a curvilinear Dixon plot suggesting partial inhibition of nucleotide activation. The data suggest that nucleotide activation of Ca2+ATPase is functionally coupled to the phospholamban interaction site. These compounds through their interaction with the adenine binding domain of the nucleotide binding site prevent or dissociate phospholamban regulation. Clearly, this portion of Ca2+ATPase needs further study to elucidate its role in phospholamban inhibition. PMID- 10029539 TI - Three-dimensional structure of ribonuclease T1 complexed with an isosteric phosphonate substrate analogue of GpU: alternate substrate binding modes and catalysis. AB - The X-ray crystal structure of a complex between ribonuclease T1 and guanylyl(3' 6')-6'-deoxyhomouridine (GpcU) has been determined at 2. 0 A resolution. This ligand is an isosteric analogue of the minimal RNA substrate, guanylyl(3' 5')uridine (GpU), where a methylene is substituted for the uridine 5'-oxygen atom. Two protein molecules are part of the asymmetric unit and both have a GpcU bound at the active site in the same manner. The protein-protein interface reveals an extended aromatic stack involving both guanines and three enzyme phenolic groups. A third GpcU has its guanine moiety stacked on His92 at the active site on enzyme molecule A and interacts with GpcU on molecule B in a neighboring unit via hydrogen bonding between uridine ribose 2'- and 3'-OH groups. None of the uridine moieties of the three GpcU molecules in the asymmetric unit interacts directly with the protein. GpcU-active-site interactions involve extensive hydrogen bonding of the guanine moiety at the primary recognition site and of the guanosine 2'-hydroxyl group with His40 and Glu58. On the other hand, the phosphonate group is weakly bound only by a single hydrogen bond with Tyr38, unlike ligand phosphate groups of other substrate analogues and 3'-GMP, which hydrogen-bonded with three additional active-site residues. Hydrogen bonding of the guanylyl 2'-OH group and the phosphonate moiety is essentially the same as that recently observed for a novel structure of a RNase T1-3'-GMP complex obtained immediately after in situ hydrolysis of exo-(Sp) guanosine 2',3'-cyclophosphorothioate [Zegers et al. (1998) Nature Struct. Biol. 5, 280-283]. It is likely that GpcU at the active site represents a nonproductive binding mode for GpU [Steyaert, J., and Engleborghs (1995) Eur. J. Biochem. 233, 140-144]. The results suggest that the active site of ribonuclease T1 is adapted for optimal tight binding of both the guanylyl 2'-OH and phosphate groups (of GpU) only in the transition state for catalytic transesterification, which is stabilized by adjacent binding of the leaving nucleoside (U) group. PMID- 10029540 TI - Role of cysteine-82 in the catalytic mechanism of human S-adenosylmethionine decarboxylase. AB - S-Adenosylmethionine decarboxylase is a pyruvate-dependent enzyme. The enzyme forms a Schiff base with substrate, S-adenosylmethionine, through the pyruvoyl moiety. This facilitates the release of CO2 from the substrate, which must then be protonated on the alpha carbon in order to permit hydrolysis of the Schiff base to release the product. The catalytic mechanism of human S adenosylmethionine decarboxylase was investigated via mutagenic and kinetic approaches. The results of enzyme kinetic studies indicated that Cys-82 is a crucial residue for activity and this residue has a basic pKa. Iodoacetic acid inhibited wild-type enzyme activity in a time- and pH-dependent manner but did not affect the already reduced activity of mutant C82A. Reaction of this mutant with iodoacetic acid led to approximately one less mole of reagent being incorporated per mole of enzyme alphabeta dimer than with wild-type S adenosylmethionine decarboxylase. Both wild-type and C82A mutant S adenosylmethionine decarboxylases were inactivated by substrate-mediated transamination, but this reaction occurred much more frequently with C82A than with wild-type enzyme. A major proportion of the recombinant C82A mutant protein was in the transaminated form in which the pyruvoyl cofactor is converted into alanine. This suggests that incorrect protonation of the pyruvate, rather than the substrate, occurs much more readily when Cys-82 is altered. On the basis of these results, it was postulated that residue Cys-82 may be the proton donor of the decarboxylation reaction catalyzed by S-adenosylmethionine decarboxylase. PMID- 10029541 TI - Protein stability: functional dependence of denaturational Gibbs energy on urea concentration. AB - Determination of protein stability (DeltaGD0) from the conformational transition curve induced by a chemical denaturant is problematic; for different values of DeltaGD0, the value of the Gibbs energy change on denaturation (DeltaGD) in the absence of the denaturant are obtained when different extrapolation methods are used to analyze the same set of (DeltaGD, denaturant concentration) data [Pace, C. N. (1986) Methods Enzymol. 131, 266-280]. We propose a practical solution to this problem and use it to test the dependence of DeltaGD of lysozyme, ribonuclease-A, and cytochrome-c on [urea], the molar urea concentration. This method employs (i) measurements of the urea-induced denaturation in the presence of different guanidine hydrochloride (GdnHCl) concentrations which by themselves disrupt the native state of the protein at the same temperature and pH at which denaturations by urea and GdnHCl have been measured; (ii) estimation of DeltaGDcor, the value of DeltaGD corrected for the effect of GdnHCl on the urea induced denaturation using the relation (DeltaGDcor = DeltaGD + mg [GdnHCl] = DeltaGD0 - mu [urea], where mg and mu are the dependencies of DeltaGD on [GdnHCl] and [urea], respectively) whose parameters are all determined from experimental denaturation data; and (iii) mapping of DeltaGDcor onto the DeltaGD versus [urea] plot obtained in the absence of GdnHCl. Our results convincingly show that (i) [urea] dependence of DeltaGD of each protein is linear over the full concentration range; (ii) the effect of urea and GdnHCl on protein denaturation is additive; and (iii) KCl affects the urea-induced denaturation if the native protein contains charge-charge interaction and/or anion binding site, in a manner which is consistent with the crystal structure data. PMID- 10029542 TI - Interaction of the N-terminus of chicken skeletal essential light chain 1 with F actin. AB - Skeletal myosin has two isoforms of the essential light chain (ELC), called LC1 and LC3, which differ only in their N-terminal amino acid sequence. The LC1 has 41 additional residues containing seven pairs of Ala-Pro, which form an elongated structure, and two pairs of lysines located near the N-terminus. When myosin subfragment-1 (S1) binds to actin, these lysines may interact with the C-terminus of actin and be responsible for the isoform specific properties of myosin. Here we employ cross-linking to identify the LC1 residues that are in contact with actin. S1 was reconstituted with various LC1 mutants and reacted with the zero length cross-linker 1-ethyl-3-[3-dimethyl-aminopropyl]-carbodiimide (EDC). Cross linking occurred only when actin was in molar excess over S1. Wild-type LC1 could be cross-linked through the terminal alpha-NH2 group, as well as via the two pairs of lysines. In a mutant ELC, where the lysines were deleted but two arginines were introduced near the N-terminus, the light chain could still be cross-linked via the terminal alpha-NH2 group. When the charge was reduced in the N-terminal region while retaining the Ala-Pro rich region, the mutant could not be cross-linked. These results suggest that as long as the N-terminus contains charged residues and an Ala-Pro rich extension, the binding between LC1 and actin can occur. PMID- 10029543 TI - Protease-activated receptor-1 can mediate responses to SFLLRN in thrombin desensitized cells: evidence for a novel mechanism for preventing or terminating signaling by PAR1's tethered ligand. AB - The thrombin receptor PAR1 is activated when thrombin cleaves the receptor's amino-terminal exodomain to reveal the new N-terminal sequence SFLLRN which then acts as a tethered peptide ligand. Free SFLLRN activates PAR1 independent of receptor cleavage and has been used to probe PAR1 function in various cells and tissues. PAR1-expressing cells desensitized to thrombin retain responsiveness to SFLLRN. Toward determining the mechanism of such responses, we utilized fibroblasts derived from a PAR1-deficient mouse. These cells were unresponsive to thrombin and SFLLRN and became sensitive to both ligands after transfection with human PAR1 cDNA. Moreover, PAR1-transfected cells responded to SFLLRN after thrombin-desensitization, indicating that signaling of thrombin-desensitized cells to SFLLRN was mediated by PAR1 itself. SFLLRN caused signaling in thrombin desensitized cells when no uncleaved PAR1 was detectable on the cell surface; however, cleaved PAR1 was present. To determine whether the cleaved receptors could still signal, fibroblasts were transfected with a PAR1 mutant containing a trypsin site/SFLLRN sequence carboxyl terminal to the native thrombin site. These cells retained responsiveness to trypsin after thrombin-desensitization. Conversely, fibroblasts expressing a PAR1 mutant with the trypsin site/SFLLRN sequence amino terminal to the native thrombin site retained responsiveness to thrombin after trypsin-desensitization. This suggests that a population of thrombin-cleaved PAR1 can respond both to exogenous SFLLRN and to a second tethered ligand. In this population, the tethered ligand unmasked by thrombin cleavage must not be functional, suggesting the possibility of a novel mechanism of receptor shutoff involving sequestration or modification of the tethered ligand to prevent or terminate its function. PMID- 10029544 TI - Isoform-specific effects of charged residues at borders of the M1-M2 loop of the Na,K-ATPase alpha subunit. AB - The Na,K-ATPase is specifically inhibited by the cardiac glycoside, ouabain. Via a largely undefined mechanism, the ouabain affinity of the Na,K-ATPase can be manipulated by mutating the residues at the borders of the first extracellular (M1-M2) loop of the alpha subunit [Price, E. M., Rice, D. A., and Lingrel, J. B. (1990) J. Biol. Chem. 265, 6638-6641]. To address this issue, we compared the effects of two combinations of charged residues at the M1-M2 loop border, R113, D124 and D113,R124 (numbered according to the rat alpha1 subunit), on the ouabain sensitivity of the alpha1 and alpha2 isoforms. We report that ouabain sensitivity is dependent not only upon the identity of the residues at the M1-M2 loop border but also upon the context into which they are introduced. Furthermore, at low concentrations of ATP, the identity of the residues at the M1-M2 loop border affects the regulation of ATP hydrolysis by potassium in an isoform-specific manner. Analysis of chimeric alpha subunits reveals that the effects of potassium are determined primarily by the interaction of the N-terminus and M1-M2 loop with the C-terminal third of the alpha subunit. M1-M2 loop border residues may, therefore, influence ouabain sensitivity indirectly by altering the stability or structure of the intermediate of the Na,K-ATPase catalytic cycle which is competent to bind ouabain. PMID- 10029545 TI - Intracellular cholesterol transport in synchronized human skin fibroblasts. AB - Normal human skin fibroblasts maintained in serum-containing medium were synchronized with aphidicolin. After removal of inhibitor, free cholesterol (FC) homeostasis was determined at intervals during the following cell cycle. FC mass per cell doubled following S-phase, and reached its maximum well before mitosis. This increase was mainly the result of stimulation of the rate of selective uptake of FC from medium lipoproteins, and reduction of FC efflux. Rates of cholesterol synthesis, endocytosis of intact low-density lipoprotein, and HDL receptor (CLA-1) activity were relatively low and little changed during the cell cycle. The expression of caveolin (structural protein of cell surface caveolae) and caveolar FC were decreased along with FC efflux. To test the hypothesis that regulation of caveolin expression could contribute to changes in FC efflux during cell division, cells were transfected with human caveolin cDNA, synchronized with aphidicolin, and then allowed to divide. In the transfected cells, caveolar FC and FC efflux were both increased. FC accumulation and entry into mitosis were markedly inhibited compared to controls. The contribution of transcriptional regulation to caveolin mRNA levels was determined with a 705 bp caveolin 5' flanking sequence ligated to the pGL3 luciferase expression vector. Expression of the reporter gene was downregulated at S-phase of synchronized cells. Deletion of a hybrid E2F/ Sp1-like site between -139 and -150 bp abolished this downregulation. These data are consistent with a role for caveolin in cell cycle kinetics, which may be mediated, at least in part, at the transcriptional level. PMID- 10029546 TI - The core histone N-terminal domains are required for multiple rounds of catalytic chromatin remodeling by the SWI/SNF and RSC complexes. AB - SWI/SNF and RSC are large, distinct multi-subunit complexes that use the energy of ATP hydrolysis to disrupt nucleosome structure, facilitating the binding of transcription factors or restriction enzymes to nucleosomes [Cote, J., Quinn, J., Workman, J. L., and Peterson, C. L. (1994) Science 265, 53-60 (1); Lorch, Y., Cairns, B. R., Zhang, M., and Kornberg, R. D. (1998) Cell 94, 29-34 (2)]. Here we have used a quantitative assay to measure the activities of these ATP-dependent chromatin remodeling complexes using nucleosomal arrays reconstituted with hypoacetylated, hyperacetylated, or partially trypsinized histones. This assay is based on measuring the kinetics of restriction enzyme digestion of a site located within the central nucleosome of a positioned 11-mer array [Logie, C., and Peterson, C. L. (1997) EMBO J. 16, 6772-6782 (3)]. We find that the DNA stimulated ATPase activities of SWI/SNF and RSC are not altered by the absence of the histone N-termini. Furthermore, ATP-dependent nucleosome remodeling is also equivalent on all three substrate arrays under reaction conditions where the concentrations of nucleosomal array and either SWI/SNF or RSC are equivalent. However, SWI/SNF and RSC cannot catalytically remodel multiple nucleosomal arrays in the absence of the histone termini, and this catalytic activity of SWI/SNF is decreased by histone hyperacetylation. These results indicate that the histone termini are important for SWI/SNF and RSC function; and, furthermore, our data defines a step in the remodeling cycle where the core histone termini exert their influence. This step appears to be after remodeling, but prior to intermolecular transfer of the remodelers to new arrays. PMID- 10029547 TI - Heparin is essential for a single keratinocyte growth factor molecule to bind and form a complex with two molecules of the extracellular domain of its receptor. AB - Keratinocyte growth factor (KGF or FGF-7) is a member of the heparin binding fibroblast growth factor (FGF) family and is a paracrine mediator of proliferation and differentiation of a wide variety of epithelial cells. To examine the stoichiometry of complexes formed between KGF and its receptor, we have utilized a soluble variant of the extracellular region of the KGF receptor containing two tandem immunoglobulin-like loops, loops II and III (sKGFR). Ligand receptor complexes were examined by size exclusion chromatography, light scattering, N-terminal protein sequencing, and sedimentation velocity. In the presence of low-molecular mass heparin ( approximately 3 kDa), we demonstrate the formation of complexes containing two molecules of sKGFR and one molecule of KGF. In the absence of heparin, we were unable to detect any KGF-sKGFR complexes using the above techniques, and additional studies in which sedimentation equilibrium was used show that the binding is very weak (Kd >/= 70 microM). Furthermore, using heparin fragments of defined size, we demonstrate that a heparin octamer or decamer can promote formation of a 2:1 complex, while a hexamer does not. Utilizing the highly purified proteins and defined conditions described in this study, we find that heparin is obligatory for formation of a KGF-sKGFR complex. Finally, 32D cells, which appear to lack low-affinity FGF binding sites, were transfected with a KGFR-erythropoeitin receptor chimera and were found to require heparin to achieve maximal KGF stimulation. Our data are consistent with the previously described concept that cell- or matrix-associated heparan sulfate proteoglycans (HSPGs) and FGF ligands participate in a concerted mechanism that facilitates FGFR dimerization and signal transduction in vivo. PMID- 10029548 TI - X-ray crystallography and mass spectroscopy reveal that the N-lobe of human transferrin expressed in Pichia pastoris is folded correctly but is glycosylated on serine-32. AB - The ferric form of the N-lobe of human serum transferrin (Fe(III)-hTF/2N) has been expressed at high levels in Pichia pastoris. The Fe(III)-hTF/2N was crystallized in the space group P41212, and X-ray crystallography was used to solve the structure of the recombinant protein at 2.5 A resolution. This represents only the second P. pastoris-derived protein structure determined to date, and allows the comparison of the structures of recombinant Fe(III)-hTF/2N expressed in P. pastoris and mammalian cells with serum-derived transferrin. The polypeptide folding pattern is essentially identical in all of the three proteins. Mass spectroscopic analyses of P. pastoris- hTF/2N and proteolytically derived fragments revealed glycosylation of Ser-32 with a single hexose. This represents the first localization of an O-linked glycan in a P. pastoris-derived protein. Because of its distance from the iron-binding site, glycosylation of Ser 32 should not affect the iron-binding properties of hTF/2N expressed in P. pastoris, making this an excellent expression system for the production of hTF/2N. PMID- 10029549 TI - The conformations of a substrate and a product bound to the active site of S adenosylmethionine synthetase. AB - S-Adenosylmethionine (AdoMet) is the most widely used alkyl group donor in biological systems. The formation of AdoMet from ATP and L-methionine is catalyzed by S-adenosylmethionine synthetase (AdoMet synthetase). Elucidation of the conformations of enzyme-bound substrates, product, and inhibitors is important for the understanding of the catalytic mechanism of the enzyme and the design of new inhibitors. To obtain structural data for enzyme-bound substrates and product, we have used two-dimensional transferred nuclear Overhauser effect spectroscopy to determine the conformation of enzyme-bound AdoMet and 5'-adenylyl imidodiphosphate (AMPPNP). AMPPNP, an analogue of ATP, is resistant to the ATP hydrolysis activity of AdoMet synthetase because of the presence of a nonhydrolyzable NH-link between the beta- and gamma-phosphates but is a substrate for AdoMet formation during which tripolyphosphate is produced. AdoMet and AMPPNP both bind in an anti conformation about the glycosidic bond. The ribose rings are in C3'-exo and C4'-exo conformations in AdoMet and AMPPNP, respectively. The differences in ribose ring conformations presumably reflect the different steric requirements of the C5' substituents in AMPPNP and AdoMet. The NMR-determined conformations of AdoMet and AMPPNP were docked into the E. coli AdoMet synthetase active site taken from the enzyme.ADP. Pi crystal structure. Since there are no nonexchangeable protons either in the carboxy-terminal end of the methionine segment of AdoMet or in the tripolyphosphate segment of AMPPNP, these portions of the molecules were modeled into the enzyme active site. The interactions of AdoMet and AMPPNP with the enzyme predict the location of the methionine binding site and suggest how the positive charge formed on the sulfur during AdoMet synthesis is stabilized. PMID- 10029550 TI - Activators of phosphorylase kinase alter the cross-linking of its catalytic subunit to the C-terminal one-sixth of its regulatory alpha subunit. AB - Phosphorylase kinase, a regulatory enzyme of glycogenolysis in skeletal muscle, is a hexadecameric oligomer consisting of four copies each of a catalytic subunit (gamma) and three regulatory subunits (alpha, beta, and delta, the last being endogenous calmodulin). The enzyme is activated by a variety of effectors acting through its regulatory subunits. To probe the quaternary structure of nonactivated and activated forms of the kinase, we used the heterobifunctional, photoreactive cross-linker N-5-azido-2-nitrobenzoyloxysuccinimide. Mono derivatization of the holoenzyme with the succinimidyl group, followed by photoactivation of the covalently attached azido group, resulted in intramolecular cross-linking to form two distinct heterodimers: a major (alphagamma) and a minor (betadelta) conjugate. Formation of both conjugates was significantly altered in activated conformations of the enzyme induced by phosphorylation, alkaline pH, and several allosteric activators (ADP, exogenous calmodulin/Ca2+, and Ca2+ alone). Of these activating mechanisms, all increased formation of alphagamma, except Ca2+ alone, which inhibited its formation. When cross-linking was carried out at alkaline pH or in the presence of ADP or exogenous calmodulin/Ca2+, the cross-linked enzyme remained activated following removal of the activators; however, cross-linking in the presence of Ca2+ resulted in sustained inhibition. The results indicate that perturbations in the subunit cross-linking forming the alphagamma dimer reflect the subsequent extent of sustained activation of the holoenzyme that is measured. The region cross linked to the catalytic gamma subunit was confined to the C-terminal 1/6th of the alpha subunit, which contains known regulatory regions. These results suggest that activators of the phosphorylase kinase holoenzyme perturb interactions between the C-terminal region of the inhibitory alpha subunit and the catalytic gamma subunit, ultimately leading to activation of the latter. PMID- 10029551 TI - Structure analysis of a fusogenic peptide sequence from the sea urchin fertilization protein bindin. AB - The structure of "B18", an 18-residue fusogenic peptide from the sea urchin fertilization protein bindin, was investigated in several membrane-mimicking environments with circular dichroism and nuclear magnetic resonance spectroscopy. The fully conserved peptide sequence represents the minimal functional part of the 24 kDa protein, which can bind to membranes and induce fusion of lipid vesicles. The B18 peptide undergoes a coil-helix transition in the presence of TFE, showing a transient tendency to self-associate. Its NMR structure in 30% TFE exhibits two helical regions at either side, connected by a flexible loop. In DPC and SDS detergent micelles, this loop becomes distinctly bent, presumably due to the high degree of curvature of the micelles. The loop contains a histidine-rich motif for binding zinc, which is required for the fusogenic function of the peptide. Therefore, we monitored the structural response of B18 and of recombinant bindin toward this ion. Like TFE, and in a mutually cooperative manner, zinc induces a partially helical structure in both the peptide and the protein. Complex formation via the histidine residues rigidifies the flexible loop and is accompanied by self-association of the molecules. The data suggest that the zinc-bound functional state is a continuous amphipathic alpha-helix, bearing some resemblance to a leucine zipper. Two hydrophobic patches on one face could favorably penetrate into a membrane, while two arginines on the other face could interact with lipid phosphate groups. The three-dimensional model of the B18 sequence thus contributes to a better understanding of peptide-induced vesicle fusion in general, and of the lipid-protein interactions of sperm bindin in particular. PMID- 10029552 TI - Comparing the thermodynamic stabilities of a related thermophilic and mesophilic enzyme. AB - Several models have been proposed to explain the high temperatures required to denature enzymes from thermophilic organisms; some involve greater maximum thermodynamic stability for the thermophile, and others do not. To test these models, we reversibly melted two analogous protein domains in a two-state manner. E2cd is the isolated catalytic domain of cellulase E2 from the thermophile Thermomonospora fusca. CenAP30 is the analogous domain of the cellulase CenA from the mesophile Cellulomonas fimi. When reversibly denatured in a common buffer, the thermophilic enzyme E2cd had a temperature of melting (Tm) of 72.2 degrees C, a van't Hoff enthalpy of unfolding (DeltaHVH) of 190 kcal/mol, and an entropy of unfolding (DeltaSu) of 0.55 kcal/(mol*K); the mesophilic enzyme CenAP30 had a Tm of 56.4 degrees C, a DeltaHVH of 107 kcal/mol, and a DeltaSu of 0. 32 kcal/(mol*K). The higher DeltaHVH and DeltaSu values for E2cd suggest that its free energy of unfolding (DeltaGu) has a steeper dependence on temperature at the Tm than CenAP30. This result supports models that predict a greater maximum thermodynamic stability for thermophilic enzymes than for their mesophilic counterparts. This was further explored by urea denaturation. Under reducing conditions at 30 degrees C, E2cd had a concentration of melting (Cm) of 5.2 M and a DeltaGu of 11.2 kcal/mol; CenAP30 had a Cm of 2.6 M and a DeltaGu of 4.3 kcal/mol. Under nonreducing conditions, the Cm and DeltaGu of CenAP30 were increased to 4.5 M and 10.8 kcal/mol at 30 degrees C; the Cm for E2cd was increased to at least 7.4 M at 32 degrees C. We were unable to determine a DeltaGu value for E2cd under nonreducing conditions due to problems with reversibility. These data suggest that E2cd attains its greater thermal stability (DeltaTm = 15.8 degrees C) through a greater thermodynamic stability (DeltaDeltaGu = 6.9 kcal/mol) compared to its mesophilic analogue CenAP30. PMID- 10029553 TI - Backbone dynamics of apocytochrome b5 in its native, partially folded state. AB - The backbone dynamics in the native state of apocytochrome b5 were studied using 15N nuclear magnetic spin relaxation measurements. The field (11.7 and 14.1 T) and temperature (10-25 degrees C) dependence of the relaxation parameters (R1, R2, and R1rho) and the 1H-15N NOE established that the protein undergoes multiple time scale internal motions related to the secondary structure. The relaxation data were analyzed with the reduced spectral density mapping approach and within the extended model-free framework. The apoprotein was confirmed to contain a disordered heme-binding loop of approximately 30 residues with dynamics on the sub-nanosecond time scale (0.6 < S2 < 0.7, 100 ps < taue < 500 ps). This loop is attached to a structured hydrophobic core, rigid on the picosecond time scale (S2 > 0.75, taue < 50 ps). The inability to fit the data for several residues with the model-free protocol revealed the presence of correlated motion. An exchange contribution was detected in the transverse relaxation rate (R2) of all residues. The differential temperature response of R2 along the backbone supported slower exchange rates for residues in the loop (tauex > 300 micros) than for the folded polypeptide chain (tauex < 150 micros). The distribution of the reduced spectral densities at the 1H and 15N frequencies followed the dynamic trend and predicted the slowing of the internal motions at 10 degrees C. Comparison of the dynamics with those of the holoprotein [Dangi, B., Sarma, S., Yan, C., Banville, D. L., and Guiles, R. D. (1998) Biochemistry 37, 8289-8302] demonstrated that binding of the heme alters the time scale of motions both in the heme-binding loop and in the structured hydrophobic core. PMID- 10029554 TI - 8-Nitro-2'-deoxyguanosine, a specific marker of oxidation by reactive nitrogen species, is generated by the myeloperoxidase-hydrogen peroxide-nitrite system of activated human phagocytes. AB - Reactive intermediates generated by phagocytes damage DNA and may contribute to the link between chronic inflammation and cancer. Myeloperoxidase, a heme protein secreted by activated phagocytes, is a potential catalyst for such reactions. Recent studies demonstrate that this enzyme uses hydrogen peroxide (H2O2) and nitrite (NO2-) to generate reactive nitrogen species which convert tyrosine to 3 nitrotyrosine. We now report that activated human neutrophils use myeloperoxidase, H2O2, and NO2- to nitrate 2'-deoxyguanosine, one of the nucleosides of DNA. Through HPLC, UV/vis spectroscopy, and mass spectrometry, the two major products of this reaction were identified as 8-nitroguanine and 8-nitro 2'-deoxyguanosine. Nitration required each component of the complete enzymatic system and was inhibited by catalase and heme poisons. However, it was independent of chloride ion and little affected by scavengers of hypochlorous acid, suggesting that the reactive agent is a nitrogen dioxide-like species that results from the one-electron oxidation of NO2- by myeloperoxidase. Alternatively, 2'-deoxyguanosine might be oxidized directly by the enzyme to yield a radical species which subsequently reacts with NO2- or NO2* to generate the observed products. Human neutrophils stimulated with phorbol ester also generated 8-nitroguanine and 8-nitro-2'-deoxyguanosine. The reaction required NO2 and was inhibited by catalase and heme poisons, implicating myeloperoxidase in the cell-mediated pathway. These results indicate that human neutrophils use the myeloperoxidase-H2O2-NO2- system to generate reactive species that can nitrate the C-8 position of 2'-deoxyguanosine. Our observations raise the possibility that reactive nitrogen species generated by myeloperoxidase and other peroxidases contribute to nucleobase oxidation and tissue injury at sites of inflammation. PMID- 10029556 TI - Location of diphenylhexatriene (DPH) and its derivatives within membranes: comparison of different fluorescence quenching analyses of membrane depth PMID- 10029555 TI - Viscosity dependence of the folding kinetics of a dimeric and monomeric coiled coil. AB - We measured whether solvent viscosity, and hence chain diffusion, plays a role in the rate-limiting step of the folding reactions of GCN4-p2', a simple alpha helical coiled coil derived from the leucine zipper region of bZIP transcriptional activator GCN4. To deconvolute the dual effects of viscosogenic solvents on both viscosity, eta, and stability, earlier attempts assumed that the cosolvent and denaturant interact to the same degree in the transition state. Applying this analysis to GCN4-p2' yielded a nearly 1/eta dependence between folding rates and viscosity for both the dimeric and the cross-linked, monomeric versions of the coiled coil, but it revealed no such coherent relationship for cytochrome c. We also developed a method to determine the relative viscosity dependence of the dimeric and monomeric forms of the coiled coil independent of the assumption concerning the transition state's relative interaction with cosolvents and denaturants. Application of this method indicated that the effect of viscosity on both the folding and the unfolding rates was the same for the dimeric and monomeric versions, further supporting the view that the folding of the dimeric version is folding-limited rather than encounter-limited. The finding that GCN4-p2' folding appears to exhibit a 1/eta viscosity dependence implies that the rate-limiting step in folding is opposed predominantly by solvent derived rather than internal frictional forces. These results are interpreted in relation to various models for protein folding. PMID- 10029557 TI - Genetic determinants of diabetic nephropathy. AB - Diabetic nephropathy is the most serious complication of diabetes mellitus. Progression of the condition leads to end-stage renal failure, and other complications of diabetes are also common in this group of patients. The onset of overt albuminuria in a patient with diabetes heralds an increased risk of death, particularly from cardiovascular disease. There is considerable evidence to show that nephropathy is influenced by genetic factors. Epidemiological studies show that only a minority of patients with diabetes develop nephropathy irrespective of glycaemic control, suggesting that a subgroup of patients are at higher risk of nephropathy. Marked ethnic variation is observed, with nephropathy being more common in certain ethnic groups. Familial clustering of nephropathy is also observed. Parental history of hypertension, diabetes or cardiovascular disease appears to predispose to nephropathy in patients with diabetes. A number of methods are available to dissect polygenic disease: animal models, genetic association studies (case-control studies), affected sib-pair studies, discordant sib-pair studies and transmission distortion analysis. Most published work has been based on association studies. Association studies have shown conflicting results often due to small numbers of cases and controls, and poor phenotypic characterization. The angiotensin-converting enzyme gene insertion (I)/deletion (D) polymorphism has been studied in detail, but does not appear to be a strong risk marker for nephropathy. It does, however, appear to have a role in response to angiotensin-converting enzyme inhibition, with II homozygotes being the most responsive and DD homozygotes the least. A number of other genetic loci have also shown positive associations with nephropathy, including apolipoprotein E, heparan sulphate and aldose reductase. More recently, affected sib-pair analysis and discordant sib-pair analysis have suggested possible genetic loci on chromosomes 3, 7, 9, 12 and 20. These have yet to be reproduced in larger numbers of families, and the specific gene regions on these chromosomes remain elusive. The evidence presented in this review strongly supports the role of genetic factors in nephropathy. Detection of strong genetic risk markers for nephropathy will allow further insights into the pathogenesis of nephropathy, and possibly the development of novel therapeutic agents for its treatment. It will also allow preventive therapy to be directed at those patients with the greatest risk for development of diabetic nephropathy. PMID- 10029558 TI - Human complex sound analysis. AB - The analysis of complex sound features is important for the perception of environmental sounds, speech and music, and may be abnormal in disorders such as specific language impairment in children, and in common adult lesions including stroke and multiple sclerosis. This work addresses the problem of how the human auditory system detects features in complex sound, and uses those features to perceive the auditory world. The work has been carried out using two independent means of testing the same hypotheses; detailed psychophysical studies of neurological patients with central lesions, and functional imaging using positron emission tomography and functional magnetic resonance imaging of normal subjects. The psychophysical and imaging studies have both examined which brain areas are concerned with the analysis of auditory space, and which are concerned with the analysis of timing information in the auditory system. This differs from many previous human auditory studies, which have concentrated on the analysis of sound frequency. The combined lesion and functional imaging approach has demonstrated analysis of the spatial property of sound movement within the right parietal lobe. The timing work has confirmed that the primary auditory cortex is active as a function of the time structure of sound, and therefore not only concerned with frequency representation of sounds. PMID- 10029559 TI - Endothelial dysfunction by acute hyperhomocyst(e)inaemia: restoration by folic acid. AB - Recent evidence demonstrates that hyperhomocyst(e)inaemia is a novel risk factor for cardiovascular diseases. In patients with chronic hyperhomocyst(e)inaemia, endothelial function is impaired. However, whether hyperhomocyst(e)inaemia per se is a cause or an epiphenomenon of endothelial dysfunction remains unknown. In this study, we examined the effects of methionine-induced acute hyperhomocyst(e)inaemia on human endothelial function. In healthy volunteers we administered methionine (0.1 g/kg body weight, per os), a substrate of homocyst(e)ine, with or without folic acid (20 mg, per os) and examined flow mediated vasodilatation of the brachial artery by high-resolution ultrasonography as a non-invasive measure of endothelial function. We also measured plasma levels of homocyst(e)ine before and 3, 8 and 24 h after methionine loading. Methionine administration increased plasma levels of homocyst(e)ine by four times the basal level at 8 h (P<0.0001, ANOVA). The plasma levels returned to baseline at 24 h. Flow-mediated vasodilatation was significantly decreased to half of the baseline value at 8 h and returned to baseline at 24 h (P<0.0001, ANOVA), whereas endothelium-independent vasodilatation by glyceryl trinitrate was not affected by the methionine loading. Co-administration of folic acid did not attenuate methionine-induced hyperhomocyst(e)inaemia but completely prevented endothelial dysfunction. Our results suggest that in humans a methionine-rich diet may acutely impair endothelial function, which can be prevented by folic acid supplementation. PMID- 10029560 TI - Investigation of distal aortic compliance and vasodilator responsiveness in heart failure due to proximal aortic stenosis in the guinea pig. AB - Hypotension and syncope are recognized features of chronic aortic stenosis. This study examined vasomotor responses and dynamic compliance in isolated abdominal aortae after chronic constriction of the ascending aorta. Guinea pigs underwent constriction of the ascending aorta or sham operation. Sections of descending aorta were removed for studies of contractile performance and compliance. Dynamic compliance was measured using a feedback-controlled pulsatile pressure system at frequencies of 0.5, 1.5 and 2.5 Hz and mean pressures from 40 to 100 mmHg. Chronic (149+/-6 days) aortic constriction resulted in significant increases in organ weight/body weight ratios for left ventricle (58%), right ventricle (100%) and lung (61%). The presence of heart failure was indicated by increased lung weights, left ventricular end-diastolic pressure and systemic vascular resistance, reduced cardiac output and increased levels of plasma atrial natriuretic peptide (166%), adrenaline (x20), noradrenaline (106%) and dopamine (x3). Aortic rings showed similar constrictor responses to phenylephrine and angiotensin II, but maximal vasodilator responses to acetylcholine and isoprenaline were significantly increased (144% and 48% respectively). Dilator responses to sodium nitroprusside, forskolin and cromokalim were unchanged. Compliance of all vessels decreased with increasing pulsatile frequency and to a lesser extent with increased mean pressure, but were similar in aortic constricted and control groups. Chronic constriction of the ascending aorta resulted in heart failure and increased vasodilator responses to acetylcholine and isoprenaline in the distal aorta while dynamic compliance was unchanged. We hypothesize that increased endothelium-mediated vasodilatation may contribute to hypotension and syncope in patients with left ventricular outflow obstruction. PMID- 10029561 TI - Beta2-adrenoceptor polymorphism and bronchoprotective sensitivity with regular short- and long-acting beta2-agonist therapy. AB - The aim of the present study was to investigate bronchoprotective sensitivity in patients receiving regular treatment with short- and long-acting beta2-agonists and to evaluate any possible association with genetic polymorphism. Thirty-eight patients with stable mild to moderate asthma and receiving inhaled corticosteroids were randomized in a parallel group, double-blind, double-dummy fashion to receive 2 weeks of treatment with either formoterol (12 microg once daily, 6 microg twice daily or 24 microg twice daily) or terbutaline (500 microg four times daily). Bronchoprotection against methacholine challenge (as a provocative dose to produce a 20% fall in forced expiratory volume in 1.0 s: PD20) was measured at baseline (unprotected) after an initial 1 week run-in without beta2-agonist, and at 1 h after the first and last doses of each treatment. The PD20 values were log-transformed and calculated as change from baseline. Percentage desensitization of log PD20 for first- versus last-dose bronchoprotection was calculated and analysed according to effects of treatment and beta2-adrenoceptor polymorphism at codon 16 or 27. The mean degree of desensitization for bronchoprotection was comparable with all four treatments and there were no significant differences in absolute PD20 values after 2 weeks of chronic dosing. The PD20 values were (as microg of methacholine, geometric means+/-S. E.M.): formoterol, 12 microg once daily, 99+/-42 microg; formoterol, 6 microg twice daily, 107+/-44 microg; formoterol, 24 microg twice daily, 108+/-45 microg; terbutaline, 500 microg four times daily, 88+/-37 microg. All patients receiving formoterol, 24 microg twice daily, exhibited a loss of protection greater than 30% which was unrelated to polymorphism at codon 16 or 27. For codon 16, the use of lower doses of formoterol (12 microg once daily or 6 microg twice daily) showed wider variability in the propensity for protection loss in patients who were heterozygous, in contrast to a more uniform protection loss seen with homozygous glycine patients. The amount of protection loss was not significantly related to polymorphism at codon 16 or 27, expressed as values (mean+/-S.E.M.) for percentage desensitization according to each genotype (pooled treatments): Gly-16, 66+/-11%; Het-16, 53+/-8%; Arg-16, 69+/-18%; Glu-27, 68+/-12%; Het-27, 58+/-8%; Gln-27, 52+/-12%. The results of this preliminary study showed that bronchoprotective desensitization occurred readily in response to short- or long acting beta2-agonist exposure irrespective of beta2-adrenoceptor polymorphism at codon 16 or 27. Further studies with larger patient numbers are required to further evaluate the effects of polymorphisms with lower doses of regular formoterol. PMID- 10029562 TI - Angiotensin II increases the release of endothelin-1 from human cultured endothelial cells but does not regulate its circulating levels. AB - We investigated the effect of angiotensin II on endothelin-1 secretion in vitro and in vivo. In vivo, angiotensin II was given intravenously to 23 essential hypertensive and 8 control subjects according to different protocols: Study A, 1.0 ng x min-1 x kg-1 and 3.0 ng x min-1 x kg-1 angiotensin II for 30 min each; Study B, 1.0 ng x min-1 x kg-1 and 3.0 ng x min-1 x kg-1 angiotensin II for 120 min each; Study C, 3.0 ng x min-1 x kg-1 angiotensin II for 30 min followed by a dose increment of 3.0 ng x min-1 x kg-1 every 30 min until mean blood pressure levels increased by 25 mmHg; Study D, 1.0 ng x min-1 x kg-1 followed by 3.0 ng x min-1 x kg-1 angiotensin II for 60 min each on two different NaCl diets (either 20 mmol NaCl/day or 220 mmol NaCl/day, both for 1 week). In all in vivo studies neither plasma nor urine endothelin-1 levels changed with angiotensin II infusion. In contrast, angiotensin II (10(-9), 10(-8), 10(-7) mol/l) stimulated endothelin-1 secretion from cultured human vascular endothelial cells derived from umbilical cord veins in a time- and dose-dependent manner. The in vitro angiotensin II effects were abolished by candesartan cilexetil, an inhibitor of the membrane-bound AT1 receptor, and also by actinomycin D, an RNA synthesis inhibitor, and cycloheximide, a protein synthesis inhibitor, indicating that endothelin-1 release depended on AT1 receptor subtype and de novo protein synthesis. Our findings indicate that angiotensin II regulates endothelin-1 release by cultured endothelial cells through an AT1 receptor-dependent pathway, but does not influence circulating endothelin-1 levels in vivo. PMID- 10029563 TI - Venous duplex scanning of the leg: range, variability and reproducibility. AB - Despite the many studies on venous haemodynamics using duplex, only a few evaluated the normal values, variability and reproducibility. Therefore, the range and variability of venous diameter, compressibility, flow and reflux were measured. To obtain normal values, 42 healthy individuals (42 limbs, 714 vein segments) with no history of venous disease were scanned by duplex. To determine the reproducibility the intra-observer variability was measured in 11 healthy individuals (187 vein segments) and the inter-observer variability in 15 healthy individuals (255 vein segments) and 13 patients (169 vein segments) previously diagnosed with deep venous thrombosis. Of the 714 normal vein segments, 708 (99%) were traceable, including the crural veins. Of the traceable vein segments, 675 (95%) were compressible and in 696 (98%) flow was present. Of the 42 common femoral vein segments, in 25 (60%) the reflux duration exceeded 1.0 s, but in the other proximal vein segments the reflux duration was less than 1.0 s (95% confidence interval 3.0-10.0). With the exception of the distal long saphenous vein, in the distal vein segments the reflux duration was less than 0.5 s (95% confidence interval 3.5-8.2). The coefficient of variation of the diameter measurements ranged from 14 to 50% and that of the reflux measurements from 28 to 60%. The kappa-coefficient of the inter-observer variability in the classification of compressibility measurements in the patients was 0. 77 and that of the reflux measurements was 0.86. This study shows that almost all veins were compressible in healthy individuals, except the distal femoral veins. In healthy individuals the duration of reflux of the proximal veins was less than 1.0 s and in the distal veins it was less than 0.5 s. The inter-observer variability of the reflux and compressibility measurements in the patients was good. PMID- 10029564 TI - Increased phosphoglycerate kinase in the brains of patients with Down's syndrome but not with Alzheimer's disease. AB - Impaired glucose metabolism in Down's syndrome (DS) has been well-documented in vivo, although information on the underlying biochemical defect is limited and no biochemical studies on glucose handling enzymes have been carried out in the brain. Through gene hunting in fetal DS brain we found an overexpressed sequence homologous to the phosphoglycerate kinase (PGK) gene. This finding was studied further by investigating the activity levels of this key enzyme of carbohydrate metabolism in the brains of patients with DS. PGK activity was determined in five brain regions of nine patients with DS, nine patients with Alzheimer's disease and 14 controls. PGK activity was significantly elevated in the frontal, occipital and temporal lobe and in the cerebellum of patients with DS. PGK activity in corresponding brain regions of patients with Alzheimer's disease was comparable with controls. We conclude that our findings complement previously published data on impaired brain glucose metabolism in DS evaluated by positron emission tomography in clinical studies. Furthermore, we show that in DS, impaired glucose metabolism, represented by increased PGK activity, is a specific finding rather than a secondary phenomenon simply due to neurodegeneration or atrophy. These observations are also supported by data from subtractive hybridization, showing overexpressed PGK in DS brains at the transcriptional level early in life. PMID- 10029565 TI - Systemic inflammatory response syndrome without systemic inflammation in acutely ill patients admitted to hospital in a medical emergency. AB - Criteria of the systemic inflammatory response syndrome (SIRS) are known to include patients without systemic inflammation. Our aim was to explore additional markers of inflammation that would distinguish SIRS patients with systemic inflammation from patients without inflammation. The study included 100 acutely ill patients with SIRS. Peripheral blood neutrophil and monocyte CD11b expression, serum interleukin-6, interleukin-1beta, tumour necrosis factor-alpha and C-reactive protein were determined, and severity of inflammation was evaluated by systemic inflammation composite score based on CD11b expression, C reactive protein and cytokine levels. Levels of CD11b expression, C-reactive protein and interleukin-6 were higher in sepsis patients than in SIRS patients who met two criteria (SIRS2 group) or three criteria of SIRS (SIRS3 group). The systemic inflammation composite score of SIRS2 patients (median 1.5; range 0-8, n=56) was lower than that of SIRS3 patients (3.5; range 0-9, n=14, P=0.013) and that of sepsis patients (5.0; range 3-10, n=19, P<0.001). The systemic inflammation composite score was 0 in 13/94 patients. In 81 patients in whom systemic inflammation composite scores exceeded 1, interleukin-6 was increased in 64 (79.0%), C-reactive protein in 59 (72.8%) and CD11b in 50 (61.7%). None of these markers, when used alone, identified all patients but at least one marker was positive in each patient. Quantifying phagocyte CD11b expression and serum interleukin-6 and C-reactive protein concurrently provides a means to discriminate SIRS patients with systemic inflammation from patients without systemic inflammation. PMID- 10029566 TI - Effects of chronic nitric oxide activation or inhibition on early hepatic fibrosis in rats with bile duct ligation. AB - Hepatic fibrosis or increased liver collagen contents drive functional abnormalities that, when extensive, may be life threatening. The purpose of this study was to assess the effects of the chronic stimulation or inhibition of nitric oxide synthesis in rats with hepatic fibrosis induced by permanent common bile duct ligation (3 weeks) and the role of expression of the different nitric oxide synthase isoforms. Bile duct ligation led to an important accumulation of collagen in the hepatic parenchyma, as shown both histologically and by the hydroxyproline contents of livers. Bilirubin and serum enzyme activities (measured as markers of cholestasis) increased several-fold after bile duct ligation. The area of fibrotic tissue, liver hydroxyproline content and serum markers of cholestasis were clearly related in obstructed rats. The absence of modifications in haemodynamic parameters excludes circulatory changes from being responsible for the development of liver alterations. In animals treated with NG nitro-L-arginine methyl ester (L-NAME) the area of fibrosis was similar to that of untreated animals, the signs of cholestasis and cellular injury being more evident. In rats treated with L-arginine the area of fibrosis was almost three times larger than that found in bile duct ligated rats and in L-NAME-treated bile duct ligated rats, although the observed biochemical changes were similar to those seen in rats treated with L-NAME. Our results with inducible nitric oxide synthase, obtained by Western blots and immunohistochemistry, indicate a greater expression of the inducible enzyme in bile duct ligated and L-arginine-treated animals and a lower expression in the L-NAME and control groups. Constitutive nitric oxide synthase expression, obtained by Western blots, was very similar in all groups, except for the L-arginine-treated rats in which it was lower. These results suggest that nitric oxide production may be a key factor in the development of fibrosis in bile duct ligated rats. They also support the hypothesis of a dual role for nitric oxide; one beneficial, mediated by its circulatory effects, and the second negative, through its local toxic effects. PMID- 10029567 TI - Divergent effects of intracerebroventricular and peripheral leptin administration on feeding and hypothalamic neuropeptide Y in lean and obese (fa/fa) Zucker rats. AB - Leptin inhibits feeding and decreases body weight. It may act partly by inhibiting hypothalamic neurons that express neuropeptide Y, a powerful inducer of feeding and obesity. These neuropeptide Y neurons express the Ob-Rb leptin receptor and are overactive in the fatty (fa/fa) Zucker rat. The fa mutation affects the extracellular domain of the leptin receptor, but its impact on leptin action and neuropeptide Y neuronal activity is not fully known. We compared the effects of three doses of leptin given intracerebroventricularly and three doses of leptin injected intraperitoneally on food intake and hypothalamic neuropeptide Y mRNA, in lean and fatty Zucker rats. In lean rats, 4-h food intake was reduced in a dose-related fashion (P<0.01) by all intracerebroventricular leptin doses and by intraperitoneal doses of 300 and 600 microg/kg. Neuropeptide Y mRNA levels were reduced by 28% and 21% after the highest intracerebroventricular and intraperitoneal doses respectively (P<0. 01 for both). In fatty rats, only the highest intracerebroventricular leptin dose reduced food intake (by 22%; P<0. 01). Neuropeptide Y mRNA levels were 100% higher in fatty rats than in lean animals, and were reduced by 18% (P<0.01) after the highest intracerebroventricular leptin dose. Intraperitoneal injection had no effect on food intake and neuropeptide Y mRNA. The fa/fa Zucker rat is therefore less sensitive to leptin given intracerebroventricularly and particularly intraperitoneally, suggesting that the fa mutation interferes both with leptin's direct effects on neurons and its transport into the central nervous system. Obesity in the fa/fa Zucker rat may be partly due to the inability of leptin to inhibit hypothalamic neuropeptide Y neurons. PMID- 10029568 TI - Evolution in BLOOD PMID- 10029569 TI - Resolving conflicting signals: cross inhibition of cytokine signaling pathways. PMID- 10029570 TI - Downregulation of interleukin-12 (IL-12) responsiveness in human T cells by transforming growth factor-beta: relationship with IL-12 signaling. AB - Interleukin-12 (IL-12) is a cytokine that plays a central role in the control of cell-mediated immunity. We have previously shown that transforming growth factor beta1 (TGF-beta) inhibitory effects on human primary allogeneic cytotoxicity and proliferative responses interfere with IL-12 pathway. The present study was undertaken to further elucidate the biochemical basis of the functional interaction between these two cytokines and to define the site of TGF-beta action on the signaling pathway activated by IL-12. Our data indicate that TGF-beta induced an inhibition of interferon-gamma (IFN-gamma) production without affecting the IL-12Rbeta1 and IL-12Rbeta2 subunits mRNA expression by activated T cells. We further show that TGF-beta has a significant inhibitory effect on the early signal transduction events following interaction of IL-12 with its receptor on activated T cells, resulting in the inhibition of both JAK2 and Tyk2 phosphorylation. In addition, TGF-beta was found to significantly inhibit IL-12 induced phosphorylation of the STAT4 transcription factor. Electrophoretic mobility shift assay indicated that TGF-beta induced a decrease in IL-12-induced STAT4 DNA binding activity in T lymphocytes. This study suggests that TGF-beta influences IL-12 responsiveness at least in part by inhibiting early signaling events essential to gene induction in IL-12-activated T cells. PMID- 10029571 TI - Interleukin-10 inhibits expression of both interferon alpha- and interferon gamma induced genes by suppressing tyrosine phosphorylation of STAT1. AB - Interleukin-10 (IL-10) helps maintain polarized T-helper cells in a T-helper lymphocyte 2 (Th2) phenotype. Part of this process involves the prevention of the development of Th1 cells, which are a primary source of interferon gamma (IFNgamma), a potent activator of monocytes and an inhibitor of Th2 proliferation. Because monocytes and macrophages are important mediators of Th1 type responses, such as delayed-type hypersensitivity, we sought to determine if IL-10 could directly mediate inhibition of IFNgamma- and IFNalpha-induced gene expression in these cells. Highly purified monocytes were incubated with IL-10 for 60 to 90 minutes before the addition of IFNgamma or IFNalpha. IL-10 preincubation resulted in the inhibition of gene expression for several IFN induced genes, such as IP-10, ISG54, and intercellular adhesion molecule-1. The reduction in gene expression resulted from the ability of IL-10 to suppress IFN induced assembly of signal transducer and activator of transcription (STAT) factors to specific promoter motifs on IFNalpha- and IFNgamma-inducible genes. This was accomplished by preventing the IFN-induced tyrosine phosphorylation of STAT1, a component of both IFNalpha- and IFNgamma-induced DNA binding complexes. Therefore, IL-10 can directly inhibit STAT-dependent early response gene expression induced by both IFNalpha and IFNgamma in monocytes by suppressing the tyrosine phosphorylation of STAT1. This may occur through the ability of IL-10 to induce expression of the gene, suppressor of cytokine signaling 3 (SOCS3). PMID- 10029572 TI - NADPH oxidase: an update. PMID- 10029573 TI - Constitutive degradation of PML/RARalpha through the proteasome pathway mediates retinoic acid resistance. AB - PML/RARalpha is the leukemogenetic protein of acute promyelocytic leukemia (APL). Treatment with retinoic acid (RA) induces degradation of PML/RARalpha, differentiation of leukaemic blasts, and disease remission. However, RA resistance arises during RA treatment of APL patients. To investigate the phenomenon of RA resistance in APL, we generated RA-resistant sublines from APL derived NB4 cells. The NB4.007/6 RA-resistant subline does not express the PML/RARalpha protein, although its mRNA is detectable at levels comparable to those of the parental cell line. In vitro degradation assays showed that the half life of PML/RARalpha is less than 30 minutes in NB4.007/6 and longer than 3 hours in NB4. Treatment of NB4.007/6 cells with the proteasome inhibitors LLnL and lactacystin partially restored PML/RARalpha protein expression and resulted in a partial release of the RA-resistant phenotype. Similarly, forced expression of PML/RARalpha, but not RARalpha, into the NB4/007.6 cells restored sensitivity to RA treatment to levels comparable to those of the NB4 cells. These results indicate that constitutive degradation of PML/RARalpha protein may lead to RA resistance and that PML/RARalpha expression is crucial to convey RA sensitivity to APL cells. PMID- 10029574 TI - Detection of Kaposi's sarcoma herpesvirus DNA sequences in multiple myeloma bone marrow stromal cells. AB - Whether Kaposi's sarcoma herpesvirus (KSHV) is associated with multiple myeloma (MM) remains controversial. We assayed for KSHV DNA sequences in long-term bone marrow stromal cells (BMSCs) from 26 patients with MM and 4 normal donors. Polymerase chain reaction (PCR) using primers which amplify a KSHV gene sequence to yield a 233-bp fragment (KS330233 within open reading frame 26) was negative in all cases. Aliquots of these PCR products were used as templates in subsequent nested PCR, with primers that amplify a 186-bp product internal to KS330233. BMSCs from 24 of 26 (92%) patients with MM and 1 of 4 normal donors were KSHV PCR+. DNA sequence analyses showed interpatient specific mutations (2 to 3 bp). Both Southern blot and sequence analyses confirmed the specificity of PCR results. The presence of the KSHV gene sequences was further confirmed by amplifying T 1.1 (open reading frame [ORF] K7) and viral cyclin D (ORF 72), two other domains within the KSHV genome. Immunohistochemical studies of KSHV PCR+ MM BMSCs demonstrate expression of dendritic cell (DC) lineage markers (CD68, CD83, and fascin). Serological studies for the presence of KSHV lytic or latent antibodies were performed using sera from 53 MM patients, 12 normal donors, and 5 human immunodeficiency virus (HIV)/KSHV+ patients. No lytic or latent antibodies were present in sera from either MM patients or normal donors. Taken together, these findings show that KSHV DNA sequences are detectable in BMSCs from the majority of MM patients, but that serologic responses to KSHV are not present. Ongoing studies are defining whether the lack of antibody response is caused by the absence of ongoing infection, the presence of a novel viral strain associated with MM, or underlying immunodeficiency in these patients. PMID- 10029575 TI - Bone marrow and peripheral blood dendritic cells from patients with multiple myeloma are phenotypically and functionally normal despite the detection of Kaposi's sarcoma herpesvirus gene sequences. AB - Multiple myeloma (MM) cells express idiotypic proteins and other tumor-associated antigens which make them ideal targets for novel immunotherapeutic approaches. However, recent reports show the presence of Kaposi's sarcoma herpesvirus (KSHV) gene sequences in bone marrow dendritic cells (BMDCs) in MM, raising concerns regarding their antigen-presenting cell (APC) function. In the present study, we sought to identify the ideal source of DCs from MM patients for use in vaccination approaches. We compared the relative frequency, phenotype, and function of BMDCs or peripheral blood dendritic cells (PBDCs) from MM patients versus normal donors. DCs were derived by culture of mononuclear cells in the presence of granulocyte-macrophage colony-stimulating factor and interleukin-4. The yield as well as the pattern and intensity of Ag (HLA-DR, CD40, CD54, CD80, and CD86) expression were equivalent on DCs from BM or PB of MM patients versus normal donors. Comparison of PBDCs versus BMDCs showed higher surface expression of HLA-DR (P =.01), CD86 (P =. 0003), and CD14 (P =.04) on PBDCs. APC function, assessed using an allogeneic mixed lymphocyte reaction (MLR), demonstrated equivalent T-cell proliferation triggered by MM versus normal DCs. Moreover, no differences in APC function were noted in BMDCs compared with PBDCs. Polymerase chain reaction (PCR) analysis of genomic DNA from both MM patient and normal donor DCs for the 233-bp KSHV gene sequence (KS330233) was negative, but nested PCR to yield a final product of 186 bp internal to KS330233 was positive in 16 of 18 (88.8%) MM BMDCs, 3 of 8 (37.5%) normal BMDCs, 1 of 5 (20%) MM PBDCs, and 2 of 6 (33.3%) normal donor PBDCs. Sequencing of 4 MM patient PCR products showed 96% to 98% homology to the published KSHV gene sequence, with patient specific mutations ruling out PCR artifacts or contamination. In addition, KHSV-specific viral cyclin D (open reading frame [ORF] 72) was amplified in 2 of 5 MM BMDCs, with sequencing of the ORF 72 amplicon revealing 91% and 92% homology to the KSHV viral cyclin D sequence. These sequences again demonstrated patient specific mutations, ruling out contamination. Therefore, our studies show that PB appears to be the preferred source of DCs for use in vaccination strategies due to the ready accessibility and phenotypic profile of PBDCs, as well as the comparable APC function and lower detection rate of KSHV gene sequences compared with BMDCs. Whether active KSHV infection is present and important in the pathophysiology of MM remains unclear; however, our study shows that MMDCs remain functional despite the detection of KSHV gene sequences. PMID- 10029576 TI - Susceptibility to childhood acute lymphoblastic leukemia: influence of CYP1A1, CYP2D6, GSTM1, and GSTT1 genetic polymorphisms. AB - Although acute lymphoblastic leukemia (ALL) is the most common childhood cancer, factors governing susceptibility to this disease have not yet been identified. As such, ALL offers a useful opportunity to examine the glutathione S-transferase and cytochrome P450 genes in determining susceptibility to pediatric cancers. Both enzymes are involved in carcinogen metabolism and have been shown to influence the risk a variety of solid tumors in adults. To determine whether these genes played a similar role in childhood leukemogenesis, we compared the allele frequencies of 177 childhood ALL patients and 304 controls for the CYP1A1, CYP2D6, GSTM1, and GSTT1 genes. We chose the French population of Quebec as our study population because of its relative genetic homogeneity. The GSTM1 null and CYP1A1*2A genotypes were both found to be significant predictors of ALL risk (odds ratio [OR] = 1.8). Those possessing both genotypes were at an even greater risk of developing the disease (OR = 3.3). None of the other alleles tested for proved to be significant indicators of ALL risk. Unexpectedly, girls carrying the CYP1A1*4 were significantly underrepresented in the ALL group (OR = 0.2), suggesting that a gender-specific protective role exists for this allele. These results suggest that the risk of ALL may indeed be associated with xenobiotics metabolism, and thus with environmental exposures. Our findings may also explain, in part, why ALL is more prevalent among males than females. PMID- 10029577 TI - A prospective study on TT virus infection in transfusion-dependent patients with beta-thalassemia. AB - A novel DNA virus designated TT virus (TTV) has been reported to be involved in the development of posttransfusion non-A-C hepatitis. We evaluated the frequency and natural course of TTV infection in a cohort of transfusion-dependent thalassemic patients in a 3-year follow-up study. Ninety-three serum hepatitis C virus (HCV) antibody-negative patients (median age of 8 years; range, 0 to 25) from eight centers were studied. Of them, 34 (37%) had an abnormal alanine aminotransferase (ALT) baseline pattern, and the other 12 (13%) showed ALT flare ups during the follow-up. TTV DNA in patient sera collected at the time of enrollment and at the end of follow-up was determined by polymerase chain reaction (PCR). In parallel, serum samples from 100 healthy blood donors were also tested. At baseline, 87 patient sera (93.5%) tested positive for the TTV DNA. Of these TTV DNA-positive patients, 84 (96.5%) remained viremic at the end of the study period. Of the 6 TTV DNA-negative patients, 3 acquired TTV infection during follow-up. However, no definite relation was observed between the results of TTV DNA determination and ALT patterns. TTV viremia was also detectable in 22% of blood donors. In conclusion, TTV infection is frequent and persistent among Italian transfusion-dependent patients. The high rate of viremia observed in healthy donors indicates that the parenteral route is not the only mode of TTV spread. PMID- 10029578 TI - Rapid death of adoptively transferred T cells in acquired immunodeficiency syndrome. AB - Human immunodeficiency virus (HIV)-specific cytotoxic T lymphocytes (CTL) probably play the major role in controlling HIV replication. However, the value of adoptive transfer of HIV-specific CTL expanded in vitro to HIV+ patients has been limited: this contrasts with the success of CTL therapy in treating or preventing Epstein-Barr virus and cytomegalovirus disease after bone marrow transplantation (BMT). We investigated the fate of expanded HIV-specific CTL clones in vivo following adoptive transfer to a patient with acquired immunodeficiency syndrome (AIDS). Two autologous CTL clones specific for HIV Gag and Pol were expanded to large numbers (>10(9)) in vitro and infused into an HIV infected patient whose viral load was rising despite antiretroviral therapy. The fate of one clone was monitored by staining peripheral blood mononuclear cells (PBMCs) with T-cell receptor-specific tetrameric major histocompatibility complex (MHC)-peptide complexes. Although the CTL transfer was well tolerated, there were no significant changes in CD4 and CD8 lymphocyte counts and virus load. By tracking an infused clone using soluble MHC-peptide complexes, we show that cells bearing the Gag-specific T-cell receptors were rapidly eliminated within hours of infusion through apoptosis. Thus, the failure of adoptively transferred HIV specific CTL to reduce virus load in AIDS may be due to rapid apoptosis of the infused cells, triggered by a number of potential mechanisms. Further trials of adoptive transfer of CTL should take into account the susceptibility of infused cells to in vivo apoptosis. PMID- 10029579 TI - Phenotypic and functional evidence for the expression of CXCR4 receptor during megakaryocytopoiesis. AB - The identification of stromal cell-derived factor (SDF)-1alpha as a chemoattractant for human progenitor cells suggests that this chemokine and its receptor might represent critical determinants for the homing, retention, and exit of precursor cells from hematopoietic organs. In this study, we investigated the expression profile of CXCR4 receptor and the biological activity of SDF 1alpha during megakaryocytopoiesis. CD34(+) cells from bone marrow and cord blood were purified and induced to differentiate toward the megakaryocyte lineage by a combination of stem-cell factor (SCF) and recombinant human pegylated megakaryocyte growth and development factor (PEG-rhuMGDF). After 6 days of culture, a time where mature and immature megakaryocytes were present, CD41(+) cells were immunopurified and CXCR4mRNA expression was studied. High transcript levels were detected by a RNase protection assay in cultured megakaryocytes derived from cord blood CD34(+) cells as well as in peripheral blood platelets. The transcript levels were about equivalent to that found in activated T cells. By flow cytometry, a large fraction (ranging from 30% to 100%) of CD41(+) cells showed high levels of CXCR4 antigen on their surface, its expression increasing in parallel with the CD41 antigen during megakaryocytic differentiation. CXCR4 protein was also detected on peripheral blood platelets. SDF-1alpha acts on megakaryocytes by inducing intracellular calcium mobilization and actin polymerization. In addition, in in vitro transmigration experiments, a significant proportion of megakaryocytes was observed to respond to this chemokine. This cell migration was inhibited by pertussis toxin, indicating coupling of this signal to heterotrimeric guanine nucleotide binding proteins. Although a close correlation between CD41a and CXCR4 expession was observed, cell surface markers as well as morphological criteria indicate a preferential attraction of immature megakaryocytes (low level of CD41a and CD42a), suggesting that SDF-1alpha is a potent attractant for immature megakaryocytic cells but is less active on fully mature megakaryocytes. This hypothesis was further supported by the observation that SDF-1alpha induced the migration of colony forming unit megakaryocyte progenitors (CFU-MK) and the expression of activation-dependent P selectin (CD62P) surface antigen on early megakaryocytes, although no effect was observed on mature megakaryocytes and platelets. These results indicate that CXCR4 is expressed by human megakaryocytes and platelets. Furthermore, based on the lower responses of mature megakaryocytes and platelets to SDF-1alpha as compared with early precursors, these data suggest a role for this chemokine in the maintenance and homing during early stages of megakaryocyte development. Moreover, because megakaryocytes are also reported to express CD4, it becomes important to reevaluate the role of direct infection of these cells by the human immunodeficiency virus (HIV)-1 in HIV-1-related thrombocytopenia. PMID- 10029580 TI - Enhanced myeloid progenitor cell cycling and apoptosis in mice lacking the chemokine receptor, CCR2. AB - Chemokines regulate hematopoiesis in part by influencing the proliferative status of myeloid progenitor cells (MPC). Human MCP-1/murine JE, a myelosuppressive chemokine, specifically binds C-C chemokine receptor 2 (CCR2). Transgenic mice containing a targeted disruption in CCR2 that prevents expression of CCR2 mRNA and protein and have MPC that are insensitive to inhibition by MCP-1 and JE in vitro were assessed for potential abnormalities in growth of bone marrow (BM) and spleen MPC. MPC in both unseparated and c-kit+lin- populations of BM from CCR2 deficient (-/-) mice were in a greatly increased proliferation state compared with CCR2 littermate control (+/+) mice, an effect not apparent with progenitors from spleens of CCR2 (-/-) mice. Increased cycling status of CCR2 (-/-) BM MPC did not result in increased numbers of nucleated cells or MPC in BM or spleens of CCR2 (-/-) mice. Possible reasons for this apparent discrepancy were highlighted by flow cytometric analysis of c-kit+lin- BM cells and colony formation by MPC subjected to delayed addition of growth factors. The c-kit+lin- population of BM cells from CCR2 (-/-) mice had a significantly higher percentage of apoptotic cells than those from CCR2 (+/+) BM. However, elevated apoptosis was not associated with decreased numbers of c-kit+lin- cells. The increased percentage of apoptotic c-kit+lin- cells was due to elevated apoptosis within the c kitdimlin-, but not the c-kitbrightlin-, subpopulations of cells. Consistent with enhanced apoptosis of phenotypically defined cells, MPC from CCR2 (-/-) BM and purified c-kit+lin- cells demonstrated decreased cell survival in vitro upon delayed addition of growth factors. The data suggest that signals received by CCR2 limit proliferation of progenitor cells in the BM, but also enhance survival of these cells. PMID- 10029581 TI - Autografting with philadelphia chromosome-negative mobilized hematopoietic progenitor cells in chronic myelogenous leukemia. AB - Intensive chemotherapy given in early chronic phase of chronic myelogenous leukemia (CML) has resulted in high numbers of circulating Philadelphia (Ph) chromosome-negative hematopoietic progenitor cells (HPC). We have autografted 30 consecutive patients with CML in chronic phase with HPC collected in this way to facilitate restoration of Ph-negative hematopoiesis in bone marrow after high dose therapy. Hematopoietic recovery to greater than 0.5 x10(9)/L neutrophils and to greater than 25 x 10(9)/L platelets occurred in all patients, a median of 13 (range, 9 to 32) days and 16 (range, 6 to 106) days postautograft, respectively. Regenerating marrow cells were Ph-negative in 16 (53%) patients and greater than 66% Ph-negative in 10 (33%) patients. Twenty-eight patients are alive 6 to 76 months (median, 24 months) after autografting. Three patients have developed blast crisis from which 2 have died. Eight patients are in complete cytogenetic remission at a median of 20 (range, 6 to 44) months with a median ratio BCR ABL/ABL of 0.002 (range, <0.001 to 0.01). Eight patients are in major cytogenetic remission at a median of 22 (range, 6 to 48) months. No patient died as a consequence of the treatment. All patients had some degree of stomatitis that was severe in 15 (50%) patients. Gastrointestinal and hepatic toxicities were observed in about one fourth of patients. Thus, autografting with Ph-negative mobilized HPC can result in prolonged restoration of Ph-negative hematopoiesis for some patients with CML; moreover, most autograft recipients report normal or near normal activity levels, suggesting that this procedure need not to be associated either with prolonged convalescence or with chronic debility. PMID- 10029582 TI - H-Ras is involved in the inside-out signaling pathway of interleukin-3-induced integrin activation. AB - The proto-oncogene product, p21(ras), has been implicated in the cellular mechanism of adhesion, although its precise role has been controversial. Numerous cytokines and growth-factors activate Ras, which is an important component of their growth-promoting signaling pathways. On the other hand, the role of Ras in cytokine-induced adhesion has not been elucidated. We therefore investigated the function of H-Ras in the inside-out signaling pathway of interleukin-3 (IL-3) induced integrin activation in the murine Baf3 cell line after transfection of cells with either constitutively active, dominant-negative, or wild-type H-Ras cDNAs. Adhesion of Baf3 cells to fibronectin was induced by IL-3 in a dose dependent manner via very late antigen-4 (VLA-4; alpha4beta1 integrins) and VLA-5 (alpha5beta1 integrins) activation. On the other hand, IL-4 did not induce the adhesion of Baf3 cells to fibronectin, although IL-4 did stimulate the cell proliferation of Baf3 cells. Constitutively active H-Ras-transfected Baf3 cells adhered to fibronectin without IL-3 stimulation through VLA-4 and VLA-5, whereas dominant-negative H-Ras-transfected Baf3 cells showed significantly less adhesion induced by IL-3 compared with wild-type and constitutively active H-Ras transfected Baf3 cells. Anti-beta1 integrin antibody (clone; 9EG7), which is known to change integrin conformation and activate integrins, induced the adhesion of dominant-negative H-Ras-transfected Baf3 cells as much as the other types of H-Ras-transfected Baf3 cells. 8-Br-cAMP, Dibutyryl-cAMP, Ras-Raf-1 pathway inhibitors, and PD98059, a MAPK kinase inhibitor, suppressed proliferation and phosphorylation of MAPK detected by Western blotting with anti phospho-MAPK antibody, but not adhesion of any type of H-Ras-transfected Baf3 cells, whereas U-73122, a phospholipase C (PLC) inhibitor, suppressed adhesion of these cells completely. These data indicate that H-Ras and PLC, but not Raf-1, MAPK kinase, or the MAPK pathway, are involved in the inside-out signaling pathway of IL-3-induced VLA-4 and VLA-5 activation in Baf3 cells. PMID- 10029583 TI - In vitro hematopoietic and endothelial cell development from cells expressing TEK receptor in murine aorta-gonad-mesonephros region. AB - Recent studies have shown that long-term repopulating hematopoietic stem cells (HSCs) first appear in the aorta-gonad-mesonephros (AGM) region. Our immunohistochemistry study showed that TEK+ cells existed in the AGM region. Approximately 5% of AGM cells were TEK+, and most of these were CD34(+) and c Kit+. We then established a coculture system of AGM cells using a stromal cell line, OP9, which is deficient in macrophage colony-stimulating factor (M-CSF). With this system, we showed that AGM cells at 10.5 days postcoitum (dpc) differentiated and proliferated into both hematopoietic and endothelial cells. Proliferating hematopoietic cells contained a significant number of colony forming cells in culture (CFU-C) and in spleen (CFU-S). Among primary AGM cells at 10.5 dpc, sorted TEK+ AGM cells generated hematopoietic cells and platelet endothelial cell adhesion molecule (PECAM)-1(+) endothelial cells on the OP9 stromal layer, while TEK- cells did not. When a ligand for TEK, angiopoietin-1, was added to the single-cell culture of AGM, endothelial cell growth was detected in the wells where hematopoietic colonies grew. Although the incidence was still low (1/135), we showed that single TEK+ cells generated hematopoietic cells and endothelial cells simultaneously, using a single-cell deposition system. This in vitro coculture system shows that the TEK+ fraction of primary AGM cells is a candidate for hemangioblasts, which can differentiate into both hematopoietic cells and endothelial cells. PMID- 10029584 TI - Organ-selective homing defines engraftment kinetics of murine hematopoietic stem cells and is compromised by Ex vivo expansion. AB - Hematopoietic reconstitution of ablated recipients requires that intravenously (IV) transplanted stem and progenitor cells "home" to organs that support their proliferation and differentiation. To examine the possible relationship between homing properties and subsequent engraftment potential, murine bone marrow (BM) cells were labeled with fluorescent PKH26 dye and injected into lethally irradiated hosts. PKH26(+) cells homing to marrow or spleen were then isolated by fluorescence-activated cell sorting and assayed for in vitro colony-forming cells (CFCs). Progenitors accumulated rapidly in the spleen, but declined to only 6% of input numbers after 24 hours. Although egress from this organ was accompanied by a simultaneous accumulation of CFCs in the BM (plateauing at 6% to 8% of input after 3 hours), spleen cells remained enriched in donor CFCs compared with marrow during this time. To determine whether this differential homing of clonogenic cells to the marrow and spleen influenced their contribution to short-term or long-term hematopoiesis in vivo, PKH26(+) cells were sorted from each organ 3 hours after transplantation and injected into lethally irradiated Ly-5 congenic mice. Cells that had homed initially to the spleen regenerated circulating leukocytes (20% of normal counts) approximately 2 weeks faster than cells that had homed to the marrow, or PKH26-labeled cells that had not been selected by a prior homing step. Both primary (17 weeks) and secondary (10 weeks) recipients of "spleen-homed" cells also contained approximately 50% higher numbers of CFCs per femur than recipients of "BM-homed" cells. To examine whether progenitor homing was altered upon ex vivo expansion, highly enriched Sca-1(+)c-kit+Lin- cells were cultured for 9 days in serum-free medium containing interleukin (IL)-6, IL-11, granulocyte colony-stimulating factor, stem cell factor, flk-2/flt3 ligand, and thrombopoietin. Expanded cells were then stained with PKH26 and assayed as above. Strikingly, CFCs generated in vitro exhibited a 10-fold reduction in homing capacity compared with fresh progenitors. These studies demonstrate that clonogenic cells with differential homing properties contribute variably to early and late hematopoiesis in vivo. The dramatic decline in the homing capacity of progenitors generated in vitro underscores critical qualitative changes that may compromise their biologic function and potential clinical utility, despite their efficient numerical expansion. PMID- 10029585 TI - Role of cytokine signaling molecules in erythroid differentiation of mouse fetal liver hematopoietic cells: functional analysis of signaling molecules by retrovirus-mediated expression. AB - Erythropoietin (EPO) and its cell surface receptor (EPOR) play a central role in proliferation, differentiation, and survival of erythroid progenitors. Signals induced by EPO have been studied extensively by using erythroid as well as nonerythroid cell lines, and various controversial results have been reported as to the role of signaling molecules in erythroid differentiation. Here we describe a novel approach to analyze the EPO signaling by using primary mouse fetal liver hematopoietic cells to avoid possible artifacts due to established cell lines. Our strategy is based on high-titer retrovirus vectors with a bicistronic expression system consisting of an internal ribosome entry site (IRES) and green fluorescent protein (GFP). By placing the cDNA for a signaling molecule in front of IRES-GFP, virus-infected cells can be viably sorted by fluorescence-activated cell sorter, and the effect of expression of the signaling molecule can be assessed. By using this system, expression of cell-survival genes such as Bcl-2 and Bcl-XL was found to enhance erythroid colony formation from colony-forming unit-erythroid (CFU-E) in response to EPO. However, their expression was not sufficient for erythroid colony formation from CFU-E alone, indicating that EPO induces signals for erythroid differentiation. To examine the role of EPOR tyrosine residues in erythroid differentiation, we introduced a chimeric EGFR EPOR receptor, which has the extracellular domain of the EGF receptor and the intracellular domain of the EPOR, as well as a mutant EGFR-EPOR in which all the cytoplasmic tyrosine residues are replaced with phenylalanine, and found that tyrosine residues of EPOR are essential for erythroid colony formation from CFU E. We further analyzed the function of the downstream signaling molecules by expressing modified signaling molecules and found that both JAK2/STAT5 and Ras, two major signaling pathways activated by EPOR, are involved in full erythroid differentiation. PMID- 10029586 TI - Receptor clearance obscures the magnitude of granulocyte-macrophage colony stimulating factor responses in mice to endotoxin or local infections. AB - Marrow cells from mice lacking high-affinity receptors for granulocyte-macrophage colony-stimulating factor (GM-CSF; betac-/- mice) were shown to bind and internalize much less GM-CSF than cells from normal (betac+/+) mice. betac-/- mice were used to determine the effect of negligible receptor-mediated clearance on detectible GM-CSF responses to the intravenous injection of endotoxin or the intraperitoneal injection of casein plus microorganisms. Unlike the minor serum GM-CSF responses to endotoxin seen in betac+/+ mice, serum GM-CSF levels rose 30 fold to 9 ng/mL in betac-/- mice even though loss of GM-CSF in the urine was greater than in betac+/+ mice. Organs from betac-/- and betac+/+ mice had a similar capacity to produce GM-CSF in vitro, as did peritoneal cells from both types of mice when challenged in vitro by casein. However, when casein was injected intraperitoneally, betac-/- mice developed higher and more sustained levels of GM-CSF than did betac+/+ mice. The data indicated that receptor dependent removal of GM-CSF masks the magnitude of GM-CSF responses to endotoxin and local infections. Because of this phenomenon, serum GM-CSF concentrations can be a misleading index of the occurrence or nonoccurrence of GM-CSF responses to infections. PMID- 10029587 TI - Structural and functional abnormalities in the spleen of an mFtz-F1 gene disrupted mouse. AB - The spleen has two main functions. The first is to provide a proper microenvironment to lymphoid and myeloid cells, whereas the second involves clearance of abnormal erythrocytes. Ad4BP/SF-1, a product of the mammalian FTZ-F1 gene (mFTZ-F1), was originally identified as a steroidogenic, tissue-specific transcription factor. Immunohistochemical examination of the mammalian spleens confirmed the expression of Ad4BP/SF-1 in endothelial cells of the splenic venous sinuses and pulp vein. In mFtz-F1 gene-disrupted (KO) mice, several structural abnormalities were detected in the spleen, including underdevelopment and nonuniform distribution of erythrocytes. Examination of the spleen of KO fetuses showed failure of development of certain tubular structures during embryogenesis. These structures are normally assembled by Ad4BP/SF-1 immunoreactive cells, and most likely form the vascular system during later stages of development. Other structural abnormalities in the spleen of the KO mice included defects in the tissue distribution of type-IV collagen, laminin, c-kit, and vimentin. These morphologic defects in the vascular system were associated with a decrease in the proportion of hematopoietic cells, although differentiation of these cells was not affected significantly. A high number of abnormal red blood cells containing Howell-Jolly bodies were noted in the KO mice, indicating impaired clearance by the splenic vascular system. We also detected the presence of an mRNA-encoding cholesterol side-chain cleavage P450 in the spleen, resembling the findings in steroidogenic tissues such as the gonads and adrenal cortex. The mRNA transcript was not involved in splenic structural defects as it was detected in the spleens of both normal and KO mice, indicating that the regulatory mechanism of the P450 gene in the spleen is different from that in steroidogenic tissues. Our results indicate that a lack of the mFtz-F1 gene in mice is associated with structural and functional abnormalities of the splenic vascular system. PMID- 10029588 TI - Prospective evaluation of the thrombotic risk in children with acute lymphoblastic leukemia carrying the MTHFR TT 677 genotype, the prothrombin G20210A variant, and further prothrombotic risk factors. AB - The reported incidence of thromboembolism in children with acute lymphoblastic leukemia (ALL) treated with L-asparaginase, vincristine, and prednisone varies from 2.4% to 11.5%. The present study was designed to prospectively evaluate the role of the TT677 methylenetetrahydrofolate reductase (MTHFR) genotype, the prothrombin G20210A mutation, the factor V G1691A mutation, deficiencies of protein C, protein S, antithrombin, and increased lipoprotein (a) concentrations in leukemic children treated according to the ALL-Berlin-Frankfurt-Muenster (BFM) 90/95 study protocols with respect to the onset of vascular events. Three hundred and one consecutive leukemic children were enrolled in this study. Fifty-five of these 301 subjects investigated had one established single prothrombotic risk factor: 20 children showed the TT677 MTHFR genotype; 5 showed the heterozygous prothrombin G20210A variant; 11 were carriers of the factor V G1691A mutation (heterozygous, n = 10; homozygous, n = 1); 4 showed familial protein C, 4 protein S, and 2 antithrombin type I deficiency; 9 patients were suffering from familially increased lipoprotein (a) [Lp(a)] concentrations (>30 mg/dL). In addition, combined prothrombotic defects were found in a further 10 patients: the FV mutation was combined with the prothrombin G20210A variant (n = 1), increased Lp(a) (n = 3), protein C deficiency (n = 1), and homozygosity for the C677T MTHFR gene mutation (n = 1). Lp(a) was combined with protein C deficiency (n = 2) and the MTHFR TT 677 genotype (n = 2). Two hundred eighty-nine of the 301 patients were available for thrombosis-free survival analysis. In 32 (11%) of these 289 patients venous thromboembolism occurred. The overall thrombosis-free survival in patients with at least one prothrombotic defect was significantly reduced compared with patients without a prothrombotic defect within the hemostatic system (P <.0001). In addition, a clear-cut positive correlation (P <.0001) was found between thrombosis and the use of central lines. However, because the prothrombotic defects diagnosed in the total childhood population studied were all found within the prevalences reported for healthy Caucasian individuals, the interaction between prothrombotic risk factors, ALL treatment, and further environmental factors is likely to cause thrombotic manifestations. PMID- 10029589 TI - The Megakaryocyte/Platelet-specific enhancer of the alpha2beta1 integrin gene: two tandem AP1 sites and the mitogen-activated protein kinase signaling cascade. AB - The alpha2beta1 integrin, a collagen receptor on platelets and megakaryocytes, is required for normal platelet function. Transcriptional regulation of the alpha2 integrin gene in cells undergoing megakaryocytic differentiation requires a core promoter between bp -30 and -92, a silencer between bp -92 and -351, and megakaryocytic enhancers in the distal 5' flank. We have now identified a 229-bp region of the distal 5' flank of the alpha2 integrin gene required for high-level enhancer activity in cells with megakaryocytic features. Two tandem AP1 binding sites with dyad symmetry are required for enhancer activity and for DNA-protein complex formation with members of the c-fos/c-jun family. The requirement for AP1 activation suggested a role for the mitogen-activated protein kinase (MAPK) signaling pathway in regulating alpha2 integrin gene expression. Inhibition of the MAP kinase cascade with PD98059, a specific inhibitor of MAPK kinase 1, prevented the expression of the alpha2 integrin subunit in cells induced to become megakaryocytic. We provide a model of megakaryocytic differentiation in which expression of the alpha2 integrin gene requires signaling via the MAP kinase pathway to activate two tandem AP1 binding sites in the alpha2 integrin enhancer. PMID- 10029590 TI - Contribution of natural killer cells to inhibition of angiogenesis by interleukin 12. AB - Interleukin-12 (IL-12) inhibits angiogenesis in vivo by inducing interferon-gamma (IFN-gamma) and other downstream mediators. Here, we report that neutralization of natural killer (NK) cell function with antibodies to either asialo GM1 or NK 1.1 reversed IL-12 inhibition of basic fibroblast growth factor (bFGF)-induced angiogenesis in athymic mice. By immunohistochemistry, those sites where bFGF induced neovascularization was inhibited by IL-12 displayed accumulation of NK cells and the presence of IP-10-positive cells. Based on expression of the cytolytic mediators perforin and granzyme B, the NK cells were locally activated. Experimental Burkitt lymphomas treated locally with IL-12 displayed tumor tissue necrosis, vascular damage, and NK-cell infiltration surrounding small vessels. After activation in vitro with IL-12, NK cells from nude mice became strongly cytotoxic for primary cultures of syngeneic aortic endothelial cells. Cytotoxicity was neutralized by antibodies to IFN-gamma. These results document that NK cells are required mediators of angiogenesis inhibition by IL-12, and provide evidence that NK-cell cytotoxicity of endothelial cells is a potential mechanism by which IL-12 can suppress neovascularization. PMID- 10029591 TI - Labeling of the internal pool of GP IIb-IIIa in platelets by c7E3 Fab fragments (abciximab): flow and endocytic mechanisms contribute to the transport. AB - Abciximab is a new antiplatelet therapeutic in ischemic cardiovascular disease. The drug, chimeric Fab fragments of a murine monoclonal antibody (MoAb) (c7E3), blocks GP IIb-IIIa function. However, its capacity to reach all receptor pools in platelets is unknown. Electron microscopy and immunogold labeling were used to localize abciximab in platelets of patients receiving the drug for up to 24 hours. Studies on frozen-thin sections showed that c7E3 Fab, in addition to the surface pool, also labeled the surface-connected canalicular system (SCCS) and alpha-granules. Analysis of gold particle distribution showed that intraplatelet labeling was not accumulative and in equilibrium with the surface pool. After short-term incubations of platelets with c7E3 Fab in vitro, gold particles were often seen in lines within thin elements of the SCCS, some of which appeared in contact with alpha-granules. Little labeling was associated with Glanzmann's thrombasthenia platelets, confirming that the channels contained bound and not free c7E3 Fab. Endocytosis of abciximab in clathrin-containing vesicles was visualized by double staining and constitutes an alternative mechanism of transport. The remaining free pool of GP IIb-IIIa was evaluated with the MoAb AP 2; flow cytometry showed it to be about 9% on the surface of nonstimulated platelets but 33% on thrombin-activated platelets. The ability of drugs to block all pools of GP IIb-IIIa and then to be associated with secretion-dependent residual aggregation must be considered when evaluating their efficiency in a clinical context. PMID- 10029592 TI - Interleukin-10-treated human dendritic cells induce a melanoma-antigen-specific anergy in CD8(+) T cells resulting in a failure to lyse tumor cells. AB - Dendritic cells (DC) are critically involved in the initiation of primary immune processes, including tumor rejection. In our study, we investigated the effect of interleukin-10 (IL-10)-treated human DC on the properties of CD8(+) T cells that are known to be essential for the destruction of tumor cells. We show that IL-10 pretreatment of DC not only reduces their allostimulatory capacity, but also induces a state of alloantigen-specific anergy in both primed and naive (CD45RA+) CD8(+) T cells. To investigate the influence of IL-10-treated DC on melanoma associated antigen-specific T cells, we generated a tyrosinase-specific CD8(+) T cell line by several rounds of stimulation with the specific antigen. After coculture with IL-10-treated DC, restimulation of the T-cell line with untreated, antigen-pulsed DC demonstrated peptide-specific anergy in the tyrosinase-specific T cells. Addition of IL-2 to the anergic T cells reversed the state of both alloantigen- or peptide-specific anergy. In contrast to optimally stimulated CD8(+) T cells, anergic tyrosinase-specific CD8(+) T cells, after coculture with peptide-pulsed IL-10-treated DC, failed to lyse an HLA-A2-positive and tyrosinase expressing melanoma cell line. Thus, our data demonstrate that IL-10-treated DC induce an antigen-specific anergy in cytotoxic CD8(+) T cells, a process that might be a mechanism of tumors to inhibit immune surveillance by converting DC into tolerogenic antigen-presenting cells. PMID- 10029593 TI - Reduced folate carrier expression in acute lymphoblastic leukemia: a mechanism for ploidy but not lineage differences in methotrexate accumulation. AB - Methotrexate (MTX) is one of the most active and widely used agents for the treatment of acute lymphoblastic leukemia (ALL). To elucidate the mechanism for higher accumulation of MTX polyglutamates (MTX-PG) in hyperdiploid ALL and lower accumulation in T-lineage ALL, expression of the reduced folate carrier (RFC) was assessed by reverse transcription-polymerase chain reaction in ALL blasts isolated from newly diagnosed patients. RFC expression exhibited a 60-fold range among 29 children, with significantly higher expression in hyperdiploid B-lineage ALL (median, 11.3) compared with nonhyperdiploid ALL (median, 2.1; P <.0006), but no significant difference between nonhyperdiploid B-lineage and T-lineage ALL. Furthermore, mRNA levels of RFC (mapped by FISH to chromosome 21) were significantly related to chromosome 21 copy number (P =.0013), with the highest expression in hyperdiploid ALL blasts with 4 copies of chromosome 21. To assess the functional significance of gene copy number, MTX-PG accumulation was compared in ALL blasts isolated from 121 patients treated with either low-dose MTX (LDMTX; n = 60) or high-dose MTX (HDMTX; n = 61). After LDMTX, MTX-PG accumulation was highest in hyperdiploid B-lineage ALL with 4 copies of chromosome 21 (P =.011), but MTX-PG accumulation was not significantly related to chromosome 21 copy number after HDMTX (P =.24). These data show higher RFC expression as a mechanism for greater MTX accumulation in hyperdiploid B-lineage ALL and indicate that lineage differences in MTX-PG accumulation are not due to lower RFC expression in T-lineage ALL. PMID- 10029594 TI - Clonality of isolated eosinophils in the hypereosinophilic syndrome. AB - The idiopathic hypereosinophilic syndrome (IHES) is a rare disorder characterized by unexplained, persistent eosinophilia associated with multiple organ dysfunction due to eosinophilic tissue infiltration. In the absence of karyotypic abnormalities, there is no specific test to detect clonal eosinophilia in IHES. Analysis of X-chromosome inactivation patterns can be used to determine whether proliferative disorders are clonal in origin. Methylation of HpaII and Hha I sites near the polymorphic trinucleotide repeat of the human androgen receptor gene (HUMARA) has been shown to correlate with X-inactivation. In this study, we have used the polymerase chain reaction (PCR) with nested primers to analyze X inactivation patterns of the HUMARA loci in purified eosinophils from female patients with eosinophilia. Peripheral blood eosinophils were isolated by their autofluoresence using flow cytometric sorting. Eosinophils purified from a female patient presenting with IHES were found to show a clonal pattern of X inactivation. Eosinophil-depleted leukocytes from this patient were polyclonal by HUMARA analysis, thus excluding skewedness of random X-inactivation. After corticosteroid suppression of her blood eosinophilia, a clonal population of eosinophils could no longer be detected in purified eosinophils. In contrast, eosinophils purified from a patient with Churg-Strauss syndrome and from six patients with reactive eosinophilias attributed to allergy, parasitic infection, or drug reaction showed a polyclonal pattern of X-inactivation by HUMARA analysis. The finding of clonal eosinophilia in a patient presenting with IHES indicates that such patients may have, in reality, a low-grade clonal disorder that can be distinguished from reactive eosinophilias by HUMARA analysis. Further, the method described can be used to monitor disease progression. PMID- 10029596 TI - Expression and function of leptin receptor isoforms in myeloid leukemia and myelodysplastic syndromes: proliferative and anti-apoptotic activities. AB - The receptor for the gene product of the obesity gene, leptin, was recently reported to be expressed on murine and human hematopoietic progenitor cells. Therefore, we studied the expression of the leptin receptor, OB-R, in normal myeloid precursors, human leukemia cell lines, and primary leukemic cells using reverse-transcriptase polymerase chain reaction. In normal hematopoiesis, OB-R was expressed in CD34(+) cells. Normal promyelocytes (CD34(-)33(+) and CD34( )13(+)) expressed only very low levels of the short, presumably nonsignaling isoform. Both the long and short isoforms of OB-R were expressed in 10 of 22 samples from patients with newly diagnosed primary or secondary acute myeloid leukemia (AML), with a higher incidence of the long isoform in primary AML (87.6% v 28.6%; P =.01). The incidence of OB-R expression was higher in recurrent than in newly diagnosed AML (P <.001), and samples from four patients with refractory AML showed strong expression of both isoforms. Both OB-R isoforms were also expressed in newly diagnosed and recurrent acute promyelocytic leukemia cells but were essentially absent in samples of chronic or acute lymphocytic leukemia. In vitro growth of myeloid leukemic cell lines and of blasts from 14 primary AMLs demonstrated that recombinant human leptin alone induced low level proliferation, significantly (P <.05) increased proliferation induced by recombinant human granulocyte colony-stimulating factor, interleukin 3, and stem cell factor in a subset of AML and increased colony formation (P <.005). Also, leptin reduced apoptosis induced by cytokine withdrawal in MO7E and TF-1 cells. Serum leptin levels correlated only with body mass index (P <. 001) and gender (P =.03). Results confirm the reported expression of leptin receptor in normal CD34(+) cells and demonstrate the frequent expression of leptin receptors in AML blasts. While normal promyelocytes lack receptor expression, leukemic promyelocytes express both isoforms. We also demonstrate proliferative effects of leptin alone and in combination with other physiologic cytokines, and anti-apoptotic properties of leptin. These findings could have implications for the pathophysiology of AML. PMID- 10029595 TI - Cell adhesion mediated drug resistance (CAM-DR): role of integrins and resistance to apoptosis in human myeloma cell lines. AB - Integrin-mediated adhesion influences cell survival and may prevent programmed cell death. Little is known about how drug-sensitive tumor cell lines survive initial exposures to cytotoxic drugs and eventually select for drug-resistant populations. Factors that allow for cell survival following acute cytotoxic drug exposure may differ from drug resistance mechanisms selected for by chronic drug exposure. We show here that drug-sensitive 8226 human myeloma cells, demonstrated to express both VLA-4 (alpha4beta1) and VLA-5 (alpha5beta1) integrin fibronectin (FN) receptors, are relatively resistant to the apoptotic effects of doxorubicin and melphalan when pre-adhered to FN and compared with cells grown in suspension. This cell adhesion mediated drug resistance, or CAM-DR, was not due to reduced drug accumulation or upregulation of anti-apoptotic Bcl-2 family members. As determined by flow cytometry, myeloma cell lines selected for drug resistance, with either doxorubicin or melphalan, overexpress VLA-4. Functional assays revealed a significant increase in alpha4-mediated cell adhesion in both drug resistant variants compared with the drug-sensitive parent line. When removed from selection pressure, drug-resistant cell lines reverted to a drug sensitive and alpha4-low phenotype. Whether VLA-4-mediated FN adhesion offers a survival advantage over VLA-5-mediated adhesion remains to be determined. In conclusion, we have demonstrated that FN-mediated adhesion confers a survival advantage for myeloma cells acutely exposed to cytotoxic drugs by inhibiting drug-induced apoptosis. This finding may explain how some cells survive initial drug exposure and eventually express classical mechanisms of drug resistance such as MDR1 overexpression. PMID- 10029597 TI - Role of folylpolyglutamate synthetase and folylpolyglutamate hydrolase in methotrexate accumulation and polyglutamylation in childhood leukemia. AB - Inefficient polyglutamylation is a mechanism of resistance to methotrexate (MTX) in childhood T-lineage acute lymphoblastic leukemia (T-ALL) and in acute myeloid leukemia (AML) in comparison with childhood c/preB-ALL. We analyzed the profile of MTX polyglutamylation in childhood c/preB-ALL, T-ALL, and AML (n = 45, 15, and 14, respectively), the activity of the MTX-polyglutamate synthesizing enzyme folylpolyglutamate synthetase (FPGS) (n = 39, 11, and 19, respectively) and of the MTX-polyglutamate breakdown enzyme folylpolyglutamate hydrolase (FPGH) (n = 98, 25, and 34, respectively). MTX-Glu4-6 accumulation after 24 hours exposure to 1 micromol/L [3H]-MTX in vitro was lower in T-ALL (threefold) and AML (fourfold) compared with c/preB-ALL (P /=3 cm, 9 or more mitoses, or >/=300 Ki67-positive cells per 10 high-power fields identified 26 of 33 (79%) malignant (metastatic or deeply invasive) tumors, and size <1 cm and/or growth restricted to the mucosa characterized 46 of 69 (67%) tumors with benign behavior during a median follow-up of 39 months. Malignancy-predictive models were developed using angioinvasion, size, clinicopathologic type, mitotic index, and Ki67 index. The same variables, in addition to deep gastric wall invasion and histological grade, predicted patient outcome. CONCLUSIONS: Criteria for the assessment of malignancy risk and patient outcome were developed for the different tumors, providing a basis for treatment guidelines. PMID- 10029612 TI - Micrometastases in esophagogastric cancer: high detection rate in resected rib segments. AB - BACKGROUND & AIMS: Micrometastases within bone marrow indicate a poor prognosis. We prospectively examined micrometastases in patients undergoing resection of esophagogastric cancers for (1) prevalence in rib marrow; (2) comparative detection rates in rib and iliac crest marrow; (3) responsiveness to neoadjuvant therapy; and (4) viability and tumorigenicity. METHODS: In 50 consecutive patients, marrow was obtained before manipulation of the primary tumor. Micrometastatic cells were detected by staining contaminant cytokeratin-18 positive cells. Viability and tumorigenicity were determined by culture and xenograft. RESULTS: Micrometastases were detected in rib marrow from 88% of patients (44 of 50). When bilateral iliac crest marrow was also obtained, micrometastases were found in 15% (4 of 27) compared with 89% (24 of 27) for ribs (P < 0.001). Detection rates were independent of histological type or nodal status and were similar in patients with and without neoadjuvant therapy. Metastatic cells were cultured from rib marrow of 5 of 7 patients and were tumorigenic in nude mice. CONCLUSIONS: Most patients undergoing resection of esophagogastric malignancies have micrometastases in rib marrow. Detection rates based on iliac crest marrow are underestimates. Hematogenous spread of metastatic cells is independent of histological type or nodal status. The metastatic cells are viable, tumorigenic, and resistant to neoadjuvant therapy. PMID- 10029613 TI - Safety and efficacy of dynamic muscle plasty for anal incontinence: lessons from a prospective, multicenter trial. AB - BACKGROUND & AIMS: Dynamic muscle plasty has been advocated as therapy for refractory fecal incontinence and for anorectal reconstruction to avoid colostomy after abdominoperineal resection. This study evaluates the results of a multicenter experience with dynamic muscle plasty in the treatment of fecal incontinence and total anal reconstruction. METHODS: One hundred thirty-nine patients were enrolled at 12 centers between June 1992 and November 1994 and followed up through June 1996. Intramuscular leads and neurostimulators were implanted to stimulate transposed gracilis or gluteus muscle. Success was defined as 70% reduction in solid stool incontinence for patients with baseline incontinence and zero incontinence to solid stool for patients with baseline stomas and for patients undergoing total anal reconstruction. RESULTS: Overall, 85 of 128 graciloplasty patients (66%) achieved and maintained a successful outcome over the follow-up period. By etiology, these proportions were 71%, 50%, and 66% for patients with acquired fecal incontinence, congenital incontinence, and total anal reconstruction, respectively. One third of graciloplasty patients experienced a major wound complication, with therapy failing in 41%. Experienced centers had better outcomes and lower complication rates than inexperienced centers. Of the 11 gluteoplasty patients, 5 (45%) achieved and maintained a successful outcome. CONCLUSIONS: Dynamic graciloplasty may be an effective procedure for patients with refractory, end-stage fecal incontinence as well as for patients who require anorectal excision for low-lying malignancy. However, the procedure has significant morbidity that can lead to functional failure. Outcome after dynamic graciloplasty appears to correlate with surgical experience. In contrast to graciloplasty, the use of dynamic gluteoplasty should be limited to investigational purposes. PMID- 10029614 TI - Lamina propria T cells in Crohn's disease and other gastrointestinal inflammation show defective CD2 pathway-induced apoptosis. AB - BACKGROUND & AIMS: Normal human lamina propria lymphocytes manifest increased unstimulated apoptosis compared with peripheral lymphocytes, which are enhanced after stimulation via the CD2 activation pathway. This activation-induced apoptosis down-regulates cell expansion and cytokine production. In previous studies, it was shown that lamina propria T cells from patients with Crohn's disease and ulcerative colitis manifest abnormal proliferation and cytokine production. It was therefore of interest to determine if such cells also showed abnormal patterns of apoptosis. METHODS: Apoptosis was evaluated by propidium iodide staining of cells followed by flow cytometric analysis. Fas expression and Bcl-2 levels in cells were evaluated by immunofluorescence. RESULTS: Lamina propria lymphocytes from patients with Crohn's disease and ulcerative colitis as well as from 2 patients with diverticulitis showed defective CD2 pathway-induced apoptosis. Studies of the mechanisms of this defect focusing on cells from patients with Crohn's disease showed that Crohn's disease lamina propria lymphocytes from inflamed tissues express the same amount of cell surface Fas but are less sensitive to Fas-mediated apoptosis than control cells. In addition, lamina propria lymphocytes from inflamed Crohn's disease tissues manifest increased expression of Bcl-2 after CD2 pathway stimulation and elevated Bcl-2 levels in cultures of unstimulated T cells. CONCLUSIONS: T cells isolated from areas of inflammation in Crohn's disease, ulcerative colitis, and other inflammatory states manifest decreased CD2 pathway-induced apoptosis. Studies of cells from inflamed Crohn's disease tissue indicate that this defect is accompanied by elevated Bcl-2 levels. These changes are probably caused by the chronic inflammation and may aggravate the underlying disease processes that are present. PMID- 10029615 TI - Serum immunoglobulin A from patients with celiac disease inhibits human T84 intestinal crypt epithelial cell differentiation. AB - BACKGROUND & AIMS: Celiac disease is characterized by disturbed jejunal crypt villus axis biology with immunoglobulin (Ig) A deposits underlining the epithelium. The aim of this study was to test whether celiac disease serum IgA (reticulin/endomysial autoantibodies) interferes with the mesenchymal-epithelial cell cross-talk. METHODS: Differentiation of T84 epithelial cells was induced with IMR-90 fibroblasts or transforming growth factor beta in three-dimensional collagen gel cultures. The effects of purified celiac IgA and monoclonal tissue transglutaminase antibodies (CUB7402) were studied by adding the antibodies to the cocultures. RESULTS: Active celiac disease IgA, reactive for tissue transglutaminase, significantly inhibited T84 epithelial cell differentiation (P < 0.001) and increased epithelial cell proliferation (P = 0.024). Similar effects were obtained with antibodies against tissue transglutaminase. CONCLUSIONS: Celiac disease-associated IgA class antibodies disturb transforming growth factor beta-mediated fibroblast-epithelial cell cross-talk in this in vitro crypt-villus axis model. This primary finding indicates that celiac disease-specific autoantibodies may also contribute to the formation of the gluten-triggered jejunal mucosal lesion in celiac disease. PMID- 10029616 TI - Modulation of gastric sensory and motor functions by nitrergic and alpha2 adrenergic agents in humans. AB - BACKGROUND & AIMS: Disturbed gastric accommodation and sensation contribute to postprandial symptoms in dyspepsia, but the controlling mechanisms are unclear. Nitrergic and alpha2-adrenergic modulation of gastric sensory and motor function were assessed in this study. METHODS: Using a factorial design, we assessed drug effects on gastric sensation during isobaric distentions and fasting and postprandial gastric motor function in 32 healthy volunteers. Each participant received one treatment: placebo; 0.3 or 0.5 microgram. kg-1. min-1 intravenous nitroglycerin; 0.0125, 0.025, or 0.1 mg clonidine orally; or combined nitroglycerin plus clonidine. In 16 other healthy subjects, the effects of clonidine and placebo on gastric emptying of solids were evaluated using the 13C octanoic acid breath test. RESULTS: Clonidine and nitroglycerin increased gastric compliance, but normal postprandial accommodation was still observed despite the induced relaxation. Clonidine but not nitroglycerin reduced aggregate and pain perception averaged over four distention levels. There were no significant drug interactions. No dose effect of clonidine was observed on gastric emptying. CONCLUSIONS: Clonidine relaxes the stomach and reduces gastric sensation without inhibiting accommodation or emptying. Nitroglycerin relaxes the stomach without altering perception. Studies of the effects of clonidine on these gastric functions and symptoms in disease are warranted. PMID- 10029617 TI - Protease-activated receptors mediate apamin-sensitive relaxation of mouse and guinea pig gastrointestinal smooth muscle. AB - BACKGROUND & AIMS: Protease-activated receptor (PAR)-1 and PAR-2 are expressed on gastrointestinal smooth muscle, but knowledge of their functionality is limited. The aim of this study was to determine if PAR-1 and PAR-2 mediate gastrointestinal smooth muscle relaxation and to clarify the underlying mechanisms. METHODS: Responses to PAR activation using the serine proteases thrombin and trypsin and the peptide agonists for PAR-1 and PAR-2, SFLLRN-NH2 and SLIGRL-NH2, respectively, were investigated in submaximally contracted longitudinal strips of mouse gastric fundus and guinea pig taenia coli. RESULTS: In mouse gastric fundus, both thrombin and trypsin caused relaxations followed by contractions. SFLLRN-NH2 and SLIGRL-NH2 caused similar biphasic responses, the relaxation components of which were eliminated by apamin or ryanodine. For SFLLRN NH2, apamin and ryanodine revealed contractions. Nifedipine inhibited both relaxations and contractions to each peptide. In guinea-pig taenia coli, thrombin but not trypsin caused relaxation, whereas SFLLRN-NH2 and SLIGRL-NH2 caused concentration-dependent relaxations that were eliminated by apamin but were unaffected by ryanodine. CONCLUSIONS: The mouse gastric fundus and guinea pig taenia coli contain functional PAR-1 and PAR-2 that mediate relaxations via ryanodine-sensitive and -insensitive activation of small-conductance, Ca2+ activated K+ channels. We propose that smooth muscle PARs act as sensors for inflammatory signals in gut and respond by inhibiting gut motility during peritoneal infections or tissue damage. PMID- 10029618 TI - Tumor necrosis factor inhibitor ameliorates murine intestinal graft-versus-host disease. AB - BACKGROUND & AIMS: Transfer of T helper cells from DBA/2 mice to irradiated allogeneic B6D2F1 mice leads to development of colonic graft-versus-host disease with pathological features of inflammatory bowel disease. To examine the role of tumor necrosis factor (TNF) in graft-versus-host disease enteropathy, an adenoviral vector encoding a TNF inhibitor protein was administered. METHODS: Irradiated B6D2F1 mice were infused with DBA/2 bone marrow and spleen cells. Mice then received either a control beta-galactosidase-encoding adenovirus or an adenovirus encoding a TNF inhibitor, composed of the extracellular domain of the human 55-kilodalton TNF receptor linked to the murine immunoglobulin G1 heavy chain. Mucosal permeability to sucralose and colonic histology were assessed 14 and 25 days after transplantation. RESULTS: Less diarrhea was observed in DBA/2 - > B6D2F1 mice expressing the TNF inhibitor, and colonic sections from these mice had significantly less inflammation and epithelial cell abnormalities. In TNF inhibitor recipients, mucosal permeability to sucralose was similar to that in nonirradiated control mice and significantly less than in recipients of the control adenovirus. CONCLUSIONS: TNF inhibition decreases the severity of enteropathy in the DBA/2 --> B6D2F1 murine model of colonic graft-versus-host disease. PMID- 10029620 TI - Transcytosis of immunoglobulin A in the mouse enterocyte occurs through glycolipid raft- and rab17-containing compartments. AB - BACKGROUND & AIMS: Glycolipid "rafts" have been shown to play a role in apical membrane trafficking in the enterocyte. The present study characterized the membrane compartments of the enterocyte involved in transepithelial transport of small intestinal immunoglobulin A (IgA). METHODS: Immunogold electron microscopy and radioactive labeling of mouse small intestinal explants were performed. RESULTS: IgA and the polymeric immunoglobulin receptor/secretory component were present in a raft compartment. Raft association occurred posttranslationally within 30 minutes, preceding secretion into the culture medium. IgA labeling was seen primarily in enterocytes along the basolateral plasma membrane and over endosomes and small vesicles in the basolateral and apical regions of the cytoplasm. IgA and a brush border enzyme, aminopeptidase N, were colocalized in apical endosomes and small vesicles and were also frequently seen associated with the same vesicular profiles of glycolipid rafts. Colocalization of IgA and rab17, a small guanosine triphosphatase involved in transcytosis, was seen mainly along the basolateral plasma membrane and over basolateral endosomes and vesicles, but also in the apical region of the cytoplasm. CONCLUSIONS: IgA is transcytosed through a raft-containing compartment, most likely the apical endosomes. Our data also support the notion that rab17 is involved in transcytotic membrane traffic. PMID- 10029619 TI - Mesalamine blocks tumor necrosis factor growth inhibition and nuclear factor kappaB activation in mouse colonocytes. AB - BACKGROUND & AIMS: Derivatives of 5-aminosalicylic acid (mesalamine) represent a mainstay in inflammatory bowel disease therapy, yet the precise mechanism of their therapeutic action is unknown. Because tumor necrosis factor (TNF)-alpha is important in the pathogenesis of inflammatory bowel disease, we investigated the effect of mesalamine on TNF-alpha-regulated signal transduction and proliferation in intestinal epithelial cells. METHODS: Young adult mouse colon cells were studied with TNF-alpha, epidermal growth factor, or ceramide in the presence or absence of mesalamine. Proliferation was studied by hemocytometry. Mitogen activated protein (MAP) kinase activation and IkappaBalpha expression were determined by Western blot analysis. Nuclear transcription factor kappaB (NF kappaB) nuclear translocation was determined by confocal laser immunofluorescent microscopy. RESULTS: The antiproliferative effects of TNF-alpha were blocked by mesalamine. TNF-alpha and ceramide activation of MAP kinase were inhibited by mesalamine, whereas epidermal growth factor activation of MAP kinase was unaffected. TNF-alpha-stimulated NF-kappaB activation and nuclear translocation and the degradation of Ikappa-Balpha were blocked by mesalamine. CONCLUSIONS: Mesalamine inhibits TNF-alpha-mediated effects on intestinal epithelial cell proliferation and activation of MAP kinase and NF-kappaB. Therefore, it may function as a therapeutic agent based on its ability to disrupt critical signal transduction events in the intestinal cell necessary for perpetuation of the chronic inflammatory state. PMID- 10029622 TI - Real-time detection system for quantification of hepatitis C virus genome. AB - BACKGROUND & AIMS: For diagnosis of hepatitis C virus infection and monitoring of viral load in patients, a highly sensitive and accurate hepatitis C virus quantification system is essential. METHODS: Hepatitis C virus genome was detected by real/time detection system using an ABI Prism 7700 sequence detector (Perkin Elmer Corp./Applied Biosystems, Foster City, CA). RESULTS: As few as 10 copies of the genome were detected, and the quantification range was between 10(1) and 10(8) copies (r > 0.99). This system was 10-100-fold more sensitive than an Amplicor monitor (Roche Diagnostic Systems, Branchburg, NJ). The coefficient of variation values for both intra-assay precision and interassay reproducibility of identifying the genome quantification ranged from 0.37% to 2.00% and 0.88% to 4.66%, respectively. The system could detect the genome in 98% of patients with chronic hepatitis, 95.8% of patients with liver cirrhosis, and 100% of patients with hepatocellular carcinoma who had the antibody to hepatitis C virus, but could not detect the genome in patients without the antibody. CONCLUSIONS: The establishment of a real-time detection system enables more accurate diagnosis of infection and monitoring of viral load in interferon treated patients via quantification of viral genome. PMID- 10029621 TI - Pituitary adenylate cyclase-activating polypeptide modulates gastric enterochromaffin-like cell proliferation in rats. AB - BACKGROUND & AIMS: Gastric carcinoids (types I and II) involve the transformation of naive enterochromaffin-like (ECL) cells to the neoplastic state and are associated primarily with hypergastrinemia. In this study, we evaluated the effects of two related neuropeptides, pituitary adenylate cyclase-activating polypeptide (PACAP) and vasoactive intestinal polypeptide (VIP), on ECL cell proliferation and characterized the receptor subtype(s) and signal transduction pathways that mediate this effect. METHODS: Purified rat ECL cells were analyzed in culture for DNA synthesis as measured by 24-hour 5-bromo-2-deoxyuridine (BrdU) uptake. Reverse-transcription polymerase chain reaction (RT-PCR) with gene specific oligonucleotide primers was performed to characterize the PACAP/VIP receptor subtype(s). RESULTS: PACAP/VIP neuropeptide-stimulated BrdU uptake was significantly greater (3.4-3.8-fold greater than control) than that at the maximal dose of gastrin (2.2-fold greater than control). PACAP-stimulated ECL cell proliferation (EC50, approximately 3 x 10(-)14 mol/L) was approximately 100 fold more potent than VIP (EC50, approximately 3x 10(-)12 mol/L). The stimulated BrdU uptake by both PACAP and VIP was competitively inhibited by PACAP-receptor antagonist (IC50, 10(-)9 mol/L, 3 x 10(-)9 mol/L, respectively) and VIP-receptor antagonist (IC50, 3 x 10(-)7 mol/L, 5 x 10(-)7 mol/L, respectively). RT-PCR identified the presence of the PACAP-specific but not PACAP/VIP receptor subtypes. The PACAP-stimulated BrdU uptake was inhibited (70%-80%) by inhibitors of adenosine 3',5'-cyclic monophosphate, phosphatidylinositol 3 kinase, and protein tyrosine kinase as well as mitogen-activated protein kinase. CONCLUSIONS: PACAP/VIP-related peptides are more potent modulators of ECL cell proliferation than gastrin, and their effect is mediated by a PACAP-specific receptor whose activation is transduced by multiple intracellular messenger systems. PMID- 10029623 TI - Formiminotransferase cyclodeaminase is an organ-specific autoantigen recognized by sera of patients with autoimmune hepatitis. AB - BACKGROUND & AIMS: Anti-liver cytosol type 1 autoantibodies have been reported in association with anti-liver-kidney microsome type 1 autoantibodies in 30% of patients with autoimmune hepatitis type II. In 10% of cases, anti-liver cytosol type 1 antibodies are the only liver-related circulating autoantibodies. The liver cytosol antigen is a liver-specific 62-kilodalton protein present in the cell as an oligomer of approximately 240 kilodaltons. The aim of this study was to identify the antigen recognized by anti-liver cytosol antibody. METHODS: To identify the liver cytosol antigen, an anti-liver cytosol type 1-positive serum was used for the screening of a complementary DNA library from HepG2 cells. Double immunodiffusion method was used to show the identity between the cytosolic and the cloned protein. RESULTS: The sequence of two isolated clones showed 85.2% homology with the formiminotransferase cyclodeaminase (FTCD) enzyme from pig liver. Antibodies purified by affinity with the recombinant protein and sera from mice immunized with FTCD recognized a 62-kilodalton human cytosolic protein when tested by immunoblot. The identity of precipitation lines was found between the cytosolic antigen and FTCD. CONCLUSIONS: This enzyme is a liver-specific antigen recognized by the sera of patients with autoimmune hepatitis. PMID- 10029624 TI - Differential antigen-processing pathways of the hepatitis B virus e and core proteins. AB - BACKGROUND & AIMS: Hepatitis B e antigen (HBeAg) and hepatitis B core antigen (HBcAg) seem to play different roles in the induction and regulation of the antiviral immune response, although the two antigens share all major CD4(+) T cell epitopes, and these epitopes can be processed from both antigens via the exogenous antigen-presenting pathway. The aim of this study was to test the ability of antigen-presenting cells to present epitopes from endogenously synthesized HBcAg/HBeAg on HLA class II molecules. METHODS: Lymphoblastoid cell lines infected with recombinant vaccinia viruses containing various HBcAg or HBeAg constructs and stable transfectants were tested for their ability to stimulate HBcAg/HBeAg-specific CD4(+) T-cell clones. RESULTS: Only antigen presenting cells infected with HBeAg constructs but not those infected with HBcAg constructs were able to stimulate HBcAg/HBeAg-specific CD4(+) T-cell clones. T cell activation by HBeAg constructs was completely inhibited by brefeldin A but not affected by chloroquin. In contrast, T-cell activation by exogenous, recombinant HBcAg was inhibited by chloroquin but not by brefeldin A. CONCLUSIONS: The findings indicate that processing and HLA class II-associated presentation of endogenously synthesized HBeAg in virus-infected cells, including hepatocytes, may occur. This mechanism may be involved in the regulation of the CD4(+) T-cell response to HBcAg/HBeAg. PMID- 10029625 TI - Protective and therapeutic effect of DNA-based immunization against hepadnavirus large envelope protein. AB - BACKGROUND & AIMS: Studies in the murine model suggest that injection of DNA encoding hepatitis B virus structural proteins is promising for the induction of a specific immune response. We used the duck hepatitis B virus (DHBV) model to study the protective and therapeutic effects of naked DNA immunization against hepadnaviral large envelope protein. METHODS: A pCI-preS/S plasmid expressing the DHBV large protein was used for intramuscular immunization of ducks. The humoral response was tested by enzyme-linked immunosorbent assay, immunoblotting, neutralization, and in vivo protection tests. For DNA therapy, DHBV-carrier ducks received four injections of this plasmid. Viremia was monitored for 10 months; thereafter, liver biopsies were performed. RESULTS: Immunization with pCI-preS/S plasmid induced a specific, long-lasting, neutralizing, and highly protective anti-preS humoral response in uninfected animals. After pCI-preS/S treatment, a significant and sustained decrease in serum and liver DHBV DNA was observed for carrier ducks compared with the controls. CONCLUSIONS: DNA immunization against DHBV large protein results in a potent and protective anti-preS response in the duck model. The results of long-term follow-up of DNA-treated chronically infected ducks are promising and show the usefulness of this model for the study of genetic immunization in chronic hepatitis B therapy. PMID- 10029626 TI - Involvement of CD95 (Apo-1/Fas) ligand expressed by rat Kupffer cells in hepatic immunoregulation. AB - BACKGROUND & AIMS: CD95 (Apo-1/Fas) ligand suppresses inflammatory responses in immune-privileged organs. In this study, modulation of the hepatic CD95 receptor/ligand system by interferon gamma and cyclosporin A was investigated. METHODS: CD95 receptor and ligand expression were measured at the messenger RNA level by using quantitative reverse-transcription polymerase chain reaction and immunocytochemistry in primary cultures of rat Kupffer cells, hepatocytes, and T lymphocytes. Soluble CD95 in culture supernatants was detected by enzyme-linked immunosorbent assay and apoptosis by the TUNEL method. RESULTS: Interferon gamma treatment led to an increase in CD95 ligand messenger RNA levels in Kupffer cells followed by an overexpression of the soluble CD95 receptor. Supernatants derived from 24-hour but not from 48-hour interferon gamma-treated Kupffer cells killed lymphocytes by a CD95-dependent mechanism. Cyclosporin A inhibited CD95 ligand expression in Kupffer cells and lymphocyte killing. In liver parenchymal cells, interferon gamma increased messenger RNA levels of the transmembrane CD95 isoform and sensitivity of these cells toward CD95-mediated apoptosis. CONCLUSIONS: The expression pattern of CD95 receptor and ligand in response to interferon gamma points to a coordinated interplay between Kupffer cells, hepatocytes, and T lymphocytes in which Kupffer cells may regulate programmed cell death of T lymphocytes and hepatocytes. PMID- 10029627 TI - Excess membrane cholesterol alters human gallbladder muscle contractility and membrane fluidity. AB - BACKGROUND & AIMS: The relationship between muscle contractility, plasma membrane cholesterol, and fluidity was investigated in human gallbladders with gallstones. METHODS: Isolated gallbladder muscle cells were used to measure contraction. Plasma membranes of gallbladder muscle were purified in a sucrose gradient and measured for cholesterol content and cholesterol/phospholipid mole ratio. Membrane fluidity was determined by using fluorescence polarization and was expressed as the reciprocal of anisotropy. RESULTS: The maximal contraction induced by cholecystokinin octapeptide was significantly less in gallbladders with cholesterol stones than in those with pigment stones. The membrane cholesterol content and cholesterol/phospholipid mole ratio were significantly higher in gallbladders with cholesterol stones than in those with pigment stones. Membrane anisotropy was also higher than in gallbladders with pigment stones, reflecting lower membrane fluidity in gallbladders with cholesterol stones. After muscle cells from cholesterol stone gallbladders were incubated with cholesterol free liposomes for 4 hours, cholecystokinin octapeptide-induced contraction, membrane cholesterol content and cholesterol/phospholipid ratio, and membrane fluidity returned to normal levels. CONCLUSIONS: Gallbladder muscle from patients with cholesterol stones has increased membrane cholesterol/phospholipid mole ratio and decreased membrane fluidity resulting in impaired muscle contractility. These abnormalities are corrected by removing the excess cholesterol from the plasma membranes. PMID- 10029628 TI - Mild hypothermia modifies ammonia-induced brain edema in rats after portacaval anastomosis. AB - BACKGROUND & AIMS: The pathogenesis of brain edema in fulminant hepatic failure is still unresolved. Mild hypothermia (33 degrees-35 degreesC) can ameliorate brain edema after traumatic brain injury. We evaluated mild hypothermia in a model of ammonia-induced brain edema in which accumulation of brain glutamine has been proposed as a key pathogenic factor. METHODS: After portacaval anastomosis, anesthetized rats were infused with ammonium acetate at 33 degrees, 35 degrees, and 37 degreesC or vehicle at 37 degreesC. Water and glutamine levels in the brain, cardiac output, and regional and cerebral hemodynamics were measured when intracranial pressure increased 3-4-fold (ammonia infusion at 37 degrees) and matched times (other groups). RESULTS: Mild hypothermia reduced ammonia-induced brain swelling and increased intracranial pressure. Brain glutamine level was not decreased by hypothermia. Brain edema was accompanied by a specific increase in cerebral blood flow and oxygen consumption, which were normal in both hypothermic groups. When the ammonia infusion was continued in hypothermic rats, plasma ammonia levels continued to increase and brain swelling eventually developed. CONCLUSIONS: Mild hypothermia delays ammonia-induced brain edema. In this model, an increase in cerebral perfusion is required for brain edema to become manifest. Mild hypothermia could be tested for treatment of intracranial hypertension in fulminant hepatic failure. PMID- 10029629 TI - The role of intercellular adhesion molecule 1 and neutrophils in acute pancreatitis and pancreatitis-associated lung injury. AB - BACKGROUND & AIMS: Intercellular adhesion molecule 1 (ICAM-1) and neutrophils play important roles in many inflammatory processes, but their importance in both acute pancreatitis and pancreatitis-associated lung injury has not been defined. METHODS: To address this issue, mice that do not express ICAM-1 were used and depleted of neutrophils by administration of antineutrophil serum. Pancreatitis was induced by administering either supramaximal doses of the secretagogue cerulein or feeding a choline-deficient, ethionine-supplemented diet. The severity of pancreatitis was evaluated by quantitating serum amylase, pancreatic edema, acinar cell necrosis, and pancreas myeloperoxidase activity (i.e., neutrophil content). Lung injury was evaluated by quantitating lung myeloperoxidase activity and pulmonary microvascular permeability. ICAM-1 was quantitated by enzyme-linked immunosorbent assay and was localized by light microscopic immunohistochemistry. RESULTS: It was found that serum, pancreas, and lung ICAM-1 levels increase during pancreatitis. Both pancreatitis and the associated lung injury are blunted, but not completely prevented, in mice deficient in ICAM-1. Neutrophil depletion also reduces the severity of both pancreatitis and lung injury. However, the combination of neutrophil depletion with ICAM-1 deficiency does not reduce the severity of pancreatitis or lung injury to a greater extent than either neutrophil depletion or ICAM-1 deficiency alone. Neither pancreatitis nor pancreatitis-associated lung injury are completely prevented by ICAM-1 deficiency, neutrophil depletion, or combined ICAM 1 deficiency plus neutrophil depletion. CONCLUSIONS: The observations indicate that ICAM-1 plays an important, neutrophil-mediated, proinflammatory role in pancreatitis and pancreatitis-associated lung injury. The studies also indicate that ICAM-1 and neutrophil-independent events also contribute to the evolution of pancreatitis and lung injury in these models. PMID- 10029631 TI - American Gastroenterological Association medical position statement on anorectal testing techniques. American Gastroenterological Association. AB - This document presents the official recommendations of the American Gastroenterological Association (AGA) on Anorectal Testing Techniques. It was approved by the Clinical Practice and Practice Economics Committee on May 17, 1998, and by the AGA Governing Board on July 24, 1998. PMID- 10029630 TI - Development of the human gastrointestinal tract: twenty years of progress. AB - A combination of approaches has begun to elucidate the mechanisms of gastrointestinal development. This review describes progress over the last 20 years in understanding human gastrointestinal development, including data from both human and experimental animal studies that address molecular mechanisms. Rapid progress is being made in the identification of genes regulating gastrointestinal development. Genes directing initial formation of the endoderm as well as organ-specific patterning are beginning to be identified. Signaling pathways regulating the overall right-left asymmetry of the gastrointestinal tract and epithelial-mesenchymal interactions are being clarified. In searching for extrinsic developmental regulators, numerous candidate trophic factors have been proposed, but compelling evidence remains elusive. A critical gene that initiates pancreas development has been identified, as well as a number of genes regulating liver, stomach, and intestinal development. Mutations in genes affecting neural crest cell migration have been shown to give rise to Hirschsprung's disease. Considerable progress has been achieved in understanding specific phenomena, such as the transcription factors regulating expression of sucrase-isomaltase and fatty acid-binding protein. The challenge for the future is to integrate these data into a more complete understanding of the physiology of gastrointestinal development. PMID- 10029632 TI - AGA technical review on anorectal testing techniques. AB - This literature review and the recommendations therein were prepared for the American Gastroenterological Association Clinical Practice and Practice Economics Committee. Following external review, the paper was approved by the committee on May 17, 1998. PMID- 10029633 TI - Functional dyspepsia: a case of indecision. PMID- 10029634 TI - "Real-time" polymerase chain reaction. PMID- 10029636 TI - Molecular staging of colorectal cancer: a step forward PMID- 10029635 TI - Do T cells "see" the hepatitis B core and e antigens differently? PMID- 10029638 TI - Stress management PMID- 10029637 TI - Early trypsinogen activation in acute pancreatitis PMID- 10029639 TI - Microscopic and collagenous colitis in treated celiac disease due to food allergy? PMID- 10029640 TI - Thrombosis, factor V Leiden, and inflammatory bowel disease. PMID- 10029641 TI - Vegetative infection of TIPS leading to "endotipsitis"? PMID- 10029642 TI - Effect of the interval between pregnancies on perinatal outcomes. AB - BACKGROUND: A short interval between pregnancies has been associated with adverse perinatal outcomes. Whether that association is due to confounding by other risk factors, such as maternal age, socioeconomic status, and reproductive history, is unknown. METHODS: We evaluated the interpregnancy interval in relation to low birth weight, preterm birth, and small size for gestational age by analyzing data from the birth certificates of 173,205 singleton infants born alive to multiparous mothers in Utah from 1989 to 1996. RESULTS: Infants conceived 18 to 23 months after a previous live birth had the lowest risks of adverse perinatal outcomes; shorter and longer interpregnancy intervals were associated with higher risks. These associations persisted when the data were stratified according to and controlled for 16 biologic, sociodemographic, and behavioral risk factors. As compared with infants conceived 18 to 23 months after a live birth, infants conceived less than 6 months after a live birth had odds ratios of 1.4 (95 percent confidence interval, 1.3 to 1.6) for low birth weight, 1.4 (95 percent confidence interval, 1.3 to 1.5) for preterm birth, and 1.3 (95 percent confidence interval, 1.2 to 1.4) for small size for gestational age; infants conceived 120 months or more after a live birth had odds ratios of 2.0 (95 percent confidence interval, 1.7 to 2.4);1.5 (95 percent confidence interval, 1.3 to 1.7), and 1.8 (95 percent confidence interval, 1.6 to 2.0) for these three adverse outcomes, respectively, when we controlled for all 16 risk factors with logistic regression. CONCLUSIONS: The optimal interpregnancy interval for preventing adverse perinatal outcomes is 18 to 23 months. PMID- 10029643 TI - A multistate, foodborne outbreak of hepatitis A. National Hepatitis A Investigation Team. AB - BACKGROUND: We investigated a large, foodborne outbreak of hepatitis A that occurred in February and March 1997 in Michigan and then extended the investigation to determine whether it was related to sporadic cases reported in other states among persons who had consumed frozen strawberries, the food suspected of causing the outbreak. METHODS: The cases of hepatitis A were serologically confirmed. Epidemiologic studies were conducted in the two states with sufficient numbers of cases, Michigan and Maine. Hepatitis A virus RNA detected in clinical specimens was sequenced to determine the relatedness of the virus from outbreak-related cases and other cases. RESULTS: A total of 213 cases of hepatitis A were reported from 23 schools in Michigan and 29 cases from 13 schools in Maine, with the median rate of attack ranging from 0.2 to 14 percent. Hepatitis A was associated with the consumption of frozen strawberries in a case control study (odds ratio for the disease, 8.3; 95 percent confidence interval, 2.1 to 33) and a cohort study (relative risk of infection, 7.5; 95 percent confidence interval, 1.1 to 53) in Michigan and in a case-control study in Maine (odds ratio for infection, 3.4; 95 percent confidence interval, 1.0 to 14). The genetic sequences of viruses from 126 patients in Michigan and Maine were identical to one another and to those from 5 patients in Wisconsin and 7 patients in Arizona, all of whom attended schools where frozen strawberries from the same processor had been served, and to those in 2 patients from Louisiana, both of whom had consumed commercially prepared products containing frozen strawberries from the same processor. CONCLUSIONS: We describe a large outbreak of hepatitis A in Michigan that was associated with the consumption of frozen strawberries. We found apparently sporadic cases in other states that could be linked to the same source by viral genetic analysis. PMID- 10029644 TI - Effects of family history and place and season of birth on the risk of schizophrenia. AB - BACKGROUND: Although a family history of schizophrenia is the best-established risk factor for schizophrenia, environmental factors such as the place and season of birth may also be important. METHODS: Using data from the Civil Registration System in Denmark, we established a population-based cohort of 1.75 million persons whose mothers were Danish women born between 1935 and 1978. We linked this cohort to the Danish Psychiatric Central Register and identified 2669 cases of schizophrenia among cohort members and additional cases among their parents. RESULTS: The respective relative risks of schizophrenia for persons with a mother, father, or sibling who had schizophrenia were 9.31 (95 percent confidence interval, 7.24 to 11.96), 7.20 (95 percent confidence interval, 5.10 to 10.16), and 6.99 (95 percent confidence interval, 5.38 to 9.09), as compared with persons with no affected parents or siblings. The risk of schizophrenia was associated with the degree of urbanization of the place of birth (relative risk for the capital vs. rural areas, 2.40; 95 percent confidence interval, 2.13 to 2.70). The risk was also significantly associated with the season of birth; it was highest for births in February and March and lowest for births in August and September. The population attributable risk was 5.5 percent for a history of schizophrenia in a parent or sibling, 34.6 percent for urban place of birth, and 10.5 percent for the season of birth. CONCLUSIONS: Although a history of schizophrenia in a parent or sibling is associated with the highest relative risk of having the disease, the place and season of birth account for many more cases on a population basis. PMID- 10029645 TI - Racial differences in the outcome of left ventricular dysfunction. AB - BACKGROUND: Population-based studies have found that black patients with congestive heart failure have a higher mortality rate than whites with the same condition. This finding has been attributed to differences in the severity, causes, and management of heart failure, the prevalence of coexisting conditions, and socioeconomic factors. Although these factors probably account for some of the higher mortality due to congestive heart failure among blacks, we hypothesized that racial differences in the natural history of left ventricular dysfunction might also have a role. METHODS: Using data from the Studies of Left Ventricular Dysfunction (SOLVD) prevention and treatment trials, in which all patients received standardized therapy and follow-up, we conducted a retrospective analysis of the outcomes of asymptomatic and symptomatic left ventricular systolic dysfunction among black and white participants. The mean (+/ SD) follow-up was 34.2+/-14.0 months in the prevention trial and 32.3+/-14.8 months in the treatment trial among the black and white participants. RESULTS: The overall mortality rates in the prevention trial were 8.1 per 100 person-years for blacks and 5.1 per 100 person years for whites. In the treatment trial, the rates were 16.7 per 100 person-years and 13.4 per 100 person-years, respectively. After adjustment for age, coexisting conditions, severity and causes of heart failure, and use of medications, blacks had a higher risk of death from all causes in both the SOLVD prevention trial (relative risk, 1.36; 95 percent confidence interval, 1.06 to 1.74; P=0.02) and the treatment trial (relative risk, 1.25; 95 percent confidence interval, 1.04 to 1.50; P=0.02). In both trials blacks were also at higher risk for death due to pump failure and for the combined end point of death from any cause or hospitalization for heart failure, our two predefined indicators of the progression of left ventricular systolic dysfunction. CONCLUSIONS: Blacks with mild-to-moderate left ventricular systolic dysfunction appear to be at higher risk for progression of heart failure and death from any cause than similarly treated whites. These results suggest that there may be racial differences in the outcome of asymptomatic and symptomatic left ventricular systolic dysfunction. PMID- 10029646 TI - Images in clinical medicine. Yolk sac with blood island. PMID- 10029647 TI - The effect of race and sex on physicians' recommendations for cardiac catheterization. AB - BACKGROUND: Epidemiologic studies have reported differences in the use of cardiovascular procedures according to the race and sex of the patient. Whether the differences stem from differences in the recommendations of physicians remains uncertain. METHODS: We developed a computerized survey instrument to assess physicians' recommendations for managing chest pain. Actors portrayed patients with particular characteristics in scripted interviews about their symptoms. A total of 720 physicians at two national meetings of organizations of primary care physicians participated in the survey. Each physician viewed a recorded interview and was given other data about a hypothetical patient. He or she then made recommendations about that patient's care. We used multivariate logistic-regression analysis to assess the effects of the race and sex of the patients on treatment recommendations, while controlling for the physicians' assessment of the probability of coronary artery disease as well as for the age of the patient, the level of coronary risk, the type of chest pain, and the results of an exercise stress test. RESULTS: The physicians' mean (+/-SD) estimates of the probability of coronary artery disease were lower for women (probability, 64.1+/-19.3 percent, vs. 69.2+/-18.2 percent for men; P<0.001), younger patients (63.8+/-19.5 percent for patients who were 55 years old, vs. 69.5+/-17.9 percent for patients who were 70 years old; P<0.001), and patients with nonanginal pain (58.3+/-19.0 percent, vs. 64.4+/-18.3 percent for patients with possible angina and 77.1+/-14.0 percent for those with definite angina; P=0.001). Logistic-regression analysis indicated that women (odds ratio, 0.60; 95 percent confidence interval, 0.4 to 0.9; P=0.02) and blacks (odds ratio, 0.60; 95 percent confidence interval, 0.4 to 0.9; P=0.02) were less likely to be referred for cardiac catheterization than men and whites, respectively. Analysis of race sex interactions showed that black women were significantly less likely to be referred for catheterization than white men (odds ratio, 0.4; 95 percent confidence interval, 0.2 to 0.7; P=0.004). CONCLUSIONS: Our findings suggest that the race and sex of a patient independently influence how physicians manage chest pain. PMID- 10029648 TI - The prevention of ventilator-associated pneumonia. PMID- 10029650 TI - The interval between pregnancies and the outcome of subsequent births. PMID- 10029651 TI - The case for routine childhood vaccination against hepatitis A. PMID- 10029652 TI - Understanding the causes of schizophrenia. PMID- 10029654 TI - Correction: Treatment of Asthma with Drugs Modifying the Leukotriene Pathway. PMID- 10029653 TI - Correction: Treatment of Hypokalemia. PMID- 10029656 TI - Pushing the Envelope of Health Care. PMID- 10029657 TI - Characterization of RNA in Cytologic Samples Preserved in a Methanol-Based Collection Solution. AB - Background: ThinPrep is a fluid-based technique for collection and processing of cytologic specimens. The present study was designed to determine whether the collection solution preserved RNA for molecular analysis. Methods and Results: Cervical cancer cell lines and cord blood lymphocytes were used to test the efficacy of various protocols for fixation, storage, and extraction of RNA. Total RNA was extracted and analyzed by denaturing gel electrophoresis. Preserved cells stored for 24 hours at room temperature or 4 degreesC had intact 28S and 18S ribosomal RNA. Both cellular and viral messenger RNAs were amplified from preserved samples by reverse transcription polymerase chain reaction (RT-PCR). Viral messenger RNA (mRNA) could be detected in a mixture of preserved cells containing 10% human papillomavirus (HPV) positive cells. RNA preservation in clinical samples was adequate for RT-PCR of cellular mRNA. Conclusions: Both experimental samples and clinical samples collected in the preservation media had intact total RNA. Amplification of both cellular and HPV ad mRNA was sucessful. PMID- 10029655 TI - The American health care system: Wall Street and health care. PMID- 10029658 TI - Comparison of Two Nonradioactive, Single-Strand Conformation Polymorphism Electrophoretic Methods for Identification of rpoB Mutations in Rifampin- Resistant Isolates of Mycobacterium tuberculosis. AB - Background: Diverse mutations in an 81 bp region of the rpoB gene are found in approximately 95% of rifampin-resistant (RIFr) Mycobacterium tuberculosis isolates. Various methods to detect these mutations have been evaluated for their usefulness as rapid screens for rifampin resistance. Methods and Results: Two nonradioactive variations of single-strand conformation polymorphism (SSCP) electrophoresis were optimized and evaluated for their ability to distinguish nine rpoB mutations present in a collection of 51 RIFr M. tuberculosis isolates. One of the methods used polymerase chain reaction products (128 bp) encompassing the 81 bp region of the rpoB gene, which were denatured in the presence of methyl mercury hydroxide, subjected to polyacrylamide gel electrophoresis (PAGE) and detected by staining with ethidium bromide. For the second method, fluorogenically labeled primers were used to generate products that were electrophoresed in an ABI Model 310 Genetic Analyzer equipped with a 3% GeneScan Polymer Column (Applied Biosystems Inc; Foster City, CA). Mobility shifts for all nine mutations were clearly discernible from the wild-type pattern by methods when tested in blind analyses. When an additional 30 isolates were tested by both SSCP methods in a blinded fashion, correlations with RIF susceptibility testing were complete for susceptible and homogeneously resistant isolates. Among three isolates with heterogeneously resistant populations, however, two were correctly identified by fluorescent SSCP compared with one by the PAGE SSCP method. Subpopulations of the His 526-->Tyr rpoB mutant, which is frequently encountered among RIFr strains, could be detected using templates prepared from mixtures of broth cultures with a susceptible strain. Conclusions: SSCP electrophoresis is useful for rapid screening for RIF resistance in susceptible and fully resistant isolates of M. tuberculosis. However, conventional susceptibility testing is still necessary for two reasons: (1) <100% of RIF strains have mutations in the 81 bp hotspot rpoB genomic region, and (2) SSCP may not offer sufficient sensitivity to detect clinically important emergent mutant subpopulations, especially those present as <10% of the total population in a sample. Whereas PAGE SSCP is less costly than fluorescent SSCP, the latter method is somewhat easier to perform and generates quantitative data. PMID- 10029659 TI - Comparative Evaluation of Cleavase Fragment Length Polymorphism With PCR-SSCP and PCR-RFLP to Detect Antimicrobial Agent Resistance in Mycobacterium tuberculosis. AB - Background: Several molecular methods potentially useful in the detection of Mycobacterium tuberculosis mutations, specifically in rpoB and katG, were compared. Methods and Results: DNA from 24 M. tuberculosis clinical isolates, with mutations associated with resistance to rifampin and/or isoniazid, was analyzed. A 128 bp amplicon, spanning the 81 bp rpoB region containing most mutations leading to rifampin resistance, was analyzed by polymerase chain reaction-single-strand conformation polymorphism (PCR-SSCP) and a recently introduced mutation scanning method, cleavase fragment length polymorphism (CFLP) analysis. Also, a 350 bp amplicon encompassing that region was analyzed by the CFLP method. CFLP analysis of the 350 bp amplicon (23 isolates) identified 14 of 17 mutants; however, CFLP analysis of the 128 bp amplicon accurately identified all mutants as did PCR-SSCP with interpretative difficulty for two codon 513 mutations. CFLP and PCR-restriction fragment length polymorphism (RFLP) analyses of a 623 bp amplicon encompassing katG codons 315 and 463 showed that the CFLP method identified single and dinucleotide codon 315 substitutions with or without codon 463 (CGG-->CTG) changes, whereas PCR-RFLP (MspI) missed one codon 315 polymorphism (AGC-->ACA) in three isolates. Conclusion: Both PCR-SSCP and CFLP analyses were sensitive in identifying all mutations on short sequences in the rpoB mutants. CFLP appears to be more efficient than SSCP and RFLP for the detection of mutations in large amplicons. PMID- 10029660 TI - Expression of the Cell Adhesion Molecule CD44 in Human Lung Tumors and Cell Lines. AB - Background: The purpose of this study was to examine the expression of the cell adhesion molecule CD44 in normal lung, primary and metastatic lung tumors, and cell lines derived from primary lung carcinomas. Methods and Results: A total of 68 lung specimens including normal tissue and primary and metastatic tumors, as well as 28 cell lines cultured from primary lung tumors with high recurrence, were examined for CD44 expression by semiquantitative reverse transcription polymerase chain reaction. Variant exon expression was confirmed by Southern blotting and hybridization of particular samples. In tumor tissues, loss of CD44 variant expression correlated with increasing tumor stage; a smaller percentage of more aggressive and poorly differentiated tumors expressed CD44v. Tumors metastatic to the lung were negative for CD44 variant expression. In primary lung cell lines, as in tumor tissue, tumors of higher histologic grade were characterized by loss of CD44 variant expression. Conclusion: CD44 isoform expression in normal lung and tumor tissues and cell lines revealed an overall decrease in CD44 alternative splicing in lung neoplasms of increased malignancy. PMID- 10029661 TI - Mutation Detection by Cleavase in Combination With Capillary Electrophoresis Analysis: Application to Mutations Causing Hypertrophic Cardiomyopathy and Long QT Syndrome. AB - Background: Genetic screening requires methods for mutation detection that are sensitive, precise, and robust. In population screening for complex genetic diseases in which large genes and/or several genes may be affected, automation of the mutation detection analysis is desirable. Methods and Results: The combined use of Cleavase nuclease and analysis of the DNA cleavage pattern by capillary electrophoresis was evaluated with respect to sensitivity, reproducibility, and dependency of experimental conditions in detecting mutations in the human genes MYH7 and KVLQT1 (KCNA9). The cleavage patterns obtained by capillary electrophoresis were very reproducible and robust. Conclusions: The combination of a sensitive enzymatic mutation detection method capillary electrophoresis may prove to be a useful system for automated, large-scale genetic screening. PMID- 10029662 TI - Novel Mitochondrial DNA Variant That May Give a False Positive Diagnosis for the T8993C Mutation. AB - Background: Two of the most common mutations in the mitochondrial DNA (mtDNA) of children occur at nucleotide 8993 (nt8993). The base substitutions of T to G (T8993G) and T to C (T8993C) are known to cause neurologic disorders and are routinely screened for in patients suspected of having a mitochondrial disorder. Methods and Results: Both mutations at nt8993 create a novel HpaII restriction endonuclease site and are usually detected by polymerase chain reaction (PCR) amplification of a section of the mtDNA containing nt8993, followed by HpaII digestion. The resulting fragment sizes are then analyzed by agarose gel electropho resis. Initial testing on a child referred for analysis suggested that the proband and his maternal relatives all had the common mtDNA mutation T8993C; however, subsequent restriction endonuclease and DNA sequencing analysis showed that the proband and his maternal relatives were homoplasmic for a novel variant at nt8856. This variant also creates an Hpa II restriction endonuclease site, and the fragments generated by the site are almost identical in size to those generated as a result of the nt8993 mutation when commonly used primers amplify the PCR product. Conclusions: A novel mutation in the mtDNA at nt8856 creates an HpaII restriction endonuclease site that has the potential to generate false positives when PCR products are tested for mutations at nt8993. This emphasizes the need for restriction endonuclease-based diagnostic tests for mtDNA mutations to account for the highly polymorphic nature of the mtDNA sequence and the importance of confirming a mutation by a second method. PMID- 10029663 TI - The Importance of Heteroduplexes in Interpreting the Results of PCR-RED Diagnostic Assays: Application to the Analysis of Mutations in the Steroid 21 Hydroxylase Gene in a Case of Congenital Adrenal Hyperplasia. AB - Background: Congenital adrenal hyperplasia (CAH) due to deficiency of steroid 21- hydroxylase (CYP21) is an autosomal recessive disease that is a major cause of ambiguous genitalia at birth in females. The milder late-onset form of the disease can cause mild virilization in women including hirsutism, infertility, and acne. Characterization of the causative mutations in a patient requires finding mutations on both chromosomes. Methods and Results: We use polymerase chain reaction (PCR) followed by restriction enzyme digestion (RED), among several other methods, to detect mutations in the CYP21 gene. The authors found two different point mutations in a patient with CAH, V281L and Q318X. Did we find two mutations in trans which would account for the disease, or two mutations in cis with a still unknown mutation(s) on the other chromosome? We devised a method to determine the cis/trans nature of the mutations using PCR amplification, digestion with a restriction enzyme (ApaL I) diagnostic for V281L, gel purification of the mutant band which lacks the cutting site, digestion with a second restriction enzyme (Pst I) which detects Q318X, and gel electrophoretic analysis of the products. Although the results initially supported a a cis orientation, consideration of the impact of heteroduplex formation during the PCR on the products of RED showed that the orientation was actually trans. Conclusions: When DNA that is heterozygous for a mutation is amplified using the PCR, four double-stranded DNA products can be formed: the two homoduplexes and two heteroduplexes. The heteroduplex DNA must be considered to ensure correct interpretation of the results of PCR-RED analysis. PMID- 10029664 TI - Both the rate and spectrum of loss of heterozygosity differ between human lymphoblastoid cells derived from various donors. AB - Loss of heterozygosity (LOH) contributes significantly to the inactivation of tumor suppressor genes and may involve a variety of mechanisms. Studying loss of HLA-A2 alleles in human lymphoblastoid cell lines, we previously showed that mitotic recombination and chromosome loss with concomitant duplication of the non selected chromosome were the most frequent mechanisms of LOH. In the present study we used the HLA system to determine the rate and spectrum of LOH mutations in the EBV transformed lymphoblastoid cell line R83-4915. Spontaneous loss of HLA A2 in R83-4915 occurred with a rate of 7.9x10-7 which was 5 to 10-times lower compared to the previously observed rate of loss of HLA-A2 in other lymphoblastoid cell lines. Among the HLA-A2 mutants, 27% did not show LOH of additional chromosome 6 markers. Molecular analysis showed that neither large deletion nor gene conversion was the cause for their mutant phenotype. The remaining mutants showed LOH, which was caused by mitotic recombination (40%) and chromosome loss (33%). However, the chromosome loss observed in mutants of R83 4915 was not accompanied by the duplication of the remaining chromosome. Instead 3 out of 5 mutants became polyploid suggesting that different mechanisms exist to compensate for chromosome loss. In conclusion, the rate and types of LOH that can be observed in cell lines obtained from various donors may depend on the genetic make-up or the transformation status of these cells PMID- 10029665 TI - Challenges to evolution theory. PMID- 10029666 TI - Analysis of bleomycin- and cytosine arabinoside-induced chromosome aberrations involving chromosomes 1 and 4 by painting FISH. AB - The genomic frequency of chromosomal aberrations obtained by chromosome painting is usually extrapolated from the observed frequency of aberrations by correcting for the DNA content of the labelled chromosomes. This extrapolation is based upon the assumption of random distribution of breakpoints from which aberrations are generated. However, the validity of this assumption has been widely questioned. While extensive investigations have been performed with ionizing radiation as chromosome breaking agent, little efforts have been done with chemical clastogens. In order to investigate interchromosomal differences in chemically induced chromosome damage, we have used multicolour chromosome painting to analyse bleomycin-induced aberrations involving chromosomes 1 and 4, two chromosomes that differ in gene density. In addition, we have measured the effect of cytosine arabinoside upon the repair of bleomycin-induced DNA damage in chromosomes 1 and 4. Our results show that these chromosomes are equally sensitive to the clastogenic effect of bleomycin with a similar linear dose effect relationship. However, the high gene density chromosome 1 appeared to be more sensitive to repair inhibition by Ara-C than chromosome 4. This enhanced sensitivity to repair inhibition in chromosome 1 could be mediated by preferential repair of open chromatin and actively transcribed regions. PMID- 10029667 TI - Oxidative damage elicited by imbalance of free radical scavenging enzymes is associated with large-scale mtDNA deletions in aging human skin. AB - Mitochondrial DNA (mtDNA) mutations and impaired respiratory function have been demonstrated in various tissues of aged individuals. We hypothesized that age dependent increase of ROS and free radicals production in mitochondria is associated with the accumulation of large-scale mtDNA deletions. In this study, we first confirmed that the proportion of mtDNA with the 4977 bp deletion in human skin tissues increases with age. We then investigated the 8-hydroxy-2' deoxyguanosine (8-OH-dG) content in skin tissues and lipid peroxides content of the skin fibroblasts from subjects of different ages. The results showed an age dependent increase of 8-OH-dG level in the total DNA of skin tissues of the subjects above the age of 60 years. The specific content of malondialdehyde, an end product of lipid peroxidation, was also found to increase with age. On the other hand, we examined the enzyme activities of Cu, Zn-superoxide dismutase (Cu,Zn-SOD), Mn-superoxide dismutase (Mn-SOD), catalase, and glutathione peroxidase (GPx) in the skin fibroblasts. The activities of Cu,Zn-SOD, catalase and glutathione peroxidase were found to decrease with age. However, the activity of Mn-SOD was increased with age before 60 years but was decreased thereafter. Moreover, the activity ratios of Mn-SOD/catalase and Mn-SOD/GPx exhibited the same pattern of change with age. This indicates that free radical scavenging enzymes can effectively dispose of ROS and free radicals before 60 years of age. However, elevated oxidative stress caused by an imbalance between the production and removal of ROS and free radicals occurred in skin fibroblasts after 60 years of age. Taken together, we suggest that the functional decline of free radical scavenging enzymes and the elevation of oxidative stress may play an important role in eliciting oxidative damage and mutation of mtDNA during the human aging process. PMID- 10029668 TI - Comparison of cytogenetic effects of 3,4-epoxy-1-butene and 1,2:3, 4 diepoxybutane in mouse, rat and human lymphocytes following in vitro G0 exposures. AB - To understand better the species differences in carcinogenicity caused by 1,3 butadiene (BD), we exposed G0 lymphocytes (either splenic or peripheral blood) from rats, mice and humans to 3, 4-epoxy-1-butene (EB) (20 to 931 microM) or 1,2:3,4-diepoxybutane (DEB) (2.5 to 320 uM), two of the suspected active metabolites of BD. Short EB exposures induced little measurable cytogenetic damage in either rat, mouse, or human G0 lymphocytes as measured by either sister chromatid exchange (SCE) or chromosome aberration (CA) analyses. However, DEB was a potent inducer of both SCEs and CAs in G0 splenic and peripheral blood lymphocytes. A comparison of the responses among species showed that the rat and mouse were approximately equisensitive to the cytogenetic damaging effects of DEB, but the situation for the human subjects was more complex. The presence of the GSTT1-1 gene (expressed in the erythrocytes) reduced the relative sensitivity of the lymphocytes to the SCE-inducing effects of DEB. However, additional factors also appear to influence the genotoxic response of humans to DEB. This study is the first direct comparison of the genotoxicity of EB and DEB in the cells from all three species. PMID- 10029669 TI - A comparison of mutational specificity of mutations induced by S9-activated B[a]P and benzo[a]pyrene-7,8-diol-9,10-epoxide at the endogenous aprt gene in CHO cells. AB - We have determined the mutational specificity of S9-activated benzo[a]pyrene (B[a]P) at the endogenous aprt locus in a hemizygous Chinese hamster ovary cell line. The aprt gene of recovered mutants was amplified using the polymerase chain reaction (PCR) and directly sequenced. This spectrum was then compared to mutations recovered following treatment with the B[a]P metabolite, benzo[a]pyrene diol-epoxide (BPDE). No significant difference between the two spectra in the types of mutations produced, or their distribution was observed. This observation supports the hypothesis that BPDE is the reactive metabolite of B[a]P, responsible for the significant biological effects caused by this ubiquitous polycyclic aromatic hydrocarbon. The major mutation recovered was the G:C-->T:A transversion, and mutations were primarily localized within runs of guanines. We also confirmed our previous finding that mutation by B[a]P is non-random, targeting events in runs of guanines flanked by adenine residues. This same target hotspot region is found in codon 61 of the human c-Ha-ras1 proto-oncogene. This may help explain the selective activation of this codon by BPDE. PMID- 10029670 TI - Nucleotide variation in the p53 tumor-suppressor gene of voles from Chernobyl, Ukraine. AB - The 1986 Chernobyl disaster contaminated vast regions of Ukraine and Belarus with a variety of radioactive isotopes and heavy metals. While over 90% of the radioactive isotopes have decayed into stable compounds, radiation levels in contaminated areas are still extraordinarily high. In fact, some rodents living near the reactor have internal 134,137Cs concentrations approaching 80 000 Bq/g. Several recent genetic analyses of vertebrates have illustrated that mutation rates of organisms exposed to radiation from Chernobyl are higher than in control groups, but none have studied DNA sequences. Nucleotide sequences of rodent mitochondrial genes were originally reported to have been hypervariable, but those results were subsequently retracted. Herein, I report the results of a pilot study to determine the extent of nucleotide variation at the p53 gene in four species of rodents (voles) from Chernobyl and from control sites. I sequenced a 788 bp region (coding and non-coding) of p53 in 30 different mice comprising four different species of Microtus. Nucleotide variation at the population level was due to deletions and substitutions; both were limited to introns. There were no significant differences between the number of haplotypes in radioactive and control populations (p=0.60). Rare or private alleles might have arisen due to unique mutational pressures at Chernobyl. Alternatively, natural selection might have favored one allele over others (i.e., a selective sweep). Neither scenario is strongly supported by these data. Thus, no apparent genetic effects of the Chernobyl disaster on the p53 gene of resident voles were revealed; more extensive surveys will be necessary to determine if mutation rates are indeed elevated in mice from Chernobyl. However, two salient points emerge; the first involves the utility of introns as markers for mutations in coding regions and the second considers the relative merits of cloning in mutation detection studies. PMID- 10029671 TI - Aflatoxin B1-induced Hprt mutations in splenic lymphocytes of Fischer 344 rats. Results of an intermittent feeding trial. AB - In a previous study, we found an increase in the mutant frequency at the Hypoxanthine phosphoribosyl transferase (Hprt) locus in the splenic lymphocytes of Fischer 344 rats acutely exposed to aflatoxin B1 (AFB1). Because an acute exposure may not reflect the exposure pattern of individuals whose diet may contain AFB1-contaminated foodstuffs, we sought to determine if the feeding regimen affected the induction of Hprt mutations in the rat splenic lymphocyte. Thus, Fischer 344 rats were fed either (A) a control diet, (B) various doses of AFB1 for three four-week periods interspersed with two four-week periods of the control diet, or (C) continuously fed 1.6 ppm of AFB1. Not only was a significant increase in the mutant frequency detected in the lymphocytes of rats fed a dose as low as 0. 01 ppm of AFB1, but the increase in the mutant frequency at the end of the 20-week experimental period was consistent with an accumulation of damage induced by AFB1. These results indicate that the rat lymphocyte/Hprt assay is useful for detecting chronic low level exposures. Further, these data suggest that an intermittent, low-level exposure to AFB1 may present a human health risk. PMID- 10029672 TI - Comparison of SYBR Green I nucleic acid gel stain mutagenicity and ethidium bromide mutagenicity in the Salmonella/mammalian microsome reverse mutation assay (Ames test). AB - SYBR Green I nucleic acid gel stain is an unsymmetrical cyanine dye developed for sensitive detection of nucleic acids in electrophoretic gels. Its mechanism of nucleic acid binding is not known, whereas the most commonly used nucleic acid gel stain, ethidium bromide, is a well-characterized intercalator. We compared the mutagenicity of SYBR Green I stain with that of ethidium bromide in Salmonella/mammalian microsome reverse mutation assays (Ames tests). As expected [J. McCann, E. Choi, E. Yamasaki, B.N. Ames, Proc. Natl. Acad. Sci. USA, 72 (1975) 5135-5139], ethidium bromide showed high revertant frequencies in several frameshift indicator strains (averaging 68-fold higher than vehicle controls in TA98, 80-fold higher in TA1538, 15-fold higher in TA1537, and 4.4-fold higher in TA97a), only in the presence of rat liver extracts (S9). Small increases in revertant frequencies were observed for ethidium bromide in the base-substitution indicator strain TA102 both in the presence and absence of S9 (averaging 2.0- and 1.8-fold higher than vehicle controls, respectively) and in base-substitution indicator strain TA100 in the presence of S9 (averaging 1.6-fold higher than vehicle controls). A small mutagenic effect was detected for SYBR Green I stain in frameshift indicator strain TA98 (averaging 2. 2-fold higher than vehicle controls) only in the absence of S9 and in base-substitution indicator strain TA102, both in the presence and absence of S9 (averaging 2.2- and 2.7-fold higher than vehicle controls, respectively). Thus, SYBR Green I stain is a weak mutagen and appears to be much less mutagenic than ethidium bromide. These results suggest that SYBR Green I stain may not intercalate, and if it does, that its presence does not give rise to point mutations at a high frequency. PMID- 10029673 TI - P53 integrity in the genetically engineered mammalian cell lines AHH-1 and MCL-5. AB - Recently, a C to T transition mutation in exon 8 of the p53 gene has been identified in a subculture of the genetically engineered human lymphoblastoid cell line AHH-1 and this mutation was proposed to cause a loss of function of the p53 suppressor protein and may limit the use of this cell culture in genotoxicology test assays. This led us to investigate early passage cultures of AHH-1 and its derivative MCL-5 to determine the distribution of the mutation. In order to characterise the presence of mutations at the p53 locus, exon 8 was analysed using restriction enzyme analysis and automated sequencing to locate possible changes of sequence. Mutations were identified at codon 282, and treatment with the Msp1 restriction enzyme led to incomplete digestion suggesting the presence of heterozygosity at the site which was confirmed by sequencing. Our results indicate that the p53 gene is heterozygous at the interface between the codons 281 and 282 in both AHH-1 and MCL-5. An Annexin V labeling study was carried out and both AHH-1 and MCL-5 cell lines were shown to undergo DNA damage induced cell death after a 1-h exposure to MNNG. PMID- 10029674 TI - Epimerization of benzo[a]pyrene-tetrols after acid hydrolysis, implications for determination of benzo[a]pyrene adducts in protein and DNA. AB - Determination of benzo[a]pyrene-DNA or protein adducts with high performance liquid chromatography (HPLC) after acid hydrolysis at high temperature (90 degrees C) enables four isomers of benzo[a]pyrene tetrahydrotetrol to be identified and quantitated. We have investigated the effect of acid treatment of benzo[a]pyrene-tetrahydrotetrol isomers using HPLC and nuclear magnetic resonance spectroscopy (NMR) analysis. By HPLC, we found reversible epimerization of (+/-) benzo[a]pyrene-r-7,t-8,9, 10-tetrahydrotetrol to (+/-)-benzo[a]pyrene-r-7,t-8,9, c-10-tetrahydrotetrol and of (+/-)-benzo[a]pyrene-r-7,t-8,c-9, t-10 tetrahydrotetrol to (+/-)-benzo[a]pyrene-r-7,t-8,c-9, 10-tetrahydrotetrol, but no interconversion between the two isomer groups. After acid hydrolysis, we found an equilibrium of 87% (+/-)-benzo[a]pyrene-r-7,t-8,9,c-10-tetrahydrotetrol and 9% (+/-)-benzo[a]pyrene-r-7,t-8,9,10-tetrahydrotetrol and 68% (+/-)-benzo[a]pyrene-r 7,t-8,c-9,10-tetrahydrotetrol and 20% (+/-)-benzo[a]pyrene-r-7,t-8,c-9,t-10 tetrahydrotetrol. Minor amounts of two unknown compounds with similar chromatographic characteristics were also found. We have established a NMR method for determination of underivatized (+/-)-benzo[a]pyrene-r-7,t-8,9, c-10 tetrahydrotetrol and (+/-)-benzo[a]pyrene-r-7,t-8,9, 10-tetrahydrotetrol confirming the epimerization of (+/-)-benzo[a]pyrene-r-7,t-8,9,10 tetrahydrotetrol to (+/-)-benzo[a]pyrene-r-7,t-8,9,c-10- tetrahydrotetrol. (+/-) Benzo[a]pyrene-r-7,t-8,9,10-tetrahydrotetrol was treated with aqueous hydrochloric acid in tetrahydro- furan-d8 to give (+/-)-benzo[a]pyrene-r-7,t 8,9,c-10-tetrahydrotetrol at 57 degrees C while observing the 1H NMR resonances at 500 MHz. Gradient-selected correlation spectroscopy (COSY), heteronuclear multiple quantum correlation (HMQC) and heteronuclear multiple bond correlation (HMBC) experiments were performed to confirm the assignments of the aliphatic hydrogens in the product (+/-)-benzo[a]pyrene-r-7,t-8,9, c-10-terahydrotetrol. Thus, when analyzing benzo[a]pyrene-DNA or protein adducts by cleaving the adducts with acid hydrolysis, the only ratio of biological significance is between (+/-)-benzo[a]pyrene-r-7,t-8,9,c-10-tetrahydrotetrol plus (+/-) benzo[a]pyrene-r-7,t-8,9,10-tetrahydrotetrol and (+/-)-benzo[a]pyrene-r-7,t-8,c 9,10-tetrahydrotetrol plus (+/-)-benzo[a]pyrene-r-7,t-8,c-9,t-10 tetrahydrotetrol, due to interconversion (epimerization) at C-10. PMID- 10029676 TI - Time versus replication dependence of EMS-induced delayed mutation in Chinese hamster cells. AB - We have previously observed in Chinese hamster cells that ethyl methane sulfonate (EMS) induces mutations which are distributed over at least 10-14 cell divisions following treatment. This delayed appearance of mutations could be explained by EMS-induced lesions which remain in DNA and have a probability that is significantly less than 1.0 of producing base mispairing errors during successive replication cycles (replication-dependent). Alternatively, delayed mutation may be a time-dependent process in which a slow acting or damage inducible error prone repair process removes persistent DNA lesions and replaces them with an incorrect base during the course of 7-10 days of colony growth following EMS exposure. To address this question, the distribution of HGPRT delayed mutation events (fifth division or later) in cells plated immediately for exponential growth after EMS treatment was compared with the distribution in cells which remained under confluent growth conditions for 8 days and then were replated. Both the distribution and rate of accumulation of delayed mutations (mutations/cell division) were similar in the two culture conditions. In contrast, the frequency of early mutations (before the fifth division) in the confluent population was reduced more than 2-fold compared to dividing cells. A comparison of the frequency of EMS-induced DNA lesions in the two populations revealed that the density inhibited population contained one third the DNA lesions of the exponential population. These results argue against a time dependent process since, if this mechanism applies, one would expect an increase in early mutant events and a decrease in delayed events in the confluent population. The results, however, are consistent with a replication model in which potential early mutant lesions are preferentially removed in the density inhibited culture during the 8 days of incubation while lesions producing late mutants are not removed. PMID- 10029675 TI - Genotoxicity testing of six insecticides in two crosses of the Drosophila wing spot test. AB - Among the great variety of genotoxicity assays available, the wing spot test in Drosophila melanogaster has some characteristics that make it very suited for the screening of genotoxic activity, i.e., it is an easy and inexpensive assay using a eukaryotic organism in vivo. One of the most interesting characteristics of the assay is its capacity to detect genotoxic activity of promutagens without the necessity of an exogenous metabolic activation system. In this paper we present results obtained with a recently developed high bioactivation cross of the wing spot test (NORR cross). The positive results obtained with the five well-known procarcinogens 7, 12-dimethylbenz[a]anthracene, N-nitrosopyrrolidine, p dimethylaminoazobenzene, diethylnitrosamine and urethane clearly show that the NORR strains are similar to the other high bioactivation strains previously described, but they lack their methodological disadvantages. We have tested six insecticides, which are characterised by having contradictory results in other genotoxicity tests, using both the standard and the high bioactivation (NORR) cross. The six insecticides analysed are the pyrethroid allethrin, the methylenedioxyphenolic compound piperonyl butoxide, the chlorinated hydrocarbons dieldrin and endrin, and the organophosphates dimethoate and malathion. We obtained negative results for all six compounds. Our results show the suitability of the wing spot test for the evaluation of compounds at the first level of genotoxicity testing. PMID- 10029677 TI - Studies on the genotoxicity of endosulfan in bacterial systems. AB - Endosulfan, an organochlorine pesticide, was subjected to the differential sensitivity assay in repair-deficient and repair-proficient strains of Escherichia coli K12, prophage lambda induction assay in WP2s (lambda) and mutation induction in E. coli K12. The induction of umu gene expression with endosulfan was studied also in Salmonella typhimurium TA1535/pSK1002 cells. The differential sensitivity assay revealed that the recA 13 strain was the most sensitive. Endosulfan induced prophage lambda in E. coli and umu gene expression in S. typhimurium cells; however, the extent of the effects were low. Endosulfan also induced a dose-dependent increase in forward mutations in E. coli K12 cells from ampicillin sensitivity to ampicillin resistance. Our studies indicate the genotoxic potential of endosulfan and the role of the recA gene in the repair of endosulfan-induced DNA damage. PMID- 10029678 TI - Uptake, cellular distribution and DNA damage produced by mercuric chloride in a human fetal hepatic cell line. AB - A human hepatic cell line (WRL-68 cells) was employed to investigate the uptake of the toxic heavy metal mercury. Hg accumulation in WRL-68 cells is a time and concentration dependent process. A rapid initial phase of uptake was followed by a second slower phase. The transport does not require energy and at low HgCl2 concentrations (<50 microM) Hg transport occurs by temperature-insensitive processes. Subcellular distribution of Hg was: 48% in mitochondria, 38% in nucleus and only 8% in cytosolic fraction and 7% in microsomes. Little is known at the molecular level concerning the genotoxic effects following the acute exposure of eucaryotic cells to low concentrations of Hg. Our results showed that Hg induced DNA single-strand breaks or alkali labile sites using the single-cell gel electrophoresis assay (Comet assay). The percentage of damaged nucleus and the average length of DNA migration increased as metal concentration and time exposure increased. Lipid peroxidation, determined as malondialdehyde production in the presence of thiobarbituric acid, followed the same tendency, increased as HgCl2 concentration and time of exposure increased. DNA damage recovery took 8 h after partial metal removed with PBS-EGTA. PMID- 10029679 TI - Genotoxicity evaluation of tetramethylbenzenes. AB - The three tetramethyl isomers of benzene (prenitene, 1,2,3,4-; izodurene, 1,2,3,5 ; and durene, 1,2,4,5-tetramethylben- zene) were studied using in vitro mutagenicity and in vivo genotoxicity tests. Potency of mutate induction by these solvents was evaluated in Salmonella typhimurium cells with, and without S9-mix made from Aroclor 1254-induced rat liver S9. The potency of induction of micronuclei (MN) and sister chromatid exchanges (SCEs) by solvents was evaluated in bone marrow of mice. Izodurene displayed mutagenic potency in strains TA97a, TA98 and TA100 only in the absence of the S9-mix. In MN tests, all three tetramethylbenzenes demonstrated no clastogenic activity on the bone marrow cells. All the tested solvents were active as genotoxic compounds in the SCE tests, demonstrating a dose-response relationships. PMID- 10029680 TI - Stabilization of the intermediate in frameshift mutation. AB - A mismatch repair, proofreading deficient mutant of Escherichia coli lost a C from a C8 run at a rate 10 times higher than the loss of A from an A8 sequence in the same double mutant. This greater frameshift instability of a homopolymeric run of C's may be due to stabilization of a stacked intermediate. Gain of a (CA) unit in a similarly constructed (CA)15 sequence occurred at a rate about 1/3 that previously reported for a (CA)14 construct losing a (CA) repeat unit. PMID- 10029681 TI - The distribution of chromosome damage, non-reciprocal translocations and clonal aberrations in lymphocytes from Chernobyl clean-up workers. AB - In this paper we determined whether the frequencies of translocations and insertions are proportional to chromosome size in peripheral blood lymphocytes from Chernobyl nuclear accident clean-up workers and healthy unexposed control subjects. The frequency of aberrations among chromosomes 1, 2 and 4 in both groups was found to be significantly different from the distribution expected on the basis of chromosome size, although the difference was only marginally significant in controls. We also determined whether differences exist in aberration frequencies measured by two scoring systems: the classical method, where reciprocal exchanges are scored as one event, and PAINT, where each break junction is scored as a single event. The two scoring systems gave highly correlated results which yielded an interpretable arithmetic relationship between frequency measurements using the two systems. Approximately 34% of all translocations were observed to be non-reciprocal, and cells bearing clones of abnormal cells were observed in 6 of 198 subjects (3.0%). Our results demonstrate that clones of abnormal cells and the presence of non-reciprocal translocations contribute to the non-proportional distribution of radiation-induced and spontaneous cytogenetic damage. PMID- 10029682 TI - Taxol-induced meiotic maturation delay, spindle defects, and aneuploidy in mouse oocytes and zygotes. AB - To increase our understanding about the potential risks of chemically-induced aneuploidy, more information about the various mechanisms of aneuploidy induction is needed, particularly in germ cells. Most chemicals that induce aneuploidy inhibit microtubule polymerization. However, taxol alters microtubule dynamics by enhancing polymerization and stabilizing the polymer fraction. We tested the hypothesis that taxol induces meiotic delay, spindle defects, and aneuploidy in mouse oocytes and zygotes. Super-ovulated ICR mice received 0 (control), 2.5, 5.0, and 7.5 mg/kg taxol intraperitoneally immediately after HCG. Females were paired (1:1) with males for 17 h after taxol treatment. Mated females were given colchicine 25 h after taxol and their one-cell zygotes were collected 16 h later. Ovulated oocytes from non-mated females were collected 17 h after taxol. Chromosomes were C-banded for cytogenetic analyses. Oocytes were also collected from another group of similarly treated females for in situ chromatin and microtubule analyses. Taxol significantly (p<0.01) enhanced the proportion of oocytes exhibiting parthenogenetic activation, chromosomes displaced from the meiotic spindle, and sister-chromatid separation. Moreover, 7.5 mg/kg taxol significantly (p<0.01) increased the proportions of metaphase I and diploid oocytes and polyploid zygotes. A significant (p<0.01) dose response for taxol induced hyperploidy in oocytes and zygotes was found. These results support the hypothesis that taxol-induced meiotic delay and spindle defects contribute to aneuploid mouse oocytes and zygotes. PMID- 10029683 TI - Induction of micronuclei in vitro by organochlorine compounds in beluga whale skin fibroblasts. AB - Beluga whales (Delphinapterus leucas) inhabiting the St. Lawrence estuary are highly contaminated with environmental pollutants and have a high incidence of cancer. Environmental contaminants may be partly responsible for the high cancer incidence observed in this population. DNA damage plays an important role in the development of cancer. The micronuclei (MN) assay was used to test the genotoxic potential of organochlorine (OC) pesticides with and without external metabolic factor in skin fibroblasts of an Arctic beluga whale. Toxaphene, chlordane and p,p'-DDT induced significant (p<0. 05) concentration-response increases of micronucleated cells (MNCs). Statistically significant increases in MNCs, ranging from 1.7- to 5-folds when compared to control cultures, were observed for 0.05, 0. 5, 5 and 10 microg/ml toxaphene, 2, 5 and 10 microg/ml chlordane and 10 and 15 microg/ml p,p'-DDT. Presence of exogeneous metabolic factor (S9) completely abolished the MN induction potency of chlordane and p,p'-DDT, and toxaphene induced MN formation at higher concentrations (0.5 microg/ml) than without S9 mix. The ecotoxicological significance of MN induction by low concentrations of toxaphene is unknown and do not imply that toxaphene is involved in the etiology of cancer in St. Lawrence beluga whales. However, because of the known genotoxicity of toxaphene and the long lifespan of beluga whales, it cannot be excluded that toxaphene may pose a long-term genetic hazard to the more contaminated whales of this population. PMID- 10029685 TI - Urinary cyclophosphamide excretion and micronuclei frequencies in peripheral lymphocytes and in exfoliated buccal epithelial cells of nurses handling antineoplastics. AB - In this study, urinary cyclophosphamide (CP) excretion rate, as well as micronuclei (MN) in peripheral lymphocytes and in buccal epithelial cells were determined for 26 nurses handling antineoplastics and 14 referents matched for age and sex. In urine samples of 20 out of 25 exposed nurses CP excretion rate was found in a range of 0.02-9.14 microg CP/24 h. Our results of the analyses of CP in urine demonstrates that when the nurses were handling CP (and other antineoplastic drugs) this particular compound was observed in urine. The mean values (+/-SD) of MN frequencies (%) in peripheral lymphocytes from the nurses and controls were 0.61 (+/-0. 32) and 0.28 (+/-0.16), respectively (p<0.01). The mean value (+/-SD) of MN frequency (%) in buccal epithelial cells of nurses was 0.16 (+/-0.19) and also mean MN frequency in buccal epithelial cells for controls was found to be as 0.08 (+/-0.08), (p>0.05). Age, sex and smoking habits have not influenced the parameters analyzed in this study. Handling time of antineoplastics, use of protective equipment and handling frequency of drugs have no effect on urinary and cytogenetic parameters analyzed. No correlation was found between the urinary CP excretion and the cytogenetic findings in nurses. Neither could we find any relationship between two cytogenetic endpoints. Our results have identified the possible genotoxic damage of oncology nurses related to occupational exposure to at least one antineoplastic agent, which is used as a marker for drug handling. As a whole, there is concern that the present handling practices of antineoplastic drugs used in the several hospitals in Ankara will not be sufficient to prevent exposure. PMID- 10029684 TI - Satellite DNA hypomethylation vs. overall genomic hypomethylation in ovarian epithelial tumors of different malignant potential. AB - Rearrangements in heterochromatin in the vicinity of the centromeres of chromosomes 1 and 16 are frequent in many types of cancer, including ovarian epithelial carcinomas. Satellite 2 DNA is the main sequence in the unusually long heterochromatin region adjacent to the centromere of each of these chromosomes. Rearrangements in these regions and hypomethylation of satellite 2 DNA are a characteristic feature of patients with a rare recessive genetic disease, ICF (immunodeficiency, centromeric region instability, and facial anomalies). In all normal tissues of postnatal somatic origin, satellite 2 DNA is highly methylated. We examined satellite 2 DNA methylation in ovarian tumors of different malignant potential, namely, ovarian cystadenomas, low malignant potential (LMP) tumors, and epithelial carcinomas. Most of the carcinomas and LMP tumors exhibited hypomethylation in satellite 2 DNA of both chromosomes 1 and 16. A comparison of methylation of these sequences in the three types of ovarian neoplasms demonstrated that there was a statistically significant correlation between the extent of this satellite DNA hypomethylation and the degree of malignancy (P<0.01). Also, there was a statistically significant association (P<0.005) between genome-wide hypomethylation and undermethylation of satellite 2 DNA among these 17 tumors. In addition, we found abnormal hypomethylation of satellite alpha DNA in the centromere of chromosome 1 in many of these tumors. Our findings are consistent with the hypothesis that one of the ways that genome-wide hypomethylation facilitates tumor development is that it often includes satellite hypomethylation which might predispose cells to structural and numerical chromosomal aberrations. Several of the proteins that bind to pericentromeric heterochromatin are known to be sensitive to the methylation status of their target sequences and so could be among the sensors for detecting abnormal demethylation and mediating effects on chromosome structure and stability. PMID- 10029686 TI - Sperm chromatin damage associated with male smoking. AB - Cigarette smoke is a rich source of mutagens and carcinogens; thus, we have investigated the effects of male smoking on the DNA of human sperm. This was performed using the sperm chromatin structure assay (SCSA), which measures the sensitivity of sperm DNA to acid induced denaturation, and the terminal deoxynucleotidyl transferase assay (TdTA), which measures DNA strand breaks by addition of the biotinylated nucleotide dUTP to 3'-OH ends of DNA, sites of DNA breakage, using the enzyme terminal deoxynucleotidyl transferase. Sperm from subjects who smoked were significantly more sensitive to acid induced denaturation than non-smokers (P<0.02) and possessed higher levels of DNA strand breaks (P<0.05). We hypothesise that smoking damages the chromatin structure and produces endogenous DNA strand breaks in human sperm. These changes may result in sperm DNA mutations, that predispose offspring to greater risk of malformations, cancer and genetic diseases. PMID- 10029687 TI - Elevated frequencies of hypoxanthine phosphoribosyltransferase lymphocyte mutants are detected in Russian liquidators 6 to 10 years after exposure to radiation from the Chernobyl nuclear power plant accident. AB - This study was conducted to determine whether the frequency of hypoxanthine phosphoribosyltransferase (HPRT) deficient lymphocyte mutants would detect an effect of radiation exposure in a population of Russians who were exposed to low levels of radiation while working in 1986 and 1987 as liquidators cleaning up after the Chernobyl nuclear power reactor accident. The HPRT lymphocyte cloning assay was performed on peripheral blood lymphocytes collected between 1992 and 1996 from 142 liquidators and 66 Russian controls, and between 1989 and 1993 from 231 American controls. Russian and American controls were not significantly different for either cloning efficiency or mutant frequency (MF); inclusion of both sets of controls in the analysis increased the ability to detect a Chernobyl exposure effect in the liquidators. After adjusting for age and smoking, the results revealed no significant difference in cloning efficiency of Chernobyl liquidators relative to Russian controls but a significant, 24% increase in liquidator HPRT mutant frequency over Russian controls (90% confidence interval was 7% to 45% increase). The analytical method also accounted for differences in precision of the individual estimates of log CE and log MF and accommodated for outliers. The increase in HPRT mutant frequency of liquidators is an attribute of the exposed population as a whole rather than of individuals. These results demonstrate that, under appropriate circumstances, the HPRT specific locus mutation assay of peripheral blood lymphocytes can be used to detect a semi acute, low dose radiation exposure of a population, even 6 to 10 years after the exposure. PMID- 10029688 TI - The micronucleus test in rat erythrocytes from bone marrow, spleen and peripheral blood: the response to low doses of ionizing radiation, cyclophosphamide and vincristine determined by flow cytometry. AB - The frequency of micronucleated polychromatic erythrocytes (fMPCE) was determined in samples from bone marrow, spleen and peripheral blood of rats exposed to low doses of X-rays, cyclophosphamide or vincristine. The fMPCE values were lower in the peripheral blood than in bone marrow or spleen. This is due to the elimination of MPCE from the circulating blood, which was confirmed by the results from prolonged exposure of rats to gamma-radiation. When the analysis was restricted to the youngest PCE in peripheral blood, the sensitivity of the assay was considerably improved. This can be reproducibly achieved with the flow cytometric analysis. PMID- 10029689 TI - Rapid method for improving slide quality in the bone marrow micronucleus assay; an adapted cellulose column procedure. AB - Micronuclei are routinely scored in anucleate erythrocytes in bone marrow smears stained with acridine orange. Intense fluorescence from the many nucleated cells in the preparations can interfere with micronucleus detection and cause fatigue in the reader. A method for removing nucleated cells by filtering bone marrow through cellulose packed in syringes was developed by Romagna some ten years ago, but has not been used routinely because of the excessive time needed to prepare columns. We have modified the method very simply by filling chromatography columns by pipet with a cellulose suspension. We show here that column filtration of bone marrow does not affect the numbers of micronucleated polychromatic erythrocytes (MN-PCEs) scored from mice treated with the chromosome breaking agents mitomycin C and cyclophosphamide, or the aneuploidy-inducing spindle poisons, colchicine and vinblastine. The extra preparation time is only about half an hour for a full scale micronucleus assay, and results in better slides and faster scoring. PMID- 10029690 TI - Tk+/- mouse model for detecting in vivo mutation in an endogenous, autosomal gene. AB - Tk+/- transgenic mice were created using an embryonic stem cell line in which one allele of the endogenous thymidine kinase (Tk) gene was inactivated by targeted homologous recombination. Breeding Tk+/- parents produced viable Tk-/- knockout (KO) mice. Splenic lymphocytes from KO mice were used in reconstruction experiments for determining the conditions necessary for recovering Tk somatic cell mutants from Tk+/- mice. The cloning efficiency of KO lymphocytes was not affected by the toxic thymidine analogues 5-bromo-2'-deoxyuridine (BrdUrd) or trifluorothymidine (TFT), or by BrdUrd in the presence of lymphocytes from Tk+/- animals; however, it was easier to identify clones resistant to BrdUrd than to TFT when Tk+/- cells were present. Tk+/- mice were treated with vehicle or 100 mg/kg of N-ethyl-N-nitrosourea (ENU), and after 4 months, the frequency of Tk mutant lymphocytes was measured by resistance to BrdUrd. The frequency of Tk mutants was 22+/-5.9x10-6 in control animals and 80+/-31x10-6 in treated mice. In comparison, the frequency of Hprt mutant lymphocytes, as measured by resistance to 6-thioguanine, was 2.0+/-1.2x10-6 in control animals and 84+/-28x10-6 in the ENU-treated mice. Analysis of BrdUrd-resistant lymphocyte clones derived from the ENU-treated animals revealed point mutations in the non-targeted Tk allele. These results indicate that the selection of BrdUrd-resistant lymphocytes from Tk+/- mice may be used for assessing in vivo mutation in an endogenous, autosomal gene. PMID- 10029691 TI - Comparison of HepG2 feeder cells generated by exposure to gamma-rays, X-rays, UV C light or mitomycin C for ability to activate 7,12-dimethylbenz[a]anthracene in a cell-mediated Chinese hamster V79/HGPRT mutation assay. AB - The cell-mediated Chinese hamster V79/HGPRT mutagenicity assay is an established in vitro testing method. Although gamma-irradiated human HepG2 hepatoma cells have been used recently for chemical activation, an alternative is now needed due to scheduled retirement of the available gamma-source. X-irradiation, 254 nm UV-C light and mitomycin C were examined as possible HepG2 mitotic inhibitors, and treated cells compared for activation of 7, 12-dimethylbenz[a]anthracene (DMBA). In colony-forming assays, V79 and HepG2 cells differed in sensitivity to DMBA, with V79 survival declining sharply between 1-2.5 microM (LD50=1.75 microM) while HepG2 survival decreased gradually, beginning at 0.01 microM DMBA (LD50=0.045 microM). When HepG2 feeder cells generated by each method were included in V79/HGPRT mutation assays, activation of 1 microM DMBA was found to vary according to the mitotic inhibitor used, with mutation frequencies decreasing in the order 4000 rads gamma-rays>25 microg/ml mitomycin C>4000 rads X-rays>25 J/m2 UV-C light. Only assays containing gamma-irradiated HepG2 cells generated an increase (2-3-fold) in mutation frequency when DMBA exposure was extended from 24 to 48 h. The effect of HepG2 preincubation with either Aroclor 1254 or DMBA on feeder cell activation of DMBA was also assessed using concentrations of Aroclor 1254 (10 microg/ml) or DMBA (1.0 microM) which were found to produce optimum induction of ethoxyresorufin-O-deethylase (EROD) activity (3.1-fold and 2-fold increases, respectively). Compared to results obtained with uninduced HepG2 cells, assays incorporating HepG2 cells activated by either Aroclor 1254 or DMBA produced slightly increased V79/HGPRT mutation frequencies after 24 h of exposure to mutagen; however, a 48 h incubation with mutagen in the presence of HepG2 preincubated with either Aroclor 1254 or DMBA resulted in higher mutation frequencies regardless of the mitotic inhibitor treatment. EROD activity was also induced 1.4-fold following exposure of HepG2 cells to mitomycin C alone. Although gamma-irradiation remains the treatment of choice for producing metabolically active HepG2 feeder cells, comparison of the alternatives tested suggests that mitomycin C would be a convenient and suitable replacement. PMID- 10029692 TI - Inhibitory effects of isopropyl-2-(1,3-dithietane-2-ylidene)-2- [N-(4 methylthiazol-2-yl)carbamoyl]acetate (YH439) on benzo[a]pyrene-induced skin carcinogenesis and micronucleated reticulocyte formation in mice. AB - Recently, a great deal of attention has been devoted to organosulfur compounds with potential cancer chemopreventive properties. Many sulfur-containing substances present in Brassica plants have been reported to possess striking anticarcinogenic and antimutagenic activities. Besides naturally occurring organosulfur compounds, certain synthetic sulfur-containing pharmaceuticals, such as oltipraz and sulindac, are known to exert substantial chemopreventive or chemoprotective effects. Isopropyl-2-(1, 3-dithietane-2-ylidene)-2-[N-(4 methylthiazol-2-yl)carbamoyl ]acetate (YH439) was initially developed for its possible use as a hepatoprotectant. The compound has been found to up-regulate the expression of cytochrome P-450 IA1 [I.J. Lee, K.S. Jeong, B.J. Roberts, A.T. Kallarakal, P. Fernandez-Salguero, F.J. Gonzalez, B.J. Song, Transcriptional induction of the cytochrome P-450 1A1 gene by a thiazolium compound YH439, Mol. Pharmacol. 49 (1996) 980-988.] which plays a pivotal role in metabolism of the majority of polycyclic aromatic carcinogens and mutagens, such as benzo[a]pyrene (B[a]P). In the present study, we found that oral administration of YH439 to CD-1 mice significantly suppressed B[a]P-initiated skin tumorigenesis. B[a]P-induced formation of micronuclei in mouse peripheral reticulocytes was also attenuated by YH439 pretreatment. Likewise, diallyl sulfide, a major volatile thioether present in garlic, also protected against B[a]P-induced skin tumorigenesis and micronucleated reticulocyte formation in mice. PMID- 10029693 TI - DNA damage caused by etoposide and gamma-irradiation induces gene conversion of the MHC in a mouse non-germline testis cell line. AB - We have explored the effects of gamma-irradiation and etoposide on the gene conversion frequency between the endogenous major histocompatibility complex class II genes Abk and Ebd in a mouse testis cell line of non-germline origin with a polymerase chain reaction assay. Both gamma-rays and etoposide were shown to increase the gene conversion frequency with up to 15-fold compared to untreated cells. Etoposide, which is an agent that stabilise a cleavable complex between DNA and DNA topoisomerase II, shows an increased induction of gene conversion events with increased dose of etoposide. Cells treated with gamma rays, which induce strand breaks, had an increased gene conversion frequency when they were subjected to low doses of irradiation, but increasing doses of irradiation did not lead to an increase of gene conversion events, which might reflect differences in the repair process depending on the extent and nature of the DNA damage. These results where DNA damage was shown to be able to induce gene conversion of endogenous genes in mouse testis cells suggests that the DNA repair system could be involved in the molecular genetic mechanism that results in gene conversion in higher eukaryotes like mammals. PMID- 10029694 TI - Molecular interactions of ruthenium complexes in isolated mammalian nuclei and cytotoxicity on V79 cells in culture. AB - In this paper, the molecular interactions in isolated mammalian nuclei of three ruthenium complexes, which are putative antineoplastic chemotherapeutic agents effective in reducing metastatic tumours in vivo, have been investigated and compared with the well-known antitumour drug CDDP (cis-diamminedichloroplatinum). The compounds studied are: Natrans-RuCl4(DMSO)Imidazole (NAMI), Natrans RuCl4(DMSO)Oxazole (NAOX) and Natrans-RuCl4(TMSO)- Isoquinoline (TEQU). This study shows that the drugs bind to DNA but induce few, if any, DNA interstrand crosslinks, which are considered as the main biological lesions involved in the cytotoxic activity of several already known antitumour drugs, whilst in the same experimental conditions, CDDP is confirmed to induce them. On the other hand, proteins appear to be an important target in the cell for these drugs, since proteins-DNA crosslinks are shown to be induced by the complexes. Moreover, we investigated Ru complexes for their direct cytotoxicity on V79 cells in culture, showing that two of them (NAMI and NAOX) do not significantly reduce the cloning efficiency of the cells even at concentrations as high as 2-3 mg/ml: only TEQU both reduces cloning efficiency and induces a significant number of mutants in V79 cells in culture. PMID- 10029695 TI - Chlorothalonil: lack of genotoxic potential. AB - Based upon analyses using a number of validated structure-activity relationship models, it is concluded that the carcinogenicity in rodents of chlorothalonil is not due to a genotoxic mechanism. PMID- 10029697 TI - Corrigendum to: 'Utilization of microhomologous recombination in yeast to generate targeting constructs for mammalian genes' PMID- 10029698 TI - [Bright note on the molecular mechanisms of oncogenic transformation]. PMID- 10029699 TI - [Update on genetic markers of cancer]. PMID- 10029700 TI - [Cytogenetics of malignant hemopathies: update]. PMID- 10029701 TI - [Angiogenesis update]. PMID- 10029702 TI - [Cytokines and cancer: update in 1998]. PMID- 10029703 TI - [Apoptosis and chemotherapy]. PMID- 10029704 TI - [Melanoma update]. PMID- 10029705 TI - [AIDS-related cancers]. PMID- 10029706 TI - [Nuclear oncology update]. PMID- 10029707 TI - [Update on reconstructive surgery in cancer]. PMID- 10029708 TI - [Radiotherapy update]. PMID- 10029709 TI - [Concurrent chemoradiotherapy update]. PMID- 10029710 TI - [Anticancer drugs pharmacokinetics update]. PMID- 10029712 TI - [Update on mechanisms of drug resistance]. PMID- 10029711 TI - [New anticancer molecules: drugs for tomorrow?]. PMID- 10029713 TI - [Pain and cancer: update]. PMID- 10029715 TI - Allosteric effects of a monoclonal antibody against thrombin exosite II PMID- 10029714 TI - [A balance of clinical trials in gene therapy]. PMID- 10029716 TI - On the dangers of accepting the part when you need the whole. PMID- 10029717 TI - Are you ready for your 15 minutes of fame? PMID- 10029718 TI - Making quality happen: lab technicians give students a unique perspective. PMID- 10029719 TI - It's been a hard day's night. PMID- 10029720 TI - Managed care, independent practice of hygiene, and the garbage can. PMID- 10029721 TI - Ethics and psychology: who's who or hit-and-run? PMID- 10029722 TI - Then drill, fill, bill. Selectives offer choices. PMID- 10029723 TI - The new preclinical lab moves dental education into the twenty-first century. PMID- 10029724 TI - Ethics and psychology: is there some duty to treat? PMID- 10029725 TI - What if Socrates were on the next accreditation site visit team? PMID- 10029726 TI - Playing in the big leagues. Team dentists take on the pros. PMID- 10029727 TI - Trial run. UOP embraces clinical research. PMID- 10029728 TI - Intellectual capital. PMID- 10029729 TI - The first P. AB - The marketing mix is the complete offer a seller makes to any potential buyer. In classical marketing theory it is composed of four parts: the product, its price, channels of distribution (colloquially called place in order to have a term beginning with the letter P), and promotion which includes incentives, public relations, and advertising. These are the four P's which every MBA student must master. PMID- 10029730 TI - Help along the way. PMID- 10029731 TI - Ethics and psychology: informed consent. PMID- 10029732 TI - Bonafauxverity. PMID- 10029733 TI - Ethics and psychology: dual relationship. PMID- 10029734 TI - Pride is in the teamwork. PMID- 10029735 TI - The big picture. A new teaching model provides a new perspective. PMID- 10029736 TI - One step at a time. PMID- 10029737 TI - Multi-media based education. AB - Computers are changing the way we do everything from paying our bills to programming our home entertainment systems. If you thought that dental education was not likely to benefit from computers, consider this: Computer technology is revolutionizing dental instruction in ways that promise to improve the quality and efficiency of dental education. It is providing a challenging learning opportunity for dental educators as well. Since much of dental education involves the visual transfer of both concepts and procedures from the instructor to the student, it makes sense that using computer technology to enhance conventional teaching techniques--with materials that include clear, informative images and real-time demonstrations melding sound and animation to deliver to the student in the classroom material that complements textbooks, 35mm slides, and the lecture format. Use of computers at UOP is about teaching students to be competent dentists by making instruction more direct, better visualized, and more comprehensible. PMID- 10029738 TI - If it ain't broke... PMID- 10029739 TI - The moral life isn't so easy. PMID- 10029740 TI - Just log on.... PMID- 10029741 TI - Selecting the best and the brightest. AB - The University of the Pacific School of Dentistry is one of the most unique dental schools in the country, and the process of admissions at UOP is one that focuses on selecting the best and brightest students," explains Dr. Bill Harman, associate dean of student services. The development of an outstanding applicant pool begins outside the dental school, under the guidance of UOP alumni, faculty members, and predental advisors. However, the final selection of the entering class occurs after a rigorous, four-step process managed by the Admissions Committee. The goal of this committee, made up of faculty and staff is to make a "fit" between the student and the education program which will lead to some of the most prepared clinicians in the nation." PMID- 10029742 TI - Service for people with disabilities. AB - A couple of years ago a newspaper commentator wrote that even though the current era compares unfavorably in many ways to American life in the 1940s and 50s, we are better off in one way. "We are kinder to one another," she said, remarking on how far we've come in how we treat people with disabilities or non-mainstream looks and lifestyles. We may sometimes verge on a mindless political correctness in our kindness, and we may sometimes practice such kindness through clenched teeth, but all in all, she said, we are better at it than we were forty years ago. The kindness has certainly extended to new groups of dental patients. At UOP, the Special Needs Clinic of the Department of Dental Practice has become symbolic of the school's outreach to formerly underserved communities. Since its founding in 1985 as an adjunct to the department, the Special Needs Clinic has wracked up an impressive list of accomplishments: It has included disabled teens and adults among the populations that UOP routinely serves in its community dental programs; advised state agencies on how to deal with disabled adults and their dental problems (and won more than $600,000 in consultant contracts from those same agencies); produced a preventive dentistry x-raying program that is used as a video on how to teach dental hygiene to developmentally disabled people that later shocked the department when it won the equivalent of an Oscar in its field against competition on far bigger budgets. PMID- 10029743 TI - Ethics and psychology: the work of others. PMID- 10029744 TI - A look at the facts. PMID- 10029745 TI - Off come the gloves. PMID- 10029746 TI - Dr. Levine says Dr. Stack's July editorial lacks some facts. PMID- 10029747 TI - Dr. Westesson recommends changes in the New Jersey Automobile Insurance Cost Reduction Act. PMID- 10029748 TI - The treatment of temporomandibular disorders through repositioning splint therapy: a follow-up study. AB - The purpose of this study was to investigate the effectiveness of repositioning splint therapy as a conservative treatment modality for TMD patients. The treatment sequence of 160 randomly sampled TMD patients was monitored in order to assess different aspects of the patients' response to splint therapy. Included among these aspects were the pretreatment symptoms; the treatment duration required for initial and final alleviation of symptoms; the number of patients requiring surgery; and the particular appliance and its wear pattern utilized to maintain the treatment results. The treatment success was based on the remission of symptoms including but not limited to pain to palpation, headaches, earaches, jaw locking, and joint noises. Eighty-nine and four tenths percent (89.4%) of the patients experienced a complete remission of symptoms and did not require any surgical intervention. The average time for initial improvement was 22.3 days, while the average time for complete remission of symptoms was 4.3 months. The results of the study indicate that repositioning splint therapy is an effective treatment modality for the conservative treatment of temporomandibular disorders. PMID- 10029749 TI - Low velocity impact, vehicular damage and passenger injury. AB - Low velocity motor vehicle accidents are a source of injury to many people every year, but the existence of these injuries is often challenged in the courts. The question raised is: "If the vehicle did not suffer any damage, how could the occupant become injured?" This paper reviews the pertinent literature and explains the mechanism of injury. The factors influencing the probability of injury are discussed. Fallacies of research methodology are explored as they relate to "real" victims. PMID- 10029750 TI - The effects of glucosamine and chondroitin sulfate on osteoarthritis of the TMJ: a preliminary report of 50 patients. AB - The signs and symptoms of osteoarthritis are common complaints seen in patients suffering with chronic temporomandibular disorders (TMD), specifically, internal derangements with a diagnosis of osteoarthritis. With or without the complaints of pain and swelling, joint noises are bothersome and annoying to both the patient and at times, to those seated close to the patient during mealtime. In fact, many patients are driven to seek care by family members because of his or her TMJ noises. For years in veterinarian medicine, glucosamine and chondroitin sulfates have been used to treat symptoms of osteoarthritis. Recently, the use of these two supplements has been recommended for human beings as well. Reports of decreased joint noises, pain and swelling after the administration of therapeutic doses of these supplements have sparked an interest in their possible use in the treatment of osteoarthritis. PMID- 10029751 TI - A protocol for magnetic resonance imaging of the temporomandibular joints. AB - The complex concepts and procedures of magnetic resonance imaging (MRI) are unfamiliar to many dentists. Similarly, many radiologists lack understanding of the clinical requirements of the dentist for accurate assessment of TMJ abnormalities. Thus, TMJ imaging procedures may be inadequate or incomplete, may vary from facility to facility, and sometimes from patient to patient in a given facility. A protocol for TMJ imaging is presented which meets dental requirements and is rapidly performed in the MRI facility. The protocol may be copied and attached to the prescription to the imaging center. It may be modified or expanded to accommodate specific patient requirements or equipment performance. PMID- 10029752 TI - TMJ static disk: correlation between clinical findings and pseudodynamic magnetic resonance images. AB - The aim of this study was to analyze the position and mobility of the temporomandibular joint (TMJ) articular disk by means of pseudodynamic magnetic resonance imaging (MRI) and to compare: clinical features, osseus and muscular degenerative changes, the different types of static and their signs and symptoms. The study was performed on 101 patients with clinical and MRI diagnosis of TMJ internal derangement with closed lock (permanent or episodic). On the MRI survey the following was evaluated: disk displacement, disk mobility, condylar translation, bone, and muscular fatty atrophy. Pain was more frequent in static disks (SD) than in mobile disks (MD) in all types of disk displacements (p < 0.01). Condylar translation was always lower in SD than in MD, independently from the position of the articular disk (p < 0.01). Localized sclerosis was more frequent in joints with SD. There were no statistically significant differences in the incidence of fatty atrophy considering disk mobility. The results of the study indicate that clinical diagnosis of closed lock with high frequency is related to the presence of a static disk. Clinical diagnosis of SD can be confirmed with a pseudodynamic MRI survey. PMID- 10029753 TI - Observations on the correlation between posture and jaw position: a pilot study. AB - The aim of this pilot study was twofold. The first was to show a method for having an objective and dynamic analysis of body posture, evaluating weight distribution and its connections with different mandibular positions. The second was to verify if a neuromuscularly stimulated occlusal position, called myocentric occlusal position, is associated with a positive or negative postural charge. For the second aim a group of 20 subjects (including both males and females), was chosen. Posture of each subject was analyzed in three different conditions: centric occlusion, rest position and myocentric position. To evaluate the dynamic of posture a platform capable of measuring the weight on the feet supporting points and the related variations during time of observation and the swinging of body barycenter was used. The data showed that there is an improvement in the position of the barycenter from the centric occlusion to the myocentric position. Such an improvement can't be observed from the intercuspal position to the rest position. The results of this pilot study are discussed. PMID- 10029754 TI - Effects of physical and sexual abuse in facial pain: direct or mediated? AB - Research has identified a relationship between a history of physical and/or sexual abuse and a range of psychological, functional, and physical factors; however, the nature of this relationship has not been tested. We hypothesize two different mechanisms through which an abuse history could influence later life distress and dysfunction. A history of abuse could increase an individual's vulnerability to emotional distress or could increase an individual's tendency to attend, amplify, and over-interpret somatic symptoms. The purpose of this study was to test the influence of emotional distress and somatic focus on the relationship between a history of physical and/or sexual abuse and later chronic painrelated disability in patients with temporomandibular disorders. The subjects were 139 female patients evaluated at a facial pain clinic. Of the 139 subjects, 49% (n = 69) reported a history of physical and/or sexual abuse. Abused subjects reported significantly higher levels of anxiety, depression, and somatic symptoms than nonabused subjects. Path analysis with latent variables, using the LISREL-8 (Scientific Software International, Inc., Chicago, Illinois) statistical program was used to test the hypothesized relationships. When emotional distress and somatic focus were tested as mediators, the path coefficient from somatic focus to physical functioning was significant (beta = -0.38) while the path coefficient from negative emotion to physical functioning was not significant. These results favor somatization as the hypothesized mechanism over the emotional distress vulnerability hypotheses. PMID- 10029755 TI - Interrelationships of brain, cranial base and mandible. AB - The purpose of this study is to evaluate the neural and masticatory growth factors that contribute to the development of the cranial base. Cephalometric and submentovertex (SMV) radiographs of 66 adult human skulls, of Caucasian (India) origin and unknown gender were used in this study. Results indicate that the cranial base, posterior to the foramen caecum, develops in response to brain growth. The part anterior to the foramen caecum develops in response to the mandible. Our findings indicate that: 1. the glabella instead of the nasion should be considered as the most anterior point of the cranial base. Mandibular dimensions (the height and the length) have a better correlation with CG than CN. 2. Instead of a single parameter, sella-nasion (SN), two parameters, the foramen caecum-glabella (CG) and the foramen caecum-sella (CS) should be considered. In cephalometry the more stable line CS, rather than SN, can be used for registration of successive radiographs; 3. The typical mandibular retrognathia, and/or the decrease in the posterior height (ascending ramus) of a Class II malocclusion could be explained by their positive correlation with SB (sella basion) and the negative correlation with angle GSB. PMID- 10029756 TI - Electromyographic activity of the jaw-closing muscles before and after unilateral coronoidectomy performed on a patient with coronoid hyperplasia: a case study. AB - There have been few reports analyzing the activity of the jaw-closing muscles after coronoidectomy performed on a patient with coronoid hyperplasia. This paper presents a case study using electromyograms (EMGs) to evaluate the effects of unilateral coronoidectomy on the activity of masseter and temporal muscles. The patient was a 25-year-old male whose maximal range of jaw opening was 24 mm. After coronoidectomy of the left region, the range improved to 43 mm. EMGs were recorded in the center of the masseter muscles and the anterior part of the temporal muscles during gum chewing. Preoperatively, no abnormal EMG activity was observed. Eight months after surgery, increase in the ratio of the bilateral temporal muscle activity and a decrease in the ratio of the right masseter muscle activity were observed, and the proportion of activity of jaw closing muscles was out of the normal range. Eighteen months after surgery, there was slight return to the preoperative EMG activity. It was concluded that unilateral coronoidectomy could result in EMG changes of masseter and temporal muscles with a gradual return. PMID- 10029757 TI - Medical managed care for temporomandibular disorders and orofacial pain. PMID- 10029758 TI - The Automobile Insurance Cost Reduction Act identification of diagnosis tests final committee report. PMID- 10029759 TI - The Pac Man syndrome: a game or a real-time event? PMID- 10029760 TI - Observations and thoughts on the changing constellation of cranial deformities. PMID- 10029761 TI - Computer tomography determined intracranial volume of infants with deformational plagiocephaly: a useful "normal"? AB - Over the last 10 years, children with deformational (nonsynostotic) plagiocephaly have undergone computed tomography scans using the same protocols as children with lambdoid craniosynostosis because of their similarly distorted head shapes. These children are believed to have normal intracranial volume. Given the recent questioning of what is the normal range of intracranial volume in human populations, the authors have undertaken a comparison of the intracranial volume of children with deformational plagiocephaly and Lichtenberg's normal population (Lichtenberg R. Radiographie du crane de 226 enfants normaux de la naissance a 8 ans: Impressions digitiformes, capacite, angles et indices [thesis]. Paris: University of Paris, 1960). The intracranial volume was determined for 20 females and 46 males with deformational plagiocepahly ranging in age from 2.5 to 20.7 months using computed tomography scan data. Although no significant differences were found for the females, the authors found that the intracranial volume of the males with deformational plagiocephaly were significantly larger than Lichtenberg's population. The authors conclude that this is because Lichtenberg's data do not adequately reflect the normal range of intracranial volume for males ranging in age from 2.5 to 20.7 months, rather than gender differences associated with deformational plagiocephaly. Further, until a more suitable normal becomes available, the deformational (nonsynostotic) plagiocephaly data could be used as substitute normal reference material in the measured age range for assessment of the intracranial volumes of children with craniosynostosis. PMID- 10029762 TI - Controlled multiplanar distraction of the mandible, Part II: Laboratory studies of sagittal (anteroposterior) and vertical (superoinferior) movements. AB - The application of distraction osteogenesis in craniofacial surgery has significantly altered the treatment of congenital mandibular deficiencies. However, evaluation of results in both animal studies and clinical cases has revealed deficiencies, particularly in two areas. First, distraction using a uniplanar device in an anteroposterior direction can result in a persistent anterior open bite. Second, the lateralization of the distracted hemimandible was often limited, with insufficient incremental gain in the bigonial distance. To overcome these shortcomings, a multiplanar distraction device was developed and tested in the canine model. This report details canine studies addressing the first problem: combined anteroposterior or sagittal (z-axis) and superoinferior or vertical (y-axis) movements. Six dogs underwent bilateral mandibular distraction with an external (extraoral), multiplanar device and completed sagittal plus vertical distraction. Evaluation included clinical examination (facial form, jaw position, and occlusion), photography, cephalograms (posteroanterior, basilar, and lateral), three-dimensional computed tomography reconstructions, and examination of dry skulls. The dogs averaged 18.5 mm (range, 15-20 mm) of sagittal distraction and 41.0 degrees (range, 21-50 degrees) of vertical distraction. Marked anterior open bites were produced after vertical distraction secondary to premature contact of the maxillary and mandibular molars. Distraction in the vertical direction also had the additive effect of increasing the sagittal gains by approximately 5% to 10%. In conclusion, a multiplanar distraction device (with the potential for distraction in three planes) was effective in increasing mandibular anteroposterior thrust (sagittal distraction) and also in creating an anterior open bite (vertical or superoinferior distraction). Vertical distraction probably requires bilateral osteotomies to obtain optimal results. The preliminary gains in sagittal length are modified (reduced or increased) after distraction in a second plane (vertical and horizontal). Specifically, vertical distraction in the inferior direction (creating an open bite) also leads to isolated increases in the anteroposterior plane. Conversely, vertical distraction in the superior direction (closing an open bite), as seen in a human malocclusion, may lead to isolated decreases in the anteroposterior plane, but this question remains to be investigated in the laboratory. PMID- 10029763 TI - Avoidance of implicit hazards: the realignment of maxillary and mandibular arches in comminuted and facial fractures. AB - The authors introduce an attempt to elevate the problem of proper realignment of the maxillary and mandibular arches to achieve an exact transversal width of the lower third of the face with an index of the sum of the maxillary and mandibular central incisors, together with a new Artex-Callotte System (Karl Storz GmbH, Tuttlingen, Germany). This allows individual and anatomically correct restoration of the dental arches. This is especially helpful if either a large number of teeth or portions of dental alveolar processes have been lost in comminuted panfacial fractures. In addition, a sequential, step-management concept of comminuted panfacial fractures is described and illustrated. The goals of treatment with this method are to reestablish the midfacial height and projection and the occlusion, and reestablish the integrity of the nose, the orbit, and the transversal dimension of the lower jaw. This simple method is not yet well appreciated. PMID- 10029764 TI - Nasal reconstruction in children: a review of 29 patients. AB - Acquired large nasal defects are much more common in adulthood than in childhood because of the frequency of skin tumors after a certain age. However, from their experience in treating a number of children with sequelae of noma and burns, the authors have collected a series of 17 total and 12 partial nasal reconstructions in children aged 1 to 15 years. After reviewing the various methods used for recreating the lining, the support, and the skin cover in the whole series, three cases are reported in detail. A 1-year-old patient received a tempororetroauricular flap after total amputation of the nose and was observed for 17 years. Another patient, who was burned as a baby, underwent reconstruction at age 10 with a deltopectoral flap and was observed for 7 years. The third patient underwent total nose reconstruction at age 12 with an Indian forehead flap. From their experience, the authors conclude that, for psychosocial reasons, nasal reconstruction should be started early, despite possible reoperation at a later age. The best results are certainly obtained at the end of growth or at least after the age of 12. Adjacent bone or soft tissue defects further enhance the difficult challenge of restoring a satisfactory aesthetic appearance in these children. PMID- 10029765 TI - Cranio-orbital-temporal neurofibromatosis: are we treating the whole problem? AB - Cranio-orbital-temporal neurofibromatosis is an uncommon subtype of neurofibromatosis 1 characterized by pulsatile exophthalmos, orbital neurofibromas, sphenoid wing dysplasia, expansion of the temporal fossa, and herniation of the temporal lobe into the orbit. The cause of the sphenoid wing dysplasia is uncertain. Reconstruction of the sphenoid defect, separating the orbit and cranial vault, has been problematic because of resorption of bone grafts. This reports illustrates one potential cause of the sphenoid defect and a possible cause of the bone graft resorption. PMID- 10029766 TI - A de novo discharging sinus of the fronto-orbital suture: a rare presentation of a dermoid cyst. AB - Dermoid cysts are developmental anomalies, resulting primarily from trapped germinal epithelium. In the neck and head region, the most common location is the fronto-orbital upper outer quadrant of the orbit. Because only a few cases of dermoid cysts with discharging sinus of the fronto-orbital area have been reported in the literature, the authors present an unusual case of a frontozygomatic suture dermoid cyst, presenting as a sinus, in an 56-year-old man. The histologic report confirmed that the cystic lesion was a dermoid cyst with a tract. Diagnosis and management are discussed. PMID- 10029768 TI - Atypical Frey syndrome as a complication of Obwegeser osteotomy. AB - A patient with Frey syndrome on the left cheek area as a complication of an Obwegeser osteotomy is reported. Flushing, sweating of skin, and hypoesthesia of buccal mucosae were present 6 months after surgery. An injury to the auriculotemporal nerve during desperiostization of the posterior border of the mandibular ramus is believed to be the principal cause. The physiopathologic mechanism is thought to occur in relation to aberrant regeneration of the postganglionic secretomotor parasympathetic nerve fibers carried in this nerve. These regenerated fibers erroneously reach the sweat glands of the cheek skin through anastomosis with the buccal nerve and temporofacial ramus of the facial nerve. Direct injury of the buccal nerve may be another cause, because of its close anatomic course with the external pterygoid muscle and the mandibular ramus. An extensive literature review revealed no cases of this syndrome as a complication of Obwegeser osteotomy. PMID- 10029767 TI - Inverted, T-shaped silicone implant for the treatment of temporomandibular joint ankylosis. AB - Reconstruction of the ankylosed temporomandibular joint is a challenging task. Speech impairment, difficulties with mastication, poor oral hygiene, facial asymmetry, and mandibular micrognathia results in physical and psychologic disabilities. Various surgical techniques with varying success rates have been reported. Many autogenous and alloplastic materials have been proposed. The authors used an inverted, T-shaped silicone implant for the reconstruction of the temporomandibular joint after the release of the ankylosis in 10 patients without any complications in the postoperative period. The authors assert that the reconstruction of the ankylosed temporomandibular joint with an inverted, T shaped silicone implant is a reliable and effective alternative. This technique can be used according to the special requirements of each patient and obviating the need for the fixation of the implant and is a safer and better way of using silicone for the treatment of temporomandibular joint ankylosis. PMID- 10029769 TI - Computer-generated patient models for reconstruction of cranial and facial deformities. AB - The use of three-dimensional, computer-generated anatomic models can be used in the diagnosis and reconstruction of a variety of craniofacial problems. They are readily manufactured from computed tomography scans at a reasonable cost with only several weeks of preparation and delivery time. Their contemporary value is in the preoperative treatment planning, intraoperative implant fashioning, and preoperative implant fabrication in appropriately selected patients. PMID- 10029770 TI - The in utero repair of Tessier number 7 lateral facial clefts created by amniotic band-like compression. AB - The purpose of this study was to determine the effectiveness of intrauterine reconstruction of lateral facial clefts caused by surgically simulated amniotic band compression. The authors hypothesized that intrauterine lysis of these bands could: 1) prevent the progression of cleft formation; 2) normalize facial development; and 3) allow for the scarless repair of these lateral atypical facial clefts. In a prospective randomized trial, eight 65-day gestational fetal lambs (term, 140 days) were exposed via a maternal hysterotomy. A Tessier 7 facial cleft was made by applying a 2.0 nylon suture as a constriction band to the growing face. The sutures were attached to the zygomatic arch and looped circumferentially into the oral commissure. Two weeks after surgery, four of eight animals were re-exposed. All four animals developed phenotypic changes consistent with Tessier 7 lateral facial clefts. These animals were treated in utero by 1) excising the synthetic constricting band, and 2) opening the epithelialized edges of the lateral facial clefts and performing a primary repair. At birth, the bands on the four untreated animals were cut. The lambs developed to 3 months of age, at which time they were evaluated anthropomorphically for changes in soft tissue measurements, and histologically using hematoxylin and eosin and Mason trichrome stain for the degree of scar at the repair site. Tessier 7 lateral facial clefts were produced in all the untreated animals. Each developed macrostomia with an average 2.3-cm lateral displacement of the oral commissure and partial maxillary clefting induced by the pressure of the restriction band. No evidence of tissue necrosis, maceration, or ulceration was noted. In contrast, animals treated in utero were phenotypically normal. There was no evidence of macrostomia and all anthropomorphic measurements were symmetrical. No bony clefts were seen on gross examination. Histologically, there was no evidence of scar formation at the site of the cleft repair. These findings suggest that like the standard cleft lip, atypical lateral facial clefts can be repaired successfully in utero without scarring. Furthermore, lysis of a restriction band in utero can prevent the progression of this facial deformity, leading to normal development of the face. PMID- 10029771 TI - Distraction osteogenesis: the effects of orthodontic tooth movement on distracted mandibular bone. AB - The application of distraction osteogenesis in craniomaxillofacial surgery has created new treatment methods for patients with craniofacial skeletal dysplasias. Most of the applications in the craniofacial skeleton have been for the correction of severe congenital or acquired conditions. As more understanding is gained with these new approaches, refinements in techniques will enhance treatment planning and outcome. This will expand the application of distraction osteogenesis to more common, less severe types of skeletal dysplasias. One of the important areas in mandibular distraction osteogenesis is the management of the dental gap created when distraction is applied within the tooth-bearing segment of the mandibular body. In this study, the authors investigated the effects of orthodontic tooth movement into new bone created through the process of distraction osteogenesis. Orthodontic tooth movement through newly formed mandibular bone in the canine model was performed and, through histologic studies, was found to create compact bone along the path of the moving tooth. This compact bone replaced the more unstructured woven bone that was originally created by the process of mandibular distraction osteogenesis. These findings indicate that orthodontic tooth movement can be performed in distracted bone and can have significant influence on the stability and long-term structural preservation of the bone created by distraction osteogenesis within the tooth bearing segment of the mandible. PMID- 10029772 TI - Craniosynostosis and skull molding. AB - On February 20-23, 1997 in Scottsdale, Arizona, a symposium was held that was sponsored by the Plastic Surgery Educational Foundation, the American Society of Maxillofacial Surgeons, and the Joint Section on Pediatric Neurological Surgery of the American Association of Neurological Surgeons and the Congress of Neurological Surgeons. The chairs of the meeting were Jeffrey C. Posnick and Harold L. Rekate. The symposium examined issues relating to craniosynostosis and skull molding. The program consisted of three parts. Day 1 focused on the basic concepts of craniosynostosis and skull molding. Day 2 focused on evaluation and treatment of craniosynostosis. Day 3 focused on the diagnosis and treatment of craniofacial syndromes. The symposium was significant because it brought craniofacial and pediatric neurosurgeons together for the first time at a combined meeting to discuss important aspects of craniosynostosis and skull molding. This article summarizes the presentations made at the meeting. PMID- 10029773 TI - Reality check. PMID- 10029774 TI - Care for the poor is stricken dentist's legacy. PMID- 10029775 TI - TB continues its lethal ways. PMID- 10029776 TI - Quackery in dentistry. Past and present. PMID- 10029777 TI - Controversies in TMD. AB - Health professionals have dealt with temporomandibular disorders, a major cause of non-dental pain in the orofacial region, by developing a broad range of treatments, from occlusal alteration to multidisciplinary self-care regimens. Research directed toward evaluation of various TMD treatment modalities is particularly controversial due to cyclical fluctuation of symptoms, high rates of spontaneous remission, and possibility of placebo effect interference. Given this variety of treatments now current, dental professionals bear a broadening responsibility to review and assess the range of diagnostic possibilities and treatment potentials now entering into the scientific literature. PMID- 10029778 TI - The evolving demographic makeup of dental graduates. AB - The gender, racial and ethnic makeup of dental school graduates and advanced dental education program students is undergoing changes that to some extent mirror the developments in the general population. There have been marked decreases in the ratio of white dental school graduates to the white population, but limited changes in the ratio of minority group graduates to their respective national populations. Compared to their representation in dental schools, women and minority group graduates are under-represented in specialty training programs, with wide variations by specialty fields. There have been marked decreases in the proportion of dental school graduates whose immediate plans include self-employment practice and increases in the proportion anticipating some form of employment. PMID- 10029779 TI - Effect of doxycycline on the apical seal of retrograde filling materials. AB - In this study, we examined the effect of doxycycline hydrochloride (DH) on the apical seal. Results indicated that teeth that were retrofilled with IRM or amalgam following doxycycline irrigation had significantly less dye penetration (p < 0.05). Due to its antimicrobial activity, smear layer removal ability, and improvement of apical seal, doxycycline solution may be used as an irrigant. PMID- 10029780 TI - The effect of bioburden on in-depth disinfection of denture base acrylic resin. AB - This study evaluated the effectiveness of three different disinfectant solutions against denture bioburden absorbed within the depth of acrylic resin. Specimens were taken from dentures that had been worn by the patients for 15 to 20 years and were scheduled for replacement. PMID- 10029781 TI - HHS awards $479 million in grants for HIV/AIDS care and support services. PMID- 10029783 TI - Prevention of malaria and diarrhea in travelers. PMID- 10029784 TI - The changing spectrum of HIV care. PMID- 10029785 TI - Clinical evaluation and treatment options for herniated lumbar disc. AB - Degeneration of the intervertebral disc from a combination of factors can result in herniation, particularly at the L4-5 and L5-S1 levels. The presence of pain, radiculopathy and other symptoms depends on the site and degree of herniation. A detailed history and careful physical examination, supplemented if necessary by magnetic resonance imaging, can differentiate a herniated lumbar disc from low back strain and other possible causes of similar symptoms. Most patients recover within four weeks of symptom onset. Many treatment modalities have been suggested for lumbar disc herniation, but studies often provide conflicting results. Initial screening for serious pathology and monitoring for the development of significant complications (such as neurologic defects, cauda equina syndrome or refractory pain) are essential in the management of lumbar disc herniation. PMID- 10029786 TI - Preterm labor. AB - Preterm labor is the leading cause of perinatal morbidity and mortality in the United States. It is characterized by cervical effacement and/or dilatation and increased uterine irritability before 37 weeks of gestation. Women with a history of preterm labor are at greatest risk. Strategies for reducing the incidence of preterm labor and delivery have focused on educating both physicians and patients about the risks for preterm labor and methods of detecting preterm cervical dilatation. Methods used to predict preterm labor include weekly cervical assessment, transvaginal ultrasonography, detection of fetal fibronectin and home uterine activity monitoring. As yet, it is unclear if any of these strategies should be routinely employed. At present, management of preterm labor may include the use of tocolytic agents, corticosteroids and antibiotics. PMID- 10029787 TI - Incorporating advance care planning into family practice [see comment]. AB - Despite widespread support for the concept of advance care planning, few Americans have a living will or a health care proxy. Advance care planning offers the patient the opportunity to have an ongoing dialog with his or her relatives and family physician regarding choices for care at the end of life. Ultimately, advance care planning is designed to clarify the patient's questions, fears and values, and thus improve the patient's well-being by reducing the frequency and magnitude of overtreatment and undertreatment as defined by the patient. An advance directive consists of oral and written instructions about a person's future medical care in the event he or she becomes unable to communicate. There are two types of advance directives: a living will and a health care power of attorney. Family physicians are in an ideal position to discuss advance care plans with their patients. By introducing the subject during a routine office visit, physicians can facilitate a structured discussion of the patient's wishes for end-of-life care. At the next visit, further discussion can include the patient and his or her proxy. A document that clearly delineates the patient's wishes is then developed. The patient should be assured that the directive can be changed at any time according to the patient's wishes. The advance care plan should be reviewed periodically to make sure the specifications continue to be in line with the patient's wishes. PMID- 10029788 TI - Exfoliative dermatitis. AB - Exfoliative dermatitis, also known as erythroderma, is an uncommon but serious skin disorder that family physicians must be able to recognize and treat appropriately. Although the etiology is often unknown, exfoliative dermatitis may be the result of a drug reaction or an underlying malignancy. The approach to treatment should include discontinuation of any potentially causative medications and a search for any underlying malignancy. One of the most common malignancies associated with exfoliative dermatitis is cutaneous T-cell lymphoma, which may not manifest for months or even years after the onset of the skin condition. Hospitalization is usually necessary for initial evaluation and treatment. In the hospital, special attention must be given to maintaining temperature control, replacing lost fluids and electrolytes, and preventing and treating infection. The long-term prognosis is good in patients with drug-induced disease, although the course tends to be remitting and relapsing in idiopathic cases. The prognosis of cases associated with malignancy typically depends on the outcome of the underlying malignancy. PMID- 10029789 TI - Warfarin therapy: evolving strategies in anticoagulation. AB - Warfarin is the oral anticoagulant most frequently used to control and prevent thromboembolic disorders. Prescribing the dose that both avoids hemorrhagic complications and achieves sufficient suppression of thrombosis requires a thorough understanding of the drug's unique pharmacology. Warfarin has a complex dose-response relationship that makes safe and effective use a challenge. For most indications, the dose is adjusted to maintain the patient's International Normalized Ratio (INR) at 2 to 3. Because of the delay in factor II (prothrombin) suppression, heparin is administered concurrently for four to five days to prevent thrombus propagation. Loading doses of warfarin are not warranted and may result in bleeding complications. Interactions with other drugs must be considered, and therapy in elderly patients requires careful management. Current dosing recommendations are reviewed, and practical guidelines for the optimal use of warfarin are provided. PMID- 10029790 TI - Photo quiz. Vaginal bleeding at 16 weeks. PMID- 10029792 TI - HIV testing for all pregnant women. PMID- 10029791 TI - When a parent insists on antibiotics for a virus. PMID- 10029793 TI - Strategically planning for the future of nursing in California. PMID- 10029794 TI - The vow of silence. PMID- 10029795 TI - Chaos theory. Learning a new science. PMID- 10029796 TI - Protecting your healthcare organization from liability for sexual harassment by employees and non-employees. PMID- 10029797 TI - Shaping systems to promote desired outcomes. The magnet hospital model. AB - The organization of nurses' work is a major determinant of patient and staff welfare. Magnet hospitals have demonstrated organizational attributes that enable nurses to fully use their knowledge and expertise to provide high-quality patient care. The empirical evidence that this type of organization produces better patient and staff outcomes is compelling. Therefore when reconfiguring the delivery of care, the organizational form found in the magnet hospitals should shape systems to promote desired outcomes. PMID- 10029798 TI - The hospitalist: the new addition to the inpatient management team. AB - To coordinate care and manage costs, physicians are being added to the inpatient management team. To assist the chief nurse executive in assimilating this new team member into the patient care provider group, the authors describe the role of the hospitalist, the goals of the organization in using the new role, questions to ask and steps to take to ensure success for the whole-care team and the organization. PMID- 10029799 TI - Some impacts of nursing on acute care hospital outcomes. AB - Measuring nursing-sensitive patient outcomes using publicly available data provides exciting opportunities for the nursing profession to quantify the patient care impact of staffing changes at individual hospitals and to make comparisons among hospitals with differing staffing patterns. Using data from California and New York, this study tested the feasibility of measuring such outcomes in acute care hospitals and examining relationships between these outcomes and nurse staffing. Nursing intensity weights were used to acuity-adjust the patient data. Both higher nurse staffing and higher proportion of RNs were significantly related to shorter lengths of stay. Lower adverse outcome rates were more consistently related to a higher proportion of RNs. PMID- 10029800 TI - Factors to consider when buying a mobile health unit. AB - Purchasing a mobile unit to deliver healthcare services can be an expensive undertaking, and there is little information in the literature on planning or designing these vehicles. The authors discuss guidelines to help nurse administrators make better decisions regarding the purchase of mobile health units (MHUs). The guidelines resulted from a synthesis of the literature, correspondence with the chief executive officers of firms that manufacture MHUs, and onsite visits to agencies with an MHU. PMID- 10029801 TI - Nurse case managers in rural hospitals. AB - Many rural hospitals are struggling to survive the capitated care environment by implementing nursing case management. However, little is known about what rural nurse case managers (NCMs) do to achieve outcomes or what their qualifications should be. This national survey of NCMs (N = 302) in rural hospitals suggests that individual advocacy, teaching, and clinical practice play key roles in the practice of rural NCMs and that the education and experience of NCMs does affect their practice. PMID- 10029802 TI - Humanizing voice mail in healthcare. AB - Over the past few years, voice mail has spread rapidly through the corporate environment. Healthcare facilities were slow to adopt this form of telecommunication until it became clear that healthcare was indeed a business, and this innovative technology was becoming a permanent fixture in the business world. Unfortunately, basic two-way communication with compassion, which is so critical to the success of healthcare, became peripheral to computer-mediated technology. While there is debate over the voice mail appropriateness in healthcare, one point of agreement is that voice mail is here to stay. The author examines one hospital's experience with computer-mediated communication, its initiative for improvement without monetary options, and its evolution toward a more compassionate, humanistic system for its internal and external customers. PMID- 10029803 TI - Comments from the Editor-in-Chief. PMID- 10029804 TI - Asparaginases: where do we go from here? PMID- 10029805 TI - Prognostic significance of early response to a single dose of asparaginase in childhood acute lymphoblastic leukemia. AB - PURPOSE: The in vitro and in vivo efficacy of a single dose of asparaginase in children with newly diagnosed acute lymphoblastic leukemia and the correlation between in vitro and in vivo antileukemic response and long-term outcome were prospectively evaluated. PATIENTS AND METHODS: Two hundred fifty-one patients were randomized to receive 1 of 3 asparaginase preparations (Escherichia coli, Erwinia chrysanthemi [Erwinia], or pegaspargase). In vitro assessment of efficacy was expressed as the percent total cell kill (TCK), based on the number of viable cells found after 5 days of culture in the presence of asparaginase. In vivo leukemia cell kill (LCK) was calculated by comparing bone marrow cellularity and percent leukemic blasts in marrow obtained before and 5 days after treatment with a single dose of asparaginase. Acute toxicity was determined by clinical and laboratory assessment. RESULTS: There was equivalent cell kill with all three types of asparaginase. The mean in vitro TCKs for E. coli, Erwinia, and pegaspargase were 31%, 39%, and 36%, respectively (P = 0.63). The mean LCKs in marrow of patients exposed to E. coli, Erwinia, and pegaspargase were 69%, 74%, and 65%, respectively (P = 0.88). The lack of response to asparaginase in vitro predicted a higher risk for clinical relapse regardless of risk assignment (12 leukemic events among 21 in vitro nonresponders; 57%, P < 0.001). There was no difference in acute toxicity among the three asparaginase preparations. CONCLUSIONS: All three asparaginase preparations produced equivalent LCKs in in vitro and in vivo analyses. In vitro response to asparaginase provided a risk group-independent prognostic factor. PMID- 10029806 TI - Clinical impact and prognostic value of metaiodobenzylguanidine imaging in children with metastatic neuroblastoma. AB - PURPOSE: The clinical value of metaiodobenzylguanidine (mIBG) scintigraphy in patients with disseminated neuroblastoma (NB) at the time of diagnosis and after induction chemotherapy was evaluated. PATIENTS AND METHODS: The medical records and imaging studies of 30 patients with stage 4 NB who underwent mIBG scintigraphy and 99mTc hydroxy methylene diphosphonate bone scintigraphy at the time of diagnosis were reviewed. Scores were calculated for the mIBG and bone scintigrams, and outcome according to the initial and follow-up imaging studies was determined. RESULTS: Discrepancies between bone scintigraphy and mIBG osteomedullary localization were seen in six patients. For the entire cohort, 2 year event-free survival did not significantly differ for the group of patients with initial mIBG or bone scintigraphy scores > or = 10 compared to those with scores < 10 (P = 0.23 and 0.61, respectively). However, for patients older than 1 year, a trend associating worse outcome with mIBG scores > or = 10 at diagnosis was seen (P = 0.08). A trend correlating abnormal mIBG scintigraphy after induction therapy and poor outcome was also observed (P = 0.09). Outcome did not correlate with the results of the bone scintigram studies performed after induction chemotherapy (P = 0.68). CONCLUSION: Because a discordance between mIBG and bone scintigraphy results were seen in a subset of stage 4 NB patients, both imaging studies should be performed at the time of diagnosis. mIBG imaging studies performed at the time of diagnosis and after induction chemotherapy may be of prognostic value, particularly in stage 4 patients older than 1 year. PMID- 10029807 TI - Coexpression of genes involved in apoptosis in central nervous system neoplasms. AB - PURPOSE: Apoptosis plays a crucial role in normal development and mediates tumor response to chemotherapy. This study investigated the pattern of apoptotic gene expression in brain tumor tissue specimens and cell lines. MATERIALS AND METHODS: BCL2, BCLXL, BCLXS, and BAX transcripts were amplified using reverse transcriptase polymerase chain reaction in 7 high-grade gliomas (HGGs), 7 ependymomas, and 6 cell lines (2 glioblastomas, 3 medulloblastomas, and 1 supratentorial-primitive neuroectodermal tumor [PNET]). Immunohistochemical staining for BCL2, BCLX, BAX, and p53 was performed in 7 pediatric low-grade gliomas (LGGs) and 7 pediatric HGGs. RESULTS: Six of seven gliomas, all ependymomas, and all glioblastoma and medulloblastoma cell lines expressed BCLXL and BAX. BCL2 expression was only detected in the supratentorial PNET line PFSK. BCLXS was absent in all tumors. By immunohistochemistry, no glial tumors stained positively for BCL2. Similar BAX and BCLX protein expression was observed in LGG and HGG. Three of five glioblastomas showed significant p53 expression. CONCLUSIONS: Coexpression of proapoptotic and antiapoptotic genes in human brain tumors supports the hypothesis that the relative expression of competing genes determines apoptotic threshold. PMID- 10029809 TI - Evidence for a hybrid macrophage phenotype in erythrophagocytic histiocytosis. AB - PURPOSE: The phenotype of the proliferating cells in two patients with erythrophagocytic histiocytosis is described. These 6- and 18-month-old female patients presented with fever, anemia, hepatosplenomegaly, and lymphadenopathy. MATERIALS AND METHODS: Clinical histories were reviewed, and pathological specimens of both patients were studied by histology, and electron microscopy/immunohistochemistry using antibodies against macrophage and Langerhans cell (LC) antigens. RESULTS: Histology revealed prominent erythrophagocytosis of proliferating histiocytes. By immunohistochemistry, conventional macrophage (HAM-56, alpha 1-antitrypsin, alpha 1-antichymotrypsin, lisozyme, CD68, and alpha-subunit of S-100 protein) and LC (CD1a and S-100 protein) markers were positive, as well as double labeling for CD1a and alpha 1 antichymotrypsin, in a majority of proliferating cells. Ultrastructural examination revealed Birbeck granules and prominent phagolysosomes frequently in the same cell. CONCLUSIONS: The hybrid ultrastructural and immunohistochemical phenotype between phagocytic macrophage and LC of proliferating histiocytes supports the common origin of these different histiocyte subtypes. This unusual phenotype might be the expression of the proliferating (hybrid) precursor or be the effect of unknown stimuli. Additional cases of childhood erythrophagocytic histiocytosis should be studied with immunophenotyping and ultrastructure to determine whether the hybrid phenotype represents a specific entity or an epiphenomenon. PMID- 10029808 TI - Pharmacokinetics and cerebrospinal fluid penetration of daunorubicin, idarubicin, and their metabolites in the nonhuman primate model. AB - PURPOSE: Idarubicin (4-demethoxy-daunorubicin) is more potent and less cardiotoxic than the commonly used anthracyclines, doxorubicin and daunorubicin. In addition, idarubicin is metabolized to an active metabolite, idarubicinol, in contrast to other anthracyclines whose alcohol metabolites are much less active than the parent drug. The current study was performed in nonhuman primates to determine the plasma and cerebrospinal fluid (CSF) pharmacokinetics of idarubicin and idarubicinol and to compare them to the pharmacokinetics of daunorubicin and daunorubicinol. METHODS: A dose of 30 mg/m2 of daunorubicin or 8 mg/m2 of idarubicin was administered intravenously over 15 minutes. Plasma and CSF were sampled frequently from the end of the infusion to 72 to 96 hours after infusion. Drug and metabolite concentrations were measured using high-pressure liquid chromatography (HPLC). RESULTS: Daunorubicin elimination from plasma was triphasic with a terminal half-life of 5.9 +/- 1.8 hours, area under the concentration-time curve (AUC) 22.5 +/- 9.2 mumol/L.min, and clearance 2790 +/- 960 mL/min/m2. Daunorubicinol elimination was biphasic with a terminal half-life 10.2 +/- 2.3 hours and an AUC 74.5 +/- 5.3 mumol/L.min. Idarubicin elimination was triphasic with terminal half-life of 12.3 +/- 11.4 hours, a AUC 10.8 +/- 3.7 mumol/L.min, and clearance 1650 +/- 610 mL/min/m2. Idarubicinol elimination was biphasic with a terminal half-life 28.7 +/- 4.2 hours and AUC 67 +/- 9.8 mumol/L.min. CSF penetration was low for both parent drugs and their metabolites. CSF idarubicin was measurable at a single time point (1 hour after administration) for 2 animals, and was not measurable for the third. The CSF to plasma concentration ratio at that time point was 8% in 1 animal and 15% in the other. Idarubicinol was detected in 2 to 4 samples at various times, appearing as early as 1 hour in 1 animal and persisting as late as 48 hours in another. The CSF to plasma concentration ratio at corresponding time points was 1.9 +/- 0.6%. Daunorubicin was measurable for < 6 hours after intravenous administration. For individual animals, the mean CSF to plasma concentration ranged from 4% to 12%. Daunorubicinol was detectable by 1 hour in 2 of 3 animals and by 3 hours in the other, and remained detectable at 24 hours in 2 of 3. The terminal half-life of daunorubicinol in CSF was 8.8 +/- 1.3 hours, the AUC was 1.8 +/- 1.5 mumol/L.min, and the AUCCSF to AUCplasma ratio was 2.4 +/- 1.9%. CONCLUSION: Idarubicin, idarubicinol, daunorubicin, and daunorubicinol penetrate poorly into the CSF after intravenous administration. PMID- 10029810 TI - Subcutaneous panniculitic T-cell lymphoma developing in a child with idiopathic myelofibrosis. AB - PURPOSE: Subcutaneous panniculitic T-cell lymphoma is reported in a child with idiopathic myelofibrosis. Both disease entities are rarely seen in children. PATIENT AND METHODS: A girl aged 5 years and 9 months had pancytopenia and severe constitutional symptoms. Idiopathic myelofibrosis was subsequently diagnosed. RESULTS: A transient response was achieved after treatment with a course of high dose methylprednisolone therapy. However, proptosis and skin nodules developed during tapering of steroid therapy. A computed tomography scan of the orbit also revealed a mass lesion in the right lacrimal gland region. A skin biopsy specimen showed a subcutaneous panniculitic T-cell lymphoma. The clinical course was marked by high fever, profound pancytopenia, massive gastrointestinal bleeding, and severe, recurrent infections. Her condition rapidly deteriorated, and she died from polymicrobial sepsis 4 months after her initial examination. CONCLUSIONS: Subcutaneous panniculitic T-cell lymphoma is a distinctive clinicopathologic entity that is rarely seen in children. The association of myelofibrosis and peripheral T-cell lymphoma as seen in this has been rarely reported. PMID- 10029812 TI - Massive splenomegaly and Epstein-Barr virus-associated infectious mononucleosis in a patient with Gaucher disease. AB - PURPOSE: Gaucher disease should be considered in the differential diagnosis of a patient with Epstein-Barr virus (EBV) infection who has unexplained or disproportionate splenomegaly. PATIENTS AND METHODS: A previously asymptomatic adolescent with EBV-associated infectious mononucleosis and massive splenomegaly is described. He was found to have Gaucher disease on bone marrow biopsy, which was performed to exclude a hematologic malignancy. The diagnosis was confirmed by assay of beta-glucosidase enzyme activity. RESULTS: Regression of splenomegaly and improving hematologic indices. CONCLUSION: Patients with infectious mononucleosis and disproportionate organomegaly should be investigated to exclude a hematologic malignancy or an underlying storage disorder such as Gaucher disease. PMID- 10029811 TI - Central nervous system T-cell lymphoproliferative disorder in a patient with chronic active Epstein-Barr virus infection. AB - PURPOSE: Central nervous system (CNS)-T cell lymphoproliferative disorder (T-LPD) developing during the course of chronic active Epstein-Barr virus (CAEBV) infection is reported. PATIENTS AND METHODS: CAEBV was diagnosed in a 14-month old boy with fever, cytopenia, hepatosplenomegaly, and abnormal high titers of anti-Epstein-Barr virus (EBV) antibodies. At 8 years of age, he had a splenectomy because of progressive disease. RESULTS: After 27 months of clinical remission, muscle weakness and paresthesia developed. Magnetic resonance imaging of his brain showed spotty T2 prolongation in left parietal, bilateral frontal, and temporal white matter with meningeal enhancement. Brain biopsy revealed the cerebral infiltration of CD3+, CD4+, CD8-, CD45RO+, CD56-, and EBV-encoded RNA 1+ cells. CONCLUSIONS: The CNS involvement of EBV-associated T-LPD is a rare but serious complication in CAEBV without known underlying immunodeficiency. PMID- 10029813 TI - Ki-1+ large-cell anaplastic lymphoma after Ewing sarcoma. AB - PURPOSE: A large cell anaplastic lymphoma that developed after treatment of a Ewing sarcoma (ES) is described. PATIENT: An 11-year-old girl with a pelvic ES developed a large cell, Ki-1+, anaplastic lymphoma in the same anatomic location 10 months after multimodal therapy. RESULTS: ES recurred in the primary site 16 months after allogeneic marrow transplantation and 3.5 years after initial diagnosis, but the patient remains in remission from her lymphoma. CONCLUSION: The occurrence of lymphoma and ES in a short time interval in the same patient is very unusual. Whether etiologic factors other than chemoradiotherapy, including genetic disposition, play a role remains to be elucidated. PMID- 10029814 TI - Successful treatment of a patient with stage IV rhabdoid tumor of the kidney: case report and review. AB - The clinical course of a 31-month-old patient with advanced (stage IV) rhabdoid tumor of the kidney (RTK) and an analysis of treatment variables that may impact survival are presented. Treatment included complete resection of abdominal disease, radiation therapy to the abdomen and chest, and chemotherapy on a schedule of dose intensification by reduction of the interval between cycles. Inclusion of doxorubicin in treatment was associated with survival among patients in published series (P = 0.002). The patient was in continuous complete remission 60 months from diagnosis. Stage IV rhabdoid tumor of the kidney can be effectively treated with intensive multimodal therapy. Doxorubicin may be an important component of a successful therapeutic regimen. PMID- 10029815 TI - Multifocal osteosarcoma: an unusual presentation. AB - PURPOSE: Report the unusual presentation, clinical course, and cytogenetic abnormalities in a child with multifocal osteosarcoma. PATIENTS AND METHODS: A 10 year-old boy had multifocal osteosarcoma involving the entire skeleton, pleura, bone marrow, and lungs. He had marked anemia, thrombocytopenia, and severe hypocalcemia at diagnosis. RESULTS: Despite aggressive chemotherapy, he died from progressive disease 1 month after diagnosis. Cytogenetic analysis of tumor cells within the pleural fluid showed multiple chromosomal abnormalities with amplification of the c-myc oncogene. CONCLUSION: Multifocal osteosarcoma should be considered in the differential diagnosis of a child with pancytopenia and multiple bone lesions. Amplification of the c-myc oncogene may have had a significant role in the pathogenesis, etiology, and rapid progression of this patient's multifocal disease. Additional studies will be needed to determine the biologic significance of c-myc amplification in multifocal osteosarcoma. PMID- 10029816 TI - Transient leukemia with extreme basophilia in a phenotypically normal infant with blast cells containing a pseudodiploid clone, 46,XY i(21)(q10). AB - PURPOSE: Transient leukemia and extreme basophilia occurred in a phenotypically normal newborn with expression of isochromosome (21)(q10) in the blast population. PATIENTS AND METHODS: A newborn boy was found to have an elevated white blood cell count of 120,800 with 33% blasts. The peripheral blood also contained elevated numbers of basophils and neutrophils with unusual staining properties. The blasts, evaluated by flow cytometry and light and electron microscopy, had the properties of megakaryoblasts. Cytogenetic studies revealed 46,XY karyotype in peripheral blood lymphocytes; however, analysis of the blast cells from the bone marrow showed an abnormal chromosome 21. RESULTS: The blast cells in the peripheral blood disappeared by day 42 without chemotherapy. The red blood cell count and platelet count normalized by 2 months. Chromosomal analysis of skin fibroblasts and bone marrow after the disappearance of the blast cells in the peripheral blood showed a 46,XY phenotype. CONCLUSIONS: The leukemic cell of transient leukemia has the potential of forming cells of basophil and megakaryocyte lineages. Trisomy of the q arm of chromosome 21 contains sufficient genetic information for the development of transient leukemia in a phenotypically normal newborn. PMID- 10029817 TI - Prolonged survival of a patient with sickle cell trait and metastatic renal medullary carcinoma. AB - PURPOSE: The treatment and outcome of a patient with sickle cell trait and metastatic renal medullary carcinoma is described. PATIENT AND METHODS: A 12-year old boy with sickle cell trait had metastatic renal medullary carcinoma. After surgical resection of the primary tumor, he received chemotherapy with methotrexate, vinblastine, doxorubicin, and cisplatin. The carcinoma progressed after a 6-month period of stable disease. At that time, he received chemotherapy including ifosfamide, etoposide, carboplatin, and topotecan. RESULTS: The patient died of progressive disease 15 months from diagnosis. The patient's tumor in this report showed no progression while he was receiving methotrexate, vinblastine, doxorubicin, and cisplatin, but eventually became refractory to these and other cytotoxic agents. CONCLUSION: Renal medullary carcinoma is a highly chemotherapy resistant tumor. Average survival after diagnosis is 15 weeks; the longest survival reported in the literature is 12 months from diagnosis. The patient in this report survived longer than the previously described patients before dying from progressive disease. PMID- 10029818 TI - Anti-s antibody-associated delayed hemolytic transfusion reaction in patients with sickle cell anemia. AB - PURPOSE: Signs and symptoms of delayed hemolytic transfusion reaction (DHTR) may resemble those of vaso-occlusive crises in patients with sickle cell anemia (SCA). The diagnosis of DHTR therefore presents a challenge to the clinician when treating such patients. The current study describes a patient with SCA and DHTR secondary to red cell anti-s antibody, manifesting as painful extremeties, severe hemolytic anemia, and acute oliguric renal failure. PATIENTS AND METHODS: A 17 year-old patient with homozygous hemoglobin S presented 8 days after partial exchange transfusions with severe anemia and signs and symptoms resembling vaso occlusive crisis. Clinical course was complicated by intravascular hemolysis and acute renal failure. RESULTS: Anti-s antibody was detected in the eluate. Diagnosis of DHTR was made. Treatment included single volume whole blood exchange transfusion and continuous veno-venous hemofiltration with dialysis. CONCLUSIONS: The possibility of DHTR should be considered in a patient with SCA with hemolytic anemia. Acute renal failure is a rare complication of anti-s antibody-associated DHTR. Such reactions can be successfully managed with exchange transfusion and continuous hemofiltration with dialysis. PMID- 10029819 TI - Transient hypoplastic anemia caused by primary human parvovirus B19 infection in a previously untreated patient with hemophilia transfused with a plasma-derived, monoclonal antibody-purified factor VIII concentrate. AB - BACKGROUND: Modern plasma-derived clotting factor concentrates are produced using various virus-inactivation protocols and are assumed to be safer than they were previously with regard to the risk for transmitting viral infections such as human immunodeficiency virus, hepatitis B, and hepatitis C. The risks from viruses that are relatively resistant to the current inactivation procedures remain uncertain. PATIENT: A 7-year-old with mild hemophilia A who had not been previously infused with any blood products was treated with a plasma-derived, monoclonal antibody-purified factor VIII concentrate to cover orthopedic surgery after traumatic fracture of his left arm. RESULTS: A typical primary human parvovirus (HPV)-B19 infection was observed associated with transient hypoplastic anemia. Retrospective studies including serologic examination and polymerase chain reaction analysis confirmed that the HPV-B19 infection was transmitted by the factor VIII concentrate. CONCLUSIONS: Clotting factor concentrates for the treatment of hemophilia retain a risk for HPV-B19 contamination. HPV-B19 viral infection might induce hypoplastic anemia in these patients, particularly during enhanced hemopoiesis after acute blood loss. PMID- 10029820 TI - Low-dose cyclosporin A therapy in children with refractory immune thrombocytopenic purpura. AB - Although splenectomy is the most effective treatment for chronic idiopathic thrombocytopenic purpura (ITP), many post-splenectomy patients have recurrent thrombocytopenia refractory to multiple medical therapies. Three consecutive patients with relapsed ITP after splenectomy and who were refractory to multiple medical therapies were treated with low dose cyclosporin A (CsA). In all 3 patients, the platelet count increased dramatically within 1 month from the onset of CsA therapy. The only detectable toxicity was hypomagnesemia and mild hypertension in 1 patient. CsA may be efficacious in treating patients with chronic ITP, which is refractory to all medical and surgical therapies currently being used. PMID- 10029821 TI - Fatal coagulase-negative staphylococci infection after bone marrow transplantation in a patient with persistent adverse reactions to vancomycin. PMID- 10029822 TI - Treating infants who may die. PMID- 10029823 TI - Emotions, ethics, and decisions in primary care. PMID- 10029824 TI - Toward an ethical standard for coerced mental health treatment: least restrictive or most therapeutic? PMID- 10029825 TI - Assessing competency without judging merit. PMID- 10029826 TI - Do patients' treatment decisions match advance statements of their preferences? PMID- 10029827 TI - Optimizing discussions about resuscitation: development of a guide based on patients' recommendations. PMID- 10029828 TI - Avoiding conflicts of interest in surrogate decision making: why ethics committees should assign surrogacy to a separate committee. PMID- 10029829 TI - Disclosure of operating practices by managed-care organizations to consumers of healthcare: obligations of informed consent. PMID- 10029830 TI - Ethics by the numbers: monitoring physicians' integrity in managed care. PMID- 10029831 TI - Physicians' responsibilities in the care of suicidal patients: three case studies. PMID- 10029832 TI - Decision making in the nursery: an ethical dilemma. PMID- 10029833 TI - Legal trends in bioethics. PMID- 10029834 TI - Intersexuality: what should careproviders do now. PMID- 10029835 TI - A history of intersexuality: from the age of gonads to the age of consent. PMID- 10029836 TI - The Hanukkah bush: ethical implications in the clinical management of intersex. PMID- 10029837 TI - Management of intersex: a shifting paradigm. PMID- 10029838 TI - Betwixt and between: the past and future of intersexuality. PMID- 10029839 TI - Surgical progress is not the answer to intersexuality. PMID- 10029840 TI - A surgeon's response to the intersex controversy. PMID- 10029841 TI - Pediatric ethics and the surgical assignment of sex. PMID- 10029842 TI - For the sake of the children: destigmatizing intersexuality. PMID- 10029843 TI - Legal trends in bioethics. PMID- 10029844 TI - Poultry industry faces Campylobacter challenge. PMID- 10029845 TI - Mesocestoides infections: recurrence or reinfection? PMID- 10029846 TI - What is your diagnosis? A 2-cm rounded structure similar in opacity to adjacent falciform fat located between the apex of the heart and the cupula of the diaphragm along the ventral midline of the thorax. PMID- 10029847 TI - What is your diagnosis? A large, elongated mineral opacity extending proximal from the navicular bone. PMID- 10029848 TI - A theoretical model for human health and the pet connection. PMID- 10029849 TI - Employment, starting salaries, and educational indebtedness of 1998 graduates of US veterinary medical colleges. PMID- 10029850 TI - Relationships between results of the Ortolani method of hip joint palpation and distraction index, Norberg angle, and hip score in dogs. AB - OBJECTIVE: To determine whether results of the Ortolani method of hip joint palpation in dogs were related to distraction index (DI), Norberg angle, or radiographic hip score. DESIGN: Cross-sectional study. ANIMALS: 459 clinically normal dogs. PROCEDURE: Dogs were sedated for radiography and palpation of the hip joints. Results of hip joint palpation were classified as negative, mild positive, moderate positive, or severe positive. Distraction indices were measured for all dogs. Norberg angles were measured for 380 dogs for which ventrodorsal hip-extended radiographic projections were available. Hip scores assigned by the Orthopedic Foundation for Animals (OFA) were available for 95 dogs. RESULTS: Age, weight, and sex were not significantly associated with results of hip joint palpation. There was moderate correlation between results of hip joint palpation and DI (r = 0.636), low-moderate correlation between results of hip joint palpation and OFA hip scores (rs = 0.437), and weak negative correlation (r = -0.236) between results of hip joint palpation and Norberg angle. For joints without degenerative joint disease (DJD), there was a significant linear relationship between results of hip palpation and DI; however, for joint with DJD, there was not. Results of hip joint palpation were 5.3-fold as likely to be negative for dogs with DJD as for dogs without. CLINICAL IMPLICATIONS: Results of hip joint palpation were at best moderately correlated with radiographic measures of hip joint laxity. Therefore, hip joint palpation should be combined with hip-extended and stress radiography when assessing hip joint quality. PMID- 10029851 TI - Evaluation of serologic and viral detection methods for diagnosing feline herpesvirus-1 infection in cats with acute respiratory tract or chronic ocular disease. AB - OBJECTIVE: To determine the value of virus isolation (VI), immunofluorescent antibody (IFA) assay, serum neutralization (SN), and ELISA for the diagnosis of clinical feline herpesvirus-1 (FHV-1) infection in cats. ANIMALS: 46 clinically normal cats, 17 cats with signs of acute respiratory tract disease, and 38 cats with signs of chronic ocular disease. PROCEDURE: Conjunctival swabs for VI, conjunctival scrapings for IFA testing, and venous blood samples for SN or ELISA testing were obtained from all cats. RESULTS: FHV-1 was detected in 10.9 and 28.3% of clinically normal cats and in 18.2 and 33.3% of cats with FHV-1 associated disease by VI and the IFA assay, respectively. There were no significant differences in the viral detection rate between cats with acute respiratory tract disease and cats with chronic ocular disease or between diseased cats and clinically normal cats; however, FHV-1 was never detected by both methods in clinically normal cats. Overall FHV-1 seroprevalence was 97% when tested by ELISA and 66% when tested by SN. Seroprevalence did not vary significantly among the 3 groups for either serologic test. Magnitude of SN and ELISA titers varied greatly but independently of presence or absence of clinical signs of FHV-1-associated disease. Sensitivity, specificity, and positive and negative predictive values were assessed for VI and the IFA assay--jointly and individually--and for each SN and ELISA titer magnitude. Values never all exceeded 50%. CLINICAL IMPLICATIONS: Because FHV-1 can be detected commonly in clinically normal cats by the IFA assay or VI, neither test appears to aid in the clinical diagnosis of FHV-1 infection. Seroprevalence does not appear to vary between affected and clinically normal cats. SN, ELISA, VI, and the IFA assay appear to be of limited value in the diagnosis of FHV-1-associated disease in cats. Concurrent assessment of the IFA assay and VI results may permit exclusion of FHV-1 as an etiologic agent if results of both tests are negative. PMID- 10029852 TI - Tracheal rupture in cats: 16 cases (1983-1998). AB - OBJECTIVE: To determine causes of tracheal rupture in cats and the mechanism of injury. DESIGN: A retrospective study was conducted to identify cats with tracheal rupture. A second study was conducted to establish mechanism of injury, and a third study was conducted to determine volume of air needed to obtain an airtight seal when inflating the cuff of an endotracheal tube in a cat. ANIMALS: 16 cats with clinical signs of tracheal rupture, 10 cat cadavers, and 20 clinically normal cats that were undergoing anesthesia. PROCEDURES: Details were extracted from medical records of 16 cats with tracheal rupture (9 treated surgically and 7 treated conservatively). For the cadaver study, the trachea of each cat cadaver was intubated and observed during overinflation of the endotracheal tube cuff. For clinically normal cats, volume of air needed to obtain an airtight seal for the endotracheal tube was recorded. RESULTS: Most ruptures were associated with cats anesthetized for dental procedures. Clinical signs associated with tracheal rupture included subcutaneous emphysema, coughing, gagging, dyspnea, anorexia, and fever. Tracheoscopy was the method of choice for documenting tracheal rupture. Surgical and conservative management were successfully used, unless the injury extended to the carina. In the cadaver study, overinflation of the endotracheal tube cuff with > 6 ml of air resulted in tracheal rupture in 7 of 10 cadavers. For clinically normal cats, the volume of air (mean +/- SD) needed to obtain an airtight seal was 1.6 +/- 0.7 ml. CLINICAL IMPLICATIONS: Overinflation of an endotracheal tube cuff may result in tracheal rupture in cats. PMID- 10029853 TI - Clinical features of inflammatory liver disease in cats: 41 cases (1983-1993). AB - OBJECTIVE: To compare the clinical and clinicopathologic findings in and prognosis for cats with lymphocytic portal hepatitis (LPH) versus cats with acute or chronic cholangiohepatitis (CH). DESIGN: Retrospective study. ANIMALS: 25 cats with LPH; 16 cats with CH (7 acute, 9 chronic). PROCEDURE: Cats with LPH and CH were selected by evaluating records from liver biopsy specimens submitted to the University of Minnesota Veterinary Teaching Hospital during a 10-year period. Clinical and clinicopathologic data were retrieved. RESULTS: Cats with CH had higher segmented and band neutrophil counts, alanine aminotransferase activities, and total bilirubin concentrations than did cats with LPH. Cats with acute CH had higher segmented and band neutrophil counts and lower serum alkaline phosphatase activities and total bilirubin concentrations than did cats with chronic CH. Twelve of 14 cats with LPH or CH had coarse or nodular texture to the liver on ultrasonography, with loss of portal vein wall clarity noticed in 4 of 8 cats with LPH. Sixteen of 23 cats with LPH and 8 of 15 cats with CH survived > 1 year. Of those cats living < 1 year, all cats with LPH and 5 of 7 cats with CH had a serious concurrent illness that may have been responsible for their deaths. CLINICAL IMPLICATIONS: LPH and CH can be detected and tentatively differentiated through evaluation of clinical laboratory test results, but histologic evaluation of liver specimens is necessary for definitive differentiation. Survival time was good regardless of the type of inflammatory liver disease. PMID- 10029854 TI - Deep digital flexor tenotomy as a treatment for chronic laminitis in horses: 35 cases (1988-1997) AB - OBJECTIVE: To determine long-term prognosis for horses with laminitis treated by deep digital flexor (DDF) tenotomy and to identify factors affecting success of the surgical procedure. DESIGN: Retrospective study. ANIMALS: 35 horses with laminitis treated by DDF tenotomy between 1988 and 1997. PROCEDURE: Information was obtained from individual medical records and follow-up telephone interviews with owners and referring veterinarians. Cumulative proportions of horses that survived 6 months and 2 years after tenotomy were determined. Effect of Obel grade of lameness on 6-month and 2-year survival and effect of distal phalangeal rotation on survival and future performance were evaluated by chi 2 analysis. Body weights of horses that survived > or = 2 years were compared with those of horses that survived < 2 years by ANOVA. RESULTS: 27 of the 35 (77%) horses survived > or = 6 months, and 19 of 32 (59%) survived > 2 years. Obel grade of lameness and body weight at time of surgery had no effect on 6-month or 2-year survival. Degree of distal phalangeal rotation had no effect on 2-year survival or the ability of horses to be used for light riding. Twenty-two of the 30 (73%) owners interviewed indicated they would have the procedure repeated on their horses given similar circumstances. CLINICAL IMPLICATIONS: DDF tenotomy is a viable alternative for horses with laminitis refractory to conventional medical treatment. In some instances, the procedure may be effective in returning horses to light athletic use. PMID- 10029855 TI - Within-farm variability in number of females mated per week during a one-year period and breeding herd productivity on swine farms. AB - OBJECTIVE: To determine the effect of within-farm variability in the number of females mated per week during a 1-year period on annual breeding herd productivity in swine breeding herds and to apply statistical process control charts to measures of within-farm variability. DESIGN: Longitudinal study. SAMPLE POPULATION: 84 swine farms with a female inventory of 390 to 1,491 sows and gilts (mean, 761 females). PROCEDURE: As a measure of within-farm variability in a breeding herd, SD for the number of females mated per week during a 1-year period was evaluated. Two types of production records for 84 farms were evaluated. One file contained within-farm variability (SD) in mated females for each farm, and the second included annual productivity 19 weeks after week of mating. We also defined forewarning limits as mean +/- 2 SD, using a statistical process control chart. RESULTS: Larger within-farm variability in number of mated females was associated with lower annual measurements, such as fewer pigs weaned per mated female per year and lower farrowing rate. In addition, farms that did not have any weeks outside the forewarning limits for number of mated females produced more pigs weaned per mated female per year than those with 1 or more weeks of over- or underproduction. Furthermore, the number of weeks outside of forewarning limits was positively associated with within-farm variability in number of mated females. CLINICAL IMPLICATIONS: We recommend that farm managers determine a target range for the number of females mated per week to prevent large week-to week variations in breeding herd operations. PMID- 10029856 TI - Prevalence of lesions and body condition scores among female swine at slaughter. AB - OBJECTIVE: To determine prevalence of foot lesions, dermatitis, shoulder lesions, mammary gland abnormalities, and visceral lesions, and body condition scores among culled female swine at slaughter. DESIGN: Observational study. ANIMALS: Culled gilts and sows killed during a 1-week period at a Midwest slaughterhouse. PROCEDURE: Carcasses were examined, and lesions were recorded. Body condition was scored on the basis of standard criteria. RESULTS: 58.9% (1,029/1,747) of the carcasses had foot lesions, 67.3% (1,178/1,751) had dermatitis, and 4.6% (80/1,751) had shoulder lesions. Body condition score was significantly associated with detection of dermatitis and shoulder lesions. Mean +/- SE number of teats (n = 1,432 carcasses) was 13.86 +/- 0.02. Mean numbers of normal appearing teats in the left and right mammary chains were 6.57 +/- 0.02 and 6.58 +/- 0.02, respectively. Feet from 48% (688/1,433) of the carcasses were condemned. Visceral lesions were found in 48.8% (624/1,278) of the carcasses; of the carcasses with lesions, 412 (66%) had liver spots, and 268 (42.9%) had pneumonia. CLINICAL IMPLICATIONS: Lesions that potentially could have adversely affected production were found in a large percentage of culled gilts and sows at slaughter. Knowledge of lesions commonly found at slaughter may help direct changes in herd health programs. PMID- 10029857 TI - Use of bovine somatotropin at the time of surgery for left displacement of the abomasum in dairy cows. Minnesota Dairy Practitioners Study Group. AB - OBJECTIVE: To evaluate the effect of a single dose of recombinant bovine somatotropin (bST) on certain metabolic values, health, and milk production of dairy cows undergoing surgery for left displacement of the abomasum. DESIGN: Blinded clinical trial. ANIMALS: 413 cows with left displacement of the abomasum. PROCEDURE: A single 500-mg dose of bST was administered to dairy cows following surgery in field practice conditions for left displacement of the abomasum. A placebo of the same carrier without bST was administered to control cows in this blinded study. Metabolic and production responses in a short-term follow-up period were measured. RESULTS: Blood glucose concentrations in cows 3 to 5 days after surgery were statistically higher for treated cows than for control cows. A higher proportion of treated cows had improved urine ketone test results than did controls. Significant differences in other metabolic values, health, and milk production were not detected. CLINICAL IMPLICATIONS: Treatment of metabolically compromised cows with bST may have some positive effects, but further investigation is needed to confirm therapeutic value. PMID- 10029858 TI - Removal of an ectopic left kidney through a ventral midline celiotomy in a calf. AB - A 4-month-old Holstein heifer was examined because of poor growth, weight loss, dysuria, hematuria, pyuria, and a palpable mass in the right caudal quadrant of the abdomen. Clinicopathologic abnormalities included hyperfibrinogenemia, hyperproteinemia, anemia, and leukocytosis, and were consistent with chronic inflammation. Results of ultrasonographic evaluation of the umbilical cord remnants were suggestive of urachal abscess formation. Transabdominal ultrasonography of the kidneys was attempted; the right kidney appeared normal, but the left kidney could not be imaged. The calf was anesthetized and a ventral midline celiotomy was performed. The left kidney was larger than normal, was multilobulated, and contained multiple abscess. It had also broken through the peritoneum and was located in the peritoneal cavity. Unilateral nephrectomy and resection of umbilical cord remnants were performed. The calf recovered without complications and was healthy 5 years later. In this calf, ventral midline celiotomy provided sufficient surgical exposure for removal of the ectopic left kidney and resection of umbilical cord remnants. PMID- 10029859 TI - [Angiographic study of the hepatic venous system with pressure gradient: basic evaluation or superfluous imposition]. PMID- 10029860 TI - [Angiographic aspects of the hepatic veins in portal hypertension in schistosomiasis. The importance in assessing the hepatic vein pressure]. AB - The authors comment upon the importance of the hepatic wedged venous pressure for the appraisal of the circulatory conditions of the portal system, mainly in cirrhotic patients. Wondering about the irregular results obtained in the study of schistosomotic portal hypertensive patients by occlusive catheterization and with the use of an occlusive balloon catheter, noted the scarcity of angiographic studies on the subject in this pathology. Present the angiographic aspects that were obtained from patients with schistosomotic portal hypertension complicated by digestive bleeding, by means of injecting the contrast material into a hepatic vein of the right hepatic lobe via a loosely introduced catheter. Those radiological aspects were distributed in two categories: 1) type I-presenting variable sinusoidal filling. Presence of anastomotic intraparenquimatous communications with or without calibrous anastomotic veins between the hepatic veins, 2) type II-presenting no sinusoidal filling. Presence of multiple anastomotic communications of varied calibers between the hepatic veins. Commenting the difficulty of assessing the wedged pressure in patients with schistosomotic portal hypertension because of the easy communication between the hepatic veins, the authors point out that the measured pressure, in all the cases, will be that of the opposite hepatic vein. That pressure, in this pathology, might represent the sinusoidal resistance (when present) between hepatic veins, instead of relating to the portal vein. Suggestion is made that the measure of the wedged hepatic pressure, in patients with schistosomotic portal hypertension, be appraised considering the angiographic aspects of the hepatic veins. PMID- 10029861 TI - [Videofluoroscopic evaluation of the functional significance of the epiglottis in adults]. AB - Our intention was to define the functional role of the epiglottis. Accordingly, we analysed its movements and correlation in 53 videofluroscopic exams: 26 were good health volunteers, 25 were patients with dysphagia and two were persons with pharyngeal diverticula. The exams register the rest phase, chewing, and the swallowing movements during the intake of the saliva, water, barium solution and different volumes of mass made with crumbled bread mixed with barium powder. We can see three sequential stages in epiglottic movement during swallowing. The first stage involves an upward epiglottic shift determined by hioepiglottic ligament, associated with a simultaneous bending caused by the tongue backward projection. The second stage is a posterior rotation of the epiglottis, limited by the adjustment of the epiglottic tubercle to the vestibular fold, determined by laryngeal upward shift against hyoid bone. The third stage in which occurs an eversion of the free extremity of the epiglottis beyond the horizontal plane can be absent in slow pressure swallowing. All stages of the epiglottic dynamics are passive. We have shown that the epiglottis has a protective action on the repiratory airways not limited to swallowing. It participates, during swallowing and regurgitation (vomica), through the passive adjustment of the intralaryngeal posterior surface of the epiglottis (epiglottic tubercle) to the vestibular folds. Both before and after swallowing, when frequently there are escapes of residues and small volumes out of the oral cavity, the epiglottis protects the repiratory airways, through its participation in the formation of the valleculae and as an insertion point for the aryepiglottic folds. In association with epiglottis participation there is a stretching of the aryepiglottic folds that allow a definition of the lateral channels. The upward and forward movements of the larynx associated with the opening of the pharyngoesophageal transition, that occurs synchronously with the ejection of the swallowed bolus, has been shown to be an important factor in the protective laringeal mechanism. The increase in the laryngeal resistance, in which the epiglottis takes part, is only efficient when there is wide and synchronous opening of the pharyngoesophageal transition. In this context the epiglottis is a secondary element in the protection of the respiratory airways. PMID- 10029862 TI - [Use of proteic metabolism (15N-glycine) in the early detection of disease exacerbation in patients with non-specific ulcerative colitis]. AB - Disease activity was assessed in 10 (five males and five females) ulcerative colitis patients through the following parameters: clinical, laboratory, sigmoidoscopic and histological. Protein metabolism was also assessed with 15N glycine and urinary ammonia as end product. Only one patient had exacerbation of the disease two months after the study started. This patient presented in the beginning of the study protein synthesis and breakdown of 4.51 and 3.47 g protein/kg/day, respectively, values higher than all other patients, showing an hypermetabolic state, suggesting an increase of the disease activity. However, this increase was not detected by others indicators and indexes utilized. These data allow to suggest the hypothesis that protein metabolism predicts precociously the exacerbation of disease activity in ulcerative colitis patients. PMID- 10029863 TI - [Use of the upper gastrointestinal endoscopy in dyspeptic patients]. AB - BACKGROUND AND AIMS: Dyspepsia is a common complaint that may signal the presence of diseases like cancer or peptic ulcer. The aim of our study was to assess if the clinical patterns of dyspepsia can be considered a valid guideline for the appropriate use of endoscopy. METHODS: According to the symptomatological patterns, our 243 patients were defined as sufferers from: ulcer-like (93 patients), reflux-like (25) and dismotility-like dyspepsia (125). Erosive gastritis and erosive duodenitis were regarded as minor inflammatory lesions. RESULTS: A negative endoscopy (normal or presenting minor inflammatory lesions) was found in 36.6% of ulcer-like dyspepsia patients: this rate was 52% in the reflux-like group, and 49.6% in the dismotility-like one. Duodenal ulcer was the most frequent abnormal lesion in the three groups. The frequency of negative endoscopies was significantly higher in dismotility-like than in ulcer-like (49.6% vs. 36.6%--P < 0.05) dyspepsia. In those patients with dismotility-like dyspepsia under 41 years, the rate of negative endoscopies was 72.7%, and neoplasms were not observed. CONCLUSION: Our data indicate that endoscopy could be considered inappropriate for patients under 41 years old with dismotility-like dyspepsia. These subjects account for 18.1% of the patients studied, what could lead to a good percentage of reduction in endoscopic service load. PMID- 10029864 TI - [Hepatic biliary cystadenoma. Report of 3 cases and review of the literature]. AB - Biliary cystadenoma is a rare benign disease, with unknown etiology and is considered as a pre-malignant lesion. Until 1988, only 71 cases had been reported. The authors present three cases and discuss the diagnosis and treatment and the disease. PMID- 10029865 TI - Ontogeny of the small intestine. AB - During development the gastrointestinal tract undergoes marked changes in many physiological and anatomic properties. The remarkable degree of coordination between the development of the gastrointestinal function suggests that the processes may be signalled by some factors, such as weaning, nutrient intake, growth and hormones. The interactions between nutrition and intestinal development begin when fetuses start swallowing amniotic fluid and extend past weaning. Hormonal control plays a major role in the ontogeny of the small intestine. There are late effects of early nutrition, and the normal progress of ontogeny may be important to ensure that the intestine is capable of adaptation in later life. PMID- 10029866 TI - [Indication and results of liver transplantation in adults]. AB - Increase of survival of patients submitted to transplantation is much superior when compared to other treatments in patients suffering terminal chronic hepatic failure. This fact has been allowing earlier indication of hepatic transplantation in lower operative risk patients. Pre-operative cardiocirculatory evaluation is essential, because during surgery hemodynamic and cardiac output alterations shall occur. The actual survival above 75% suggests that it is easier nowadays to look for factors responsible for mortality than to those predictable by survival. Postoperative survival analysis shows better results in cholestatic diseases (primary biliary cirrhosis and sclerosing cholangitis). Regarding hepatocelular carcinoma over cirrhotic liver, the best results are detected in small lesions up to 3 cm. PMID- 10029867 TI - [Nutritional importance of glutamine]. AB - The aim of this paper is to review nutritional aspects about this amino acid. Glutamine is the most abundant amino acid in the body. It is a neutral glucogenic amino acid that can be synthesized in the body by a wide variety of tissues rich in glutamine syntetase. Glutamine may promote muscle protein synthesis. Furthermore, glutamine is the principal carrier of nitrogen in the body, as it comprises approximately 50% of the whole-body pool of free amino acid. It is considered to be a major fuels for many cells including enterocytes, reticulocytes, stimulated lymphocytes, fibroblast and malignant cells. These cells share the common characteristics of relative rapid growth rates, high glicolitic rates, relative poor glucose oxidative capacity, and high glutaminase activity. In some clinical conditions, however, like trauma and sepsis, glutamine concentrations in tissues is decreased. These may have serious consequences for the organism, such as decreased in protein synthesis and impairement of the barrier functions of the mucosa of the gastrointestinal tract, and thereby contributy to the development of sepsis in catabolic patients. Infusion of glutamine may have therapeutic value in such conditions. PMID- 10029868 TI - Induction of acute and chronic pancreatitis with the use of the toxin of the scorpion Tityus serrulatus: experimental model in rats. AB - We observed that the purified venom of the Tityus serrulatus scorpion (T1 fraction), injected i.v. in rats, in a single dose of 0.5 mg/kg, produces: acute pancreatitis, characterized by degranulation and acinar cell vacuolization, necrosis and an inflammatory reaction, 24, 48 and 96 hours after the injection; chronic pancreatitis, characterized by interstitial fibrosis, lymphocyte infiltration, ductal and ductular dilation, acinar cell atrophy, periductal ductular hyperplasia, 20 days after injection: hyperplasia of Langerhans' islets and nesidioblastosis, associated to chronic pancreatitis. The absence of deaths in the experimental group is an interesting finding: the dose used preserved the animals from death and allowed the safe follow-up of the progression of the provoked pancreatitis. The results led us to conclude that the toxin of Tityus serrulatus scorpion is an agent of considerable efficacy in the induction of pancreatitis in rats providing an experimental model of acute and chronic form of this disease. PMID- 10029869 TI - [Immunohistological study of T-lymphocytes (total and helper) and B-lymphocytes of the colonic mucosa in children with Crohn's disease and non-specific ulcerative colitis]. AB - For one to understand better the immunological mechanism in the colonic mucosae of inflammatory bowel disease, 19 children with ulcerative colitis and 12 children with Crohn's disease were studied. The inflammatory cells identified by the immunoperoxidase technique and specific markers for total T lymphocytes (CD3), helper T lymphocytes (CD4) and B lymphocytes (CD20) in differents evolutionary periods of the disease were analysed. PI (before treatment), PII (until two years of treatment) and PIII (with more than two years of treatment). In general, all marker studied in this research, presented higher averages if comparing to the control group with different degrees of significance in the different studied periods. The marker CD3, of the total T lymphocyte, increased in the epithelial (superficial and glandular) and in the lamina propria of the involved mucosae in relation to the controlled ones, was diffusely distributed over the mucosae, concentrating itself around the microgranulomas and the nodules lymphoids. In Crohn's disease, PI, its average differed significantly from the controlled ones. Similar behave was seen in the marker CD20 of the lymphocytes in the involved mucosae, whole averages were superior in relation to the controlled ones; thought, only in the PI of the Crohn's disease this difference had been significant. The immunochromatic cells CD3 distributed themselves diffusely over the involved mucosae, concentrating themselves in the interior of the lymphoides nodules and in the injured areas, near the macrophages. The marker CD4, of helper T lymphocyte also presented in the involved mucosae high averages in relation to the controlled mucosae, but without estatistic significance. The CD4 cells distributed themselves diffusely over the whole thickness of the involved mucosae, concentrating themselves around the lymphoids nodules and microgranulomas. These results confirm the participation of these elements in the pathogenesis of inflammatory bowel disease, but did not permit the establishment of any discriminatory criteria between ulcerative colitis and Crohn's disease. The results of positive correlation between the increased of CD4 and CD20 in ulcerative colitis and CD3 and CD20 in Crohn's disease show clearly the immunoregulation action of the CD4+ cells over clonal expansion and the differenciation of the B lymphocytes from plasmocytes and the IgG syntese. PMID- 10029870 TI - Sleep habits in native Brazilian Terena children in the state of Mato Grosso do Sul, Brazil. AB - Sleep habits in childhood vary in function of physiological factors. Cultural traits also influence sleep habits. This research evaluates sleep habits of Native Brazilian Terena children. The Terena group here studied live in the central region of Mato Grosso do Sul, Brazil, on the plains; they are peaceful and dedicated mainly to agriculture. Two villages were studied, Terere and Corrego do Meio, both in Reservations. Sleep characteristics of 67 children (40M;27F), 2 to 10 year olds, were evaluated in interviews with their mothers. The results evidenced that cosleeping, in the same bed with family members is the standard Terena pattern present in every evaluated child. The presence of two or more beds and a mean of five or more people in each bedroom was the typical finding. The authors propose that cosleeping and the presence of numerous family members reflect the high values attributed to family links in the Terena culture. PMID- 10029871 TI - Anti-epileptic drug intake adherence. The value of the blood drug level measurement and the clinical approach. AB - It was evaluated the patient antiepileptic drug (AED) intake adherence in a pilot cross-sectional study carried out at a neurologic out-patient clinic of a university hospital. Ninety-three AED blood concentration (phenobarbital, phenytoin, carbamazepine) were analyzed from 24 patients. The variability of the AED blood level was measured (in the steady state period by means of the variation coefficient) and compared with the self-reported antiepileptic medication non-adherence, AED blood level according to the range (therapeutic or not), and the seizure control. It was not observed any strong correlation between the higher value of variability and the other three parameters of no adherence. The highest correlation was with the blood drug level (therapeutic or not). The evaluation of blood drug measurement alone, except in cases of extreme low adherence and variability of drug intake, is not enough for the recognition of incorrect drug intake, but the clinical markers and the self-reported adherence have to be also considered for this sort of evaluation. PMID- 10029872 TI - Medication-taking behavior and drug self regulation in people with epilepsy. AB - OBJECTIVE: To study the most important characteristics of antiepileptic drug (AED) taking behavior in epileptic people. METHODS: In a cross-sectional study, 45 consecutively seen patients answered a standardized questionnaire including questions about drug intake behavior. RESULTS: Both genders were equally represented (22M x 23F). The mean age was 30.2 years. No specific characteristic were presented in all patients. The self-reported non-use of the drug at any moment one week before (self-reported non-adherence) was 40.0%. Patients took the drug more than once in most cases (75.0%), and the only precipitating factor of seizures more frequently avoided was alcohol intake (66.7%). Forty-four percent said to be afraid of becoming addicted to the medicine, 61.4% reduced or stopped the medicine just to see what would happen, and 47.7% changed the prescription with the same purpose. There is no relationship among socio-demographic, behavior aspects or treatment characteristics, and self-reported non-adherence. CONCLUSIONS: Several patient's aspects do not seem to be strongly correlated with self-reported adherence. Nevertheless, drug self-regulation is probably related to the drug-intake behavior, and it is important for the physician to understand this parallel influence on treatment for a more realistic approach. PMID- 10029873 TI - Greater occipital nerve blockade in cervicogenic headache. AB - Cervicocogenic headache (CeH) is a relatively common disorder. Although on ideal treatment is available so far, blockades in different structures and nerves may be temporarily effective. We studied the effects of 1-2 mL 0.5% bupivacaine injection at the ipsilateral greater occipital nerve (GON) in 41 CeH patients. The pain is significantly reduced both immediately and as long as 7 days after the blockade. The improvement is less marked during the first two days, a phenomenon we called "tilde pattern". GON blockades may reduce the pool of exaggerated sensory input and antagonize a putative "wind-up-like effect" which may explain the headache improvement. PMID- 10029874 TI - Prevalence of headache in children of a school from Curitiba, Brazil, comparing data obtained from children and parents. AB - This study analyzed prevalence, frequency and cause of headache among 460 children ranging from 10 to 14 years-old from a Brazilian school. A questionnaire was handed both to children and parents to know if there would be differences among children and parental reports. The lifetime prevalence of headache was 93.5% (children reports) and 93.3% (parental reports). The last year prevalence was 90% (children) and 89.8% (parents). Headache episodes were frequent in 17.6% (children) and 18.5% (parents). The most often reported cause was "flu" (39.1% by children, and 46.7% by parents). This study demonstrated that the prevalence of headache in children is high; moreover, there were noted few differences between data obtained from children and parents. So, we could say that when the objective of a epidemiologic study is to determine the prevalence of headache in children, both children and parental reports may be used. PMID- 10029876 TI - [Prophylaxis of migraine: open study with venlafaxine in 42 patients]. AB - The present open study intended to show the prophylactic value of venlafaxine (serotonin and noradrenalin reuptake inhibitor) in 42 patients with migraine with or without aura during four months, from May to September 1997. The average age was 32.5 years and average crisis was 3.8 per month. Consistent side-effects included loss of weight, nausea and vomit. The efficacy of drug occurred in 37 patients (88.07%) with doses of 18.75 to 37.5 mg/day. We conclude that venlafaxine is an effective drug in prophylaxis of migraine patients. PMID- 10029875 TI - [Prevalence and indirect costs of headache in a Brazilian Company]. AB - Employees from a Brazilian oil company research centre (n = 993) were interviewed on the occurrence of headache during a 30 days period. Headache prevalence was 49.8%, with a mean frequency of 4.3 +/- 7.0 attacks per month, lasting 12.2 +/- 21.4 hours each. According to the International Headache Society diagnostic criteria, migraine (5.5%), episodic tension-type headache (26.4%), chronic tension-type headache (1.7%) and headaches not fulfilling the criteria for such disorders (16.2%) were observed. Women suffered comparatively more headache and specifically migraine than men. The pain interfered with work productivity in 10% of the subjects, corresponding to 538.75 hours off. According to an indirect costs estimation for each headache, the company may loose up to US$125.98 per employee annually. Since among headaches migraine has the highest indirect cost, migraine prevention and treatment is particularly important at the working environment. Migraine frequency may be prevented to a large extent, resulting on positive effects in both the quality of life and productivity. The cost-benefit ratio clearly favours therapeutic and preventive programs against chronic headaches. PMID- 10029877 TI - [Laterality of musical functions in partial epilepsy]. AB - Fourteen right handed patients with partial epilepsy (Epileptic Group) and with a median age of 31 years were divided into two groups (Right and Left), according the laterality of paroxystic activity in the electroencaphalogram. Of the 14 patients, 42.8% (6/14) presented a focus at the right side while the others 57.2% (8/14) presented a focus at the left. The Control Group consisted of 31 right handed individuals with a median age of 30 years and with no previous history of neurological disease or epileptic seizures. All the individuals had no musical skills. They carried out Music Abilities Tests including Spontaneous Rhythm, Elemental Music Functions Perception (tone color, duration, pitch, intensity and rhythm) and Complex Strutures Tests (recognition and reproduction of corporal rhythmic movements). We concluded that the focus at the right and the left cerebral hemisphere affect the development of the melodic recognition functions while in cases with focus at the left cerebral hemisphere, rhythmic reproduction and organization are more impaired when compared to the Control Group. PMID- 10029878 TI - [Electroneuromyography and somatosensory evoked potentials in HTLV-I associated myelopathy]. AB - The objective of the present study was to correlate electroneuromyography (ENMG) and evoked potentials findings with clinical aspects and intrathecal synthesis of HTLV-I antibodies production on HTLV-I myelopathy (HAM). Patients were seropositive for HTLV-I by different assays and seronegative for HIV and VDRL. They had no other causes of myelopathy and peripheral neuropathy. Peripheral neuropathy was established in 34.3% of the cases by ENMG. Peripheral neuropathy was mostly asymmetric (82%), sensory motor (90%), axonal (54.5%) or of a mixed type (45.4%). In 63.6% of these cases related symptoms were observed. ABR was abnormal in one patient and the PRVEP in 28.5%, who were symptom-free. The SEP was abnormal in 85.7% of the cases, half of them presenting clinical complaints. In only 14% of the individuals with clinical manifestations, SEP was normal. In 28% of patients with abnormal SEP the ENMG disclosed a peripheral neuropathy. PMID- 10029879 TI - [Neurologic evaluation of non-Hodgkin's lymphoma in adult patients: a prospective study]. AB - This prospective study included 67 adult patients with low, intermediate or high malignancy degrees of non-Hodgkin's lymphomas according to the Working Formulation. Patients with or without anti-HIV antibodies in the serum were considered. All patients were submitted to neurologic evaluation, and 63 of them to examination of the cerebrospinal fluid (CSF). Patients presenting neurologic signs and symptoms were 42 (62.7%). Neurologic findings and CSF changes were correlated. The association of localized thoraco-lumbar pain and CSF changes (presence of neoplastic cells, increased protein concentration and/or increased gamma globulin content) was statistically significant, as the association of abnormal muscle strength in the lower limbs and CSF changes in patients without HIV antibodies in the serum. Cranial nerve dysfunction (III, IV and VI cranial nerves) correlated with the finding of neoplastic cells in the cerebrospinal fluid. PMID- 10029880 TI - [Non-Hodgkin lymphoma in adults. Protein profile of CSF and serum in 25 patients]. AB - Twenty-five non-Hodgkin's adult patients of a cohort studied for detection of neurologic involvement were evaluated on the cerebrospinal fluid (CSF) protein profile. CSF and serum were collected in the same occasion. Blood-brain barrier and local synthesis of IgG were studied. There was an incidence of neurologic signs and symptoms in 48% of all patients. Samples analysis showed: increase of total protein in CSF in 52%; local synthesis of IgG in one HIV seropositive patient; IgG concentration increase in the CSF in the absence of malignant cells in the CSF in two patients that clinically improved after chemotherapy; oligoclonal bands only in the CSF in one HTLV-I seropositive patient. These data show that the study of CSF protein profile can contribute in the characterization of CNS involvement in non-Hodgkin lymphoma. PMID- 10029881 TI - [Prognostic factors of tuberculous meningoencephalitis lethality]. AB - In order to describe the lethality predictors of patients with tuberculous meningoencephalitis, records of 231 patients were analysed. Ages ranged from less than 1 year to 68 years. Ninety-seven patients (42%) were four years old or less. Apart from 73.2% of patients whose diagnosis was performed by clinical and epidemiologic criteria associated with response to specific therapy, 26.8% had diagnostic confirmation through cerebrospinal fluid (culture, bacilloscopy, PCR) or necropsy. The lethality predictors were: less than 4 years of age, seizures, and severe alterations of consciousness. PMID- 10029882 TI - [Is the metabolic response self-limited in head trauma? Analysis of acute phase proteins and glycemia]. AB - There are many reports supporting a self-limitation mechanism involved with hypermetabolic response after severe cranial injury. It was proposed a study with severe head injury patients, in three stages of the evolution. The first 7 days after admission (moment 1-M1), the second three days latter (M2) and the last 7 days after the first (M3). Among male patients with severe head injury, attended between January 1992 and December 1993 in University Hospital of Botucatu, UNESP, were selected 28 male patients, with Glasgow severity scale between 4 and 6, with pO2 < 70 mm Hg, weighting 60 kg or more. Among these patients, 6 finished the study, including analysis of the excretion of N, acute phase proteins, glycemia, triglycerides and amine nitrogen. During the study there were no changes in nitrogen balance and there was a decrease in protein C-reative. Glycemia tends to fall within two weeks after injury. The authors make some considerations about possible mechanisms involved in brain modulation associated with the period of dependence of hypermetabolism and hypercatabolism after closed brain injury. There are some evidences that the brain responds to head trauma with a gobal non specific way, which tends to be reorganized beyond the first two weeks after lesion. The study does not show any influence of the type and severity of head trauma. PMID- 10029883 TI - [Stereotaxic thalamotomy and pallidotomy with computerized planning in Parkinson's disease: short-term evaluation of motor function in 50 patients]. AB - We evaluated the motor function of 50 patients with Parkinson's disease, who underwent stereotaxic surgery with computerized planning, without ventriculography (ventrolateral thalamotomy- VLT- and/or posteroventral pallidotomy- PVP) before and one month after surgery. 27 unilateral TVL, 10 unilateral PVP, 6 bilateral PVP, and 7 TVL with PVP were performed. The motor evaluation was performed with the Unified Parkinson's Disease Rating Scale, motor score, during on and off periods. We observed a global motor improvement in all groups. The improvement of dyskinesias was obtained in the contralateral side of the body, in the PVP groups. From the 50 patients, 16 (32%) presented post operative complications, 9 of these (56.25%) improved completely, 6 (37.25%) improved partially, and 1 (6.25%) did not improve during the first month. These results were considered satisfactory, and a long term analysis will show whether these benefits are long lasting or not. PMID- 10029884 TI - [Three-dimensional computed tomographic angiography as preoperative examination in the treatment of cerebral aneurysms]. AB - This study is based on 36 cases selected from the radiological clinic of the Free University of Berlin and shows the advantages of spiral CT angiography over conventional cerebral angiography which provides only a few limited anatomical views: frontal, lateral and oblique. With CTA (computerized tomographic angiography) it is possible to obtain 360 degrees reformatted images in all directions getting large number of projections and showing the neck of aneurysms and its relation to vessels and the fundus in relation to the neck. CTA also depicts aneurysms in relation to bone or portions of it along the base of the skull. The CTA achieves so good sensibility as the cerebral angiography does and is used as preoperative examination for the cerebral aneurysms treatment. PMID- 10029885 TI - MR and CT imaging in the Dyke-Davidoff-Masson syndrome. Report of three cases and contribution to pathogenesis and differential diagnosis. AB - Cerebral hemiatrophy or Dyke-Davidoff-Masson syndrome is a condition characterized by seizures, facial asymmetry, contralateral hemiplegia or hemiparesis, and mental retardation. These findings are due to cerebral injury that may occur early in life or in utero. The radiological features are unilateral loss of cerebral volume and associated compensatory bone alterations in the calvarium, like thickening, hyperpneumatization of the paranasal sinuses and mastoid cells and elevation of the petrous ridge. The authors describe three cases. Classical findings of the syndrome are present in variable degrees according to the extent of the brain injury. Pathogenesis is commented. PMID- 10029886 TI - Activation of left intraparietal sulcus using a fMRI conceptual praxis paradigm. AB - The present paper reports the results of a fMRI subtraction study of the pattern of cortical activation induced by an ideational praxis paradigm in six normal right-handed subjects. The control task consisted of a sequence of complex meaningless hand movements. A complete study was done for each hand in each subject. The left intraparietal sulcus was the only structure activated in all subjects regardless of the hand used in the task. These findings, albeit preliminary, suggest that the organization of actions involving the mediation of tools and utensils are strongly lateralized to the left hemisphere and that damage to the dominant intraparietal sulcus may be critical for the development of the clinical syndrome of conceptual apraxia. PMID- 10029887 TI - Rigid spine syndrome. Case report. AB - We describe a patient who had difficulty in walking since toddling stage and presented proximal upper and lower member weakness which have evolved to a progressive limitation of neck and trunk flexure, compatible with rigid spine syndrome. The serum muscle enzymes were somewhat elevated and the electromyography showed a myopatic change. The muscle biopsy demonstrated an active and chronic myopathy. The DNA analysis through PCR did not display any abnormality for dystrophin gene. The dystrophin by immunofluorescence was present in all fibers, but some interruptions were found in the plasma membrane giving it the appearance of a rosary. The test for merosin was normal. PMID- 10029888 TI - [Neurofibromatosis associated with moyamoya arteriopathy and fusiform aneurysm: case report]. AB - We report a case of von Recklinghausen's disease associated with multiple intracranial arterial occlusion ("moyamoya-like") and a fusiform aneurysm. A 28 years-old man with type I neurofibromatosis presented with syncope, complex partial seizures and mental deterioration. After an acute headache episode associated with meningeal signs, drowsiness, and hemorrhagic CSF, the patient was evaluated with cranial CT scan, MRI and angiogram that revealed an obstructive arteriopathy compatible with moyamoya disease and a fusiform aneurysm in the posterior circulation. The authors discuss the clinical and radiological findings and the therapeutic decision in this case comparing with the few similar reports in the medical literature. Recognition of an underlying rare genetic disorder may be of considerable importance in young patients presenting with seizures. PMID- 10029889 TI - [Rett phenotype in patient with XXY karyotype: case report]. AB - We report the case of a XXY boy who presents progressive neurological disorder which has started around eleven months of age, with developmental stagnation followed by regression. The child presents as well stereotypic hand movements, loss of purposeful hands use and microcephalia. Presence of any defined systemic or neurological condition which could be pointed out as the possible etiological factor for the case was not found out by investigations. It deals with a boy with phenotypic alterations very similar to those considered typical for Rett syndrome which associated with chromosomal alteration (XYY karotype) constitute evident scientific interest. PMID- 10029890 TI - [Neonatal Streptococcus pyogenes meningitis and sagittal sinus thrombosis: case report]. AB - We report a case of Streptococcus pyogenes meningitis in a 18 days year-old-girl with clinical course complicated by sagittal sinus thrombosis. Some aspects of the pathogenesis, treatment and follow-up of the disease are discussed. The world increase of serious streptococcal infections in the last 10 years, probably will become neonatal Streptococcus pyogenes meningitis more frequent in the future and it is important to be alert for the precocious diagnosis and the possible complications of that potentially lethal infection. PMID- 10029891 TI - [Neuroleptic malignant syndrome: case report with recurrence associated with the use of olanzapine]. AB - The neuroleptic malignant syndrome (NMS) consists in an idiosyncratic reaction to neuroleptic drugs, probably related to a blockage of dopamine receptors in basal ganglia. Research criteria for diagnosing NMS from DSM-IV require severe rigidity and fever accompanied by 2 of 10 minor features including diaphoresis, dysphagia, tremor, incontinence, altered mentation, mutism, tachycardia, elevated or labile blood pressure, leukocytosis and elevation of creatine phosphokinase. From a clinical point of view, the NMS may range a large spectrum of presentations. Haloperidol is the most frequent drug associated with this syndrome. We report the case of a 30 year-old man who developed NMS at two different occasions, the first related to haloperidol and chlorpromazine and the second related to olanzapine, to our knowledge without previous mention in the indexed literature. PMID- 10029892 TI - [Spontaneous intracranial hypotension: case report]. AB - Spontaneous intracranial hypotension is a rare syndrome associated with postural cephalalgia and low pressure of the cerebrospinal fluid. We report the case of a 45 years-old man with spontaneous intracranial hypotension with MRI diffuse meningeal enhancement. PMID- 10029893 TI - [Physiopathology of migraine]. AB - The pathophysiology of migraine is not yet fully understood. The most important structures involved seem to be the central nervous system (cortex and brain stem), the trigeminovascular system and related cranial arteries, other autonomic fibres innervating such vessels, and various local vasoactive agents, including SP, CGRP, NO, VIP, NPY, ACh, NA, NKA, among others. The spreading depression phenomenon may explain clinical as well experimental findings in migraine. Its propagation velocity mirrors what is found in clinical aura, it may activate the spinal trigeminal nucleus and may induce CGRP and NO release. Circulatory changes detected with various imaging procedures during migraine also support the pathophysiological role of spreading depression. Three abnormal loci (chromosomes 1 and 19) have been recently found in familial hemiplegic migraine. This produces abnormalities in the voltage-dependent P/Q Ca channel, specific for the central nervous system, which regulates the release of various neurotransmitters, probably including serotonin. It is possible that a channelopathy underlies the pathophysiology of migraine, as in other paroxysmal neurological disorders secondary to membrane hyperexcitability. PMID- 10029894 TI - [Treatment of spasticity: an update]. AB - We present an update about the treatment of spasticity, stressing the pharmacological treatment, physical therapy and botulinum toxin therapy. PMID- 10029895 TI - Jorge Mardones: oration at his funeral service. AB - Oratios at the funeral service of Prof Jorge Mardones, MD. A very successful and influential pharmacologist, he was Chairman of the Department of Pharmacology, Faculty of Medicine, University of Chile; President of the Academy of Sciences, Institute of Chile; National Prize of Sciences, 1977; and Minister of Public Health. He also served as Chief Editor of "Archivos de Biologia y Medicina Experimentales" (former name of this journal) between 1964 and 1978. PMID- 10029896 TI - Is there a mucosal immune system associated with the mammalian oviduct? AB - The oviduct is a key component of the reproductive system where essential states such as spermatozoa capacitation, fertilization and early embryo development take place. Recently, an additional role for the entire female reproductive tract has emerged with important implications for our understanding and management of reproductive health, namely, its role in mounting local immune responses against microbial pathogens. Most of the evidence about mucosal immune responses in the female reproductive tract is related to the vagina, with less information available for the uterus. The less known segment in this regard is the oviduct, which prompted us to review and summarize the current state of knowledge on the immune system at the level of the mammalian oviduct. A comprehensive search was conducted in Medline and--for the last two years--also in Current Contents. Result demonstrate that the mammalian oviduct is endowed with many of the elements that characterize a mucosal immune system. However, there are gaps in our knowledge that, in addition to important interspecies differences, make it essential to explore further some fundamental questions regarding this system. PMID- 10029897 TI - Delta-aminolevulinic acid dehydratase (ALAD) activity in blood of Bufo arenarum (Anura). AB - The aim of the present investigation was to standardize a method for measuring delta-aminolevulinic acid dehydratase (ALAD) activity in circulating red blood cells of adult Bufo arenarum kept in controlled environmental conditions, and to obtain reference basal values suitable for environmental monitoring of lead exposure. The normal ALAD activity for B. arenarum was 131.86 +/- 14.47 U per liter of red blood cells (n = 38, mean +/- SEM; interval 72.98-236.33). In animals exposed to lead, ALAD activity decreased as lead dose increased. PMID- 10029898 TI - Subcellular distribution of prostaglandin-E2 and prostaglandin-F2 alpha in atrial tissue from patients with mitral valve disease. AB - The distribution of prostaglandin-E2 (PGE2) and prostaglandin-F2 alpha (PGF2 alpha) was studied in subcellular fractions isolated from homogenates of human atrial fresh tissue by differential centrifugation. Right and left atrial samples were excised from the same heart of six patients with mitral valve disease at the time of open heart surgery. The atrial fractions investigated were mitochondrial (8,500 g pellet), microsomal (100,000 g pellet) and cytosol soluble (100,000 g supernatant) fractions. After extraction of prostaglandins from the three atrial fractions and separation of PGE from PGF series by chromatography on silicic acid column, these prostaglandins were measured by radioimmunoassay. The results showed that PGE2 and PGF2 alpha were located mainly in the soluble cytosolic fraction of right and left atrial tissue (p < 0.001). Furthermore, the prostaglandins levels were higher in left than in right atria of these patients (p < 0.001). The relation between prostaglandins heart generation in response to elevated work load of mitral valve disease is discussed. PMID- 10029899 TI - Lactation inhibits the potentiating effect of galanin upon the GnRH-induced LH release observed in diestrous-1 rat. AB - Recent demonstrations of no changes in hypothalamic gonadotropin releasing hormone (GnRH) gene expression and GnRH levels detected at the pituitary gland in diestrous and lactating rats, indicate that lactational hypogonadotropism in this species is not associated with inhibition of hypothalamic GnRH synthesis and secretion. Hypothalamic galanin potentiates GnRH effects on luteinizing hormone (LH) secretion in male and cycling rats. To explore the interaction between GnRH and galanin during lactation, we studied in vitro the effects of pulsatile stimulation with those peptides upon LH synthesis and secretion from rat pituitaries on diestrous 1 or day 10 of lactation. Hemipituitaries were separately incubated in 1 ml Dulbecco's Minimal Essential Medium supplemented with 1% penicillin-streptomycin and fetal calf serum, at 37 degrees C in 5% CO2 air. The hemipituitaries were stimulated during 12 h with hourly pulses, 6 min each, of (a) gonadotropin releasing hormone (GnRH 25 ng/pulse), (b) rat galanin (600 ng/pulse), (c) GnRH plus galanin, or (d) saline. Medium was collected before each pulse to determine LH by radioimmunoassay. After the 12 h pulsatile regime total RNA was extracted and both actin and beta-LH mRNA were determined by reverse transcriptase polymerase chain reaction. There was a significant stimulation of LH secretion by GnRH (ANOVA, p < 0.001) without significant differences between diestrous and lactation pituitaries. Galanin alone did not modify LH secretion but it potentiated the effect of GnRH upon pituitaries from diestrous (p = 0.036) but not lactating rats. Neither peptide alone or its combination modified pituitary beta-LH mRNA levels. Results show that galanin regulates differently the secretion and synthesis of LH at the pituitary level. The disappearance of galanin-induced potentiation of GnRH effects upon LH secretion during lactation might contribute to the hypogonadotropism of lactation in the rat. PMID- 10029900 TI - Effect of atmospheric pollution on the respiratory system. AB - Santiago de Chile has a high level of air pollution with ozone (O3), carbon monoxide (CO) and particles equal or smaller than 10 microns (PM10) usually exceeding the accepted standards. This situation should be noxious for the exposed population and particularly--in the case of O3 and PM10--for the respiratory system. However, such an effect is rather difficult to demonstrate and it depends on the type of population under study. PMID- 10029901 TI - Microalgal blooms: a global issue with negative impact in Chile. AB - Ecological and health problems posed by microalgal blooms (red tides) occurring in the Southern part of Chile are reviewed. Out of the six human illnesses provoked by microalgal toxins, paralytic shellfish poisoning is the most important, because of its high mortality rate and the high levels of phycotoxins found in contaminated molluscs. Saxitoxin and its analogues bind to a receptor in the voltage-gated sodium channel of neural membranes. The most important toxin producer microalgae are Alexandrium catenella and Dinophysis acuta. Phycotoxins become concentrated by filter-feeding shellfish, like Mytilus chilensis. Highly sensitive methods available for detection of microalgal toxins are analyzed. PMID- 10029902 TI - Emerging infectious diseases 1997-1998: the role of molecular epidemiology. PMID- 10029903 TI - Putative reservoirs of Leishmania amazonensis in a sub-andean focus of Bolivia identified by kDNA-polymerase chain reaction. PMID- 10029904 TI - High rates of positive hemocultures in children and teenagers seropositive for Trypanosoma cruzi in the State of Rio Grande do Sul, Brazil. PMID- 10029905 TI - Identification of a transmission focus of Schistosoma mansoni in the southernmost Brazilian State, Rio Grande do Sul. PMID- 10029906 TI - Natural infection of Lutzomyia rangeliana (Ortiz, 1952) (Diptera: Psychodidae) with Leishmania in Barquisimeto, Lara State, Venezuela. PMID- 10029907 TI - Risk factors for human T cell lymphotropic virus type I among injecting drug users in northeast Brazil: possibly greater efficiency of male to female transmission. AB - It was observed in the city of Salvador, State of Bahia, the highest seroprevalence of human T cell lymphotropic virus type 1 (HTLV-I) infection in Brazil as demonstrated by national wide blood bank surveys. In this paper, we report results of an investigation of drug use and sexual behavior associated with HTLV-I infection among male and female injecting drug users (IDUs) in Salvador. A cross sectional study was conducted in the Historical District of Salvador from 1994-1996 (Projeto Brasil-Salvador) and 216 asymptomatic IDUs were selected using the snowball contact technique. Blood samples were collected for serological assays. Sera were screened for human immunodeficiency virus (HIV-1/2) and HTLV-I/II antibodies by ELISA and confirmed by Western blot. The overall prevalence of HTLV-I/II was 35.2% (76/216). The seroprevalence of HTLV-I, HTLV-II and HIV-I was for males 22%, 11.3% and 44.1% and for females 46.2%, 10.3% and 74.4% respectively. HTLV-I was identified in 72.4% of HTLV positive IDUs. Variables which were significantly associated with HTLV-I infection among males included needle sharing practices, duration of injecting drug use, HIV-I seropositivity and syphilis. Among women, duration of injecting drug use and syphilis were strongly associated with HTLV-I infection. Multivariate analysis did not change the direction of these associations. Sexual intercourse might play a more important role in HTLV-I infection among women than in men. PMID- 10029908 TI - Relationship between the human T-lymphotropic virus type 1 infection and clinical manifestations of tegumentary leishmaniasis in the Colombian Pacific Coast. PMID- 10029909 TI - Is Lutzomyia intermedia (Lutz & Neiva, 1912) more endophagic than Lutzomyia whitmani (Antunes & Coutinho, 1939) because it is more attracted to light? PMID- 10029910 TI - Comparative analysis by polymerase chain reaction amplified minicircles of kinetoplast DNA of a stable strain of Trypanosoma cruzi from Sao Felipe, Bahia, its clones and subclones: possibility of predominance of a principal clone in this area. AB - Molecular characterization of one stable strain of Trypanosoma cruzi, the 21 SF, representative of the pattern of strains isolated from the endemic area of Sao Felipe, State of Bahia, Brazil, maintained for 15 years in laboratory by serial passages in mice and classified as biodeme Type II and zymodeme 2 has been investigated. The kinetoplast DNA (kDNA) of parental strain, 5 clones and 14 subclones were analyzed. Schizodeme was established by comparative study of the fragments obtained from digestion of the 330-bp fragments amplified by polymerase chain reaction (PCR) from the variable regions of the minicircles, and digested by restriction endonucleases Rsa I and Hinf I. Our results show a high percentual of similarity between the restriction fragment length polymorphism (RFLP) for the parental strain and its clones and among these individual clones and their subclones at a level of 80 to 100%. This homology indicates a predominance of the same "principal clone" in the 21SF strain and confirms the homogeneity previously observed at biological and isozymic analysis. These results suggest the possibility that the T. cruzi strains with similar biological and isoenzymic patterns, circulating in this endemic area, are representative of one dominant clone. The presence of "principal clones" could be responsible for a predominant tropism of the parasites for specific organs and tissues and this could contribute to the pattern of clinico-pathological manifestations of Chagas's disease in one geographical area. PMID- 10029911 TI - Ophyra aenescens (L.) (Diptera: Muscidae) a new biological vector of Dermatobia hominis (L. Jr) (Diptera: Cuterebridae) in Minas Gerais, Brazil. PMID- 10029913 TI - Vaccination of C57BL/10 mice against cutaneous leishmaniasis. Use of purified gp63 encapsulated into niosomes surfactants vesicles: a novel approach. PMID- 10029912 TI - Immunotherapy for visceral leishmaniasis: ability of factors produced during anti leishmania responses of skin test positive adults to inhibit peripheral blood mononuclear cell activities associated with visceral leishmaniasis. AB - The course of human Leishmania chagasi infections appears to be determined by the balance between type 1 (Tl) CD4+ and CD8+ T suppressor (Ts) cell activities. Skin test positive adults living in hyperendemic areas who have no history of visceral leishmaniasis (VL) have Tl CD4+ T cell immunodominant responses against L. chagasi. The cytokines they secrete during anti-leishmania responses are a probable source of cytokines which inhibit the CD8+ Ts cells associated with VL. The ability of supernatants generated from peripheral blood mononuclear cells derived from skin test positive adults to reverse immune responses which appear to be mediated by CD8+ Ts cells was assessed in three sets of screening assays. The supernatants displayed three candidate factors. One, which could be explained by Leishmania antigens in the supernatant, decreased high endogenous IL-10 secretion characteristic of one class of VL patients. A second activity decreased high endogenous proliferation characteristic of the same class of patients without decreasing antigen specific proliferation. The third activity inhibited or killed CD8+ T cells but not CD4+ T cells. These activities might be useful in treating VL. PMID- 10029914 TI - Resolution of an infection with Leishmania braziliensis confers complete protection to a subsequent challenge with Leishmania major in BALB/c mice. AB - Both Leishmania major and L. braziliensis induce cutaneous leishmaniasis in BALB/c mice. Whereas BALB/c mice die of infection with L. major, they cure an infection with L. braziliensis. We report here that after curing an infection with L. braziliensis, BALB/c mice are resistant to challenge with L. major. When challenged with L. major, L. braziliensis pre-treated BALB/c mice mounted a delayed-type hypersensitivity response to L. major and produced high amounts of interferon-gamma (IFN-gamma) but low amounts of interleukin-4. The IFN-gamma produced by the L. braziliensis pre-infected mice was involved in the protection seen against L. major challenge since treating the mice with a neutralizing anti IFN-gamma abrogated the protection. This suggests that cross-reactive antigen epitopes exist between L. braziliensis and L. major and that pre-infection with L. braziliensis primes BALB/c mice to epitopes on L. major that can elicit a protective Th1 response to the parasite. PMID- 10029915 TI - Serodiagnosis of Trypanosoma cruzi infection using the new particle gel immunoassay--ID-PaGIA Chagas. AB - The ID-Chagas test is a particle gel immunoassay (PaGIA). Red coloured particles are sensitised with three different synthetic peptides representing antigen sequences of Trypanosoma cruzi: Ag2, TcD and TcE. When these particles are mixed with serum containing specific antibodies, they agglutinate. The reaction mixture is centrifuged through a gel filtration matrix allowing free agglutinated particles to remain trapped on the top or distributed within the gel. The result can be read visually. In order to investigate the ability of the ID-PaGIA to discriminate negative and positive sera, 111 negative and 119 positive, collected in four different Brazilian institutions, were tested by each of the participants. All sera were previously classified as positive or negative according to results obtained with three conventional tests (indirect immunofluorescence, indirect hemaglutination, and enzyme linked immunosorbent assay). Sensitivity rates of ID-PaGIA varied from 95.7% to 97.4% with mean sensitivity of 96.8% and specificity rates varied from 93.8 to 98.8% with mean specificity of 94.6%. The overall Kappa test was 0.94. The assay presents as advantages the simplicity of operation and the reaction time of 20 min. In this study, ID-PaGIA showed to be highly sensitive and specific. PMID- 10029916 TI - Circulating antigens levels in different clinical forms of the Schistosoma mansoni infection. AB - With the aim to evaluate the circulating cathodic antigen (CCA) levels in relation to the different clinical phases of Schistosoma sp. infection a sandwich ELISA using monoclonal antibody 5H11 was performed. The sera of three groups of 25 Brazilian patients with acute, intestinal and hepatosplenic forms of S. mansoni infection were tested and compared to a non-infected control group. Patients and control groups were matched for age and sex and the number of eggs per gram of feces was equally distributed among the three patient groups. Sensitivity of 100%, 72%, 52% of the assay was observed for the intestinal, hepatosplenic and acute toxemic groups respectively. The specificity was 100%. Intestinal and hepatosplenic groups presented CCA levels significantly higher in comparison to those observed for acute patients (F-ratio = 2,524; p = 0.000 and F ratio = 6,314; p = 0.015 respectively). There was no significant difference of CCA serum levels between hepatosplenic and intestinal groups (F-ratio = 1,026; p = 0.316). PMID- 10029917 TI - Myofibroblasts in schistosomal portal fibrosis of man. AB - Myofibroblasts, cells with intermediate features between smooth muscle cells and fibroblasts, have been described as an important cellular component of schistosomal portal fibrosis. The origin, distribution and fate of myofibroblasts were investigated by means of light, fluorescent, immunoenzymatic and ultrastructural techniques in wedge liver biopsies from 68 patients with the hepatosplenic form of schistosomiasis. Results demonstrated that the presence of myofibroblasts varied considerably from case to case and was always related to smooth muscle cell dispersion, which occurred around medium-sized damaged portal vein branches. By sequential observation of several cases, it was evident that myofibroblasts derived by differentiation of vascular smooth muscle and gradually tended to disappear, some of them further differentiating into fibroblasts. Thus, in schistosomal pipestem fibrosis myofibroblasts appear as transient cells, focally accumulated around damaged portal vein branches, and do not seem to have by themselves any important participation in the pathogenesis of hepatosplenic schistosomiasis. PMID- 10029918 TI - Increase of a calcium independent transglutaminase activity in the erythrocyte during the infection with Plasmodium falciparum. AB - We have studied the activity of a calcium dependent transglutaminase (EC 2.3.2.13) during the growth of the parasite Plasmodium falciparum inside the infected human erythrocyte. There is only one detectable transglutaminase in the two-cell-system, and its origin is erythrocytic. No activity was detected in preparations of the parasite devoid of erythrocyte cytoplasm. The Michaelis Menten constants (Km) of the enzyme for the substrates N'N' dimethylcaseine and putrescine were undistinguishable whether the cell extracts used in their determination were obtained from normal or from infected red cells. The total activity of transglutaminase in stringently synchronized cultures, measured at 0.5 mM Ca2+, decreased with the maturation of the parasite. However, a fraction which became irreversibly activated and independent of calcium concentration was detected. The proportion of this fraction grew with maturation; it represented only 20% of the activity in 20 hr-old-trophozoites while in 48-hr-schizonts it was more than 85% of the total activity. The activation of this fraction of transglutaminase did not depend on an increase in the erythrocyte cytoplasmic calcium, since most of the calcium was shown to be located in the parasite. PMID- 10029919 TI - Inducing enterotoxigenic properties in Campylobacter jejuni and campylobacter coli by serial intraperitoneal passage in mice. PMID- 10029920 TI - Acquired and congenital ocular toxoplasmosis experimentally induced in Calomys callosus (Rodentia, Cricetidae). AB - An experimental model for acquired and congenital ocular toxoplasmosis as well as a model to induce experimental autoimmune uveitis (EAU) was investigated in Calomys callosus. Toxoplasma gondii, ME-49 strain, was used to infect males and pregnant- and not pregnant-females while S-antigen, a major glycoprotein of the retinal photoreceptor cell, was used to induce EAU. The ocular lesions elicited by T. gondii were characterized by the presence of cysts, free tachyzoites and inflammatory cells in the retina or related tissues. In the congenital form, 40% of the fetus presented ocular lesions, i.e., presence of cysts in the retina, vitreous, and extra-retinal tissues. In the acquired form, 75% of the females and 50% of the males presented unilateral ocular cysts both at 21 and 47 days post infection. It was also demonstrated that S-antigen was not uveitogenic in the C. callosus model. No lesion was observed in the animals exclusively immunized with this retinal component, even when jacalin was used as additional adjuvant for polyclonal response to the retinal antigen. It can be concluded that C. callosus may constitute in a promising model for study both acquired and congenital ocular toxoplasmosis, particularly when it is important to make sure that a non autoimmune process is involved in the genesis of the ocular infection. PMID- 10029921 TI - Evaluation of insecticide resistance and biochemical mechanisms in a population of Culex quinquefasciatus (Diptera: Culicidae) from Sao Paulo, Brazil. AB - To establish an insecticidal resistance surveillance program, Culex quinquefasciatus mosquitoes from Sao Paulo, Brazil, were colonized (PIN95 strain) and analyzed for levels of resistance. The PIN95 strain showed low levels of resistance to organophosphates [malathion (3.3-fold), fenitrothion (11.2-fold)] and a carbamate [propoxur (3.0-fold)]. We also observed an increase of 7.4 and 9.9 in alpha and beta esterase activities, respectively, when compared with the reference IAL strain. An alteration in the sensitivity of acetylcholinesterase to insecticide inhibition was also found in the PIN95 mosquitoes. The resistant allele (Ace.1R), however, was found at low frequencies (0.12) and does not play an important role in the described insecticide resistance. One year later, Cx. quinquefasciatus mosquitoes were collected (PIN96 strain) at the same site and compared to the PIN95 strain. The esterase activity patterns observed for the PIN96 strain were similar to those of the PIN95 mosquitoes. However the occurrence of the Ace.1R allele was statistically higher in the PIN96 strain. The results show that esterase-based insecticide resistance was established in the PIN95 Cx. quinquefasciatus population and that an acethylcholinesterase based resistant mechanism has been selected for. A continuous monitoring of this phenomenon is fundamental for rational mosquito control and insecticide application programs. PMID- 10029922 TI - Insecticide resistance in a Culex quinquefasciatus strain from Rio de Janeiro, Brazil. PMID- 10029924 TI - Feeding and defecation patterns of nymphs of Triatoma rubrofasciata (De Geer, 1773) (Hemiptera: Reduviidae), and its potential role as vector for Trypanosoma cruzi. PMID- 10029923 TI - [Post-embryonic development of Ophyra aenescens (Wiedemann, 1830) (Diptera: Muscidae) with different diets, under laboratory conditions]. AB - The performance of various diets (bovine meat, fish-sardine, shrimp, dog faeces, and banana) in Ophyra aenescens development was evaluated. The biology was studied in an incubator (BOD) at 27 +/- 1 degrees C and 80 +/- 10% of RH. The developmental time from larvae to adult, the developmental time and viability of larvae and pupae, the weight of pupae as well as the sex ratio of the emerging adults were also determined. Beef and shrimp were the more efficient diets for rearing O. aenescens. PMID- 10029925 TI - Survival and molting incidence after heat and cold shocks in Panstrongylus megistus Burmeister. AB - Survival and molting incidence were studied after heat (40 degrees C) and cold (0 degree C) shocks in specimens of Panstrongylus megistus with the aim of establishing its response to temperature stress under laboratory rearing conditions and to understand occasional changes in the biological characteristics of specimens captured in nature. The response to the thermal shocks was found to vary as a function of the temperature and duration of the shock, developmental phase and sex of the specimens, and in certain cases, the insect habit and nourishment conditions. P. megistus specimens were found to be less resistant to the heat shock assay than Triatoma infestans, another reduviid species. The short cold shock affected survival of P. megistus more than did the heat shock, survival of fully-nourished specimens being preferential. The response of adults to the short cold shock was affected by sex, males being generally less resistant. The insect sylvatic habit was found to seldom affect the thermal shock response established for specimens with domestic habit. A decrease in molting frequency and sometimes a slowdown of the molting rate were found after the short heat and cold shocks, possibly promoted by change in hormonal balance, and differing from patterns reported for T. infestans. The results indicate that no generalization should be made for different reduviid species in terms of the effects of temperature shocks. PMID- 10029926 TI - Correlates of sexually transmitted bacterial infections among U.S. women in 1995. AB - CONTEXT: Sexually transmitted diseases (STDs) of bacterial origin such as gonorrhea and chlamydial infection can lead to pelvic inflammatory disease (PID) and infertility. Identifying behaviors and characteristics associated with infection may assist in preventing these often asymptomatic diseases and their sequelae. METHODS: Data from 9,882 sexually active women who participated in the 1995 National Survey of Family Growth describe the characteristics of women who report a history of infection with a bacterial STD or of treatment for PID. Multivariate analysis is used to determine which demographic characteristics and sexual and health-related behaviors affect the likelihood of infection or the occurrence of complications. RESULTS: Overall, 6% of sexually active women reported a history of a bacterial STD, and 8% reported a history of PID. Women who first had sexual intercourse before age 15 were nearly four times as likely to report a bacterial STD, and more than twice as likely to report PID, as were women who first had sex after age 18. Having more than five lifetime sexual partners also was associated with both having an STD and having PID. PID was more common among women reporting a history of a bacterial STD (23%) than among women who reported no such history (7%). In multivariate analyses, age, race, age at first intercourse and lifetime number of sexual partners had a significant effect on the risk of a bacterial STD. Education, age, a history of IUD use, douching and a history of a bacterial STD had a significant impact on the risk of PID, but early onset of intercourse did not, and lifetime number of partners had only a marginal effect. CONCLUSIONS: The pattern of characteristics and behaviors that place women at risk of infection with bacterial STDs is not uniform among groups of women. Further, the level of self-reported PID would suggest higher rates of gonorrhea and chlamydial infection than reported. PMID- 10029927 TI - Where do people go for treatment of sexually transmitted diseases? AB - CONTEXT: Major public health resources are devoted to the prevention of sexually transmitted diseases (STDs) through public STD clinics. However, little is known about where people actually receive treatment for STDs. METHODS: As part of the National Health and Social Life Survey, household interviews were performed from February to September 1992 with 3,432 persons aged 18-59. Weighted population estimates and multinomial response methods were used to describe the prevalence of self-reported STDs and patterns of treatment utilization by persons who ever had a bacterial or viral STD. RESULTS: An estimated two million STDs were self reported in the previous year, and 22 million 18-59-year-olds self-reported lifetime STDs. Bacterial STDs (gonorrhea, chlamydia, nongonococcal urethritis, pelvic inflammatory disease and syphilis) were more common than viral STDs (genital herpes, genital warts, hepatitis and HIV). Genital warts were the most commonly reported STD in the past year, while gonorrhea was the most common ever reported STD. Almost half of all respondents who had ever had an STD had gone to a private practice for treatment (49%); in comparison, only 5% of respondents had sought treatment at an STD clinic. Respondents with a bacterial STD were seven times more likely to report going to an STD clinic than were respondents with a viral STD--except for chlamydia, which was more likely to be treated at family planning clinics. Men were significantly more likely than women to go to an STD clinic. Young, poor or black respondents were all more likely to use a family planning clinic for STD treatment than older, relatively wealthy or white respondents. Age, sexual history and geographic location did not predict particular types of treatment-seeking. CONCLUSIONS: The health care utilization patterns for STD treatment in the United States are complex. Specific disease diagnosis, gender, race and income status all affect where people will seek treatment. These factors need to be taken into account when STD prevention strategies are being developed. PMID- 10029928 TI - Women's interest in vaginal microbicides. AB - CONTEXT: Each year, an estimated 15 million new cases of sexually transmitted diseases (STDs), including HIV, occur in the United States. Women are not only at a disadvantage because of their biological and social susceptibility, but also because of the methods that are available for prevention. METHODS: A nationally representative sample of 1,000 women aged 18-44 in the continental United States who had had sex with a man in the last 12 months were interviewed by telephone. Analyses identified levels and predictors of women's worry about STDs and interest in vaginal microbicides, as well as their preferences regarding method characteristics. Numbers of potential U.S. microbicide users were estimated. RESULTS: An estimated 21.3 million U.S. women have some potential current interest in using a microbicidal product. Depending upon product specifications and cost, as many as 6.0 million women who are worried about getting an STD would be very interested in current use of a microbicide. These women are most likely to be unmarried and not cohabiting, of low income and less education, and black or Hispanic. They also are more likely to have visited a doctor for STD symptoms or to have reduced their sexual activity because of STDs, to have a partner who had had other partners in the past year, to have no steady partner or to have ever used condoms for STD prevention. CONCLUSIONS: A significant minority of women in the United States are worried about STDs and think they would use vaginal microbicides. The development, testing and marketing of such products should be expedited. PMID- 10029929 TI - Condom use and HIV risk behaviors among U.S. adults: data from a national survey. AB - CONTEXT: How much condom use among U.S. adults varies by type of partner or by risk behavior is unclear. Knowledge of such differentials would aid in evaluating the progress being made toward goals for levels of condom use as part of the Healthy People 2000 initiative. METHODS: Data were analyzed from the 1996 National Household Survey of Drug Abuse, an annual household-based probability sample of the noninstitutionalized population aged 12 and older that measures the use of illicit drugs, alcohol and tobacco. The personal behaviors module included 25 questions covering sexual activity in the past year, frequency of condom use in the past year, circumstances of the last sexual encounter and HIV testing. RESULTS: Sixty-two percent of adults reported using a condom at last intercourse outside of an ongoing relationship, while only 19% reported using condoms when the most recent intercourse occurred within a steady relationship. Within ongoing relationships, condom use was highest among respondents who were younger, black, of lower income and from large metropolitan areas. Forty percent of unmarried adults used a condom at last sex, compared with the health objective of 50% for the year 2000. Forty percent of injecting drug users used condoms at last intercourse, compared with the 60% condom use objective for high-risk individuals. Significantly, persons at increased risk for HIV because of their sexual behavior or drug use were not more likely to use condoms than were persons not at increased risk; only 22% used condoms during last intercourse within an ongoing relationship. CONCLUSIONS: Substantial progress has been made toward national goals for increasing condom use. The rates of condom use by individuals at high risk of HIV need to be increased, however, particularly condom use with a steady partner. PMID- 10029931 TI - Reactions to medical abortion among providers of surgical abortion: an early snapshot. PMID- 10029930 TI - Pregnancies averted among U.S. teenagers by the use of contraceptives. AB - CONTEXT: The personal and social costs associated with teenage pregnancy in the United States concern many policymakers and researchers, yet the role of contraception in preventing these pregnancies has not been adequately quantified. METHODS: Published estimates of contraceptive effectiveness were applied to 1995 National Survey of Family Growth data on sexual and contraceptive practices in order to estimate the number of pregnancies averted through the use of contraceptives by U.S. teenagers. Four scenarios of contraceptives access--from current levels of access to highly restricted access--and teenagers' sexual and contraceptive practices in response to such restrictions are used to project the potential impact on pregnancies among teenagers. RESULTS: Current levels of contraceptive use averted an estimated 1.65 million pregnancies among 15-19-year old women in the United States during 1995. If these young women had been denied access to both prescription and over-the-counter contraceptive methods, an estimated one million additional pregnancies (ranging from 750,000 to 1.25 million) would have occurred, assuming some decrease in sexual activity. These pregnancies would have led to 480,000 live births, 390,000 abortions, 120,000 miscarriages, 10,000 ectopic pregnancies and 37 maternal deaths. CONCLUSIONS: Contraceptive use by teenage women prevents pregnancies and negative pregnancy related health consequences that can disrupt the lives of adolescent women and that have substantial societal costs. Continued and expanded access to contraceptives for adolescents is a critically important public health strategy. PMID- 10029932 TI - Provider attitudes toward dispensing emergency contraception in Michigan's Title X programs. PMID- 10029933 TI - The pill in Japan: will approval ever come? PMID- 10029934 TI - Dementia care in the UK--a single service for all. PMID- 10029935 TI - The glutamatergic system and neurodegeneration in dementia: preventive strategies in Alzheimer's disease. PMID- 10029936 TI - A review of the phenomenology and cognitive neuropsychological origins of the Capgras syndrome. AB - In this article the epidemiology, aetiology, neuroanatomy and neuropsychology of the Capgras syndrome (CS) are reviewed in detail. CS is characterized by the delusional belief that one or a few highly familiar people have been replaced by impostors who are physically very similar to the original/s. The patient acknowledges that the double and known person look alike, but maintains the belief that the significant person, in psychological terms, is absent. CS is relatively rare, occurring predominantly in the context of schizophrenia, and was traditionally considered to have its origins in psychodynamic conflict. More recently, however, it has been estimated that between 25 and 40% of cases are associated with organic disorders, which include dementia, head trauma, epilepsy and cerebrovascular disease. Neuroimaging evidence suggests a link between CS and right hemisphere abnormalities, particularly in the frontal and temporal regions. Neuropsychological research has provided empirical support for these findings, by consistently reporting the presence of impairments in facial processing--an established right hemisphere function. It is likely that the study of this symptom will lead to a greater understanding of the neurological basis of psychotic experiences and may provide a paradigm for how the psychoses should be investigated. PMID- 10029937 TI - The FEAR: a rapid screening instrument for generalized anxiety in elderly primary care attenders. AB - OBJECTIVE: To develop a shorter version of the Anxiety Disorder Scale (ADS) for use as a rapid screening instrument in primary care. DESIGN: Two-stage screening design. Primary care attenders aged 65 and over were screened for generalized anxiety in the surgery with the 11-item generalized anxiety subscale of the ADS (ADS GA), a selected subsample then proceeding to a clinical validation interview. INTERVENTIONS: None. MAIN OUTCOME MEASURES: Scores on the ADS GA, non hierarchical ICD-10 caseness for generalized anxiety established by brief clinical interview by an old age psychiatrist. RESULTS: The prevalence rate of generalized anxiety was 16% using the established cutpoint and showed an age related decline. A cutpoint of 2-3/11 appeared to give optimal performance in this small sample (sensitivity 85%, specificity 77%, positive predictive value 52%), suggesting that 36% of elderly general practice attenders might be diagnosed as having generalized anxiety. A reduced four-item version gave a predicted sensitivity of 77%, a specificity of 83% and a positive predictive value of 63% (cutpoint 1-2/4). CONCLUSIONS: A four-item version of the ADS GA, the FEAR (frequency of anxiety; enduring nature of anxiety; alcohol or sedative use; restlessness or fidgeting), has potential as a rapid screening instrument for use in primary care. PMID- 10029938 TI - Donepezil for dementia with Lewy bodies: a case study. PMID- 10029940 TI - Current awareness in geriatric psychiatry. PMID- 10029939 TI - 'Silent dependence syndrome' in old age...! PMID- 10029941 TI - Report from the ninth annual meeting of the Chiropractic Research Journal Editors' Council. PMID- 10029942 TI - Intraexaminer and interexaminer reliability of the Gillet test. AB - OBJECTIVES: The purpose of this study was to determine the intraexaminer and interexaminer reliability of the Gillet test. STUDY DESIGN: In a test-retest study the incidence of asymmetric or symmetric sacroiliac joint motion was investigated with the Gillet test. METHODS: Forty-one male subjects volunteered for this study (mean age, 23 +/- 2.24 years). Thirty-eight subjects were examined in the first test procedure, and at least 4 days later 37 subjects were examined again. The subjects were subdivided into symptomatic and asymptomatic groups on the basis of certain criteria. RESULTS: To obtain the intraexaminer and interexaminer reliability values, Cohen's kappa, the percentage agreement, bias adjusted kappa, and prevalence-adjusted bias-adjusted kappa were used. The mean Cohen's kappa did not exceed the value of 0.081. Only the percentage agreement of the symptomatic group did exceed the minimum level of 80%. When kappa was positive, the prevalence-adjusted bias-adjusted kappa was markedly higher than kappa; when kappa was negative, the prevalence-adjusted bias-adjusted kappa was only slightly higher than kappa. Only small differences were found between kappa and bias-adjusted kappa. CONCLUSION: The Gillet test, as performed in this study, does not appear to be reliable. PMID- 10029943 TI - Precision and accuracy of an electrogoniometer. AB - BACKGROUND: Spinal range of motion has been studied by use of a variety of different methods. One electrogoniometer has been used as a noninvasive, reliable, and accurate method. The accuracy and precision of this device has not been sufficiently documented. OBJECTIVE: To evaluate the precision and accuracy of an electrogoniometer in comparison with two manual protractors. STUDY DESIGN: This study investigated the precision and accuracy of an electrogoniometer (OSI CA 6000). METHODS: The precision and accuracy of the electrogoniometer were determined by a series of tests against two manual protractors. Six different movement directions were tested and 4 or 5 different angles for a given movement direction were evaluated. RESULTS: The precision of the electrogoniometer was found to be +/- 0.1 degree for 4 different angles (10 degrees, 20 degrees, 40 degrees, and 60 degrees) in 6 different movement directions (flexion, extension, left lateral flexion, right lateral flexion, left rotation, and right rotation). The accuracy was tested by comparing both manual protractors with the electrogoniometer. Substantial disagreement for 27 of 28 datasets was found. In only one dataset was there agreement between the two manual protractors and the electrogoniometer. The mean differences were in the interval 2.0% to 11.5% between the electrogoniometer and the protractors. CONCLUSION: The electrogoniometer evaluated has a very high precision when range of motion measurements are made. However, the accuracy of the device is less than acceptable. PMID- 10029944 TI - Incidence of ponticulus posterior of the atlas in migraine and cervicogenic headache. AB - BACKGROUND: The clinical significance of the ponticulus posticus is far from clear. It has been associated with headaches, Barre-Lieou syndrome, photophobia, and migraine. However, little epidemiologic evidence for this exists. OBJECTIVE: This study investigated the relationship of ponticulus posticus on x-ray studies and headache symptoms in a series of chiropractic patients. METHODS: Eight hundred ninety-five patients who visited a chiropractic clinic for the first time and whose conditions required cervical spine x-ray examinations were studied. Complaints were categorized as migraine with aura, migraine without aura, cervicogenic headache, neck pain only, and other conditions. The presence or absence of the ponticulus posticus (whether partial or complete) was determined by means of a lateral cervical film and noted as a positive or negative finding. The data were analyzed by frequency analysis and Pearson's chi 2 test. RESULTS: Forty-six percent of the sample were men and the predominant complaint was neck pain (33%). Most patients were in the fourth decade of life. The frequencies of the other complaints were migraine with aura (7%), migraine without aura (4%), cervicogenic headache (22%), other conditions (33%). An 18% prevalence of ponticulus posticus was found. This finding was significantly associated with migraine without aura (chi 2 = 4.97; P = .03) and not with any other conditions. CONCLUSION: In a chiropractic patient population that required cervical x-ray examinations, a significant association was found between ponticulus posticus and migraine without aura, with an odds ratio of 2.19:1 in favor of this complaint being present with the osseous anomaly. The mechanism for this remains obscure but may be related to ischemic compression of the vertebral artery or by dural tension at the craniocervical junction. PMID- 10029945 TI - Correlation and quantification of projected 2-dimensional radiographic images with actual 3-dimensional Y-axis vertebral rotations. AB - BACKGROUND: Historically, measurement of 2-dimensional (2-D) radiographic images on the anteroposterior radiograph has been made to assess 3-dimensional (3-D) y axis vertebral rotations. OBJECTIVES: To correlate and quantify measurements of the projected 2-D radiographic image with the degree of 3-D y-axis rotation. STUDY DESIGN: A computer model was positioned in a simulated x-ray beam. Points of model contact with the simulated beam were projected onto a line in the neutral position and the first 7 degrees of both positive and negative y-axis rotation using two different axes of rotation. A larger model, a shape-altered model, and a decreased source-object-distance model were also studied. RESULTS: 3 D y-axis rotation of vertebrae causes an off-center displacement of the 2-D projected lamina junction in relation to the projected vertebral body. The magnitude of displacement increases with increasing degrees of rotation. In our model, no clinically significant difference was found in the amount of the projected off-center displacement of the lamina junction between either of our two chosen axes of rotation. However, significant differences in the projected offset were found between vertebrae with the same degree of rotation as a result of changes in vertebral shape, size, and positioning. The projected lamina junction off-centering at a given rotation is quantified for our model. CONCLUSION: Use of millimetric measurement of the projected lamina offset on the anteroposterior radiograph is an inaccurate method for the assessment of the degree of 3-D y-axis vertebral rotation. PMID- 10029946 TI - The ability to reproduce the neutral zero position of the head. AB - OBJECTIVE: To determine how precisely asymptomatic subjects can reproduce a neutral zero position of the head. STUDY DESIGN: Repeated measures of the active cervical neutral zero position. SETTING: Institute of Medical Biology (Center of Biomechanics) at Odense University. PARTICIPANTS: Thirty-eight asymptomatic students from the University of Odense, male/female ratio 20:18 and mean age 24.3 years (range, 20 to 30 years). INTERVENTION: Measurements of the location of the neutral zero head position by use of the electrogoniometer CA-6000 Spine Motion Analyzer. Each subject's neutral zero position with eyes closed was measured 3 times. The device gives the localization of the neutral zero as coordinates in 3 dimensions (x, v, z) corresponding to the 3 motion planes. RESULTS: The mean difference from neutral zero in 3 motion planes was found to be 2.7 degrees in the sagittal plane, 1.0 degree in the horizontal plane, and 0.65 degree in the frontal plane. CONCLUSION: We found that young adult asymptomatic subjects are very good at reproducing the neutral zero position of the head. This suggests the existence of some advanced neurologic control mechanisms. PMID- 10029947 TI - Relationship between techniques taught and practice behavior: education and clinical correlation. AB - OBJECTIVE: This study was undertaken to determine the relationship between the time spent teaching various manual procedures in each of two different chiropractic colleges and the actual practice of those procedures in the graduate clinical environment of the doctors involved. METHODS: A simple questionnaire instrument was constructed to assess the frequency of use of 9 different manual evaluation treatment procedures. All graduates from the two chiropractic colleges in the state of Texas who obtained their license between 1988 and 1993 were polled. Reliability was studied by polling the first 30 qualified respondents twice and was found to be acceptable. The college curriculum with respect to the techniques studied was compared with the perceived use of the various techniques by the graduates surveyed. RESULTS: A total of 224 of 322 (70%) surveys were returned for consideration. Of these, 197 met all of the inclusion/exclusion criteria and were assessed as part of the sample. Significant differences were found between the colleges with respect to perceived practitioner use of Activator (chi 2 = 14.247, P = .004), Thompson technique (chi 2 = 57.702, P = .000), Gonstead (chi 2 = 52.173, P = .000), and flexion-distraction (chi 2 = 29.424, P = .000). CONCLUSION: Data from this research provide evidence that a relationship does exist between manual procedures taught in two different chiropractic colleges and the perceived use of those procedures in actual clinical practice. Implications of this relationship are discussed. PMID- 10029948 TI - Possible manifestation of temporomandibular joint dysfunction on chiropractic cervical X-ray studies. AB - OBJECTIVE: Our purpose was to show that biomechanical alterations toward and away from normal on x-ray studies may be the result of changes in temporomandibular joint dysfunction and to discuss possible neurologic explanations for this phenomenon. CLINICAL FEATURES: Two patients are discussed; the first had migraine headache symptoms, and the second had chronic hypomobility of mandibular opening, dizziness, headache, and neck pain and stiffness. In both patients mensuration changes in different types of cervical x-ray studies were noted in conjunction with exacerbation of, and elimination of, temporomandibular joint dysfunction. INTERVENTION: Comanagement of these cases was done with dental professionals. Chiropractic treatment included vectored/linear, upper cervical, high-velocity, low-amplitude chiropractic manipulation of the atlas vertebra, diversified manipulation, myofascial therapy, stretch and spray procedures, and soft tissue manual techniques. CONCLUSION: Temporomandibular joint dysfunction may cause cervical muscular and spinal biomechanical changes that may become visible and change on x-ray examination. Further investigation into this phenomenon is recommended. PMID- 10029949 TI - Chiropractic rehabilitation of a patient with S1 radiculopathy associated with a large lumbar disk herniation. AB - OBJECTIVE: To describe the nonsurgical treatment of acute S1 radiculopathy from a large (12 x 12 x 13 mm) L5-S1 disk herniation. CLINICAL FEATURES: A 31-year-old man presented with severe lower back pain and pain, paresthesia, and plantar flexion weakness of the left leg. His symptoms began 5 days before the initial visit and progressed despite nonsteroidal anti-inflammatory drugs and analgesic medication. An absent left Achilles reflex, left S1 dermatome hypesthesia, and left gastrocnemius/soleus weakness was noted. Magnetic resonance imaging demonstrated a large L5-S1 disk herniation. INTERVENTION AND OUTCOME: Initial treatment of this patient included McKenzie protocol press-ups to reduce and centralize symptoms, nonloading exercise for cardiovascular fitness, and lower leg isotonic exercises to prevent atrophy. Counseling was provided to reduce abnormal illness behavior risk. Later, flexion distraction and side-posture manipulation were provided to improve joint function. Sensory motor training, trunk stabilization exercises, and trigger point therapy were also used. He returned to modified work 27 days after symptom onset. A follow-up, comparative magnetic resonance imaging (MRI) study was unchanged. He was discharged as symptomatic (zero rating on both the Oswestry and numerical pain scales) after 50 days and 20 visits, although the left S1 reflex remained absent. Reassessment 169 days later revealed neither significant symptoms nor lifestyle restrictions. CONCLUSION: This case demonstrates the potential benefit of a chiropractic rehabilitation strategy by use of multimodal therapy for lumbar radiculopathy associated with disk herniation. PMID- 10029950 TI - Dysafferentation: a novel term to describe the neuropathologic effects of joint complex dysfunction--a look at likely mechanisms of symptom generation. PMID- 10029951 TI - Impact of traumatic events and organizational response. A study of bank robberies. AB - This study explored how experiencing a traumatic event in the workplace affects employee physical health, mental health, personal functioning, and work performance. Post-event use of health care services and the effectiveness of critical incident stress debriefing sessions and other coping interventions were also examined. A retrospective self-report methodology and mailed survey were used with 141 employees of 42 different bank branches that had recently been robbed. The results found that most employees had multiple negative consequences from experiencing a bank robbery while at work. Psychological, physical, work, and personal areas were all affected by the robbery. Furthermore, more threatening incidents were associated with more severe consequences. Critical incident stress debriefing interventions delivered after robbery were rated as helpful by 78% of employees who attended. The implications for health care providers and organizations are discussed. PMID- 10029952 TI - The impact of workplace screening on the occurrence of cumulative trauma disorders and workers' compensation claims. AB - Work-related musculoskeletal pain, commonly referred to more specifically as musculoskeletal disorders or cumulative trauma disorders, has continued to occur despite efforts by employers, employees, health care providers, and the government to eradicate it. The National Institute for Occupational Safety and Health has encouraged employers to establish ergonomic prevention programs; however, many employers are concerned that screening, education, and focused attention on workplace pain will cause an increase in the number of OSHA 200 events and the incidence of workers' compensation claims. This prospective cohort study demonstrated that there was no increase in the number of OSHA 200 events and no increase in the incidence of workers' compensation claims after completion of an individual risk screening program that included education and employee awareness about work-related musculoskeletal pain. Incidence of cumulative trauma disorders has been most effectively reduced by use of individual risk-screening programs. Therefore, employers should be encouraged to develop and implement prevention programs that include individual risk screening. PMID- 10029953 TI - A national survey of regional poison control centers' management of occupational exposure calls. AB - Regional poison control centers (PCCs) were surveyed nationally to assess their policies and practices in handling work-related exposures. A 24-item survey was mailed to the executive directors of 44 American Association of Poison Control Centers' certified PCCs nationwide. The survey also requested permission to call the PCC to conduct a blinded role-playing exercise of a case of work-related trichloroethane exposure. Responses on the management questionnaire were compared with the actual responses provided by information specialists in the role-playing exercise. Seventy-five percent of PCCs completed the survey; 43% completed the telephone role-playing exercise. Survey respondents generally overestimated what they thought was routinely done to assess work-related calls, compared with what actually occurred at the time of the work-related call in the role-playing exercise. For example, 32% indicated that their PCC asked about the activities of nearby workers, but none of the PCC staff actually did so. Eighty-nine percent of the PCC executive directors surveyed thought that their staff routinely advised callers to notify their employer about work-related exposure concerns, but this occurred in only 11% of the calls. We concluded that PCCs' responses to work related calls are inadequate. Given the public health impact of work-related calls, PCCs should develop, implement, and monitor written protocols to better address the public health issues of workplace poisonings. PMID- 10029954 TI - Fatal and non-fatal injuries from vessels under air pressure in construction. AB - Using a surveillance system that captures data on construction workers treated in an urban emergency department, we identified a series of injuries caused by vessels and tools under air pressure. We describe those six cases, as well as similar cases found in the Census of Fatal Occupational Injuries; we also review data from the National Surveillance for Traumatic Occupational Fatalities database and data from the Bureau of Labor Statistics. Among the injuries and deaths for which we had good case descriptions, the majority would have been prevented by adherence to existing Occupational Safety and Health Administration standards in the construction industry. PMID- 10029955 TI - Injuries to volunteer fire fighters in West Virginia. AB - The distribution and characteristics of workplace injuries for West Virginia volunteer fire fighters (VFFs) are described using 1992 workers' compensation data. Most of the injuries occurred in VFFs who were less than 30 years of age (62%). The most common type of injuries were those in the category of lacerations and contusions (28.9%), with a notable percentage of injuries due to smoke inhalation and respiratory problems (13.7%). The proportional rates related to falls in VFFs were almost twice the national figures for the same year (39.3% versus 22.3%). County population density was found to be directly associated with injury rates, even when adjusted for number of responses. Claims statistics mirror a similar geographical trend in overall workers' compensation claims for all injuries in West Virginia. The results of this study provide a foundation for additional follow-up studies in order to develop improved occupational safety policies and target educational programs aimed at the prevention of injuries in volunteer fire fighters. Several findings have already resulted in programmatic recommendations. PMID- 10029956 TI - Effect of keyboard keyswitch design on hand pain. AB - This randomized clinical trial evaluated the effects of keyboard keyswitch design on computer users with hand paresthesias. Twenty computer users were matched and randomly assigned to keyboard A (n = 10) or B (n = 10). The keyboards were of conventional layout and differed in keyswitch design. Various outcome measures were assessed during the 12 weeks of use. Subjects assigned keyboard A experienced a decrease in hand pain between weeks 6 and 12 when compared with keyboard B subjects (P = 0.05) and demonstrated an improvement in the Phalen test time (right hand, P = 0.006; left hand, P = 0.06). Keyboard assignment had no significant effect on change in hand function or median nerve latency. We conclude that use of keyboard A for 12 weeks led to a reduction in hand pain and an improved physical examination finding when compared with keyboard B. There was no corresponding improvement in hand function or median nerve latency. PMID- 10029957 TI - Lead exposure in battery-factory workers is not associated with anemia. AB - Anemia is a manifestation of lead toxicity. However, there are conflicting reports of its prevalence among lead-exposed workers, and it is uncertain whether they should be monitored by periodic hemoglobin (Hb) examinations. To explore the relationship between Hb and lead exposure, we examined the correlation between Hb, blood lead (PbB), and zinc protoporphyrin (ZPP) levels in 961 blood samples obtained from 94 workers in a lead-acid battery plant in Israel between 1980 and 1993. Blood lead levels exceeded 60 micrograms/dL (2.90 mumol/L) in 105 (14%) of the blood samples. The correlation between PbB and logZPP was 0.594. Hb levels did not correlate with PbB or ZPP. We conclude that (a) periodic Hb determinations are not a useful indicator of lead exposure in Israeli industrial workers; (b) the discrepancies between the reported correlation between PbB and Hb levels remain unexplained and in need of further study; and (c) a finding of anemia in a person with PbB levels of up to 80 micrograms/dL should be considered to be due to lead toxicity only after other causes for anemia have been excluded. PMID- 10029958 TI - Death following sedation. PMID- 10029959 TI - Effects of benzodiazepines. PMID- 10029960 TI - Managing the extremely difficult child: is general anesthesia the correct solution? PMID- 10029961 TI - Topical antimicrobial therapy in the prevention of early childhood caries. AB - PURPOSE: Early childhood caries (ECC) is microbiologically characterized by heavy infection of mutans streptococci (ms) on dental surfaces. Accordingly, it is reasonable to speculate that suppression of dental ms levels would decrease risk for ECC. On this basis, randomized double blind, placebo controlled pilot study was performed to test this concept. METHODS: The study population consisted of 31 subjects (age: 12 to 19 mos; sex: 18F/13M) who were clients of a Women, Infants, and Children (WIC) clinic in Puerto Rico. Inclusion criteria included: (1) unremarkable medical history; (2) presence of 4 maxillary primary incisors (PMI) with no visible defects; (3) clinically caries free; (4) use of a nursing bottle at naptime and/or bedtime which contained a cariogenic substrate; (5) two consecutive ms positive cultures (utilizing Mitis-Salivarius-Bacitracin (MSB) agar) from pooled PMI plaque. The subjects were randomized into 2 groups. The 15 subjects in the experimental group and the 16 subjects in the control group were evaluated every 2 months during the study period. At each evaluation, the subjects had 10% povidone iodine (experimental group) or placebo (control group) applied to their dentition. The placebo was commercial instant tea (without lemon or sweetener) and deionized water. Treatment failure was defined as the appearance of a white spot lesion(s) on any of the PMI during the study period. RESULTS: The mean duration of observation to treatment failure was 155 days; the mean duration of observation for treatment success was 217 days. Five of the 16 control subjects and 0 of the 15 experimental subjects experienced treatment failure (Fisher's exact test: P = 0.04). The Kaplan-Meier estimate for incidence of treatment failure in the placebo group was 48% over 357 days (P = 0.02). CONCLUSION: These observations suggest that topical antimicrobial therapy reduces risk for the development of ECC in high-risk children. PMID- 10029962 TI - The effect of electronic dental anesthesia on behavior during local anesthetic injection in the young, sedated dental patient. AB - PURPOSE: The purpose of this study was to evaluate the effectiveness of the 3M Electronic Dental Anesthesia (EDA) finger electrode on reducing sedated patient responsiveness during local anesthesia administration. METHODS: Thirty patients between the ages of 24 to 48 months, ASA I, and in need of treatment of maxillary anterior teeth using local anesthesia were used in this study. Each of the patients received chloral hydrate (CH) and hydroxyzine (50 mg/kg and 2 mg/kg, respectively). The patients were divided randomly in two groups. The experimental group received activated electronic dental anesthesia (AEDA) while the control group had a nonactive EDA (NAEDA). Physiological parameters were recorded and behavior was videotaped and rated using the Ohio State University Behavior Rating Scale. A repeated-measures ANOVA, Student's tests, and descriptive statistics were used. RESULTS: The results indicated that the heart rate and diastolic blood pressure of both groups were significantly affected as a function of time and dental procedures. A significant effect in the percent change of heart rate between groups was noted during local anesthetic injection with the NAEDA group having an increased heart rate. There was a higher occurrence of movement in the NAEDA compared to the AEDA. CONCLUSION: The EDA appears to be beneficial in reducing the discomfort, as judged by behavioral and physiologic observations, associated with local anesthetic administration in young sedated dental patients. PMID- 10029963 TI - Side effects of triazolam in children. AB - PURPOSE: This study examined the incidence of side effects occurring with three doses of orally administered triazolam in children undergoing restorative dental procedures. METHODS: Thirty children, aged 39-81 months, participated in the study. The children were pretested for gait ataxia, amnesia, visual acuity, stereoscopic depth perception, and diplopia during a screening session. In a subsequent appointment, children received one of three triazolam dosages (0.005, 0.015, and 0.030 mg/kg) prior to dental treatment. Dosage assignment was random and double blind. Each child received a single triazolam dosage. Tests for gait ataxia, amnesia, and visual disturbances were repeated following drug administration. RESULTS: The proportion of children experiencing ataxia, amnesia, and diplopia increased with increasing triazolam dosages. The 0.030-mg/kg triazolam dosage impaired visual acuity and stereoscopic depth perception. CONCLUSION: Triazolam produces ataxia, amnesia, and diplopia in a dose-dependent manner in children. PMID- 10029964 TI - The prevalence of pre-eruptive dentin radiolucencies in the permanent dentition. AB - PURPOSE: Although intracoronal radiolucencies in radiographs of unerupted teeth have been reported for several decades, the prevalence of this condition remains unknown. This study determined the prevalence and associated dental conditions of permanent teeth showing pre-eruptive dentin radiolucencies in bite-wing radiographs of school children attending two school dental therapy training centers. METHODS: There were 1959 subjects (934 males and 1025 females), each providing a set of bite-wing radiographs which showed the crowns of unerupted permanent teeth. The mean age of the children at radiographic exposure was 7.8 +/ 1.79 years of age. RESULTS: 126 (6%) of subjects had radiolucencies in the crowns of pre-eruptive permanent teeth. Of the 9919 teeth viewed on the radiographs, 163 (2%) were affected. There were no significant racial and gender differences in the prevalence of the defects. Of the 126 subjects with dentin radiolucencies, 93 (74%) had only 1 affected tooth compared with 31 (25%) who had two teeth affected, and 2 (2%) who had 3 affected teeth. CONCLUSIONS: Within each tooth type, the highest tooth prevalence was found in the mandibular first molar (4%), followed by the mandibular first premolar (2%), the mandibular second molar (1%), mandibular second premolar (1%), maxillary first molar (1%), maxillary first premolar (1%), and maxillary second premolar (0.2%). In addition, the group with dentin radiolucencies had a high prevalence of ectopically-positioned teeth of 14% compared with only 2% in the group without the defect, suggesting that ectopic position may predispose a tooth to pre-eruptive radiolucent defects. Other common developmental and acquired dental conditions were also examined, but no significant differences were noted between groups with and without the pre eruptive dentin radiolucencies. PMID- 10029965 TI - Presenting characteristics and treatment outcomes for tongue lacerations in children. AB - PURPOSE: Tongue lacerations in children require treatment decisions by clinicians, but there is conflicting literature on the topic of suturing. METHODS: In this prospective study, 28 patients (mean age 3.0 +/- 2.3 yr) with traumatic tongue lacerations were triaged according to an existing protocol to determine if the laceration would be sutured. At least 2 weeks post-trauma, 22 patients were evaluated by examination or report for quality of result and post trauma complications. The most common location was anterior dorsum. A fall at home was the most common situation. Mean delay from injury to treatment was 4.5 +/- 9.0 h. No statistically significant difference was found for quality of result or post-trauma morbidity between those lacerations sutured and those not. No significant relationship was found between quality of result and size of laceration or bleeding at the time of presentation. Time delay did not significantly affect the quality of result. CONCLUSION: Results suggest that suturing does not improve outcome or post-trauma course for tongue lacerations in young children. PMID- 10029966 TI - Cervical headgear therapy as a factor in obstructive sleep apnea syndrome. AB - PURPOSE: Obstructive sleep apnea syndrome (OSAS) has been a subject of increasing interest from the orthodontic point of view, but less attention has been paid to the possible influence of orthodontic treatment on its occurrence. The aim here was to study possible associations between the use of cervical headgear and nocturnal cessations of airflow and the severity of the latter. METHODS: The subjects were 30 children (12 boys, 18 girls, mean age 8.2, sd 1.61 years), divided into three groups: a group of 10 children undergoing headgear therapy, selected for this examination because of symptoms of OSAS while using headgear, an age-matched control group of 10 healthy children and a group of 10 with OSAS. Standard cephalograms of the headgear group prior to the orthodontic therapy and the corresponding cephalograms of healthy controls were analysed. A polygraphic (PG) sleep evaluation was used to assess the tendency for OSAS. Apnea and hypopnea periods were summated as apnea index (AI) and number of desaturations as desaturation index (ODI). All the subjects spent one night sleeping under laboratory conditions, those with orthodontic treatment spending the first half of the night with the headgear and the latter half without. RESULTS: The position of the mandible was found to be slightly more posterior in the headgear group than in the control group. The children in the headgear group were found to have significantly more apnea/hypopnea periods during the hours when the appliance was used, and the ODI-index showed increased values in this group. CONCLUSIONS: We suggest that headgear therapy may contribute to the occurrence of sleep apnea, when a strong predisposition, such as mandibular retrognathia to the development of upper airway occlusion already exists. PMID- 10029967 TI - A comparison of five adhesive systems to primary enamel. AB - PURPOSE: This study compared resin adhesion of five adhesive systems to primary enamel. METHODS: The labial surfaces of 115 bovine mandibular primary incisors and five different adhesive systems were used. Effects of tooth surface conditioners were observed using SEM. Shear bond strengths were tested, and the test surfaces of enamel and resin specimens were observed using SEM. RESULTS: All Etch, 10-3 solution, and K-etchant were effective tooth surface conditioners. In the nonthermocycled groups, the bond strengths of Superbond D Liner, All Bond 2, and Scotchbond Multi Purpose adhesive systems were significantly higher than those of Ketchant/Clearfil Photo Bond, and Clearfil Liner Bond adhesive systems (P < 0.01). However, in the thermocycled groups, no significant difference was obtained among the adhesive systems for bond strength. No correlation was found between the enamel-resin fracture mode and bond strength for any of the adhesive systems. CONCLUSIONS: We disagree with the theory that the use of the latest developed adhesive resin systems significantly enhance bonding of resin to primary enamel. PMID- 10029968 TI - Evaluation of a laser Doppler flowmeter to assess blood flow in human primary incisor teeth. AB - PURPOSE: This study determined whether the portable Advance Laser Flowmeter Model 21, a clinical instrument, would indicate significant values when pulpal blood flow was present or absent; whether the analog output of the flowmeter was time linked to the heart rate; and whether labial and lingual crown surfaces produced different flow values. METHODS: Teeth were tested under two conditions: with the teeth in situ and extracted, or with the pulp present and removed. RESULTS: Values before and after the teeth were extracted, and those before and after pulpectomy with the tooth in situ were significantly different. These findings verified that the flowmeter measured the presence of bloodflow. Peaks of the electrocardiogram waves and the regular signal fluctuations of the flowmeter were time-linked and verified the measurement of the heart rate from the dental pulp. Differences in the values for the lingual and labial surfaces of individual teeth were not significant. CONCLUSIONS: This instrument proved a valid means of determining the presence of pulpal blood flow in primary incisors. PMID- 10029969 TI - Sequence and timing of bone augmentation and implant insertion for the adolescent patient: three case reports. PMID- 10029970 TI - The use of a resin-bonded denture to replace primary incisors: case report. PMID- 10029971 TI - Race, culture, and psychotherapy: transference to minority therapists. AB - We present observations on the use of racial and cultural stereotypes in psychoanalytic psychotherapy with patients from the majority culture and with those from minority backgrounds. Earlier work has centered on black/white patient dyads and has not taken other possible combinations into account. "Race" and "culture" have sometimes been used synonymously. Our clinical experience indicates that there is some overlap in the themes of transferences to us as members of different racial minorities. We note, however, that for the African American therapist, projections are more often based on racial stereotypes, whereas for the Chinese-American therapist, projections are based more on cultural assumptions. When careful attention is paid to the manifestations of racial and cultural stereotyping, much can be learned about the patient's inner life, to the benefit of the analytic work. PMID- 10029972 TI - A conjoint phase of treatment involving a severely disturbed adolescent boy and his father. AB - A phase of father-son conjoint treatment during psychoanalytic psychotherapy of the son is described. The son, who met descriptive criteria for schizophrenia, felt most alive when planning revenge on his father; the father frantically dwelled on the son to the exclusion of virtually everything but work. The conjoint therapy complemented the son's individual therapy and led to a stable, hence analyzable transference. The outcome was generally positive in a case whose prognosis at the outset had appeared dismal. Questions concerning therapeutic change and clinical technique are raised. The author suggests that others in similar clinical circumstances might consider a phase of conjoint treatment. PMID- 10029973 TI - The development of time sense in middle adulthood. AB - The focus of this paper is on the normal, intrapsychic, subjective experience of time in a developmental context. Time sense in middle age is determined less by the chronological age markers of forty or sixty and more by powerful, complex dynamic factors. Issues such as physical aging and illness, relationship to spouse and children, death of parents, and retirement will be explored in terms of how time is experienced. PMID- 10029974 TI - What the analyst does not hear. AB - In the clinical situation, the analyst fails to hear more than he or she hears and spends much time working in the dark. The author raises questions about how we can take cognizance of that state of affairs in our thinking about analytic work. A clinical example illustrates how, in an analytic atmosphere, a patient will correct an analyst's failure to hear. Some ideas are offered about how to maximize the patient's participation in that effort. The author suggests that the problem may not fall precisely under the heading of technique so much as reflecting the analyst's attitude. PMID- 10029975 TI - Sleeping and dreaming on the couch viewed from the perspective of compromise formation theory. PMID- 10029976 TI - Secret weapon. PMID- 10029977 TI - Terms of endearment in clinical analysis. PMID- 10029978 TI - Herpes in the time of AIDS: a comparison of the epidemiology of HIV-1 and HSV-2 in young men in northern Thailand. AB - OBJECTIVES: To compare the epidemiologic pattern of HIV-1, a recently introduced sexually transmitted disease (STD) agent in Thailand, with the pattern of HSV-2, a well-established STD agent, so that future trends for both viruses can be better understood. METHODS: We obtained questionnaire data and determined HSV-2 (by specific gG-2) and HIV-1 seroreactivity in a cohort of 1,115 young male army conscripts who entered service in northern Thailand in 1991. RESULTS: Seroprevalence of HIV-1 and HSV-2 was 6.9% and 14.9%, respectively. For HSV-2 seropositive men who reported previous genital ulcers, HIV-1 seroprevalence was 32%. For most variables, there was a close correspondence between the prevalence ratios for HIV-1 and for HSV-2, except that prevalence ratios for HIV-1 tended to be greater than the corresponding ratios for HSV-2. The seroprevalence of both viruses was strongly related to early and frequent contact with female sex workers (FSWs), infrequent use of condoms with FSWs, and residence in the upper north region of Thailand. When differences in sexual behavior between the upper north and lower north were controlled for, the seroprevalence of both viruses still differed significantly by region. CONCLUSIONS: Although the seroprevalence levels of HSV-2 and HIV-1 were quite different in this cohort of Thai army conscripts in 1991, the patterns of infection in terms of demographic, residential, and behavioral variables were similar. Seroprevalence studies of HSV 2 in other populations, particularly where the HIV-1 epidemic is just beginning, may be useful in predicting which subgroups might be most vulnerable to the epidemic and could therefore benefit the most from public health intervention. Where differences in the patterns of the two viruses have been noted, we hypothesize that the pattern for HIV-1 will evolve toward that seen for HSV-2. PMID- 10029979 TI - The geography of sexual partnerships in Baltimore: applications of core theory dynamics using a geographic information system. AB - OBJECTIVE: Gonorrhea has a focused geographic distribution characterized by high incidence rates in defined "core" areas and decreased incidence as the radial distance from the central core increases. Dense cor group transmission has long been hypothesized. METHODS: We have previously mapped sexually transmitted disease (STD) rates in Baltimore census tracts using STD morbidity data interfaced with a geographic information system. Core areas were defined using a standard definition based on gonorrhea distribution. We studied spatial distance patterns between sexual partners, using the residential addresses of 572 individuals, representing 286 dyad partnerships recruited as part of an epidemiology and behavioral study. To determine if partners lived closer together than would be expected, a modified bootstrap algorithm using Monte Carlo models was developed to compare the distances between partners' residences and all other possible residences. RESULTS: Two distinct (east and west) core areas were previously identified. Compared with randomly selected Baltimore addresses, partners tended to reside closer to one another than would be expected by chance (z = -1.8), with a median distance of 1.7 kilometers. Within the core areas, women resided a median of 547 meters from their partner, and men resided a median of 339 meters from their reported partners. When all partnerships were considered, the median distance was 1,699 meters. Of the 500 simulation models, the minimum median distance was 4,889 meters. CONCLUSIONS: Partners of patients in core areas in Baltimore live remarkably close to one another, and the partner selection patterns in general indicate nonrandom distribution. Geographic information system-determined patterns of STD patients residing in hyperendemic census tracts support the core theory of disease transmission. In these areas, targeted geographically based interventions may be warranted. PMID- 10029980 TI - Cocaine use and high-risk sexual behavior among STD clinic patients. AB - BACKGROUND AND OBJECTIVES: Crack-smoking sexually transmitted disease (STD) patients are at high-risk for contracting HIV. GOAL OF THE STUDY: To examine the effects of cocaine use and other correlates on high-risk sexual behavior among STD clinic patients. STUDY DESIGN: This was a cross-sectional study of 1,490 consecutive patients attending three Los Angeles County STD clinics between 1992 and 1994. RESULTS: Logistic regression analysis found high-risk sexual activity was associated with being a male and being of younger age. Among women, high-risk sexual behavior was associated with crack cocaine use and a perceived need for help. Among the men in the study, ethnicity (being black) and having an arrest history were associated with high-risk behavior. CONCLUSIONS: Effective intervention strategies should address cocaine use among STD patients and provide them with referrals to drug treatment. PMID- 10029981 TI - Under the influence: risky sexual behavior and substance abuse among driving under the influence offenders. AB - BACKGROUND AND OBJECTIVES: The purpose of this study was to examine the associations between alcohol and drug abuse and risky sexual practice in a sample of 366 driving under the influence (DUI) offenders. STUDY DESIGN: Data were collected from a sample of participants at a university-operated drunk driving intervention program. Specific indicators included established or severe alcohol/drug use problems, multiple drugs used, multiple alcohol/drug related arrests, and early regular alcohol use. Multiple sexual partners, condom use, and having sex while under the influence of alcohol or drugs were used to measure risky sexual behavior patterns. Correlation and logistic regression analyses examined associations between these substance abuse and sexual risk taking measures. RESULTS: Substance abuse in general was unrelated to risky sexual behavior such as multiple sexual partners or lack of condom use. However, having sex while high from alcohol or drugs was significantly associated with substance abuse. Moreover, having sex while high was significantly related to both risky sex and a history of sexually transmitted disease. CONCLUSIONS: Having sex while high may be an important behavior to address to prevent STDs in the DUI population. Assessing relationships between substance abuse and risky sexual behavior poses a challenge to researchers because any estimates about this association may be dependent on the measure of sexual behavior that is used. An integrated intervention approach that addresses both substance abuse prevention and safe sexual practice appears crucial and effective for educating "risk takers" such as DUI offenders. However, these data caution that for those who are dependent upon alcohol and/or other drugs, education solely emphasizing risk reduction procedures is likely to be inefficient until their chemical dependency is addressed. PMID- 10029982 TI - Of vice and men: reflections on drug abuse and male prostitution. PMID- 10029983 TI - The hustler's choice. PMID- 10029984 TI - Race/ethnicity, vaginal flora patterns, and pH during pregnancy. AB - OBJECTIVES: To investigate the relationship between bacterial vaginosis during pregnancy and black race/ethnicity. STUDY DESIGN: Gram staining was used to evaluate vaginal flora in 842 women at 24 to 29 weeks' gestation. RESULTS: Overall, 22.3% of blacks and 8.5% of whites had bacterial vaginosis. Vaginal pH and flora differed significantly by race/ethnicity; blacks were more likely to have pH > or = 4.5, no lactobacilli, small gram-variable and -negative rods, and Mobiluncus compared with whites (odds ratios 1.6, 1.5, 1.4, and 10.6, respectively). Quantity of morphotypes also differed, especially for Mobiluncus. Among women with Mobiluncus present (12.0% of blacks and 1.3% of whites), 73.3% of blacks compared with 40.0% of whites had the highest level. Adjustment for sociodemographics, sexual activity, sexually transmitted diseases, health behavior, and sexual hygiene did not explain these differences. CONCLUSION: We observed race/ethnicity differences in vaginal flora ecology. These differences may ultimately play a role in the larger proportion of preterm deliveries among black women compared with white women. PMID- 10029986 TI - Networks of persons with syphilis and at risk for syphilis in Louisiana: evidence of core transmitters. AB - BACKGROUND AND OBJECTIVES: Differences in sociodemographic attributes and healthcare access may explain differences in regional sexually transmitted disease rates but don't fully explain why syphilis persists disproportionately in certain populations. GOAL OF THIS STUDY: To understand the behavioral epidemiology of syphilis, we conducted a social network analysis of persons with syphilis and their contacts and developed and applied a definition of core transmitters. STUDY DESIGN: We interviewed 10 index persons with primary or secondary untreated syphilis and 80 of their named sexual and social contacts. RESULTS: Fourteen (16%) of 90 interviewed persons met the definition of core transmitters, 9 of whom had past or current syphilis. The other interviewed persons had only moderately risky behaviors. Seventy-eight (42%) of the network sexual contacts were connected directly or indirectly to a core transmitter. CONCLUSION: This analysis suggests that syphilis transmission is maintained by a community with a small percentage of high-risk persons centrally placed amidst a larger group with moderately risky behavior. PMID- 10029985 TI - Prevalence of gonococcal and chlamydial infections in commercial sex workers in a Peruvian Amazon city. AB - BACKGROUND: Iquitos Peru, a densely populated port city housing both a large military base and a booming tourist industry, provides a thriving market for commercial sex and, consequently, sexually transmitted disease (STD). The purpose of this study was to characterize the prevalence of gonococcal and chlamydial infections among commercial sex workers (CSWs) and to correlate those findings with social/behavioral characteristics. METHODS: One hundred CSWs, recruited through street and brothel outreach, were administered questionnaires. Urine specimens were collected for gonorrhea and chlamydia testing using ligase chain reaction assays. RESULTS: Twenty-eight percent of CSWs were positive for chlamydia (22%) or gonorrhea (14%). Registered CSWs were more likely to have worked more than 5 years (p = 0.03), report 10 or more partners (p = 0.002), and work in brothels (p < 0.001). Significant associations were also noted between infection status and age, with adolescents at increased risk (odds ratio [OR] = 4.13, p = 0.001), and duration of employment, with those employed less than 5 years at increased risk (OR = 3.72, p = 0.04). The latter association, however, was because of age. Also, most CSWs believed themselves to be at no/small risk or didn't know their risk of future gonococcal infection (30%/12% and 25%, respectively) and AIDS (25%/8% and 35%, respectively), with 11% perceiving AIDS as more of a threat. CONCLUSIONS: High infection rates, lack of knowledge regarding STD/HIV risk assessment, and other high-risk behavior prevalent among this population stress the need for STD intervention. The study further suggests that educational/risk assessment programs and risk reduction interventions could be successful. PMID- 10029987 TI - Sexual practices and prevalence of HIV, HTLV-I/II, and Treponema pallidum among clandestine female sex workers in Lima, Peru. AB - BACKGROUND AND OBJECTIVES: A survey was conducted to determine the sexual behavior practices and prevalence of HIV-1, HTLV-I/II, and T. pallidum infections among unlicensed female sex workers (FSWs) in Lima, Peru. GOAL OF THIS STUDY: To assess the role of unlicensed FSWs as a potential source of retroviral and T. pallidum infection. STUDY DESIGN: Female sex workers from 15 brothels were enrolled. Sera samples were obtained and tested for antibodies to HIV-1, HTLV-I, and Treponema pallidum. RESULTS: Of 158 FSWs studied, all were negative for HIV 1, 6 were positive for HTLV-I, and 5 were positive for Treponema pallidum. Of their male clients, 75% used condoms, whereas only 3% reported condom use with their steady partners. When condoms were always used by clients, the history of a sexually transmitted disease was significantly reduced (p < 0.01), and the prevalence of HTLV-I (p < 0.05) and syphilis was lower among these workers. CONCLUSION: Data suggested that the low rate of sexually transmitted diseases among FSWs reflected the high rate of condom use by their male clients. PMID- 10029988 TI - Cloning and characterization of 1,3-beta-glucanase-encoding genes from non conventional yeasts. AB - The molecular cloning of 1,3-beta-glucanase-encoding genes from different yeast species was achieved by screening genomic libraries with DNA probes obtained by PCR-amplification using oligonucleotides designed according to conserved regions in the EXG1, EXG2 and SSG1 genes from Saccharomyces cerevisiae. The nucleotide sequence of the KlEXG1 (Kluyveromyces lactis), HpEXG1 (Hansenula polymorpha) and SoEXG1 (Schwanniomyces occidentalis) genes was determined. K1EXG1 consists of a 1287 bp open reading frame encoding a protein of 429 amino acids (49,815 Da). HpEXG1 specifies a 435-amino acid polypeptide (49,268 Da) which contains two potential N-glycosylation sites. SoEXG1 encodes a protein of 425 residues (49,132 Da) which contains one potential site for N-linked glycosylation. Expression in S. cerevisiae of KlEXG1, SoEXG1 or HpEXG1 under control of their native promoters resulted in the secretion of active 1,3-beta-glucanases. Disruption of KlEXG1 did not result in a phenotype under laboratory conditions. Comparison of the primary translation products encoded by KlEXG1, HpEXG1 and SoEXG1 with the previously characterized exo-1,3-beta-glucanases from S. cerevisiae and C. albicans reveals that enzymes with this type of specificity constitute a family of highly conserved proteins in yeasts. KlExg1p, HpExg1p and SoExg1p contain the invariant amino acid positions which have been shown to be important in the catalytic function of family 5 glycosyl hydrolases. PMID- 10029989 TI - Asymmetric distribution of phosphatidylethanolamine in C. albicans: possible mediation by CDR1, a multidrug transporter belonging to ATP binding cassette (ABC) superfamily. AB - By using two molecular probes, we demonstrate that only 4% of total phosphatidylethanolamine (PtdEtn) in the plasma membrane (PM) of a human pathogenic yeast, Candida albicans, is present in its external half. Evidence is presented to show that the availability of PtdEtn could be related to the expression of a multidrug transporter CDR1 of C. albicans, and the process is energy-dependent. A homozygous CDR1 disruptant strain of C. albicans shows almost 23% reduction in the external labelling of PtdEtn. This report shows that, similar to human MDRs, yeast multidrug transporter could also be involved in aminophospholipid translocation. PMID- 10029990 TI - Secretion of a protoxin post-translationally controlled by NaCl in a halotolerant yeast, Pichia farinosa. AB - The halotolerant yeast, Pichia farinosa KK1 secretes a killer toxin consisting of alpha (6.3 kDa) and beta (7.8 kDa) subunits, produced from a chromosomally encoded preprotoxin. In the presence of a high concentration of NaCl, a 26-kDa glycoprotein (gp26) that reacted with anti-beta-subunit antiserum was found to be secreted into the medium. Amino acid sequence analysis confirmed that gp26 is a protoxin generated by removal of the signal peptide from the preprotoxin. The purified gp26 did not have killer activity, suggesting that further processing is necessary for acquisition of this activity. Secretion of gp26 increased with increasing concentrations of NaCl in the medium and maximum secretion was observed at 2 M NaCl. Western blot analysis and RT-PCR showed that the secretion of gp26 is post-translationally controlled by NaCl. PMID- 10029991 TI - A PDR5-independent pathway of multi-drug resistance regulated by the SIN4 gene product. AB - The SIN4 locus encodes a global transcriptional regulator of various yeast genes. In this report, we demonstrate that loss of function mutations in SIN4 create a multi-drug hypersensitive phenotype that is independent of PDR5 mediated resistance. Thus, double sin4, pdr5 mutants are more sensitive than single mutants. Furthermore, SIN4 does not regulate the PDR5 locus. These observations establish that yeast cells have two genetically distinct pathways conferring resistance towards similar substrates. PMID- 10029992 TI - Over-expression of Candida albicans mitochondrial ribosomal protein S9 (MrpS9p) disturbs mitochondrial function in Saccharomyces cerevisiae. AB - A Candida albicans mitochondrial ribosomal protein S9 (MRPS9) cDNA was identified in a screen for sequences whose expression induce galactose lethality in Saccharomyces cerevisiae. MRPS9 appears to encode a protein of 346 amino acids with an N-terminal mitochondrial targeting sequence and an internal S9 signature that is conserved amongst eukaryotic mitochondrial and prokaryotic ribosomal protein S9 sequences. Expression of a GAL1-CaMRPS9 fusion in S. cerevisiae caused the slow development of a galactose-negative phenotype upon repeated subculturing, and this correlated with an increased frequency of petite mutant formation. Therefore, over-expression of CaMRPS9 interferes with S. cerevisiae mitochondrial function, which accounts for the inhibition of growth on galactose. PMID- 10029993 TI - Disruption of six novel Saccharomyces cerevisiae genes reveals that YGL129c is necessary for growth in non-fermentable carbon sources, YGL128c for growth at low or high temperatures and YGL125w is implicated in the biosynthesis of methionine. AB - Six open reading frames (ORFs) from chromosome, VII, YGL131c, YGL129c, YGL128c, YGL125w, YGL124c and YGL121c, were disrupted by deletion cassettes with short flanking regions homologous to the target locus (SFH). YGL129c is necessary for growth in non-fermentable carbon sources, YGL128c for growth at low or high temperatures and YGL125w is implicated in the biosynthesis of methionine. With regard to the other ORFs, basic phenotypic analyses did not reveal any significant clues about their function. PMID- 10029994 TI - Disruption of six unknown open reading frames from Saccharomyces cerevisiae reveals two genes involved in vacuolar morphogenesis and one gene required for sporulation. AB - In this report we describe the construction and basic phenotypic analysis of deletion mutants in six open reading frames (ORFs) of unknown function from the yeast Saccharomyces cerevisiae. Using the dominant kanMX marker and polymerase chain reaction (PCR) methods, deletion cassettes were constructed for five ORFs (YNL099c, YNL100w, YNL101w, YNL106c and YNL242w) located on chromosome XIV and one ORF (YOR109w) located on chromosome XV. The recovery of viable haploid deletant strains among the meiotic products of heterozygous deletants for each ORF demonstrated that none of the analysed ORFs was essential. With the exception of YNL242w, no alterations in growth characteristics or mating and sporulation efficiencies associated with deletion of the ORFs were observed. Homozygous diploid ynl242w delta cells obtained in three different genetic backgrounds were unable to sporulate, indicating that the product of this ORF is required for sporulation. Complementation of the sporulation defect by the cognate gene clone confirmed this observation. YNL106c and YOR109w are very similar and show strong sequence homology with a mammalian phosphatidylinositol-phosphate 5-phosphatase, synaptojanin, known to be involved in synaptic vesicle cycling. Strains bearing single and double deletions of YNL106c and YOR109w were seen to display abnormal vacuolar morphologies of varying degrees. Complementation tests indicated that YNL106c and YOR109w are redundant genes. PMID- 10029996 TI - Current awareness on yeast. PMID- 10029997 TI - Biofilms, infectious agents, and dental unit waterlines: a review. AB - Aquatic biofilms, which are widespread not only in nature but also in medical and dental devices, can be the source of serious nosocomial infections. In these hardy microbial communities, pathogens like nontuberculous mycobacteria, Pseudomonas aeruginosa, Legionella pneumophila, and other bacteria not only survive but proliferate and lie in wait for susceptible hosts. Not only are these organisms intrinsically resistant to high temperatures and biocides, but the biofilms they inhabit enhance their resistance. This should be of concern to infection control practitioners. The bacterial colonization of dental unit waterlines can be used as a model to investigate the problem of waterborne biofilms in health care settings. PMID- 10029995 TI - Disruption and basic phenotypic analysis of 18 novel genes from the yeast Saccharomyces cerevisiae. AB - In the frame of the European Network for Functional Analysis (EUROFAN) we have deleted 18 yeast open reading frames (ORFs) from chromosomes II, X and XIV using the short flanking homology-PCR strategy. Two diploid strains were used: FY1679 and CEN.PK2. The deletion kanMX6 cassettes with long flanking homology and the cognate gene clones have also been constructed. Heterozygous diploid deletant strains have been sporulated. Tetrad analysis revealed that all the ORFs studied were non-essential. However, four deletant strains exhibited phenotypes. The YBL025w delta strain showed extremely slow cellular growth under all conditions tested. The YJL204c delta strain grew slower than wild-type at 30 degrees C and 37 degrees C, was cold-sensitive, and the homozygous diploids did not sporulate. The YNL213c delta strain did not grow on glycerol and had lost mitochondrial DNA. The deletion of YNL215w caused slower growth on all media but the defect was more pronounced on glucose-minimal and glycerol-rich media than on glucose-rich medium. All deletion mutants were complemented by the corresponding plasmid borne cognate gene. The YJL204w, YNL213c and YNL215w ORFs do not bear significant homology to proteins of known function. YBL025w has recently been identified as RRN10, a gene that encodes an RNA polymerase I-specific transcription initiator factor. The deletion of the remaining fourteen ORFs did not reveal any mutant phenotype in our basic growth tests. PMID- 10029998 TI - The antimutagenic properties of a polysaccharide produced by Bifidobacterium longum and its cultured milk against some heterocyclic amines. AB - The antimutagenicity and fermentation pattern of three Bifidobacterium longum strains (B. longum, B. longum PS+, and B. longum PS-) in skim milk were studied. The increase in fermentation time significantly increased antimutagenicity with all strains tested against the mutagenicity of both 3-amino-1,4-dimethyl-5H pyrido-[4,3-b]indole (Trp-P-1) and 3-amino-1-methyl-5H-pyrido[4,3-b]indole (Trp-P 2) in an Ames-like test using streptomycin-dependent strain SD510 of Salmonella typhimurium TA98. Bifidobacterium longum PS+, a polysaccharide-producing strain, had a longer lag phase but showed the highest inhibition percentage against both mutagens tested. The viability of B. longum PS+ cells was not affected by the low pH of 4.1, probably owing to the protection offered by the polysaccharide produced. The antimutagenicity of the fermented milk against Trp-P-1 was dose dependent. The strains were also able to bind with different amino acid pyrolysates, and B. longum showed the highest binding. Acetone extracts of fermented skim milk dissolved in water showed less antimutagenicity than extracts dissolved in dimethylsulfoxide. The isolated crude polysaccharide from B. longum PS+ showed a dose-dependent inhibition of the mutagenicity of Trp-P-1. Thus, we conclude that the polysaccharide of B. longum PS+ can be used as an antimutagen. PMID- 10029999 TI - Saccharomyces paradoxus and Saccharomyces cerevisiae are associated with exudates of North American oaks. AB - Genetic hybridization and karyotypic analyses revealed the biological species Saccharomyces paradoxus and Saccharomyces cerevisiae in exudates from North American oaks for the first time. In addition, two strains collected from elm flux and from Drosophila by Phaff in 1961 and 1952 were reidentified as S. paradoxus. Each strain studied showed a unique profile of chromosomal hybridization with a probe for the retrotransposable element Ty1. The wild distribution of natural Saccharomyces sensu stricto yeasts is discussed. PMID- 10030000 TI - Use of yellow-pigmented enterococci as a specific indicator of human and nonhuman sources of faecal pollution. AB - Antibiotic susceptibility tests and restriction enzyme analysis (REA) of genomic DNA were performed to characterize the relationship between sources of isolates of yellow-pigmented enterococci. Antibiotic susceptibility tests were conducted with 10 therapeutic antibiotics and 54 isolates grouped by source (wild and other) depending on their origin. In three antibiotics, cephalothin, erythromycin, and vancomycin, there was a significant (p < or = 0.05) association between susceptibility and source. Vancomycin resistance was significantly (p < or = 0.001) higher in isolates from wild sources compared with that in isolates from other sources. The REA technique was performed on genomic DNA obtained from 17 Enterococcus mundtii isolates from: human (3), dog (4), horse (4), Canada goose (4), domestic goose (1), and Enterococcus mundtii ATCC 43186. A total of 12 different DNA types (A-L) were identified. Except for type D, 11 DNA types were unique and were distributed among dog (A, B, and C), human (E), horse (F, G, and H), Canada goose (I, J, and K), and domestic goose (L). Results suggested that vancomycin-susceptibility testing of yellow-pigmented enterococci may have potential value in the identification of sources of faecal pollution, especially when combined with traditional quantitative methods. PMID- 10030002 TI - Turning on and turning off the arginine deiminase system in oral streptococci. AB - The arginine deiminase system in oral streptococci is highly regulated. It requires induction and is repressed by catabolites such as glucose or by aeration. A comparative study of regulation of the system in Streptococcus gordonii ATCC 10558, Streptococcus rattus FA-1, and Streptococcus sanguis NCTC 10904 showed an increase in activity of the system in S. sanguis of some 1467 fold associated with induction-depression of cells previously uninduced repressed. The activity of the system was assayed in terms of levels of arginine deiminase, the signature enzyme of the system, in permeabilized cells. Increases in enzyme levels associated with induction-depression were less for the other two organisms, mainly because of less severe repression, especially for S. rattus FA 1, which was the least sensitive to catabolite repression or aeration. Regulation of the arginine deiminase system involving induction and catabolite repression was demonstrated also with monoorganism biofilms composed of cells of S. sanguis adherent to glass slides. Fully uninduced-repressed cells from suspension cultures or biofilms were compromised in their abilities to catabolize arginine to protect themselves against acid damage. However, it was found that the system can be rapidly turned on or turned off, although induction-depression did appear to require cell growth. Still, the system could respond rapidly to the availability of arginine to reestablish high capacity for alkali production. PMID- 10030003 TI - Naphthalene uptake by a Pseudomonas fluorescens isolate. AB - The uptake of naphthalene has been investigated in the metabolizing cells of Pseudomonas fluorescens utilizing [1-14C]naphthalene. The uptake displayed an affinity constant (Kt) of 11 microM and a maximal velocity (Vmax) of 17 nmol.h 1.mg-1 cellular dry weight. Naphthalene uptake was not observed in a mutant strain, TG-5, which was unable to utilize naphthalene as a sole source of carbon for growth. Uptake was significantly inhibited (approximately 90%) by the presence of growth-inhibiting levels of either azide or 2,4-dinitrophenol and was sensitive to the presence of structural analogues of naphthalene. The intracellular levels of ATP were not significantly reduced by the presence of either azide or 2,4-dinitrophenol. The presence of alpha-naphthol was found to noncompetitively inhibit naphthalene uptake, displaying a Ki of 0.041 microM. It is concluded that the first step in the utilization of naphthalene by Pseudomonas fluorescens is its transport into the cell by a specific energy-linked transport system. PMID- 10030004 TI - Random amplified polymorphic DNA analysis and demonstration of genetic variability among bifidobacteria isolated from rats fed with raw kidney beans. AB - A rise in bifidobacterial numbers resembling the Escherichia coli overgrowth phenomenon was observed in the rat small intestine in a feeding experiment with kidney beans. Bifidobacterial colony counts increased from 7.6 x 10(6) to 1.7 x 10(8) cfu.g-1 of intestinal tissue in the anterior part and from less than 1 x 10(5) to 2.65 x 10(8) cfu.g-1 in posterior part of the intestine. Fifteen bifidobacterial strains were purified and further analysed. Random amplified polymorphic DNA (RAPD) assays were used to genetically differentiate bifidobacterial isolates from rat gut and compare them with type strains of 20 different species from the genus Bifidobacterium. A total of 80 arbitrary decamere primers were screened with 6 isolates, and 7 primers were chosen for the final analysis. The amplified DNA bands were scored and analysed by the unweighted pair-group method using arithmetic averages clustering. The isolates were not identical to each other nor to the screened type strains. Whereas it was possible to group 12 of the isolates into 2 separate clusters, 3 strains showed no significant relatedness to any strain. The results of the RAPD analysis indicated that there was a large degree variability among the bifidobacteria in the rat gut and demonstrated the potential applicability of such an approach in the investigation of microbial diversity in complex ecosystems. PMID- 10030005 TI - Group-specific differentiation of Rhizobium from clover species by PCR amplification of 23S rDNA sequences. AB - Two 20-bp primers that provide group-specific detection of Rhizobium spp. by polymerase chain reaction (PCR) have been used to differentiate strains that belong to different effectiveness groups within the Rhizobium-Trifolium cross inoculation group. The target for DNA amplification was a 370-bp fragment of the 23S rDNA region. Analysis of additional root-nodule forming, as well as root associated bacterial species by PCR-primer assay revealed that variability within this 20-bp segment of the 23S rDNA region may be widespread and provide an effective identification tool. Our data suggest that strains of Rhizobium isolated from the perennial clover Trifolium semipilosum may be phylogenetically more closely related to Rhizobium etli. PMID- 10030006 TI - Isolation and characterization of an Escherichia coli B mutant strain defective in uracil catabolism. AB - A reductive pathway of uracil catabolism was shown to be functioning in Escherichia coli B ATCC 11303 by virtue of thin-layer chromatographic and enzyme analyses. A mutant defective in uracil catabolism was isolated from this strain and subsequently characterized. The three enzyme activities associated with the reductive pathway of pyrimidine catabolism were detectable in the wild-type E. coli B cells, while the mutant strain was found to be deficient for dihydropyrimidine dehydrogenase activity. The dehydrogenase was shown to utilize NADPH as its nicotinamide cofactor. Growth of ATCC 11303 cells on uracil or glutamic acid instead of ammonium sulfate as a nitrogen source increased the reductive pathway enzyme activities. The mutant strain exhibited increased catabolic enzyme activities after growth on ammonium sulfate or glutamic acid. PMID- 10030007 TI - Duplication of insertion element IS50 associated with Tn5 transposition in Azospirillum brasilense. AB - The characterization of a DNA fragment with a Tn5 insertion in a regulatory nif gene of Azospirillum brasilense is reported. Restriction endonuclease mapping, Southern hybridization with a Tn5 probe, and nucleotide sequencing revealed that IS50 had duplicated in Tn5. The duplication of an IS50 element suggests the occurrence of a replicative mechanism of transposition. A strategy, based on the bacterial ability of homologous recombination that was used to precisely eliminate Tn5 along with the duplicated IS50 element, is presented. PMID- 10030008 TI - Distributions of the vectors of heartwater, Amblyomma hebraeum and Amblyomma variegatum (Acari: Ixodidae), in Zimbabwe. AB - The tick vectors of heartwater (Cowdria ruminantium infection) in Zimbabwe, Amblyomma hebraeum and Amblyomma variegatum, historically were believed to be confined to the low-lying regions of the south and north-west of the country. However, country-wide surveys performed in 1975-1980 and 1988-1991 demonstrated that both species were also established in western parts of the highveld plateau and had started to encroach on the predominantly heartwater-free central and eastern highveld regions. To determine the current distributions of both the vectors and evaluate the potential threat of heartwater to animals in the highveld, a survey of ticks infesting cattle was performed in 1996 at 2994 locations in small-holder and large-scale commercial farming areas throughout Zimbabwe. Amblyomma hebraeum was collected at 1329 locations, A. variegatum at 72 locations and both A. hebraeum and A. variegatum at 13 locations. The results demonstrated that A. hebraeum was present, as previously recorded, throughout the southern half of the country and appeared to have undergone further limited spread into the central and eastern highveld regions. Only the northern-most region of the country appeared to be free of this species. Amblyomma variegatum was collected mainly in the north-west, as previously recorded, but was also found at isolated locations across the central highveld region and along the eastern border with Mozambique. This species was, however, still absent from the southern half and the northern-most regions of the country. An overlap of the distributions of the two species existed within a zone along the southern and eastern regions of the distribution of A. variegatum. These results suggest that the vectors of heartwater are spreading and threaten to introduce heartwater into intensive livestock-producing regions of the country. PMID- 10030009 TI - Antibiosis plays a role in the context of direct interaction during antagonism of Paenibacillus polymyxa towards Fusarium oxysporum. AB - Interaction of Fusarium oxysporum and Paenibacillus polymyxa starts with polar attachment of bacteria to the fungal hyphae followed by the formation of a large cluster of non-motile cells embedded in an extracellular matrix in which the bacteria develop endospores. Enumeration of fungal viable counts showed that less than one of 36,000 colony-forming units survived in paired cultures for 71 h. Effective antagonism was not observed below pH5 and was specific for the bacterial species. Development of F. oxysporum was inhibited in cell-free filtrates derived from cultures of P. polymyxa, but was much more strongly repressed in the presence of living bacteria. Furthermore, recovery of fungal growth started immediately after addition of antibiotics to paired cultures. Restoration of fungal growth was enhanced in filtrates that were supplemented with MgCl2, which suggests that anti-fungal compounds produced by the bacteria were counteracted by magnesium ions. In paired cultures, fungal counts remained very low, even in the presence of the magnesium salt. This study clearly showed that P. polymyxa antagonizes the plant pathogenic fungus F. oxysporum in liquid medium by means of an interaction process in which the presence of living bacteria is a prerequisite for continuous suppression of fungal growth. PMID- 10030010 TI - The effect of diet on aerobic bacterial flora associated with intestine of Arctic charr (Salvelinus alpinus L.). AB - In order to extend the knowledge on the possible effect of diet on the gastrointestinal microbial community of fish, Arctic charr (Salvelinus alpinus L.) were fed diets containing high (23.7%) and low (6.4%) levels of carbohydrate. The number of viable aerobic and facultative aerobic bacteria associated with the digestive tract were not influenced by dietary regimen. A wide range of bacterial species was isolated, and the predominant bacterial species of both rearing groups were identified as Staphylococcus. There were, however, some differences in bacterial composition between the rearing groups, as well as inter-individual variations. For example, atypical Aeromonas salmonicida were isolated from the small and large intestine of two fish fed low dietary carbohydrate, while Aer. caviae-like isolates were found in the small intestine of four fish fed high carbohydrate. Non-motile Aeromonas spp. were found in the rearing group fed high dietary carbohydrate, but at low frequencies. Dietary manipulation seemed to influence the species composition of carnobacteria, Gram-positive rods, oxidase and catalase-negative and fermentative metabolism. Carnobacterium piscicola-like bacteria were only found in the small intestine, while C. mobile-like and Carnobacterium spp. were isolated from the large intestine of fish fed high carbohydrate. On the contrary, C. divergens-like isolates were found associated with the small and large intestine of fish fed low dietary carbohydrate. PMID- 10030011 TI - Purification, amino acid sequence and mode of action of bifidocin B produced by Bifidobacterium bifidum NCFB 1454. AB - Bifidocin B produced by Bifidobacterium bifidum NCFB 1454 was purified to homogeneity by a rapid and simple three step purification procedure which included freeze drying, Micro-Cel adsorption/desorption and cation exchange chromatography. The purification resulted in 18% recovery and an approximately 1900-fold increase in the specific activity and purity of bifidocin B. Treatment with bifidocin B caused sensitive cells to lose high amounts of intracellular K+ ions and u.v.-absorbing materials, and to become more permeable to ONPG. Bifidocin B adsorbed to the Gram-positive bacteria but not the Gram-negative bacteria tested. Its adsorption was pH-dependent but not time-dependent. For sensitive cells, the adsorption and lethal action of bifidocin B was very rapid. In 5 min, 95% of bifidocin B adsorbed onto sensitive cells. Several salts inhibited the binding of bifidocin B, which could be overcome by increasing the amount of bifidocin B added. Pre-treatment of sensitive cells and cell walls with detergents, organic solvents or enzymes did not cause a reduction in subsequent cellular binding of bifidocin B, but cell wall preparations treated with methanol:chloroform and hot 20% (w/v) TCA lost the ability to adsorb bifidocin B. Also, the addition of purified heterologous lipoteichoic acid to sensitive cells completely blocked the adsorption of bifidocin B. The amino acid sequence indicated that the bacteriocin contained 36 residues. N-terminal amino acid sequence analysis yielded a sequence of KYYGNGVTCGLHDCRVDRGKATCGIINNGGMWGDIG. Curing experiments with 20 micrograms ml-1 acriflavine yielded cell derivatives that no longer produced bifidocin B but retained immunity to bifidocin B. Production of bifidocin B, but not immunity to bifidocin B, was associated with a plasmid of about 8 kb in this strain. PMID- 10030012 TI - Campylobacter infections in fattening pigs; excretion pattern and genetic diversity. AB - The excretion of campylobacter by eight individually housed fattening pigs was monitored during 15 weeks. Rectal faeces samples were collected six times from these pigs and twice from their mothers (seven sows). Campylobacter was cultured from these samples on Preston medium. In some pigs, samples positive for campylobacter alternated with negative samples. Campylobacter was detected in at least four of the six samples collected per fattening pig. The average campylobacter count per sampling showed a decreasing trend (P < 0.001). Of the seven sows, six were shown to excrete campylobacter. Campylobacter isolates of pigs and sows were typed using the Enterobacterial Repetitive Intergenic Consensus Polymerase Chain Reaction (ERIC-PCR); 28 different campylobacter types were distinguished. Up to five different types were isolated from single faeces samples. Individual porkers could harbour up to eight types during their fattening period. The three types most frequently isolated from the fattening pigs were also present in the sows. PMID- 10030013 TI - Saccharomyces cerevisiae viability is strongly dependant on rehydration kinetics and the temperature of dried cells. AB - The effects of rehydration kinetics and temperature on the viability of Saccharomyces cerevisiae dehydrated by drying were studied. During rehydration, a water activity range of 0.117-0.455 must be crossed slowly in order to maintain cell viability. If this range is crossed rapidly, cell viability can be preserved if rehydration takes place at 50 degrees C. Several hypotheses have been proposed to explain previous results. One hypothesis, which relates cell mortality after rapid rehydration to water flow through the membrane in phase transition, is the more plausible and requires further investigation. PMID- 10030014 TI - Amylase and 16S rRNA genes from a hyperthermophilic archaebacterium. AB - A hyperthermophilic and amylolytic prokaryote, designated Rt3, was isolated from a thermal spring near Rotorua, New Zealand. The 16S rRNA gene of Rt3 was cloned and sequenced with the aim of determining its phylogenetic affiliations. The phylogenetic analysis of this sequence, which included a selection of archaebacterial and eubacterial 16S rRNA sequences, indicates that Rt3 most likely belongs to the archaebacterial order Thermococcales. An amylase gene (amyA) from Rt3, encoding a highly thermostable amylase activity, was cloned and its DNA sequence determined. Transcriptional signals typical of archaebacteria were evident in this sequence. The sequence is homologous to a broad range of enzymes from the AMY superfamily and contains a typical N-terminal signal peptide. Phylogenetic analysis and comparison of structural features with other AMY superfamily enzymes reveals that, firstly, the closest homologues of the Rt3 amylase are members of the Bacillus and Plant alpha-amylase groups; and secondly, that the Rt3 amylase is closely related to only one other currently known archaebacterial enzyme, i.e. an (AMY superfamily) alpha-amylase from Natronococcus. PMID- 10030015 TI - Influence of oxygen availability on physiology, verocytotoxin expression and adherence of Escherichia coli O157. AB - A strain of Escherichia coli serotype O157 was grown in steady state chemostat culture under aerobic, oxygen-limited and anaerobic conditions. The growth and metabolic efficiency of oxygen-limited and anaerobic cultures was impaired, with biomass yield and the molar growth yield for glucose, Yglucose, reduced markedly in comparison with aerobic cultures. Steady state cells were typically short rods 2-3 microns long, and were encapsulated by a layer of extracellular material. The majority of cells were non-flagellated and fimbriae were not observed. Chemostat grown cells were significantly more adhesive for HEp-2 monolayers than cells grown in aerobic batch culture. Furthermore, oxygen-limited and anaerobic cultures were significantly more adhesive for Hep-2 cells when compared with cells grown in aerobic chemostat culture, possibly reflecting increased pathogenicity associated with the induction of novel adhesins. Type 1 pili were not responsible for increased adherence. Verocytotoxins, VT1 and VT2, were expressed constitutively and were not influenced by oxygen availability. This study demonstrates that E. coli O157 is a versatile micro-organism, which responds to environmental conditions likely to be encountered during infection by inducing a phenotype which is more adhesive for human epithelial cells. PMID- 10030016 TI - Low incidence of Vibrio vulnificus among Vibrio isolates from sea water and shellfish of the western Mediterranean coast. AB - A specific search for Vibrio vulnificus in natural marine samples from the Spanish Mediterranean Sea was carried out by nested PCR and cultural approaches using thiosulphate-citrate-bile salts-sucrose agar (TCBS) and cellobiose polymixin B-colistin agar (CPC), incubated at 40 degrees C, as selective media. Presumptive colonies were identified by PCR using specific primers against 23S rRNA sequences. This species was isolated from sea water and edible bivalves, mainly after preenrichment in alkaline peptone water (APW) at 40 degrees C followed by CPC agar. None of the V. vulnificus isolates identified corresponded to serovar E. Dominant Vibrio species on directly inoculated TCBS plates incubated at 25 degrees C were V. splendidus below 20 degrees C and V. harveyi and V. mediterranei above that temperature. Low percentages of several pathogenic vibrios were recorded but V. vulnificus was never recovered at this incubation temperature. The incidence of this species in the samples studied was lower than that described for other geographical areas, probably due to the high salinity values of the Mediterranean Sea. PMID- 10030017 TI - Influence of lactoferrin feeding and injection against systemic staphylococcal infections in mice. AB - Human and bovine lactoferrins (Lfs) and bovine lactoferrin hydrolysate (LH) were assessed in vitro and in vivo for their antibacterial effects on Staphylococcus aureus. Lactoferrins showed weak in vitro antibacterial activity while Fe saturated Lfs and LH showed no activity. Lactoferrin-treated mice (1 mg, i.v.) when injected i.v. with 10(6) staphylococci, showed 30-50% reduction in kidney infections, and viable bacterial counts in the kidneys decreased 5-12-fold. The inhibitory effect was dose-dependent up to 1 mg Lf. Lactoferrins were effective when given 1 day prior to the bacterial challenge, after which there was no significant effect even at doses up to 5 mg. Apo- and Fe-saturated forms of human and bovine Lfs were all equally effective, while LH was not protective. Human and bovine Lfs with different degrees of iron saturation (9-97%) were found to be equipotent. Feeding mice with 2% bLf in drinking water also reduced the kidney infections by 40-60%, and viable bacterial counts, 5-12-fold. The results suggest a potential for the use of Lfs as natural antibacterial proteins for preventing bacterial infections. PMID- 10030018 TI - Weak-acid preservatives: modelling microbial inhibition and response. AB - Weak-acid preservatives are widely used to prevent microbial spoilage of acidic foods and beverages. Characteristically, weak-acid preservatives do not kill micro-organisms but inhibit growth, causing very extended lag phases. Preservatives are more effective at low pH values where solutions contain increased concentrations of undissociated acids. Inhibition by weak-acids involves rapid diffusion of undissociated molecules through the plasma membrane; dissociation of these molecules within cells liberates protons, thus acidifying the cytoplasm and preventing growth. By modelling preservative action in yeast, using a thermodynamic and kinetic approach, it was possible to demonstrate that: (i) inhibition depends more on the degree to which individual preservatives are concentrated within cells, rather than on undissociated acid concentration per se; (ii) it is entirely feasible for microbes to pump protons out of the cell during extended lag phase and raise internal pH (pHi), despite further influx of preservatives; (iii) the duration of the lag phase can be predicted from the model, using a Gaussian fit of proton-pumping H(+)-ATPase activity against pHi; (iv) theoretical ATP consumption for proton pumping can be directly correlated with the reduction in cell yield observed in glucose-limited cultures. PMID- 10030019 TI - Note: susceptibility to chlorine of Aeromonas hydrophila strains. AB - The susceptibility of five Aeromonas hydrophila strains and one Escherichia coli strain to chlorine was studied under carefully controlled laboratory conditions. Of the Aer. hydrophila strains, two were from untreated water, two from tap water (immediately downstream of a water treatment plant) and one from the DSM collection. The study included disinfectant concentration (0.1, 0.2 and 0.5 mg l 1), pH (6, 7 and 8) and temperature (4, 21 and 32 degrees C) as controlled variables. The results indicated that the untreated water strains, the DSM strain and the E. coli strain were inactivated within 1 min of chlorine treatment. The strains from chlorinated water (TW11 and TW27) showed a different susceptibility to chlorine disinfection, the rate of inactivation being greater at pH6 than at pH8 for both strains. Under the standard conditions of temperature 21 degrees C, pH7 and chlorine concentration 0.2 mg l-1, an increase or decrease of approximately 1 log unit in the number of bacteria did not affect the kill rate of the strains TW11 and TW27. PMID- 10030020 TI - Personality traits in late adolescence predict mental disorders in early adulthood: a prospective-epidemiological study. AB - Prospective relations between personality traits and mental disorders were assessed in a longitudinal study of a representative birth cohort of young men and women from Dunedin, New Zealand. Personality traits were assessed via self report questionnaire at age 18, and mental disorders were assessed via diagnostic interview at both ages 18 and 21. High "negative emotionality" (a propensity to experience aversive affective states) at age 18 was linked with affective, anxiety, substance dependence, and antisocial personality disorders at age 21 when corresponding mental disorders at age 18 were controlled. Low "constraint" (difficulty inhibiting the expression of affect and impulse) at age 18 was linked with substance dependence and antisocial personality disorders at age 21 when corresponding mental disorders at age 18 were controlled. The findings are discussed in terms of their implications for the development and treatment of mental disorders in young adulthood. PMID- 10030021 TI - Cardiovascular reactivity and neuroticism: results from a laboratory and controlled ambulatory stress protocol. AB - A laboratory and controlled ambulatory protocol was used to study whether there are differences in the cardiovascular reactivity of persons varying in neuroticism, the disposition to experience negative subjective emotions. Thirty six individuals (19 men, 17 women) who scored approximately 1 standard deviation above or below the mean on the NEO PI-R Neuroticism scale (Costa & McCrae, 1992) were recruited from a larger pool of undergraduate students. Participants, who had been outfitted with an ambulatory blood pressure/heart rate monitor, were exposed to 5 laboratory stressors and 7 field stressors during a 6-hour protocol. Results indicated that individuals scoring high in neuroticism showed blood pressure reactivity to laboratory and field stressors that was comparable to that of persons low in neuroticism. Aggregrating responses across stressors, there was evidence of exaggerated heart rate responses. The results suggested that, although neuroticism is related to high levels of negative subjective experience, differences between persons scoring high versus low in neuroticism were not exhibited strongly at the cardiovascular level. The implications for stress, coping, and disease are discussed. PMID- 10030022 TI - Genetic and environmental influences on individual differences in masculinity, femininity, and gender diagnosticity: analyzing data from a classic twin study. AB - Analyzing data from Loehlin and Nichols's (1976) classic twin study, we computed measures of Masculine Instrumentality (M), Feminine Expressiveness (F), and Gender Diagnosticity (GD). Quantitative genetic modeling analyses of within-sex individual differences in M, F, and GD indicated that: (1) Additive genetic factors contribute significantly to individual differences in M, F, and GD. (2) The environmental effects on M, F, and GD tend to be nonshared. (3) The genetic and environmental components of individual differences in M, F, and GD tend not to show gender differences. Finally, (4) the estimated within-sex heritability of GD (.53) is significantly greater than the estimated within-sex heritabilities of either M (.36) or F (.38). PMID- 10030023 TI - Individual differences in reactivity to daily events: examining the roles of stability and level of self-esteem. AB - Unstable self-esteem is thought to reflect fragile and vulnerable feelings of self-worth that are affected by specific positive and negative events. Direct evidence for this contention is lacking, however. To redress this situation, we examined the extent to which level and stability of self-esteem predicted the impact that everyday positive and negative events had on individuals' feelings about themselves. Participants recorded the most positive and most negative event that occurred each day Monday through Thursday for a period of 2 weeks. They then indicated the extent to which each event made them feel better or worse about themselves. As anticipated, negative and positive events had a greater impact on the self-feelings of individuals with unstable as opposed to stable self-esteem (although the effect for positive events was marginal). Additional findings indicated that event qualities (i.e., self-esteem relevance and concerns about social acceptance/rejection) could account for the unstable self-esteem/greater reactivity link for negative events, but not for positive events. Negative, but not positive, events had a greater impact on the self-feelings of individuals with low as compared to high levels of self-esteem. Theoretical implications are discussed. PMID- 10030024 TI - An evaluation of the suitability of the European suspension test to reflect in vitro activity of antiseptics against clinically significant organisms. AB - The effectiveness of four antiseptics representing soluble phenolics (Dettol), Quaternary Ammonium Compounds (QAC) (Dettol Hospital Concentrate: DHC), mixed QAC/chlorhexidine (Hibicet Hospital Concentrate: HHC) and povidone iodine (Betadine) was assessed using the proposed phase 2 step 1 European Suspension test. The in vitro activity of the antiseptics against two of the proposed challenge strains, i.e. Staphylococcus aureus and Pseudomonas aeruginosa, was compared with that of 14 problematic clinical isolates of bacteria from a range of genera, including some multiple antibiotic resistant strains, and a clinical isolate of Candida albicans. In addition to the 5 min contact time recommended in the European test, a 1 min time was included. All four products, at their recommended use dilutions and a contact time of 5 min, achieved a Microbicidal Effect (ME) log reduction of at least 5 against the majority of organisms. Differences in activity between products were more pronounced and therefore the tests more discriminatory, when the contact time was reduced to 1 min. The clinical strains were not overtly more resistant to antiseptics than the standard test strains, suggesting that the CEN test strains mimic the antiseptic susceptibility of clinical isolates. PMID- 10030025 TI - Effect of permeabilizers on antibiotic sensitivity of Pseudomonas aeruginosa. AB - Agents which had previously been shown to act as permeabilizers against Pseudomonas aeruginosa or other Gram-negative bacteria were tested to determine whether susceptibility to various antibiotics could be increased. In the absence of a permeabilizer, Ps. aeruginosa was resistant to several hydrophobic antibiotics and vancomycin, but not to gentamicin. Tartaric and gluconic acids had weak potentiating activity, whereas ethylenediamine tetraacetic acid and citric acid were more effective permeabilizers. However, sodium polyphosphate enhanced the activity of erythromycin, fucidin, novobiocin, rifampicin and methicillin; vancomycin was unaffected and the activity of gentamicin was reduced considerably. PMID- 10030026 TI - Spacer 2 region and 5S rDNA variation of Wolbachia strains involved in cytoplasmic incompatibility or sex-ratio distortion in arthropods. AB - Bacteria in the genus Wolbachia are widespread in arthropods and can induce sex ratio distortion or cytoplasmic incompatibility in their hosts. The phylogeny of Wolbachia has been studied using 16S rDNA and the cell cycle gene ftsZ, but sequence variation of those genes is limited. The spacer 2 region (SR2) was amplified to determine whether this region would improve phylogenetic resolution. The SR2 of Wolbachia is 66 bp long, shows higher variation than ftsZ and has very low homology with closely related bacteria. Due to the small length of SR2 of Wolbachia, little phylogenetic information could be retrieved. PMID- 10030028 TI - Escherichia hermanii--a new bacterial strain for chlorobenzene degradation. AB - A new bacterial strain capable of chlorobenzene degradation has been isolated from sludge of an industrial wastewater treatment plant. The micro-organism is short, rod-shaped, Gram-negative, yellow-pigmented and has been identified as Escherichia hermanii. It was observed that high chlorobenzene concentrations (up to 394 mg l-1) had low toxic effects towards this strain, which was able to degrade chlorobenzene without any previous adaptation. PMID- 10030029 TI - Isolation of Arcobacter butzleri from ground water. AB - Arcobacter butzleri was isolated from a contaminated ground water source. These organisms, previously designated as aerotolerant Campylobacter, were capable of surviving in the ground water environment. Specific DNA probes were used to characterize the isolates in the initial identification and survival studies. Arcobacter butzleri was found to be sensitive to chlorine inactivation. PMID- 10030031 TI - Sub-lethal damage of Listeria monocytogenes after long-term chilled storage at 4 degrees C. AB - The possibility that long term in vitro chilled storage may result in sub-lethal damage to Listeria monocytogenes cells was investigated by comparing growth of chill-stored (starvation at 4 degrees C) and fresh cultures on selective and non selective media. Growth of freshly grown cells was minimally (3-8%) affected by selective LSAMM agar compared with non-selective Brain Heart Infusion agar. In contrast, numbers of chill-stored strains were reduced by greater than 99% after direct plating on the same selective and non-selective media. Furthermore, chill stored strains were able to grow in standard selective broth (Listeria Selective broth and Fraser broth) only if undiluted inocula (approximately 10(5)-10(6) cfu ml-1) were used, whereas they were capable of growth in Brain Heart Infusion broth even when the lowest dilutions were used (approximately 10(1) cfu ml-1). The potential public health consequences of this finding for the isolation of Listeria monocytogenes from foods is considered. PMID- 10030030 TI - The fate of Salmonella enteritidis PT4 in home-made mayonnaise prepared with citric acid. AB - The fate of Salmonella enteritidis PT4 in home-made mayonnaise prepared with citric acid solution (citric acid concentration of > or = 4.98% (w/v)) was investigated. It was found that pH of mayonnaise is closely related to the ratio of egg yolk to citric acid, and the inactivation rate of the micro-organisms increases as the ratio decreases and/or incubation temperature increases. To achieve Salm. enteritidis PT4-free home-made mayonnaise prepared with pure lemon juice (citric acid concentration > or = 5% (w/v)), it is recommended that the pH should be 3.30 or below, or, in practice, at least 20 ml pure lemon juice per fresh egg yolk should be used. For the use of 20-35 ml pure lemon juice per egg yolk, the product should be held at 22 degrees C or over for at least 72 h and for the use of over 35 ml pure lemon juice per egg yolk, for at least 48 h before consumption or refrigeration. PMID- 10030032 TI - PCR for the detection of Campylobacter spp. in clinical specimens. AB - The suitability of PCR (based on the amplification of the 16S rRNA gene) for use as a diagnostic test for the detection of Campylobacter spp. in human faecal specimens was assessed. A total of 493 faecal specimens from patients with symptoms of enteritis were tested for the presence of campylobacters using PCR. Results were compared with those obtained from the analyses of the same specimens by culture techniques, using chi 2 square with Fisher's exact test. PCR was found to detect significantly more positive specimens than culture (chi 2 = 200.086; P < 0.0001). The sensitivity and specificity of PCR when compared with the culture technique were found to be 91 and 97%, respectively. It is proposed that the PCR is a reliable and sensitive method which may be used as a routine diagnostic technique for the detection of campylobacters in clinical specimens. PMID- 10030033 TI - Isolation of endospore-forming bacilli toxic to Culiseta longiareolata (Diptera: Culicidae) in Jordan. AB - Ten of 80 endospore-forming bacilli, isolated from various habitats of Jordan, were found to be highly toxic to the 4th instar larvae of Culiseta longiareolata (Macquart). The bacilli were identified into the following species and strains: Bacillus sphaericus (H6), B. sphaericus (H9a, 9b), B. cereus Frankland and Frankland, B. brevis Migula and B. megaterium Bary. Bacillus cereus comprised 50% of the isolates. The toxic concentrations of these isolates against C. longiareolata ranged between 1.2 x 10(7) and 1.1 x 10(9) viable spores ml-1. PMID- 10030034 TI - The degradation of sodium O,O-diethyl dithiophosphate by bacteria from metalworking fluids. AB - The breakdown of sodium O,O-diethyl dithiophosphate (O,O-diethyl phosphorodithioate) by four bacterial strains (tentatively identified as strains of Aeromonas, Pseudomonas, Flavobacterium and Bacillus) isolated from contaminated metalworking fluids was shown to involve the successive formation of ethanol, aldehyde and orthophosphate. An acid phosphodiesterase was identified in cell-free extracts that was five- to sevenfold enhanced in specific activity in bacteria grown on O,O-diethyl dithiophosphate as sole phosphorus source, compared with bacteria grown on orthophosphate. This is thought to initiate the breakdown process. PMID- 10030035 TI - Evaluation of alkaline phosphatase- and digoxigenin-labelled probes for detection of the thermolabile hemolysin (tlh) gene of Vibrio parahaemolyticus. AB - The biochemical identification and enumeration of Vibrio parahaemolyticus as described in the FDA Bacteriological Analytical Manual is expensive and labour intensive. To reduce the time and effort necessary to verify the identity of V. parahaemolyticus, the use of a thermolabile haemolysin (tlh) gene probe is proposed. An alkaline phosphatase (AP)-labelled probe was evaluated for specificity against 26 strains of V. parahaemolyticus, 88 strains of other Vibrio species and 10 strains of non-vibrio species. Of the 124 isolates tested, the probe hybridized only with the 26 strains of V. parahaemolyticus, indicating species specificity. Two hundred and six suspect V. parahaemolyticus isolates from oysters were tested by this probe and API-20E diagnostic strips; there was 97% agreement between results. A digoxigenin (DIG)-labelled probe for detection of the tlh gene fragment was prepared by PCR and compared with the AP-labelled probe. When tested on 584 suspect V. parahaemolyticus isolates, results obtained with the AP- and DIG-labelled probes were in 98% agreement. These results suggest that the probes are equivalent for detection of the V. parahaemolyticus tlh gene. PMID- 10030036 TI - Resistance of heat-shocked cells of Listeria monocytogenes to mano-sonication and mano-thermo-sonication. AB - Heat shocks did not increase the resistance of Listeria monocytogenes to an ultrasonication treatment under pressure (Mano-Sonication; MS). While heat shocked cells (180 min, 45 degrees C) became sixfold more heat resistant than native cells (D62 = 1.8 min vs D62 = 0.24 min), the resistance of native and heat shocked cells to MS (200 kPa, 117 microns) was the same (DMS = 1.6 min). The inactivation rate of non-heat-shocked cells of L monocytogenes by a combined heat/ultrasonication treatment under pressure (Mano-Thermo-Sonication; MTS) was an additive effect. On the contrary, on heat-shocked cells, the inactivation rate of MTS was greater than that of heat added to the inactivation rate of MS (synergistic effect) in the range 62-68 degrees C. PMID- 10030037 TI - Survival and chromate reducing ability of Pseudomonas aeruginosa in industrial effluents. AB - The ability of a chromate-reducing Pseudomonas aeruginosa strain, isolated from tannery effluent, to survive and reduce chromate in the effluent of a tannery and an electroplating unit was evaluated. The test strain survived in the native tannery effluent but numbers fell sharply in the native electroplating effluent. Supplementation with a carbon (C), nitrogen (N) and phosphorus (P) source supported bacterial multiplication and chromate reduction in both types of effluents with almost equal efficiency. Chromate reduction, however, was not observed in the absence of C, N or P supplement, or in the chromate-reducing strain. PMID- 10030038 TI - Reducing bacterial resistance to antibiotics with ultrasound. AB - The effect of erythromycin on planktonic cultures of Psedomonas aeruginosa, with and without application of 70 kHz ultrasound, was studied. Ultrasound was applied at levels that had no inhibitory effect on cultures of Ps. aeruginosa. Ultrasound in combination with erythromycin reduced the viability of Ps. aeruginosa by 1-2 orders of magnitude compared with antibiotic alone, even at concentrations below the minimum inhibitory concentration (MIC). Electron-spin resonance studies suggest that ultrasound induces uptake of antibiotic by perturbing or stressing the membrane. This application of ultrasound may be useful for expanding the number of drugs available for treating localized infections by rendering bacteria susceptible to normally ineffective antibiotics. PMID- 10030039 TI - Fate of Escherichia coli O157:H7 in unpasteurized milk stored at 8 degrees C. AB - Escherichia coli O157:H7 and verocytotoxins were not found in any of 100 unpasteurized milk samples obtained from the bulk tanks of eight dairy farms located in the Puglia and Basilicata areas. Seven E. coli O157:H7 (EHEC) strains were inoculated separately into raw milk samples and then examined periodically to determine the fate of EHEC as influenced by the storage temperature (8 degrees C) and time. There was essentially no change in the viable population of three EHEC strains for up to 14 d. The remaining four strains showed an increase in population from < 2 log to 3 log cfu ml-1 in a time period of between 9 and 17 d. The results indicate good survival or even multiplication of E. coli O157:H7 in raw milk when stored at 8 degrees C and reaffirm the need for pasteurization and holding the milk at < or = 5 degrees C. PMID- 10030040 TI - [Genetic demographic study of Zulia State, Venezuela, by isonymy]. AB - The genetic structure of Zulia State, Venezuela, was studied through the distribution of surnames from individuals above 40 years of age, obtained from the register of electors. The sample studied consisted in 440, 190 individuals and 10,423 different surnames. For each of the 81 counties of the State, the following estimators were calculated: percentage of the population included in surnames which appear only once (estimator A), percentage of the population included in the seven most frequent surnames (estimator B), the coefficient of consanguinity due to random isonymy phi ii, and Karlin and McGregort's ni (v), an estimator of migration. The correlation between phi ii and B was 0.92, indicating that 85% of the variation observed in the coefficient of consanguinity due to random isonymy is due to the seven most frequent surnames. The correlation between A and ni was 0.93, so that 86% of the variation observed in ni, is due to surnames which appear only once. On the other hand, correlations between A and B, and between phi ii and v were non significant (-0.08 and -0.17 respectively), meaning that they are measuring different features of population structure: B and phi ii, isolation, while A and v, migration. The most isolated counties of Zulia are localized towards the northwestern portion of the State, within the Venezuelan Guajira, although relative isolation is also observed in the southern counties. Isolation by distance is estimated through the correlation between the logarithmic transformations of Euclidean and geographic distances, giving a value of 0.63. This high value might be partially due to the barrier effect of the Lake of Maracaibo. Eight surnames with a focal distribution within Zulia were identified: Almarza, Badell, Bastidas, Bohorquez, Cardozo, Carmona, Espina and Matos. Carriers of these surnames have a high probability of having their origin at the counties where they are localized. PMID- 10030041 TI - [Presence of lectins, tannins and protease inhibitors in venezuelan marine algae]. AB - The presence of lectins, tannins and protease inhibitors was studied in 27 algae species collected at four Venezuelan coral rift sites. Among the species studied, only six had hemagglutinating activity, apparently due to their lectin content. Higher hemagglutinating titers were obtained when the extracts were tested on pronase-treated erythrocytes. Hemagglutination was inhibited by simple sugars and by bovine submaxillary gland mucine. GaINAc was the only inhibitor of the hemagglutination caused by Grateulopia filicina extracts. None of the compounds tested inhibited the hemagglutination caused by Halimeda opuntia. The polyvinylpolypirrolidone treatment abolished the hemagglutinating activity of both brown and red algae. However, in Grateulopia filicina and Hypnea cervicornis (Rhodophyta) hemagglutinating activity persisted after the polyvinylpolypirrolidone treatment, presumably due to the presence of true lectins in those algae. Tannin content (presumably phlorotannins) was higher in the Phaeophyta as compared to the Rhodophyta. The brown alga Padina gymnospora had the higher content of these polyphenols. Trypsin inhibitors were detected, in minute ammounts, only in Padina gymnospora (Phaeophyta) and Acantophora spicifera (Rhodophyta). No subtilisin inhibition was observed whatsoever. PMID- 10030042 TI - Thioacetamide effects on the polypeptidic and nucleoporin pattern and chemical composition of rat liver nuclear envelope subfractions. AB - The effect of the administration of seven doses of the hepatocarcinogen thioacetamide on the chemical composition of rat liver nuclear envelope subfractions: associated chromatin, nuclear membranes and pore complex-lamina fraction, is analyzed. No alteration in DNA, RNA or phospholipid content is observed after the hepatocarcinogen treatment. Electrophoretic studies of each subfraction from thioacetamide treated rats show differences in the relative proportions of some polypeptides when compared with the controls. Examination of the wheat germ agglutinin binding polypeptides of each subfraction reveals a decrease in the stain of two pore complex-lamina nucleoporins of 85 and 164 kDa and an increase in one of 93 kDa; this observation can be due to changes in the quantity and/or in the agglutinin binding capacity of the nucleoporin as a result of thioacetamide administration. In view of the participation of nucleoporins in the nucleocytoplasmic transport, the changes observed suggest a relationship between changes of some O-linked N-acetyl glucosamine polypeptides components of the nuclear pore complex and the altered transport of some RNA species observed after thioacetamide administration. PMID- 10030043 TI - [Sanitary quality of water for human consumption a in rural community of Mexico]. AB - The purpose of this study was to evaluate the quality of water for human consumption in Becal, rural community of Mexico. The presence of total and fecal coliforms, as well as aerobic plate counts in differents places of the water distribution network, in intradomiciliary deep pools and rainwater cistern system were investigated. Results from this set of experiments suggest the existance of local social and environmental factors that open the way for water contamination with organic material in the water sources studied. We demonstrated the necessity of performing a careful sanitary control and proper handling of water for human consumption through programs of systematic surveillance of the water supplies in order to provide good quality water to the population of this rural community. Additionally, it is necessary to perform educational programs about procedures for preservation of hygiene with special reference to prevention of gastrointestinal diseases. PMID- 10030044 TI - [Fluorescence microscopy for detection of frauds in ground coffee]. AB - Currently, frauds in ground coffee are detected with traditional microscopy, which is a tedious and not very precise method. Therefore, a more efficient and rapid microscopical method based on fluorescence, was proposed. For the microscopy analysis, pure coffee was compared to coffee samples adulterated with rye, barley, corn and wheat at 2.5, 5.0, and 10.0% levels. Starch granules were detected and identified immediately with fluorescence microscopy, in the adulterated coffee mixtures, quite different from optical microscopy where no frauds were detected with certainty. The suggested fluorescence method for the detection of cereal frauds in coffee was found to be more efficient and precise than the current official one. PMID- 10030045 TI - [Chromosomes isolation from scallop oocytes]. AB - A methodology for chromosome isolation from non fertilized oocytes of Euvola ziczac and Nodipecten nodosus is presented. It solves most of the common problems found during preparation of samples such as the high yolk concentration, chromosome condensation and the loss of biological material during solution changes. PMID- 10030046 TI - A synergistic aggregation pheromone component in the banana weevil Cosmopolites sordidus Germar 1824 (Coleoptera: Curculionidae). AB - Cosmopolites sordidus is an important pest on banana plantations worldwide. The chemistry of the aggregation pheromone of this insect has been recently resolved and here we present the first evidence from field trails that sordidin, a compound from the male released aggregation pheromone, attracts significant number of weevils only if host plant odors are also present. Sordidin attracts few insects when it is presented without the host plant tissue. However, the attractiveness of host plant tissue increases more than tenfold when it is presented simultaneously with sordidin in field traps. We confirm experimentally that sordidin may be used as part of a system for mass trapping and monitoring this insect. PMID- 10030047 TI - [Molecular biology of dengue virus]. AB - In Venezuela the problem of Dengue infection has become worst during the last decade, turning the country into an hyperendemic region where three of the four serotypes co-circulate. The Dengue has become a problem of Public Health, so the knowledge of the virus, its life cycle and characteristics, as well as the different aspects related with its biology are extremely important to fight the virus and for the develop of a vaccine. In a general way, the present work describes different aspects related to the molecular biology of the Dengue virus and its life cycle: the structure, composition, production of structural and non structural protein and its relation to the replication cycle of the virus. Some aspects related with the assembly and release of particles from infected cells are also discussed. With this a general view of the molecular biology of the Dengue virus and its replication in the host cell is shown. PMID- 10030048 TI - [Nitric oxide in dengue pathology]. AB - Nitric oxide (NO) is a multifunctional molecule that is involved in citotoxic as well as citoprotective processes, it's synthesis is highly regulated by the cell because an alteration in NO production is associated with a variety of pathologies, such as Septic, Anaphylactic and Hemorrhagic Shock. The clinical feature of dengue virus infection has a spectrum that goes from mild, dengue fever, to a severe disease, dengue hemorrhagic fever/dengue shock. Here, some evidences are discussed that links NO with the pathology of the severe disease cause by dengue virus. PMID- 10030049 TI - Induction of programmed cell death (apoptosis) by dengue virus in vitro and in vivo. AB - Dengue is a human disease which may be fatal in its hemorrhagic form. How dengue virus- and host-specified factors underlie virulence and pathogenesis is poorly understood. An immunological disorder is thought to be involved in dengue physiological symptoms. Whether the immune response is deleterious or beneficial to the host remains a matter of debate. In this review, we summarized developments in research on viral pathogenesis in the context of apoptosis triggered by dengue virus infection. Apoptosis, an active process of cell destruction, is one of the important consequences of dengue virus infection in vitro and in vivo. Dengue virus replication induces apoptosis in mouse neurons and human hepatocytes. The ability to activate this genetically programmed cell death pathway is dependent on both viral and cellular determinants. PMID- 10030050 TI - [Basic standards in handling patients with dengue fever, hemorrhagic dengue and dengue shock]. AB - The Dengue epidemic in Venezuela has increase dramatically during the last years. There is a rise in the number of cases as well as in the severity of the disease. The fact that it circulates more than one serotype of the virus (1, 2 and 4), from the four described turn us into a hyperendemic region. The symptoms produce in the patient as a consequence of the infection with the Dengue virus, varies from a mild fever to the severe Dengue Shock. Here, the characteristics and classification of the different clinical manifestation are presented as well as the basic procedures in the management of the patient in every case. PMID- 10030051 TI - [Laboratory diagnosis to dengue virus infections]. AB - Currently, laboratory diagnosis of Dengue virus infection has a special importance because of its emerging character, showing a great geographic propagation of viral activity through out the American Continent. In general, the laboratory diagnosis of Dengue infections is similar to other human infecting viruses, the difference and difficulty of the process lies in the cross reaction activity with other flavivirus that can co-exist in the same region. The effectiveness of the diagnosis depends on the quality of the samples obtained, so it is absolutely necessary to monitor carefully the timing, conditions as well as the accompanying information during the gathering of the samples. The present article describes some of the serologic technics used in the diagnosis of dengue infection: hemaglutination inhibition, plaque reduction neutralization and IgM and IgG ELISA assays, in the same way it outlines the principles and importance of viral isolation and identification as well as the advantages of a new diagnosis technic like PCR. PMID- 10030052 TI - [Serotypes and genotypes of dengue virus circulating in Venezuela, 1990-1997]. AB - Due to the increasing severity of hemorrhagic dengue epidemics during the last years in Venezuela, a retrospective analysis was conducted to identify the behaviour of the dengue virus serotypes circulating in the country and the molecular evolution of dengue virus serotype 2. The data presented here indicates that dengue virus serotypes 1, 2 and 4 are endemic in Venezuela, they circulate simultaneously around the year in the biggest urban cities, however, one particular serotype is predominant during an epidemic period and replaces the virus serotype dominant during the previous epidemic period. The increased severity of dengue fever since 1989 in Venezuela might be associated to the introduction of the Asiatic genotype of virus which replaced the autochthonous Caribbean genotype. The Asiatic genotype is recognised as a more virulent virus. PMID- 10030053 TI - [Advances in the development of a vaccine against dengue]. AB - There are multiple factors responsible for the increase in the epidemics of dengue/dengue hemorrhagic fever in the tropical and subtropical regions. The characteristics of this disease, plus the absence of effective antiviral drugs; it is imperative to develop a vaccine against the dengue virus. To obtain such a vaccine, it is necessary an antigen that could bring protective immunity through life against the four dengue serotypes. Different strategies have been developed to obtain the vaccine, from the conventional one (attenuated virus), to the second and third generation of vaccines (immunisation with proteins and DNA respectively). The Envelope and the Membrane structural proteins, as well as the non structural NS1 and NS3, had been considered of major interest in the develop of the vaccine. In spite of the advances in this field, it is still much more research to be done, so it is considered that a vaccine against the dengue virus will not be available until the first decade of the next century. PMID- 10030054 TI - [Venezuelan hemorrhagic fever: eight years of observation]. AB - Venezuelan hemorrhagic fever (VHF) is a severe disease characterised by fever, malaise, sore throat, followed by abdominal pain, diarrhea, a variety of hemorrhagic manifestations and convulsions. The arenavirus Guanarito is the causal agent and the virus natural reservoir is the rodent Zygodontomys brevauda (cane mouse). The disease affect agricultural male workers, between 14-54 years of age, mainly from Guanarito municipality of Portuguesa state and adjacent regions of Barinas State. Since VHF emergency in 1989 up till 1997, 220 cases have been reported with a fatality rate of 33%. Epidemiological informations suggest that VHF has a cyclic behaviour, with epidemic periods of high incidence, every 4-5 years. During the interepidemic periods few VHF cases are reported. PMID- 10030055 TI - Two-year follow-up study of elderly residents in S. Paulo, Brazil: methodology and preliminary results. AB - INTRODUCTION: Previous cross-sectional studies have shown a high prevalence of chronic disease and disability among the elderly. Given Brazil's rapid aging process and the obvious consequences of the growing number of old people with chronic diseases and associated disabilities for the provision of health services, a need was felt for a study that would overcome the limitations of cross-sectional data and shed some light on the main factors determining whether a person will live longer and free of disabling diseases, the so-called successful aging. The methodology of the first follow-up study of elderly residents in Brazil is presented. METHOD: The profile of the initial cohort is compared with previous cross-sectional data and an in-depth analysis of nonresponse is carried out in order to assess the validity of future longitudinal analysis. The EPIDOSO ('Epidemiologia do Idoso') Study conducted a two-year follow-up of 1,667 elderly people (65+), living in S. Paulo. The study consisted of two waves, each consisting of household, clinical, and biochemical surveys. RESULTS AND CONCLUSIONS: In general, the initial cohort showed a similar profile to previous cross-sectional samples in S. Paulo. There was a majority of women, mostly widows, living in multigenerational households, and a high prevalence of chronic illnesses, psychiatric disturbances, and physical disabilities. Despite all the difficulties inherent in follow-up studies, there was a fairly low rate of nonresponse to the household survey after two years, which did not actually affect the representation of the cohort at the final household assessment, making unbiased longitudinal analysis possible. Concerning the clinical and blood sampling surveys, the respondents tended to be younger and less disabled than the nonrespondents, limiting the use of the clinical and laboratory data to longitudinal analysis aimed at a healthier cohort. It is worth mentioning that gender, education, family support, and socioeconomic status were not important determinants of nonresponse, as is often the case. PMID- 10030056 TI - Occurrence of suicide and seasonal variation. AB - OBJECTIVE: To review the estimated suicide rates for the Region Metropolitan, the main socio-political center in Chile, for the period 1979-1994, and to determine whether they follow a seasonal pattern. METHOD: Data available for the period 1979-94 at the Forensic Services in Chile was analyzed using Analyses of variance. RESULTS: It was register 5,386 suicides. While the "warm" months (October, November, December & January) concentrated 39.0% of cases, the so called "cold" months reported 28.7%. This contrast is made even clearer by the month-to-month analysis, showing the highest suicide rate in December (10.6%) against the lowest rate in June (7.0%). Further statistical analysis revealed these differences to be significant. CONCLUSION: The study shows that in Chile, representing as it does the Southern Hemisphere, the suicide rates tend to present a seasonal variation as has elsewhere been determined for in the North Hemisphere. PMID- 10030057 TI - [Energy expenditure in adolescent students in night school]. AB - OBJECTIVE: It is well-known that energy expenditure provides a feasible way to measure the individual's energy needs. The final aim of this paper was to discover the level of physical activity and to quantify the energy expenditure of adolescents who either participated, otherwise, in the labor market. METHODS: This paper focussed on the evaluation of the energy expenditure of 273 students of both sexes attending the evening period of six schools belonging to the State School Network of Santo Andre, State of S. Paulo, Brazil, through a self-applied questionnaire dealing with their physical, occupational and discretionary activities. RESULTS: Data revealed that the students who were employed worked from 40 to 50 hours a week, earning a monthly salary varying from 1 to 3 Brazilian minimum wages. Watching television was the discretionary activity most frequently referred to. The energy expenditure of these students was 3,000 and 2,100 calories for boys and girls, respectively. CONCLUSIONS: The results found indicated that the students who were on the labor market did not expend more energy than those who were not. PMID- 10030058 TI - [The predictive value of neonatal neurological assessment and neonatal cranial ultrasonography with respect to the development of very low birth weight premature infants]. AB - OBJECTIVE: To verify the predictive value of two tests (neurological assessment and ultrasonography) performed at the time of discharge, with respect to the neuromotor and cognitive development of premature infants. METHODS: Seventy very low birth weight premature infants (below 1,500 g), admitted to the Neonatal Department between 1992 and 1994 were studied. The average birth weight and gestation age were, respectively, 1,185 g (SD: 180 g) and 32.2 weeks (SD: 1.4). At the term correct age, neurological assessment by the Dubowitz & Dubowitz method and cerebral ultrasonography were carried out. After discharge, the development was monitored at the follow up clinic. RESULTS: At 21 months correct age (SD: 4.9), neuromotor and cognitive abnormalities were observed, respectively, in 25.7% and 20.3% of the infants evaluated. The neonatal neurological assessment was found to be more sensitive than those specific for neuromotor (sensibility: 77.7%, specificity: 57.6%) and cognitive (sensibility: 78.5%, specificity: 56.4%) abnormalities, and exhibited low predictive value for both neuromotor and cognitive abnormality. Ultrasonography exhibited high specificity with respect to both neuromotor and cognitive development. The cerebral ultrasonography has also a reasonable predictive value for neuromotor abnormality. CONCLUSION: The combination of both tests yielded higher predictive values. PMID- 10030059 TI - [Assessing breastfeeding status in an urban area of southeastern Brazil: use of a simplified method]. AB - INTRODUCTION: The diagnosis of breastfeeding status in populations is necessary to define aims and to evaluate support and promotion programs related to this practice. Thus, the feasibility of undertaking such a diagnosis concomitantly with the National Multivaccination Campaign, was tested. METHOD: A simplified questionnaire was used (3 yes/no questions) to study the present feeding of 1,550 children under 1 year old (91.8% coverage) who attended the vaccination venues in August 19th, 1995. The medians and frequencies from three patterns of breastfeeding were calculated by probit analysis technique. RESULTS: The medians were: exclusive breastfeeding = 17 days (IC: 4.6-28.7); complete breastfeeding = 64 days (IC: 53.0-74.5) and breastfeeding = 167 days (IC: 153.7-182.2). The good adjustment of three patterns was attested by R2 values and by Kolmogorov-Smirnov tests (p < 0.05). CONCLUSIONS: The results confirmed the need for this program in the city. The simplified methodology was found to be available and is recommended for breastfeeding trend management and for studies on the impact resulting from intervention. PMID- 10030060 TI - [Measurement reliability in a study on family violence and severe acute malnutrition]. AB - INTRODUCTION: This study is nested within a research program related to family violence and severe childhood malnutrition. Its aim is to evaluate the reliability of the data collection process in a case-control study. Four components of the main instrument are addressed: (a) CTS (Conflict Tactics Scales) used to measure violence at the family level; (b) CAGE (Cut-down; Annoyed; Guilty & Eye-opener) questionnaire used to gauge suspicion of drinking problems; NSDUQ (Non-student Drugs Use Questionnaire) used to indicate illicit drug consumption; and (d) height/length measurements. METHOD: Stability (intra observer or test-retest reliability) and equivalence (inter-observer reliability) were evaluated for the cited components (a), (b) and (c). Information was replicated among the first 50 subjects selected for the underlying case-control study. The Kappa index (k) was used in the analysis. A pseudo-Bayes adjustment was carried out in order to handle estimation problems. Regarding (d), only equivalence was evaluated (n = 73), using the Intraclass Correlation Coefficient as the estimator. RESULTS: By and large, all components showed acceptable stability and equivalence. Regarding stability, the estimates of k were around 0.70, 0.78 and 0.85, for CTS, CAGE e NSDUQ, respectively. With respect to equivalence, k was 1.0 for CTS and NSDUQ and 0.75 for CAGE. Equivalence for height/length estimated through the ICC was 0.99. Nevertheless, some deviant situations were detected and are further discussed. The results point to an adequate standardization of observers and reflect the good quality of the data collection procedure concerning the main study, encouraging the research team to press forward with greater assurance. PMID- 10030061 TI - [Dengue epidemic in Fortaleza, Ceara: randomized seroepidemiologic survey]. AB - OBJECTIVE: A seroepidemiological random survey was carried out in Fortaleza city, State of Ceara, Brazil, following an epidemic of dengue virus type 2 (DEN 2), with the purpose of evaluating the frequency of clinical manifestations (signs and symptoms) and the prevalence of dengue infection. METHOD: A questionnaire calling for information on address, sex, age, clinical, epidemiological and economic status was applied to the population, followed by venupuncture collection of 5-10 ml of blood for testing by hemagglutination-inhibition (HI). The sample was calculated to obtain a prevalence of 20% with relative risk of 10% and confidence interval of 95%. All information obtained was analyzed by computer using Epi Info 5.0, Lotus 123, Excel 5.0, and Stata software. RESULTS AND CONCLUSIONS: A total of 1,341 serum samples were obtained from nine Health Districts (SD) and tested by hemagglutination inhibition. Of these, 589 (44%) were positive and 752 (56%) negative. Of the positive results, 93 primary responses (PR) (7%) to DEN-2 and 496 secondary responses (SR) (37%) were observed. The global prevalence in the SD ranged from 21% to 71%. There were 41% (243/589) asymptomatic infections and 59% (346/589) symptomatic infections. Data analysis showed no difference in frequency by sex, age, on schooling, although a highly statistically significant difference was found as between the different social classes, the infection most commonly observed being among people of better social status. The stratification of positive cases showed greater prevalence of AI (p < 0.001) and SI (p < 0.0001) in both sexes, among people with SR rather than PR. The most prevalent symptoms were fever, headache, muscle pains, rash, dizziness, and joint pains. Moreover, itching, retro-bulbar pain, rash, and gingival bleeding, showed statistically significant differences. On the other hand, dizziness and joint pains were more associated in the patients with SR than PR, and statistically significant differences were also observed. PMID- 10030062 TI - [Satellite remote sensing as a tool for the analysis of the occurrence of American cutaneous leishmaniasis in an urban area of southeastern Brazil]. AB - INTRODUCTION: The occurrence of American cutaneous leishmaniasis in the region of the Paraiba valley and the Northern shore of the State of S. Paulo, Brazil, is studied by remote sensing satellite imagery and maps of the region. METHOD: The places where infections might have occurred were plotted on a false color composition made up of Landsat TM-3, 4 and 5 band images, the relevant vegetation (shrubs and trees) has been identified and correlations were sought for those areas seen as areas of risk for the disease and the environmental characteristics and their changes. The maps made it possible to add to the composite image the creeks and the contours of the tops of the large number of hills found in that region. RESULTS: An area is characterized which may prove to be a macro-habitat for vectors, reservoirs and etiological agents. The search for changes in the landscape and the evaluation of meteorological data has not yielded any possible additional risk factor. CONCLUSIONS: There is full correlation among the areas considered to present risk of infection and the presence of creeks and relevant vegetation (shrubs and trees). PMID- 10030063 TI - [Determination of HIV protein 24 in feces of Triatoma infestans fed with blood from AIDS patients]. AB - OBJECTIVE: To verify any possibility of the elimination of p24 in feces of Triatoma infestans, p24 being an antigen and one of the markers of HIV infection. The purpose of the study was the evaluation of any risk of contamination by laboratory staff who work with activities related to this particular insect, and also investigate any mechanism that might thus lead to the dissemination of HIV. METHOD: Triatoma infestans were fed with p24-marked blood from 23 AIDS patients. Twenty-four and 48 hours later, their feces were examined in order to verify the presence of the antigen. The search for p24 was performed by means of the immunoenzymatic technique. RESULT AND CONCLUSION: No protein 24 was detected in any of the samples. In accordance with the applied methodology, the purpose of showing that the elimination of p24 does not occur, was obtained. Were this question approached in other ways different results might reveal new information in terms of risks of HIV dissemination. PMID- 10030064 TI - [Blood pressure among tannery workers]. AB - INTRODUCTION: Cardiovascular diseases have been shown to be the leading cause of death in Brazil since the 1970s. High blood pressure has been the major risk factor among the above mentioned diseases. A negative correlation between occupational qualification and blood pressure has been observed among workers. The above mentioned facts bring out the importance of the knowledge of high blood pressure distribution among the different occupational groups. The aim of the present study was to describe the distribution of blood pressure in stable and homogeneous population of unskilled, low wage earning industrial workers. The Prevalence of high blood pressure was established for this specific group. This prevalence was also related to some biological and socio-economical covariates as compared with that among other occupational groups in Brazil. METHOD: The subjects were 73 active employees at a tannery in Botucatu, state of S. Paulo, Brazil, in July 1993. These subjects underwent blood pressure measurements, anamnesis and clinical examination. The results were compared with those of similar studies carried out in elsewhere Brazil. Age confounding was controlled by different techniques. RESULT: The crude prevalence of high blood pressure detected in this group of workers was of 56.1%, with 15.8% of isolated systolic hypertension. Alcohol abuse and smoking were associated with high blood pressure and isolated systolic hypertension in the population studied. DISCUSSION: Prevalence of hypertension in the group studied is significantly higher than that observed in other groups of workers studied in Brazil. Such a finding points to the need for further investigation so as to isolate those factors involved in the increased blood pressure found in this group. PMID- 10030065 TI - [Food borne disease outbreaks caused by Salmonella enteritidis]. AB - OBJECTIVE: It is to describe outbreaks of salmonellosis reported from July 1993 through June 1997 in the Northwest region of S. Paulo State, Brazil, one of the areas where several foodborne outbreaks of salmonellosis have been recently detected. METHOD: Data of 19 epidemiological investigations were analysed; 87 stool specimens and 38 food samples (including 12 of shell eggs) were processed for microbiological analysis. Salmonella strains were identified by serotyping, phagetyping and antimicrobial susceptibility testing. RESULTS: There were 906 ill persons including 295 hospitalized patients. Phage type 4 (PT 4) Salmonella Enteritidis strains were isolated from 80.5% of stool samples, from all food samples and from 41.7% of eggs. Of the outbreaks, 95.7% were associated with the consumption of food containing raw or undercooked eggs. All strains were susceptible to the 13 antimicrobials, except the strains from the nosocomial outbreak. CONCLUSIONS: The results obtained show the need for the implementation of control measures regarding egg and storage, as well as for guidance to the public as to the risks involved in the consumption of inadequately prepared eggs. PMID- 10030066 TI - Rabies in the insectivorous bat Tadarida brasiliensis in southeastern Brazil. AB - This is the first recorded case of rabies in the insectivorous bat Tadarida brasiliensis in the State of S. Paulo, Southeastern Brazil. The infected bat was found in the afternoon while hanging on the internal wall of an urban building. This observation reinforces the notion as to the caution one must exercise regarding bats found in unusual situations. PMID- 10030067 TI - [First register of Aedes (Stegomyia) albopictus (Skuse) presence in Mato Grosso do Sul, Brazil]. PMID- 10030068 TI - [Ecstasy: a pharmacological review]. AB - A literature review on 3,4 methylenedioxymethanphetaneine (MDMA), known as ecstasy, a drug with increased use among youngsters is presented. The history from its synthesis, up to its use as an adjunct to psychotherapy and, more recently, as a drug of abuse, is described. The possible pattern of abuse in several countries is reviewed with the objective of predicting what might happen in Brazil, where some reports of abuse have already appeared. The pharmacokinetics of MDMA is also reviewed to explain the consequences for pharmacological activity, toxicology and adverse effects. The clinical outcome of both short and middle-term intoxication is summarized and the clinical symptoms of severe intoxication with ecstasy, are described. The studies undertaken on its mechanism of action are detailed to explain its toxic psychiatric and physical side effects, to explain the mechanism of self-administration of the drug and to propose a therapeutic possibility of treating intoxication. PMID- 10030069 TI - Experience in the evaluation of children with hepatosplenomegaly at a teaching ambulatory, Sao Paulo, Brazil. AB - OBJECTIVES: Describe cases of children with hepatosplenomegaly (HS) attended at the General Pediatric Teaching Ambulatory (AGER) of Instituto da Crianca, Sao Paulo, identifying the main causes, evolution, necessity for hospitalization and/or referral to specialists. METHODOLOGY: Retrospective analysis of the records of children presenting HS on admission at AGER from September 1, 1993 to August 31, 1996. RESULTS: Of the 89 children included (age range, 1 to 148 months; 24 months), 64 (72%) were referred from other services for HS investigation. Most common presenting complaints were: fever--39 (44%); pallor- 26 (29%); weight loss--21 (24%) and jaundice--14 (16%). Main alterations noticed on physical examination were: pallor--47 (53%) and short stature--17 (19%). Anemia was diagnosed in 70 children (79%); 35 children (39%) had infections; 7 (8%) metabolic disorders and 5 (6%) neoplastic disorders. The most frequent infections were of the urinary tract--9 (10%) and hepatitis A--6 (7%). Thirty six children (40%) were referred to specialists, 17 of which were already diagnosed. CONCLUSIONS: Most of the children with HS present deficiency anemia associated with infections which the general pediatrician is able to diagnose. Persistence of unexplained HS for more than 2 months, especially when there is substantial volume enlargement or alteration in the organs consistency, is an indication for referral to specialists. PMID- 10030070 TI - Re-evaluation of schistosomiasis mansoni in Minas Gerais, Brazil. III. "Noroeste de Minas" mesoregion. AB - This study was conducted to assess the presence of schistosomiasis mansoni in the "Noroeste de Minas" mesoregion, an area considered non-endemic. A malacologic survey and parasitologic stool examinations were undertaken in 13 municipalities of the mesoregion. A sample of 3,283 primary school students was submitted to fecal examination by the Kato-Katz method. A total of 3,627 planorbids was collected and examined. The molluscs were identified as Biomphalaria straminea in seven municipalities (Unai, Bonfinopolis de Minas, Paracatu, Jaao Pinheiro, Vazante, Lagamar and Lagoa Grande) and as Biomphalaria peregrina in one (Presidente Olegario). All planorbids were negative for Schistosoma mansoni. Four students were diagnosed with schistosomiasis in the municipalities of Buritis, Formoso, Paracatu and Unai, but none of these cases was considered autochthonous. The data obtained indicate that the "Noroeste de Minas" mesoregion continues to be non-endemic for schistosomiasis mansoni, although the presence of intermediate hosts associated with parasitized individuals emphasizes the need for epidemiological surveillance of schistosomiasis in this mesoregion. PMID- 10030071 TI - Hepatitis B virus infection profile in central Brazilian hemodialysis population. AB - Hepatitis B has proved to be a major health hazard in hemodialysis patients. In order to investigate the hepatitis B virus (HBV) infection profile in the hemodialysis population of Goiania city--Central Brazil, all dialysis patients (N = 282) were studied. The prevalence of any HBV marker (HBsAg, anti-HBs, and anti HBc) was 56.7% (95% CI: 51.1-62.7), ranging from 33.3% to 77.7% depending on dialysis unit. HBV-DNA was detected in 67.6% and 88.2% of the HBsAg-positive serum samples, in 91.3% and 100% of the HBsAg/HBeAg-positive samples, and in 18.2% and 63.6% of the HBsAg/anti-HBe-reactive sera by hybridization and PCR, respectively. The length of time on hemodialysis was significantly associated with HBV seropositivity. Only 10% of the patients reported received hepatitis B vaccination. The findings of a high HBV infection prevalence in this population and the increased risk for HBV infection on long-term hemodialysis suggest the environmental transmission, emphasizing the urgent need to evaluate strategies of control and prevention followed in these units. PMID- 10030072 TI - Reproducibility of alkaline antigens of Leishmania major-like and Leishmania (V.) braziliensis evaluated by IgG-ELISA. Comparison of antigens added of a protein inhibitor (PMSF) or not. AB - This paper deals with the analysis of 10 batches of L.major-like and L. (V.) braziliensis antigens added or not of a proteases inhibitor evaluated by means of an IgG-ELISA on three consecutive days using positive standard sera from patients with diagnosis of American Leishmaniasis previously tested for the presence of IgG antibodies by means of ELISA. The statistical analysis showed that for L. (V.) braziliensis the PMSF-containing antigen did not show any difference among batches or days of testing; the L. (V.) braziliensis antigen without PMSF showed statistical significance for differences among batches and a two-way ANOVA showed significant differences between antigens. L.major-like antigen prepared with or without PMSF showed differences among batches; all 3 days of testing displayed differences for the PMSF antigen but only for days 1 and 2 for the antigen without inhibitor. A two-way ANOVA showed differences among batches of the antigens but not for antigens with and without the protein inhibitor. According to the statistical analysis the L.major-like antigen added or not of PMSF has shown that it is the choice antigen for mucocutaneous leishmaniasis serology. PMID- 10030073 TI - Obtention of rabies antigen through BHK21 cells adhered to microcarriers. AB - Four rabies antigen batches were produced from virus suspensions resulting from BHK21 cells adhered to microcarriers (Cytodex 1), inoculated and cultured in a bioreactor. In parallel the methodology of production of rabies virus through cultures of BHK21 cells in monolayers in bottles was used. The results obtained showed that infecting titles were 10(6.69) DL50/mL and 10(7.28) DL50/mL for suspensions cultured in bottles and in the bioreactor, respectively. The viral suspension volumes collected were on average 11,900 per batch from the bioreactor and 800mL per bottle. Ten horses were immunized with the antigen produced in the bioreactor. The means of antirabies antibody titers found were 240 and 212 IU/mL after the initial and the first booster doses, respectively. Rabies antigen with satisfactory infecting titers can be obtained on a large scale by culturing in a bioreactor inoculated BHK21 cells adhered to microcarriers. PMID- 10030074 TI - Adverse effect versus quality control of the Fuenzalida-Palacios antirabies vaccine. AB - We evaluated the components of the Fuenzalida-Palacios antirabies vaccine, which is till used in most developing countries in human immunization for treatment and prophylaxis. This vaccine is prepared from newborn mouse brains at 1% concentration. Even though the vaccine is considered to have a low myelin content, it is not fully free of myelin or of other undesirable components that might trigger adverse effects after vaccination. The most severe effect is a post vaccination neuroparalytic accident associated with Guillain-Barre syndrome. In the present study we demonstrate how the vaccines produced and distributed by different laboratories show different component patterns with different degrees of impurity and with varying protein concentrations, indicating that production processes can vary from one laboratory to another. These differences, which could be resolved using a better quality control process, may affect and impair immunization, with consequent risks and adverse effects after vaccination. We used crossed immunoelectrophoresis to evaluate and demonstrate the possibility of quality control in vaccine production, reducing the risk factors possibly involved in these immunizing products. PMID- 10030075 TI - Heart aneurysm in Chagas' disease. AB - This prospective study on 41 autopsy collected human hearts concerns the "apical" lesion in Chagas' disease. Previous report did not show a correlation between lesion frequency and heart weight then discarding a vascular factor in its pathogenesis. The present paper involves other variables besides the heart weight to evaluate the relative coronary insufficiency. Distinct colored gel (green and red) injected through the capillary beds of both coronary arteries defined the extent of both vessels before separating the atria and removing the sub epicardium fat. The Right Ventricle (RV) and Left Ventricle (LV) free walls furnished the RV/LV mass ratio. The myocardium mass colored green (right coronary artery--RC) and the whole Ventricular Weight (VW) determined the RC/VW mass ratio. The heart weight plus these mass ratios, graded and added, composed a score inversely proportional to the myocardium irrigation condition. It intended to be a more sensitive morphologic evaluation of the relative ischaemia to correlate to the apical lesion. This study showed a right deviation for the relative accumulated frequency of lesions plotted as a score function and a significant difference for higher scores in hearts with aneurysm. It suggests a ischaemic factor intervening in the apical lesion pathogenesis in Chagas' cardiopathy. PMID- 10030076 TI - Standardization of procedures of Plasmodium falciparum antigen preparation for serologic tests. AB - The objective of the present study is to standardize the technical variables for preparation and storage of Plasmodium falciparum and of antigen components extracted with the amphoteric detergent Zwittergent. P. falciparum obtained from in vitro culture was stored at different temperatures and for different periods of time. For each variable, antigen components of the parasite were extracted in the presence or absence of protease inhibitors and submitted or not to later dialysis. Products were stored for 15, 30 and 60 days at different temperatures and immunological activity of each extract was determined by SDS-PAGE and ELISA using positive or negative standard sera for the presence of IgG directed to blood stage antigens of P. falciparum. Antigen extracts obtained from parasites stored at -20 degrees C up to 10 days or at -70 degrees C for 2 months presented the best results, showing well-defined bands on SDS-PAGE and Western blots and presenting absorbance values in ELISA that permitted safe differentiation between positive and negative sera. PMID- 10030077 TI - PCR-based diagnosis of a case of herpetic whitlow in an AIDS patient. AB - Herpetic infections are common complications in AIDS patients. The clinical features could be uncommon and antiviral chemotherapy is imperative. A rapid diagnosis could prevent incorrect approaches and treatment. The polymerase chain reaction is a rapid, specific and sensible method for DNA amplification and diagnosis of infectious diseases, especially viral diseases. This approach has some advantages compared with conventional diagnostic procedures. Recently we have reported a new PCR protocol to rapid diagnosis of herpetic infections with suppression of the DNA extraction step. In this paper we present a case of herpetic whitlow with rapid diagnosis by HSV-1 specific polymerase chain reaction using the referred protocol. PMID- 10030078 TI - Scedosporium apiospermum sinusitis after bone marrow transplantation: report of a case. AB - A forty-year-old man underwent an allogeneic BMT from his HLA identical sister. GvHD prophylaxis was done with cyclosporine (CyA), methotrexate and prednisone (PDN). On day +90 extensive GvHD was noted and higher doses of immunosuppressive drugs alternating CyA with PDN were initiated. Patient's follow-up was complicated by intermittent episodes of leukopenia and monthly episodes of sinusitis or pneumonia. One year after BMT, the patient developed hoarseness and nasal voice. No etiologic agent could be identified on a biopsy sample of the vocal chord. Upon tapering the doses of immunosuppressive drugs, the patient had worsening of chronic GvHD and was reintroduced on high doses of cyclosporine alternating with prednisone on day +550. Three months later, GvHD remained out of control and the patient was started on azathioprine. On day +700, hoarseness and nasal voice recurred. Another biopsy of the left vocal chord failed to demonstrate infection. Episodes of sinusitis became more frequent and azathioprine was withheld 3 months after it was started. One month later, the patient had bloody nasal discharge and surgical drainage of maxillary sinuses was performed. Histopathology showed hyphae and cultures grew Scedosporium apiospermum. Itraconazole 800 mg/day was initiated. The patient developed progressive respiratory failure and died 15 days later. PMID- 10030079 TI - Anti-Trypanosoma cruzi antibodies in the inhabitants of urban and rural areas of Abadia dos Dourados, State of Minas Gerais, Brazil. PMID- 10030080 TI - Dermatomycosis of the toe web caused by Curvularia lunata. PMID- 10030081 TI - Seroepidemiological study of human strongyloidiasis with blood samples collected on filter paper, in Abadia dos Dourados (Minas Gerais, Brazil). PMID- 10030082 TI - Simplified diagnosis of malaria infection: GFM/PCR/ELISA a simplified nucleic acid amplification technique by PCR/ELISA. AB - We report an adaptation of a technique for the blood sample collection (GFM) as well as for the extraction and amplification of Plasmodium DNA for the diagnosis of malaria infection by the PCR/ELISA. The method of blood sample collection requires less expertise and saves both time and money, thus reducing the cost by more than half. The material is also suitable for genetic analysis in either fresh or stored specimens prepared by this method. PMID- 10030083 TI - Transfusion-transmitted virus (TTV) in Brazil. Preliminary report. AB - TTV is a recently discovered DNA virus, isolated from a patient with post transfusion hepatitis of unknown etiology by Japanese researchers. In the present study, we evaluated the presence of TTV among chronic liver diseases patients in Sao Paulo and Para states, representing two geographically distinct Brazilian regions. TTV DNA was found in 21/105 (20%) and 9/20 (45%) cases from Sao Paulo and Para States, respectively. DNA sequence data confirmed the presence of TTV genotypes 1a and 2a, as well as other genotypes not yet described. In conclusion, TTV is present in chronic liver diseases cases from Southeast and North Brazil. However, further studies involving healthy populations are necessary before establishing any causal relationship among TTV and human hepatitis. PMID- 10030084 TI - [The Hippocratic Oath]. AB - The impact of Hippocratic Oath on medical practice is universally recognized. However, some physicians raise questions about its validity and few medical schools use it in graduation ceremonies. It is postulated that this oath does not harmonize with present bioethical concepts and that the principles of beneficence, lack of harm, autonomy and justice, elaborated by Anglo-Saxon philosophers, would do so. The Hippocratic Oath contains these principles and many others, such as gratitude, compassion, justice, honesty, humbleness, sanctity, integrity, confidentiality, fidelity to the bond, and respect for human life and dignity. These are ethical values that apply to modern dilemmas in medicine. As a whole, the oath expresses an ideal of medical behavior and a life project. It must be interpreted in the context of ancient Greek culture and history. Some uncertainties about its relevance are due to a lack of understanding of its exceptional content of values. Modified versions of the oath or original texts presumptuously pretend to replace a document that has lasted 2500 years and that meant a revolution, not only to medicine, but for all mankind. Students should have the opportunity to analyze its content and the way its values are related to concrete situations of present medical practice. Medical schools should shelter it without objections, as the expression of a reflexive compromise acquired by physicians during their studies and to be applied in medical practice. PMID- 10030085 TI - [Experimental pulmonary emphysema in rats. Inflammatory phenomena and progression of lung damage]. AB - BACKGROUND: Although the hamster model of elastase induced emphysema is well characterized, the rat model has received less attention. AIM: To evaluate the effect of a single intratracheal elastase dose on lung pathological changes of Sprague-Dawley rats. MATERIAL AND METHODS: Rats were injected with a single intratracheal elastase dose of 28 U/100 g body weight or saline and studied 7, 15, 30 and 365 days after injection. RESULTS: Forty percent of rats died in the first 48 hours after injection, six were sacrificed at 7 days, 6 at 15 days, 7 at 30 days and 12 at 365 days. Progressive centroacinar emphysema was found from day 7 after elastase, with a persistent inflammatory reaction in the vicinity of emphysematous areas. CONCLUSIONS: Present findings differ from the panacinar emphysema described in the hamster using a similar elastase dose. PMID- 10030086 TI - [Prevalence of antibodies against hepatitis A in school children]. AB - BACKGROUND: As sanitary conditions of a population improve, hepatitis A virus infection occurs at higher ages, thus decreasing the prevalence of antibodies against the virus. In the eighties, the prevalence of antibodies among children was 97% and depended on the socioeconomic level. AIM: To assess the prevalence of antibodies against hepatitis A virus in school age children living in Valdivia. SUBJECTS AND METHODS: Two thousand three hundred thirty three school age children were studied. Total antibodies against hepatitis A virus were detected using an ELISA kit from Abbott. Children were stratified in age groups and school were classified as private, subsidized, municipal or foster homes. RESULTS: Antibodies were positive in 65% of children (59% in children aged 6 to 8 years old, 66% in children aged 9 to 11 years and 69% in children aged 12 to 15 years. In private schools, the prevalence was 26%, in subsidized schools the figure was 54%, in municipal schools 73% and in foster homes 91%. CONCLUSIONS: The general prevalence of antibodies against hepatitis A virus is higher in low socioeconomic level children. There is a global decrease in the prevalence of these antibodies in the last years. PMID- 10030087 TI - [Duchenne muscular dystrophy. Effects of vitamin E administration on urinary luminescence]. AB - BACKGROUND: Urinary luminescence is increased in patients with Duchenne muscular dystrophy, probably due to the higher oxidative stress present in this disease. AIM: To assess the effects of vitamin E supplementation on urinary luminescence in children with Duchenne muscular dystrophy. PATIENTS AND METHODS: Eighteen children with muscular dystrophy aged 12.2 years old and nine control children aged 10 years old, received 400 IU/day of vitamin E during one month. Prior to supplementation and twice a week thereafter, spot urine samples were obtained to measure urinary luminescence in a scintillation counter. RESULTS: There was a wide variability in urinary luminescence within and between children. Mean values decreased after vitamin E supplementation in six of nine controls and in 12 of 18 children with muscular dystrophy. CONCLUSIONS: Vitamin E supplementation significantly decreases urinary luminescence in healthy children and in patients with Duchenne muscular dystrophy. Therefore, it could be useful for the treatment of this disease. PMID- 10030088 TI - [Predictors of readmission in patients with congestive heart failure]. AB - Repeated hospitalizations among patients (pts) with congestive heart failure (CHF) are common. PURPOSE: This retrospective study was designed to determine predictors of readmission. METHODS: INCLUSION CRITERIA: admitted to University Hospital with a primary diagnosis of CHF between 10/1/94-9/30/95: lived in Jefferson county. EXCLUSIONS: cardiac transplant during study period; major comorbidity (e.g. malignancy, advanced renal failure). Predictors of readmission were determined by stepwise logistic regression analysis and predictor of time to readmission with Cox Proportionate Hazards modeling p < 0.05 was considered statistically significant. RESULTS: Mean age of the 237 pts was 66.5 yrs; 56% women. Mean left ventricular ejection fraction (LVEF) was 29%; 96% were in NYHA class III/IV. Mean length of stay was 5 days; 52 pts (22%) had > 1 admission. CHF etiologies: Ischemic (42%), hypertensive (37%), idiopathic (12%). Demographic characteristics and insurance status did not predict readmission risk. Predictors of readmission in the logistic and Cox models were similar. Increased risk of readmission was associated with myocardial ischemia (logistic OR 42.7), past NYHA Class III and IV (OR 32.8), plasmatic creatinine at discharge (OR 1.9) and continued smoking (OR 3.26). History of CABG was associated with a decreased risk of rehospitalization (OR 0.12). Beta-blocker use was associated with decreased risk, but did not achieve statistical significance. ACE-I use (prescribed in 78% of pts), did not contribute to the model. Diabetes Mellitus and a lower LVEF were more frequent in the readmitted group, but they did not predict readmission. CONCLUSION: CHF pts who have evidence of ischemia, advanced symptoms, renal dysfunction, and who continue to smoke are at increased risk for hospital readmission. Pts with these characteristics should be identified prior to hospital discharge and considered for intensive outpatient intervention. PMID- 10030089 TI - [Adherence of Acinetobacter baumannii to rat tracheal tissue]. AB - BACKGROUND: Acinetobacter baumannii is an important nosocomial pathogen whose virulence factors have not been fully elucidated. AIM: To study the adherence and hemagglutinating capacity of several biotypes of Acinetobacter baumannii. MATERIAL AND METHODS: Thirty nine strains of Acinetobacter baumannii isolated from hospitalized patients were studied. The adherence of these strains to small pieces of rat tracheal tissue was studied. Additionally, their ability to hemagglutinate human erythrocytes and the effect of D-mannose and D-galactose on the adherence and hemagglutinating capacity was assessed. Transmission electron microscopy of strains was performed looking for the presence of fimbriae. RESULTS: All strains exhibited adherence to tissues. All strains had also D mannose and D-galactose resistant hemagglutinating ability. Fimbriae were found in Acinetobacter baumannii and E coil cells. CONCLUSIONS: Adherence of Acinetobacter baumannii to rat tracheal tissue, apparently not related to the presence of fimbriae, may be a virulence mechanism of this bacterium. PMID- 10030090 TI - [Prevalence of biological and psychological symptoms in perimenopausal women from different socioeconomic levels in the city of Temuco]. AB - BACKGROUND: Psychological and biological symptoms occur in the perimenopausal period. However the real prevalence of these, is not well known in Chile. AIM: To determine the prevalence of biological and psychological symptoms and self care sexual health practices of perimenopausal women of Temuco, Chile. PATIENTS AND METHODS: A random sample of 171 women aged 45 to 55 years old, affiliated to private preventive health institutions and community organizations, were studied. These women were stratified in three income levels. Chi square, Fisher test and ANOVA were used for statistical analysis. RESULTS: Bone and muscle aches were the most frequent referred symptoms in 36% of women. Thirty one percent complained of vaginal dryness and 28% of headache. No differences in symptom frequency per age or between post or pre menopausal women, were observed. Depressive disorders were found in 39% of women, mostly in women not working outside their houses. In the previous two years, 67% of women had a PAP smear and 58% had a mammography performed. Women of low income levels had a greater prevalence of biological and psychological symptoms and a lower frequency of self care behaviors. CONCLUSIONS: The most frequent symptom among the studied women was bone and muscle aches, followed by vaginal dryness. These results differ from other publications that report flushing as the most important symptom among perimenopausal women. PMID- 10030091 TI - [Endovascular stent implantation in the treatment of coronary artery disease: angiographic, and immediate and late clinical results]. AB - BACKGROUND: Coronary revascularization allows a better survival and quality of life in high risk patients with coronary artery disease. AIM: To report the experience in stent placement as treatment for obstructive atherosclerotic coronary artery disease. PATIENTS AND METHODS: A prospective analysis of 105 stent placements. A morphological and quantitative analysis of coronary angiograms, using an electronic caliper, was performed. Patients were followed during their hospital stay and after discharge. RESULTS: In four of 112 coronary lesions, it was not possible to liberate the stent and in 108, it was successfully placed (48 in anterior descending, 19 in circumflex, 36 in right coronary arteries and 5 in saphenous aortocoronary by-pass. Lesions with stent implantation were type A in 11%, B1 in 30%, B2 in 44% and C in 15%. Reference diameter was 3.13 +/- 0.58 mm. After placement, luminal diameter increased from 0.95 +/- 0.43 to 2.99 +/- 0.46 mm, with a final stenosis of 7.2 +/- 10.1%. Angiographic success was obtained in 99% and procedure success in 98%. Hospital mortality was 0.98%. After a mean of eight months follow up, 91% of patients is free of major cardiac events. In 17% angina recurred and 5% required a new revascularization. There were no late cardiac deaths, acute stent thrombosis or infarction in relation to the treated lesion. CONCLUSIONS: In these patients, stent placement has had excellent immediate and late results. PMID- 10030092 TI - [Endovascular treatment of abdominal aortic aneurysm. Initial experience]. PMID- 10030093 TI - [Immunohistochemical tumor markers in infiltrating ductal breast carcinoma]. AB - BACKGROUND: Immunohistochemical techniques allow the study of tumoral markers with predictive or prognostic value. AIM: To study tumoral markers in mammary carcinoma and to relate these markers with age and tumoral histological grade. MATERIAL AND METHODS: The expression of nuclear estrogen receptor (RE), nuclear progesterone receptor (PGR), p53 and c-erb-B2 proteins was analyzed in 382 cases of infiltrating ductal carcinoma of the breast. RESULTS: The histological grade was I in 22% tumors, II in 56% and III in 23%. Forty nine percent of tumors had positive staining for RE, 41% for RPG, 45% for p53 and 57% for c-erb-B2. Correlation was found between histological grade and expression of RE, p53 and c erb-B2 between RE and PGR, RE and c-erb-B2 and between c-erb-B2 and p5. RE expression correlated with age. CONCLUSIONS: A reliable and rapid evaluation of these markers can be achieved using immunohistochemical staining. The present results are similar to other biochemical and immunohistochemical studies. PMID- 10030094 TI - [Decompensated diabetes mellitus and hyperchloremic metabolic acidosis: a case with both pathologies]. AB - Diabetic ketoacidosis is manifested by elevated blood glucose levels, ketosis and metabolic acidosis with increased anion gap. A transitory hyperchloremic acidosis, with normal anion gap, can appear. We report a 21 years old female with a type 2 diabetes mellitus, admitted to the emergency room of a general hospital with hyperglycemia, absence of ketonemia, severe hypokalemia and hyperchloremic metabolic acidosis. Initially, she was diagnosed and treated as a severe diabetic ketoacidosis. Normal blood glucose levels were rapidly achieved but electrolyte and acid base alterations persisted, leading to the suspicion that another associated condition was causing the acidosis and hypokalemia. Urinary pH and anion gap measurement, the study of renal acidification and a bicarbonate overload test lead to the diagnosis of a distal renal tubular acidosis, secondary to a Sjogren syndrome, that was confirmed with a Schirmer test and positive anti Ro antibodies. In this diabetic patient, the acute hyperglycemia intensified the hypokalemia of her distal renal tubular acidosis and unchained the acute metabolic condition. PMID- 10030095 TI - [Paget disease of the bone: differential diagnosis of osteolytic lesions. Report of one case]. AB - We report a 48 years old female with Paget's disease of the bone who consulted for leg pain. After exhaustive examination a magnetic nuclear resonance revealed a 7 mm intradural schwannoma that was resected without improvement. Four years later, with generalized, progressive bone pains, several osteolytic rib lesions were detected. A bone scintigraphy showed extensive areas of hyperfixation of Tc99 DPM. Biochemical tests were normal with exception of very high serum alkaline phosphatases. Looking for some neoplastic disease, a breast nodule was detected by mammography. Biopsy demonstrated benign disease. Finally, a rib lesion biopsy disclosed diagnosis of Paget's disease of the bone. Treatment with calcitonin, etidronate and vitamin D resulted in partial clinical improvement, reduction of abnormal isotope hyperfixation in bone scintigraphy and of serum alkaline phosphatase levels. PMID- 10030096 TI - [Deep venous cerebral thrombosis. Report of one case]. AB - We report a 39 years old female presenting with headache, progressive clouding of sensorium and long pathway deficit signs. Brain CAT scan showed a process involving basal ganglia, thalami and Herophilus press. A thrombosis of this vessel was suspected. The first magnetic resonance imaging was informed as a diffuse inflammatory process compatible with an encephalitis. The patient aggravated and a second magnetic resonance imaging demonstrated a partial thrombosis of sinus rectus, Galenus vein, Herophilus press and both internal cerebral veins. Intravenous heparin was started with a progressive recovery of the patient. Two months later she had an almost complete recovery with a persistent mild right brachial paresis and a memory deficit for recent events. PMID- 10030097 TI - [New multicentric studies in hypertension]. AB - Prospective, randomized and long term multicentric studies, published since 1988, on the effects of pharmacological or non pharmacological treatment of hypertension are analyzed. Former studies, performed between 1967 and 1987, are devoted, in chronological order, to special populations or to forms of hypertension not sufficiently studied previously (elders and isolated systolic hypertension), using classical pharmacological treatments such as diuretics and beta blockers. Their results confirm the reduction in mortality obtained using such therapies. Ensuing studies, focused on the analysis of new drugs such as calcium antagonists and angiotensin converting enzyme inhibitors, also demonstrated a reduction in cardiovascular risk, even in severely damaged populations. Thereafter, meta analysis of new pharmacological treatments and of non pharmacological therapies such as sodium restriction, weight reduction, avoidance of alcohol intake, calcium and potassium supplementation have appeared. These studies have emphasized the importance of prevention through changes in lifestyles. Their positive, although modest results, encourage the assessment of long term preventive and therapeutic measures in hypertension. PMID- 10030098 TI - [Nutritional risk factors for gallstones. Epidemiological analysis]. AB - This article reviews the role of nutrition in the incidence of gallstones. The epidemiological situation of gallbladder disease has wide worldwide geographical variations, being Pima Indians and the Chileans the most affected populations. The main nutritional risk factor is obesity. Other risk are serum cholesterol and triglyceride levels, unbalanced and excessive caloric intake, fasting periods of more than eight hours, hypocaloric diets of less than 700 Kcal/day, specially in obese subjects and parenteral nutrition lasting more than two weeks. The main conclusion of this revision is that nutritional behaviors of the population must be improved through public health programs, to reduce the incidence of obesity and related nutritional imbalances. PMID- 10030099 TI - [Communications difficulties during the medical interview]. AB - The aims of medical interview are to obtain diagnostic information, to obtain an empathetic communication with the patient, to educate him about his disease and to establish a personal link allowing a lasting relationship. We analyze some features of communication with patients. Individualized communication, recognizing his identity and personal aspects, "looking from the patient". Context, a shared but not mentioned value, part of the world of emotions and ideas. An analog and digital language, the former precise in words and the latter more diffuse, with gestures, not verbal. Coherence, as the similitude between what we think, feel and say. If there is no coherence, communication is impaired. Emotions, always present, rending communication more valid and real. We need to recognize, express and respond to emotions. An emotionless patient becomes a distant and impersonal object, an "it". When emotions are incorporated the patient is a "him" with whom I share and dialog. Empathy is an emotional comprehension, a personal bond. It improves relationships and creates links. Compassion is a variation of empathy that includes spiritual aspects and values. Negative emotions as rage, frustration and aggression creates communicational difficulties. We must recognize, express and clarify them to improve the situation. Difficult patients with whom communication is difficult such as confuse, agitated, terminal, elder, manipulating or hypochondriac subjects. The idea of transference and counter transference in these complicated situations is analyzed. PMID- 10030100 TI - [Recent alcohol and drug consumption in victims of work related accidents]. AB - BACKGROUND: Twenty to twenty two percent of work related accidents have a direct or indirect relationship with recent alcohol use. AIM: To detect recent alcohol or drug use in patients who required hospitalization for severe work related accidents. PATIENTS AND METHODS: Blood and urine samples were obtained from patients admitted to a hospital within 6 hours of an accident severe enough to require hospitalization. Blood alcohol and urinary metabolites of cocaine, marijuana, amphetamines and benzodiazepines were measured. Patient identity was kept confidential throughout the study. Once patients were stabilized, they were interviewed by a psychologist that was blind to laboratory results. RESULTS: Two hundred thirty men and 18 women were studied and 29% (30% of men and 17% of women) had recent use of alcohol or drugs. The most common substances were alcohol in 15% and benzodiazepines in 13%. Use of alcohol or drugs was found in 21% of professionals, in 33% of other occupational levels, half of agricultural workers and 25% of commerce workers. Only two of 60 positive cases, admitted substance use during the interview. Most of negative cases admitted the use of alcohol or other drugs during the month prior to the accident. CONCLUSIONS: Recent use of alcohol and drugs is frequent among severe work related accident victims. Probably, a high proportion of these subjects are problem drinkers. The combination of alcohol and benzodiazepines is an additional risk factor. PMID- 10030101 TI - [Relevance of intestinal metaplasia at the gastroesophageal junction]. PMID- 10030102 TI - Physical diagnosis in the contemporary era. PMID- 10030103 TI - The spectrum of bone disease in 200 chronic hemodialysis patients: a correlation between clinical, biochemical and histological findings. AB - INTRODUCTION: Renal osteodystrophy includes the complete range of mineral metabolism disorders that affect the skeleton in patients with chronic renal failure. PATIENTS AND METHODS: 200 patients with end-stage renal disease and on dialysis were investigated regarding the clinical, biochemical and histological findings of bone disease. RESULTS: The spectrum of renal osteodystrophy consisted mainly of high turnover bone lesions (74.5%), including osteitis fibrosa in 57.5%. Patients with mild bone disease were on dialysis for shorter periods of time and were mostly asymptomatic. Patients with aluminum-related bone disease (16.5%) had the greatest aluminum exposure, either orally or parenterally, and together with patients with high turnover mixed disease, were the most symptomatic. Although on a non-regular basis, the vast majority of the patients (82.5%) had been receiving vitamin D. The incidence of adynamic bone disease was high (n = 8) among parathyroidectomized patients (n = 12). Significantly higher serum levels of alkaline phosphatase were observed in osteitis fibrosa. CONCLUSIONS: The use of calcitriol and phosphate-binding agents on a non-regular basis seems to be the reason for the apparent reduced response to the treatment of secondary hyperparathyroidism. Alkaline phosphatase has been shown to be a fair marker for bone turnover in patients with osteitis fibrosa. The severity of the clinical manifestations of bone disease correlates with the histological features of bone lesion and to the time spent on dialysis. PMID- 10030104 TI - Evaluation of prostate specific antigen in the prognosis of patients with advanced prostate cancer. AB - OBJECTIVE: To evaluate the survival rate of patients with advanced prostate cancer in a univariate form, according to the preoperative and first postoperative determination of PSA levels. MATERIALS AND METHODS: From February 1987 to June 1995, 92 patients were submitted to maximum blockage androgen (subcapsular and antiandrogen orchiectomy), independent of clinical symptoms shown upon admission to the Cancer Hospital. The antiandrogens (ciproterone acetate and flutamide) were administered until the patient present progression of the disease. RESULTS: The age of patients varied from 44 to 89, with a median of 70 years old. In the 6th, 36th and 60th months the global survival rate was 80%, 38% and 20%, respectively. The preoperative PSA ranged from 2 to 4017 ng/ml, with a median of 98 ng/ml (98% had PSA greater than or equal to 10 ng/ml). The first postoperative PSA ranged from 1 to 3840 ng/ml, with a median of 20 ng/ml. There was a tendency towards a better survival rate only in patients with initial PSA from 2 to 99 ng/ml (p = 0.06745). The survival rate of patients at 36 months after the initial total blockage androgen, with first PSA level from 1 to 4, 5 to 49 and over 49 ng/ml was 72%, 48% and 8%, respectively (p = 0.00004). In the final examination, 34 (37%) patients were considered stable and 58 (63%) had disease progression. CONCLUSION: The PSA determination performed on the 30th postoperative day is important in the evaluation of advanced prostate cancer prognosis. PMID- 10030105 TI - Sudden unexpected infant death syndrome in Ribeirao Preto, Brazil. AB - CONTEXT: Sudden Infant Death Syndrome (SIDS) is the leading cause of death in the first year of life in developed countries. Brazilian and Latin American literature lack studies on the subject, which is largely unknown among health workers. OBJECTIVE: To identify cases that could be classified as SIDS among children of less than one year of age submitted to autopsy at the Servico de Verificacao de Obitos do Interior (SVOI), in Ribeirao Preto, SP, Brazil. A retrospective analysis of all autopsies from SVOI in this age group from January 1987 to December 1990 was done. RESULTS: There were 369 autopsies of which 344 (93.2%) deaths were expected and 25 (6.8%) unexpected. From the 25 unexpected cases 16 (64%) deaths could not be explained after autopsy and from these cases only 10 were eligible for the study because they had full organ sampling. There were 7 males and 3 females and the age at death ranged from 1 to 3 months (average: 1.7 months). Two were found dead, 3 died at home, 4 died on the way to hospital and 1 died while being fed. Autopsy diagnoses were aspiration (8 cases), SIDS (1 case) and undetermined (1 case). Aspiration was not confirmed by histology and the only findings were mild pulmonary edema, subcapsular petechiae and intraparenchymatous hemorrhage in thymus. CONCLUSION: That there were 10 cases of unexpected and unexplained deaths of children less than 1 year-old during the evaluated period with characteristics similar to SIDS which should therefore be classified as such. PMID- 10030106 TI - End-to-side neurorrhaphy with and without perineurium. AB - OBJECTIVE: We compared end-to-side neurorraphy with and without the perineural sheath. METHOD: Twenty rats were used. The peroneal nerve was sectioned and the distal end was sutured to the lateral face of the tibial nerve. We removed the perineural sheath only on the right side, but not on the left side. The proximal end of the peroneal nerve was curved back approximately at a 100 degrees angle and implanted into the adductor muscle. Six months later, the 14 surviving animals were submitted to electrophysiological tests, sacrificed, and the nerves and muscles were taken for histological exams. RESULTS: On the right side, the muscles that had positive response needed an average of 258.89 mV (+/- 92.31) of electric stimulus and on the left side 298.34 mV (+/- 139.32). The average weight of the tibial cranial muscles of the right side was 0.47 g (0.18) and for the left side 0.45 g (0.15). The distal end of the peroneal nerve showed averages of 310.29 (+/- 191.34) nerve fibers on the right side and 287.71 (+/- 183.60) on the left side. The tibial nerve above the neurorraphy showed averages of 939.46 (+/- 223.51) nerve fibers on the right side and 959.46 (+/- 327.48) on the left side. The tibial nerve below the neurorraphy showed averages of 935.17 (+/- 298.65) nerve fibers on the right side and 755.31 (+/- 323.26) on the left side. The average areas of the right tibial cranial muscles were 0.0162 m2 (+/- 0.008), after 230 magnification, and 0.0152 m2 (0.0064) for the left tibial cranial muscles. The histological features of the tibial cranial muscles, taking normal as 100%, were 78.21 (+/- 20.75) on the right side and 82.14 (+/- 15.89) on the left side. The statistical analysis (Student's t test) did not reveal any difference (p > 0.05) among right and left sides for all variables. CONCLUSION: The authors concluded that the two neurorraphies (with and without perineurium) did not show any difference regarding morphological and electrophysiological features studied. PMID- 10030107 TI - Metabolic and hematologic changes occurring after rapid intravenous infusion of gammaglobulin in patients with antibody deficiency syndromes. AB - OBJECTIVE: We wished to investigate whether increased IgG infusion rates are associated with metabolic and hematologic changes in pediatric patients with antibody deficiency syndromes. METHODS: We studied 7 patients (2-16 years old) with primary antibody deficiencies who had been on regular IgG replacement treatment, 350-600 mg/kg/dose every 3 weeks with a 3% IVIG preparation, for periods ranging from 6 months to 4 years. Initially, the IgG concentration of IVIG preparations was increased to 6, 9 and 12% in consecutive infusions at a constant IgG infusion rate of 4 mg/kg/min. Subsequently, the infusion rates were increased to 8, 12, and 16 mg/kg/min using the IVIG 12% preparation. RESULTS: Clinically, all patients tolerated increases in IVIG concentrations while the infusion rate was 4 mg/kg/min. However, 3 patients presented side effects when the infusion rate was increased to 8 and 16 mg/kg/min. CONCLUSION: We conclude that metabolic and hematologic sides effects occur with rapid infusion of IVIG even in patients who tolerate the increased infusion rate clinically. The advantages of using high infusion rates have to be re-evaluated. PMID- 10030108 TI - Computerized psychiatric interviews: can they help to improve medical care? AB - Studies on psychiatric disorders in Brazil have shown high prevalence rates, both in the community and in primary care centers. However, psychiatric assessments carried out by interviewers have some inherent problems which influence inter observer reliability. There is great potential for the use of computerized interviews. This article discusses some advantages of this kind of assessment, and indicates a need for investigation into its applicability to Brazilian health care settings. PMID- 10030109 TI - alpha-Interferon therapy for HBV-related glomerulonephritis. AB - We report a case of a patient with hepatitis B virus (HBV)-related membranous glomerulonephritis (MGN) who showed improvement after interferon-alpha (IFN alpha) therapy. A 35-year-old man with nephrotic syndrome and HBV antigens received a 24-week course of IFN-alpha. At the end of therapy there was an elevation in the level of plasma aminotransferase and an increase in proteinuria, which were followed by antigen/antibody seroconversion. This "flare-up" before seroconversion suggests an increase in disease activity in the liver and kidney, demonstrating in vivo HBV involvement in MGN. PMID- 10030110 TI - The rebound effect in the treatment of complex hemangioma with interferon alpha 2A. AB - The authors report the case of an infant with an extensive face hemangioma with subglottic airway obstruction which had been successfully treated with interferon alpha 2A but then reoccurred with the same dimensions and airway blockage after treatment was abruptly interrupted. The authors suggest the implementation of a standard procedure for the interruption of interferon alpha 2A treatment in order to avoid this rebound effect and advise on the need for further studies to properly evaluate dosage and administration parameters for interferon alpha 2A in the treatment of difficult hemangioma. PMID- 10030111 TI - Submental method for orotracheal intubation in treating facial trauma. AB - OBJECTIVE: To demonstrate an alternative method for intubating patients with fractures of maxilla and nose, prior to surgery. DESIGN: Cases Report. PARTICIPANTS: We studied 10 patients with facial fractures that affected maxilla and nose. INTERVENTION: The patients were submitted to surgery under general anesthesia and submental oro-tracheal intubation. RESULTS: This type of intubation allowed the surgical team to work on the whole face of the patient and left no visible scar. CONCLUSION: This procedure is indicated for patients with fractures of maxilla and nose who need surgical intervention under general anesthesia. PMID- 10030112 TI - New perspectives on old diseases. PMID- 10030113 TI - New perspectives in cataract surgery. PMID- 10030115 TI - New perspectives in corneal transplant. PMID- 10030114 TI - In office retinal detachment surgery: pneumatic retinopexy, a Rhode Island experience. PMID- 10030116 TI - Systemic autoimmune diseases and their effect on the eye. PMID- 10030117 TI - New perspectives in glaucoma. PMID- 10030118 TI - Visual impairment among Rhode Island adults. PMID- 10030119 TI - The tobacco settlement: briefing for physicians. PMID- 10030120 TI - Transfusion medicine in Rhode Island. PMID- 10030121 TI - Why didn't our doctor tell us about hospice sooner? PMID- 10030122 TI - Intra-articular ligaments: degradation is predictable but healing is not. PMID- 10030123 TI - Gait analysis comes of age. PMID- 10030124 TI - Methods, applications and limitations of gait analysis in horses. AB - Over the last 30 years, the increase in interest in horses for racing and riding activities has stimulated scientific research in equine locomotion. This paper presents a review of the measurement methods and their applications used to assess equine locomotion. After describing gaits and velocity-related changes in stride variables, the current applications of gait analysis are presented. The economic consequences of lameness justifies the great effort now being put into lameness quantification and prevention. To improve breeding and reduce the costs of training, early performance evaluation tests for each discipline are proposed. After extensive fundamental and methodological research on the various aspects of equine locomotion, the horse industry should benefit from the applications of gait analysis by improving the profitability of racing and riding activities. PMID- 10030125 TI - Histopathological findings in the medial palmar and dorsomedial intercarpal ligaments of the equine midcarpal joint. AB - Medial palmar intercarpal ligaments (MPICL) and dorsomedial intercarpal ligaments (DMICL) from the midcarpal joints of 11 adult horses in training were examined histopathologically. These were compared with ligaments from seven horses less than 12 months of age, and 10 grossly enlarged DMICLs of adult horses. Tearing of the MPICL was observed in 15 of 22 joints from adult horses. Collagen fibre bundles of the MPICLs generally were disorganized and poorly aligned, and there were large areas of loose connective tissue. In young horses there was more parallel alignment of collagen bundles and less loose connective tissue. Collagen bundles of adult DMICLs were well organized and showed parallel alignment, whereas in foals the structure appeared more like that of fibrous joint capsule. Grossly enlarged DMICLs in adults consistently had discrete areas of fibrovascular infiltration. Degeneration of the MPICL was associated with increasing age and could explain the high incidence of tearing of the ligament. Enlargement of the DMICL was associated with low-grade tearing and repair. PMID- 10030126 TI - Cardiovascular response to intravenous administration of 5-hydroxytryptamine after type-2 receptor blockade, by metrenperone, in healthy calves. AB - The cardiovascular response to 5-hydroxytryptamine (5-HT) challenge has been previously described in cattle. Abrupt bradycardia, followed by tachycardia, triphasic systemic blood pressure response, and pulmonary hypertension were the major changes elicited by 5-HT. The purpose of the present study was to determine whether the cardiovascular response to 5-HT in calves was attributable to 5-HT2 receptors. A specific 5-HT2 antagonist (metrenperone, 0.05 mg/kg) was administered intramuscular to six unsedated Friesian calves 30 min before the animals were given a 5-min intravenous 5-HT infusion. Mean systemic arterial (SAP), mean pulmonary arterial (PAP), pulmonary capillary wedge (PW) pressures were obtained by means of fluid-filled catheters, and cardiac output (CO) was measured by the thermodilution technique. Heart rate, stroke volume, systemic (SVR) and pulmonary (PVR) vascular resistances were calculated. Administration of 5-HT after metrenperone induced a short-lasting period of severe bradycardia followed by tachycardia and increased CO. The systemic blood pressure response was exclusively hypotensive and associated with a decrease in SVR. Conversely, PAP, PW, and PVR were not modified by 5-HT administration. The results establish that 5-HT induced systemic as well as pulmonary hypertension is mediated through the activation of type-2 serotonergic or alpha-adrenergic receptors, or both. In contrast, neither apnoea, bradycardia and hypotension, nor the positive chronotropic effect induced by 5-HT in cattle are mediated through such receptors. PMID- 10030127 TI - Ketoprofen and phenylbutazone attenuation of PAF-induced lung inflammation in calves. AB - The purposes of this study were: (1) to investigate which arachidonic acid metabolites contributed to platelet-activating factor (PAF) induced pulmonary dysfunction; and (2) to compare the effect of two non-steroidal anti-inflammatory drugs, phenylbutazone and ketoprofen in a model of PAF-induced reversible lung inflammation in six calves. In placebo and phenylbutazone groups, PAF infusion induced significant dysfunctions in the pattern of breathing, mechanics of breathing and gas exchange. These dysfunctions were prevented by ketoprofen pretreatment, except for the mechanics of breathing which was moderately but significantly altered by the PAF challenge. In all calves, leukotriene (LT) B4 plasma concentrations did not significantly increase above baseline values at any time. Prostaglandin (PG) E2 plasma concentrations showed a minor significant increase in phenylbutazone pretreated calves (55.8 +/- 25.8 pg/mL from 36.7 +/- 16.13 pg/mL). Thromboxane (TX) B2 plasma concentration was significantly increased during PAF challenge in placebo- and phenylbutazone-pretreated groups, but not in ketoprofen-pretreated calves (1580.0 +/- 1370 from 42.7 +/- 10.7 pg/mL; 2340 +/- 477 from 63 +/- 32 pg/mL; and 36.5 +/- 4.12 from 39.3 +/- 12.0 pg/mL, respectively). These data suggest that TXA2 is an important cyclooxygenase metabolite of arachidonic acid produced in response to PAF and that ketoprofen (intramuscular injection, 3 mg/kg) is more effective than phenylbutazone (intramuscular injection, 10 mg/kg) in preventing respiratory dysfunctions induced by the PAF challenge 30 min after drug administration. Ketoprofen did not suppress totally the PAF-induced changes in mechanics of breathing, which suggests that PAF or a secondary release of mediators could have a direct action on airway smooth muscle. PMID- 10030128 TI - The role of phosphate on the rates of mineral absorption from the forestomach of sheep. AB - Phosphorus plays an important role in calcium and magnesium homeostasis in ruminants. In five trained sheep, each with a large rumen cannula, the isolated rumen wash technique was used to measure the magnesium and calcium absorption rates from the rumen. After one control period of measurement, the intra-ruminal phosphate concentration was increased from 2 to 10 mmol/L, and there was a significant increase in the calcium and magnesium absorption rates. The same technique was also used to demonstrate the effect of hyperphosphatemia on the absorption rates of magnesium and calcium from the forestomach. Although the absorption rates of magnesium and calcium tended to increase, the changes were not statistically significant. It is concluded that intra-ruminal phosphate concentration plays a role in the absorption of magnesium and calcium ions from the forestomach of sheep. PMID- 10030129 TI - N-ethylmaliemide (NEM)-stimulated passive potassium transport in camel erythrocytes: inhibitory effects of age, furosemide, sodium fluoride and okadaic acid. AB - The effects of age, and the inhibitory effects of furosemide, sodium fluoride, and okadaic acid on N-ethylmaliemide (NEM)-stimulated, ouabain-resistant potassium influx were investigated in camel erythrocytes. The NEM-stimulated influx which declined with the age of erythrocytes, was partially inhibited by 2 mmol/L furosemide, 20 mmol/L sodium fluoride, and completely inhibited by 150 nM okadaic acid. The effect of all chemical inhibitors was significant if added before the NEM pretreatment. PMID- 10030130 TI - The efficacy of the skin delayed-type hypersensitivity using a Brucellin prepared from a mucoid strain of Brucella abortus to detect brucellosis. AB - Eight-hundred-and-ninety-six cattle belonging to herds officially designated Brucella-free, and 190 cattle belonging to infected herds were tested with the skin delayed-type hypersensitivity (SDTH) test, using brucellin (273) prepared from a mucoid strain of Brucella abortus. An increase in skinfold thickness > or = 2 mm was considered a positive SDTH test. The serum agglutination test, complement fixation test and bacteriological examination were used to confirm SDTH test results. Results show that 6 of the 896 uninfected cattle tested positive in the SDTH test, indicating a 99.3% specificity. Of the 44 cattle that tested serologically or bacteriologically positive, 33 tested positive in the SDTH test, indicating a 75% sensitivity. The value of the SDTH test was demonstrated by its ability to detect infection earlier than serological tests, and by confirming infection in cattle with ambiguous serological test results. An increase in skinfold thickness > or = 1 mm in cattle in suspected herds should not be ignored, as it may indicate specific sensitization. We recommend the use of the SDTH test in combination with serological tests for early diagnosis of brucellosis in cattle. PMID- 10030131 TI - Serological evidence of spirochaetal infections associated with digital dermatitis in dairy cattle. AB - A potentially infectious aetiology for digital dermatitis in dairy cattle was investigated and centred on the possible involvement of spirochaetes. An enzyme linked immunosorbent assay (ELISA) was developed to detect bovine anti-Borrelia burgdorferi (B31) and anti-Treponeme (USA bovine isolates) antibodies in the sera of cows; sera were further tested for antigen specificity by Western blotting. Compared to normal cows, those with digital dermatitis had a much higher seropositivity rate to B. burgdorferi and the treponemes. Significant correlations were shown between antibodies to B. burgdorferi and to Treponemes (P < 0.001), suggesting strong cross-reacting epitopes shared by these spirochaetes. In Western blotting of B. burgdorferi antigens, the main band detected by ELISA positive sera was the 41 kDa flagellar protein; lesser frequency of staining was seen with 34 (OspB), 39 and 55 kDa bands. For the USA treponeme antigens, ELISA positive sera gave reactions to the 34-kDa band and also bands at 41 and 55 kDa. Polyclonal antibodies to Treponema denticola and T. vincentii showed reactions with the bovine treponemes which were predominantly to the 34-kDa antigen. Monoclonal antibodies to B. burgdorferi flagella (41 kDa) antigen and OspA (31 kDa) did not detect any treponeme bands in Western blotting. The study has provided serological evidence that spirochaetes (which are related to human treponemes) may be involved in the pathogenesis of digital dermatitis. PMID- 10030132 TI - The ultrastructural morphology of the camel eosinophil. AB - The ultrastructural morphology of the eosinophil was studied in specimens of peripheral blood from normal adult camels and those with eosinophilia. Specific granules were extremely polymorphic. The specific granules exhibited the basic structure of an electron-dense crystalloid core surrounded by a lighter, homogeneous matrix. The crystalloid cores were extremely variable in size and shape, often were segmented and demonstrated a variety of lamellated patterns that were transverse, longitudinal or concentric to the long axis of the core. It was not uncommon to observe multiple crystalloid cores in a single granule. In addition to large specific granules, microgranules and specific microgranules were observed. The extreme polymorphism of the specific granules and variety of lamellated patterns differentiate camel eosinophils from those of other species. PMID- 10030133 TI - A comparison of endoscopic and surgical collection procedures for the analysis of the bacterial flora in duodenal fluid from cats. AB - In order to assess an endoscopic collection procedure, populations of bacteria in duodenal fluid from seven adult cats were compared in paired samples obtained by endoscopy and direct needle aspiration during laparotomy. Each sample of duodenal juice was subjected to quantitative and qualitative culture of bacteria under both aerobic and anaerobic conditions. There were no significant differences in total numbers or individual species of bacteria comparing the two collection procedures. These findings indicate that collection of duodenal juice by endoscopy using the procedure described provides a representative sample of small bowel fluid for the assessment of the bacterial flora. Therefore, there appears to be no need for more invasive or complicated sampling techniques when quantitative and qualitative culture of duodenal juice is indicated as part of an investigation of small bowel disease in cats. PMID- 10030134 TI - The effect of anti-coagulants on the osmotic fragility of erythrocytes in the yak (Poephagus grunniens). PMID- 10030135 TI - Left abomasal displacement and ulceration with perforation of abdominal musculature in two calves. PMID- 10030136 TI - Mutational status of the tumour suppressor gene (p53) in donkey sarcoid tumours. PMID- 10030137 TI - Depletion rate of N4-acetylsulphamonomethoxine in tissues of laying hens. PMID- 10030138 TI - An empirical analysis of trends in psychology. AB - The present research examined trends in the prominence of 4 widely recognized schools in scientific psychology: psychoanalysis, behaviorism, cognitive psychology, and neuroscience. The results, which replicated across 3 measures of prominence, showed the following trends: (a) psychoanalytic research has been virtually ignored by mainstream scientific psychology over the past several decades; (b) behavioral psychology has declined in prominence and gave way to the ascension of cognitive psychology during the 1970s; (c) cognitive psychology has sustained a steady upward trajectory and continues to be the most prominent school; and (d) neuroscience has seen only a modest increase in prominence in mainstream psychology, despite evidence for its conspicuous growth in general. The authors use these findings as a springboard for discussing different views of scientific prominence and conclude that psychologists should evaluate trends in the field empirically, not intuitively. PMID- 10030139 TI - AIDS drug gets quick OK. PMID- 10030140 TI - The picture of health. It's what's inside that counts with X-rays, other imaging methods. PMID- 10030141 TI - FDA sets higher standards for mammography. PMID- 10030142 TI - Questions keep sprouting about sprouts. PMID- 10030143 TI - Keeping cholesterol under control. PMID- 10030144 TI - Epilepsy: taming the seizures, dispelling the myths. PMID- 10030145 TI - Juice maker fined record amount for E. coli-tainted product. PMID- 10030146 TI - Phony doc sentenced to real jail time. PMID- 10030148 TI - AIDS and mental health--Part I. PMID- 10030147 TI - Arizona man convicted for chat room drug sales. PMID- 10030149 TI - Clinical syndromes and personality disorders. PMID- 10030150 TI - Hate crime and the economy. PMID- 10030151 TI - The sex of schizophrenic symptoms. PMID- 10030152 TI - Catching up. PMID- 10030153 TI - Do informed consent letters have a role in psychotherapy? PMID- 10030154 TI - [Experimental in vitro evaluation of the absorption capacity and control of exudate of 3 wound healing dressings]. AB - INTRODUCTION: The development of materials based in moist wound healing has meant an important step in wound care. The progressive development of knowledge referred to this issue has showed the importance of the management of wound exudate to obtain an optimal wound healing, which has concluded in a development of dressings orientated to manage exudate. METHODS AND MATERIAL: Experimental "in vitro" study to evaluate the absorption capacity and exudate management of three moist wound healing dressings, Allevyn Adhesive (dressing A), CombiDERM (dressing B) and Tielle (dressing C). For each of this dressings the following parameters have been assessed: rate between the total surface and the absorption surface of the dressing, volume needed to saturate the retention capacity, pH evolution on the absorption surface and macroscopic aspect. RESULTS: Dressing A presents the major value in the rate between the total surface and the absorption surface (with a 64% rate, versus 28.7% for dressing B and 40.5% for dressing C). Dressing B was the one which needed a major quantity of exudate to saturate, with statistical significant differences versus dressings A and C (0.51 ml/cm2 versus 0.40 and 0.37 respectively). Dressing B was also the one that presented a best performance in reference to the leakage of exudate under pressure (with a loss of its initial weight of 8.34%, versus dressing C with a loss of 9.48%, and dressing A with a loss of 24.42%). None of the dressings presented pH modifications in the absorption surface. CONCLUSIONS: The results of this study let us establish that according to the used experimental evaluation methodology and the limitations that have been described in the manuscript, the dressing which presents the best performance in reference to absorption capacity and management of wound exudate is dressing B (CombiDERM) followed by dressing A (Allevyn Adhesive) and dressing C (Tielle). Experimental and clinical research will be required to examine thoroughly the absorption capacity and management of wound exudate of these dressings. PMID- 10030155 TI - [Case report about the combined use of 2 moist wound dressings in the treatment of a chronic diabetic foot ulcer]. AB - INTRODUCTION: Approximately 4.5% of the Spanish population suffer from Diabetes Mellitus (that means around 1.8 million people). Currently, the main problem that diabetes treatment presents is controlling its chronic complications, being the diabetic foot one of them, which can end up causing an amputation. Prevalence of ulceration varies according to sex, age and population characteristics, oscillating between 2.4% and 5.6%. In Catalonia, in a community case study, the prevalence was of 7.9%. In the same way, it has been calculated that at least 15% of diabetics will suffer from foot ulcerations during their lives. MATERIAL AND METHODS: A clinical case regarding a diabetic neuropathic chronic ulcer highly exuding was made to analyze the effect of this new dressing in the daily clinical practice. CombiDERM is an absorbent dressing with an external polyurethane plate and a central part with absorbent hydroparticles, indicated for the management of the exudate and the protection of the surrounding skin. 64-year-old woman, who suffered from Diabetes Mellitus type I to 28 years evolution with Retinopathy grade II, Artropathy of Charcott and a neuropathic ulcer of 4 years evolution. She was admitted in the Vascular Surgery Service the 6th of May of 1995 presenting an ulcer with signs of local infection in the sole of her left foot. Different local treatments were established and improvement periods were alternated with non-improvement periods, giving as a result an unfavorable evolution of the wound. The treatment with CombiDERM was established, using AQUACEL Ribbon (Hydrofiber dressing) as filling material. To evaluate the continuation of the treatment photos and acetates were taken, and data was registered in a Case Report Form. RESULTS: At the beginning the ulcer presented a high level of exudate, no signs of infection, light pain and the skin surrounding the ulcer was lightly macerated. After nine days of treatment an improvement of the ulcer could be observed, with the presence of granulating tissue. On the twenty-fourth day, granulation in the bed of the wound was completed and the quantity of exudate had reduced significantly. Application and removal of the dressing was easy and without pain. The evolution of the lesion was very good, without signs of infection, and with a graded epithelization until the ulcer was completely healed, at the eleventh week of the treatment with the new dressing. (The surface of the ulcer decreased from 557.67 mm2 to 0 mm2). CONCLUSION: Having in mind the good evolution of this ulcer and the characteristics of CombiDERM, the new dressing is an optimal alternative in the treatment of highly exuding diabetic neuropathy ulcers. PMID- 10030156 TI - [Prevalence of skin ulcers in institutionalized patients of over 65 years of age]. PMID- 10030157 TI - [Health visit to the newborn]. AB - Each child's medical record was reviewed to pick out any health problems detected in 1) the Newborn Checkup, 2) the first 15 days of life, and 3) during the child's first year. The number of visits was also recorded. Each mother was interviewed about the acceptability/usefulness of these checkups. The newborn checkup facilitates compliance with programmed checkups in the health plan for a healthy child. This program is useful to detect health problems precociously, to increase the knowledge mothers possess, to build confidence in nurses, and in general, to build up links with the pediatrics services of a health center. PMID- 10030158 TI - [Nutrition during pregnancy. A continuous challenge]. AB - An increasingly greater number of discoveries convince us that the mother's diet can affect foetus body composition, thus modulating aspects of the child's health ant development in the early years and even in adulthood. Pregnancy is a physiological period in a woman's life and, therefore, should be treated as such. However, nutritional needs increase in order to meet growth requirements. Such needs can be met by maintaining a balanced diet. It should not, however, be assumed that pregnant woman always have correct nourishment prior to pregnancy. The body experiences metabolic changes in order to face the changes that pregnancy entails, though each organism adapts differently to these changes, which makes it difficult to standardise the recommendations for women as a whole. Despite this, there are International Organisations that assume the task of establishing the dietary guidelines considered optimum for pregnancy. A rich and varied diet meets the requirements of pregnancy and lactation, but the needs increase in a different manner for each nutrient and the increase of intake should be selective. There should be particular control of proteins, essential fatty acids and certain vitamins (folic acid specially) and some minerals (such as calcium, phosphors, iron and zinc). Consequently, pregnancies with a risk of suffering nutritional alterations should be ruled out, the diet should be watched and, if necessary, specific dietary supplements should be used. PMID- 10030159 TI - [Oncologic day hospital]. AB - Due to its physical and psychosocial complexity, cancer requires forms of treatment which are becoming more diverse all the time and which involve a growing number of specialists in all fields. Nursing occupies a very important place in the care of these patients, and inside of the ambulatory care which nurses deal in, nurses are in charge of informing and caring for patients receiving chemotherapy. We develop a nursing care plan based on the most common problems or complications such as secondary effects of new generation cytostatic drugs, but one can extrapolate from those already known. We use the NANDA diagnostics and we keep in mind that almost all of the problems which we deal with are interdependent. PMID- 10030160 TI - [The University Nursing School at the University of the Balear Islands]. PMID- 10030161 TI - [Interview with D. Jordis Pericas Beltran, director of the school]. PMID- 10030162 TI - [The importance of health education] PMID- 10030163 TI - [Environmental education within the education of diplomate nurses]. PMID- 10030164 TI - [The angled baby bottle. Advantages of its use in the feeding of babies]. PMID- 10030165 TI - Medicare confusion continues. PMID- 10030166 TI - Juggling professional obligations. PMID- 10030167 TI - Bridging the gap. Bringing new antiretroviral medications into the clinic. AB - Highly active antiretroviral therapy (HAART) is a strategy in which clinicians introduce potent combinations of antiretroviral medications early in the course of HIV infection. The intent is to suppress viral replication as completely as possible to forestall irreversible immune system damage. Antiretroviral agents fall into two major classes reverse transcriptase inhibitors and protease inhibitors. Each class interferes with viral replication at a different point in the viral life cycle. Recent research findings demonstrate clearly that antiretroviral treatment should begin as soon as the patient is willing and able to take the multidrug regimens. The best strategy for meeting the challenge of antiretroviral resistance is prevention. If you completely halt viral replication with potent therapy, the development of resistant strains is prevented. PMID- 10030168 TI - Repairing lacerations in children. Suture, staple or secure? AB - The challenges of pediatric laceration repair include the probability of an uncooperative participant, tense or frantic parents and a busy setting. Linear lacerations of the scalp, trunk and extremities are excellent sites for staples. Stapling may be less traumatic because it is generally quicker than suturing. Suture repair is necessary for lacerations of the face, over joints, on the hands and feet, and other areas that impede the use of a stapling device. The most common methods of anesthesia for laceration repair include topical agents, direct infiltration and blocks. All wounds that are deep, dirty or may contain a foreign body should be locally cleansed with antimicrobial agents and irrigated vigorously. PMID- 10030169 TI - Managing irritable bowel syndrome. AB - IBS is a functional gastrointestinal disorder in which the patient has chronic or recurrent gastrointestinal symptoms (diarrhea, constipation or abdominal pain and bloating) that are unexplained by any structural or biochemical abnormalities. Research has demonstrated no causal relationship between psychosocial factors and the development of IBS. IBS cannot be diagnosed through radiologic, endoscopic or laboratory studies because the symptoms are not explained by structural or chemical abnormalities. One of the most important components of treatment is the development of an effective provider patient relationship. Behavioral treatments may be helpful in select patients. Dietary management can also reduce symptoms if the patient can identify foods that trigger them. PMID- 10030170 TI - Foot ulcers in diabetes. PMID- 10030171 TI - Hypertension update. PMID- 10030172 TI - Chastity of the flesh. Health and societal issues in female circumcision. PMID- 10030173 TI - Completing the 'right to write'. Controlled substances prescribing. PMID- 10030174 TI - Too many hoops. PMID- 10030175 TI - Self-management of fibromyalgia: the role of formal coping skills training and physical exercise training programs. AB - There has been growing interest in the use of formal self-management training programs for people with fibromyalgia (FM). In these programs, health care professionals serve as trainers and provide education about FM and guided instruction in specific self-management strategies. A review of the literature on formal self-management training programs for FM suggests that they can be divided into groups: 1) those emphasizing training in coping skills (e.g., relaxation, activity pacing, and problem-solving techniques), and 2) those emphasizing training in physical exercise (e.g., cardiovascular fitness, strength, and endurance training). In this article, we review studies that have tested the efficacy of both types of programs. In addition, we identify key individual and contextual variables that are related to outcome and highlight future directions in the research and development of self-management programs. PMID- 10030176 TI - Arthritis self-management program variations: three studies. AB - OBJECTIVES: 1) Determine strengths and weaknesses of the Arthritis Self Management Program (ASMP). 2) Compare 3- and 6-week ASMP. 3) Evaluate 1.5-hour arthritis program. METHODS: Study 1: Qualitative methods incorporating incomplete block design. Study 2: Comparison of 3- and 6-week outcomes. Study 3: Pretest/posttest comparison. RESULTS: Study 1: Pain management, exercise, and sharing ranked as the most useful aspects of the ASMP. Nutrition, medications, and making decisions about nontraditional treatments ranked least useful. Study 2: Six-week ASMP subjects improved pain, health distress, illness impact, exercise, cognitive pain management, self-efficacy, and reduced visits to physicians (P < 0.05). Three-week subjects improved health distress, cognitive pain management, and self-efficacy (P < 0.05). Study 3: Improved knowledge, self efficacy, and pain (P < 0.05). CONCLUSIONS: The traditional 6-week ASMP is more effective than a 3-week version. A 1.5-hour community program is effective in increasing knowledge, self-efficacy, and contact with the Arthritis Foundation. PMID- 10030177 TI - Recruiting adults with osteoarthritis into an aquatic exercise class: strategies for a statewide intervention. AB - OBJECTIVE: Although research suggests that regular exercise can be helpful in reducing the dysfunction and discomfort of osteoarthritis, promoting exercise among older adults within this population is neither straightforward nor easily accomplished. This article describes the various methods, and their relative success rates, that were employed to recruit older adults throughout the state of Washington into an aquatic exercise program. METHODS: Strategies included a recruitment letter distributed to Arthritis Foundation (AF) members in Washington state, local media news coverage, physician referrals, and advertisements in local papers and newsletters. RESULTS: The most successful methods for enrolling participants were through the AF recruitment letters and local television coverage. The AF recruitment letter was the most expensive method of generating responses, while the television coverage was the least expensive. CONCLUSIONS: Collaborating with a well-reputed community-based organization and capitalizing on available publicity resources are important strategies researchers can use to gain access to a difficult and geographically dispersed population. PMID- 10030178 TI - Developing musculoskeletal education programs for physicians and the general public: findings from a needs assessment. AB - OBJECTIVE: To assess the educational needs and learning preferences of primary care physicians and the general public in receiving musculoskeletal health education. METHODS: Prospective surveys were mailed simultaneously to 2,250 primary care physicians and 2,250 members of the general public. The surveys included questions about demographics, motivation for attending programs, and preferred education program formats. RESULTS: The 68 responding physicians attend continuing medical education programs mainly based on topics, speakers, and timing. They prefer lectures and find question and answer sessions least helpful in supporting learning. The 96 responding members of the general public attend programs mainly based on topics, speakers, and fees. The general public stated that question and answer sessions best support learning in programs. A large percentage of responding physicians provide health education to their patients, but a small percentage of the general public respondents stated that they receive health education from physicians. DISCUSSION: Responses from physicians and the general public were generally not surprising but revealed interesting contrasts between learning preferences. While physicians and the general public both value speakers and topics, the physicians want to increase their knowledge about disease, whereas the general public wants practical information. Physicians and the general public also appear to take different approaches to learning. The contrast between availability and provision of health education is also striking. We cannot generalize our results with absolute confidence because the return rates for the surveys were so low. Nonetheless, we support the need to educate physicians and the general public in ways that match their preferred learning methods and educational needs. PMID- 10030179 TI - Preoperative education for total hip and knee replacement patients. AB - OBJECTIVE: Psychoeducational preparation is known to improve postoperative outcome. We tested two common psychoeducational procedures in elderly orthopedic patients, examining how best to match interventions to patients by psychological type. METHODS: Two hundred twenty-two elderly patients undergoing total hip or knee replacement were randomly assigned to 1) a slide-tape with information on the postoperative, in-hospital rehabilitation experience, or 2) training in Benson's Relaxation Response with a bedside audiotape, in a 2 x 2 factorial design. RESULTS: The relaxation response did not influence postoperative outcomes. The educational intervention reduced length of stay and pain medication use for patients who exhibited most denial (tendency to avoid thinking about unpleasant events), and reduced postoperative anxiety and cognitive errors on the Mini-Mental State Exam for patients with most baseline anxiety. There was no effect on postoperative pain. CONCLUSIONS: The importance of attending to the patient's psychological state and level of preparation before orthopedic surgery is reinforced. Patients who exhibit most denial and highest anxiety may benefit from educational interventions, but patients' directly expressing desire for information may be a poor guide in deciding which patients would benefit, compared with more formal psychological testing for denial and anxiety. PMID- 10030180 TI - Using a short food frequency questionnaire to estimate dietary calcium consumption: a tool for patient education. AB - OBJECTIVE: To develop a short food frequency questionnaire (FFQ) assessing calcium intake and a prediction equation for estimating total calcium intake from the short FFQ. METHODS: Data were collected from 536 women via mailed questionnaires at 3 time points. Stepwise regression analyses were used to identify those foods and beverages included in the Black Health Habits and History Questionnaire (HHHQ) that explained the most variance in participants' dietary calcium intake. A prediction equation was developed to estimate total calcium intake based only on information from the foods/beverages identified. RESULTS: Calcium obtained from 15 foods/beverages explained 97.2% of the variance in total calcium intake. The mean absolute difference between total calcium intake estimated from the 15 foods/beverages and the full HHHQ was less than 50 mg at each time point. CONCLUSION: Findings suggest that a short FFQ can provide estimates of total dietary calcium consumption comparable to the full Block HHHQ. PMID- 10030181 TI - The Human Genome Project: nursing must get on board. PMID- 10030182 TI - The developing family: how is it doing with nurturing young children? PMID- 10030183 TI - Is a healthy lifestyle related to stress, parenting confidence, and health symptoms among new fathers? AB - A healthy lifestyle is widely recognized as important in preventing disease and disability. This study examined whether in the transition to fatherhood a healthy lifestyle was related to perceived stress, parenting confidence, and physical health symptoms. Survey data from 87 fathers were examined for relationships between lifestyle, measured by 6 subscales of the Health Promoting Lifestyle Profile (HPLP), and perceived stress, parenting confidence, and health symptoms. In general, a healthier lifestyle, especially HPLP self-actualization and stress management subscales, was related to less perceived stress, more parenting confidence, and fewer health symptoms. Higher HPLP nutrition and exercise scores were related to fewer health symptoms; higher exercise and seeking-interpersonal support scores were related to higher parenting confidence. Also, higher social desirability scores, a confounding influence, were related to less perceived stress. The authors conclude that health-promotion behaviours may be an important personal resource in maintaining health and promoting well-being among new fathers. PMID- 10030184 TI - Adaptation to pregnancy in three different ethnic groups: Latin-American, African American, and Anglo-American. AB - Interview assessments on adaptation to pregnancy were made of Latin-American (N = 30), African-American (N = 34), and Anglo-American (N = 30) women in the latter half of their pregnancy. Most subjects were 18-27 years old, single, had 12 years or less education, and had a parity of 0 or 1. Psychosocial measures of adaptation to pregnancy included Acceptance of Pregnancy, Identification with Motherhood Role, Relationship with Mother and with Husband/Partner, and Preparation for Labour. Data were analyzed using chi-square for group differences. The results indicate that in all 3 groups pregnancy was unplanned but wanted. African Americans least often anticipated life changes as a result of pregnancy, cited fewest aspects of pregnancy that were gratifying to them, and least often chose to stay home with their infant. Most women in all ethnic groups reflected on their role as mother, but Latin Americans most often indicated that they wanted to be like their own mother and that they consulted with their mother about pregnancy and parenting. African Americans least often anticipated domestic help from their partner and most often expected help from other family members. Regarding intimate relationships with husband/partner, for all groups sexual intercourse decreased during pregnancy. Anglo-Americans reported the least number of problems/discomforts with intercourse, Latin Americans the most. Anglo Americans most often found alternative methods of sexually satisfying their partner, African Americans least often. The results of this exploratory study have significance for differences in the delivery of health care to the 3 ethnic groups and warrant further research. PMID- 10030185 TI - Postpartum return to work: mothering stress, anxiety, and gratification. AB - Over half of mothers with infants less than 1 year old are employed, yet there is limited research examining the early parenting experiences of these women. The purpose of this study was to examine maternal gratification, stress, and separation anxiety, in relation to employment patterns and selected health-status indicators, of women returning to work during the first postpartum year. Data were gathered from 142 employed, well-educated, partnered, predominantly Caucasian women at 1, 4, and 8 months postpartum, using a mailed questionnaire. Their parenting experiences improved throughout the first postpartum year. While depression and fatigue were associated with greater parenting stress and anxiety, as well as a decreased sense of gratification from parenting, few women experienced these symptoms at clinically significant levels. Employment patterns were unrelated to parenting stress or gratification. These findings can be used by clinicians when counselling women regarding the decision to return to work after childbirth. PMID- 10030186 TI - Breast-milk sodium as a predictor of breastfeeding patterns. AB - This study partially replicates and extends a study reporting that elevated breast-milk sodium BM [Na+] during early lactogenesis was predictive of poor breastfeeding outcomes. The present study used 6-day postpartum breast milk. Consistent with the findings of the earlier study, 80% of those with a BM [Na+] of 16 mmol/L or lower at day 6 sustained a high level of breastfeeding at week 4, compared to only 50% of those with an elevated BM [Na+] (chi 2 = 4.05, df = 1, p = .04). This difference was even greater in a subgroup of mothers predicted to be at high risk for insufficient milk supply on the basis of support density and self-perception variables. Of the latter group, 75% with low BM [Na+] sustained a high level of breastfeeding at 4 weeks postpartum, compared to only 22% with an elevated BM [Na+] (chi 2 = .65, df = 1, p = .01). In contrast, among the low-risk mothers BM [Na+] levels were not associated with any difference in breast-milk sustainment (89% and 82% sustainment for low- and high-sodium groups, respectively). Thus a normal drop in BM [Na+] is predictive of higher sustainment of breastfeeding. However, the predictive validity of this marker appears to be enhanced by combining it with the psychosocial variables of support density and self-perception of breastfeeding by the mother. PMID- 10030187 TI - Smoking in pregnancy and postpartum: relationship to mothers' choices concerning infant nutrition. AB - The objective of this study was to examine the relationship between maternal smoking status and infant nutrition. Women delivering in 5 hospitals in the Ottawa-Carleton region of Ontario were screened for eligibility over a 6-month period in 1993. Follow-up data were collected by telephone at 3 months postpartum using a validated questionnaire. Mothers were retrospectively asked about their infant-feeding choices and their smoking behaviours. Logistic regression analyses were used to determine the significance of demographic factors and maternal smoking behaviours in relationship to 3 feeding practices: bottlefeeding at birth, discontinued breastfeeding by 12 weeks, and introduction of solids by 12 weeks. A total of 796 women participated in the longitudinal study (90% follow-up rate). Less-educated; younger; single, separated or divorced; and foreign-born mothers were more likely to bottlefeed at birth. Less-educated women more often discontinued breastfeeding before 12 weeks. Mothers who had smoked during part or all of their pregnancy and were smoking at the time of the interview were significantly more likely than non-smokers to bottlefeed at birth or to discontinue breastfeeding by 12 weeks. Current smokers were also more likely than non-smokers to have introduced solid food by 12 weeks. Maternal smoking was a significant predictor of infant nutrition, with other sociodemographic factors taken into account. Smoking status should be included in clinical screening tools for infant nutrition. The relationship between other dimensions of maternal smoking (e.g., timing of quitting attempts, degree of partner support, partner's smoking behaviours) and infant-feeding practices warrants investigation. PMID- 10030188 TI - [Systematic family nursing intervention applied to the birth of a disabled child: effects on the parents' adaptation]. AB - This quasi-experimental study evaluated the effectiveness of a new systemic family nursing intervention to facilitate the adaptation of parents with a handicapped child, as well as variations in effectiveness according to the gender of the parent, family income, and type of handicap. Conducted over a 6-month period, the intervention began immediately after birth and included the participation of 198 mothers and fathers of 6-month-old babies with Down syndrome or a cleft lip and/or palate. Half of the group received the intervention, while the other half, constituting the control group, received regular services. Emotional distress was measured, as were various aspects of parental stress. The results confirm the program's effectiveness. Almost all parental stress indicators showed less stress among parents who received the intervention. For some indicators, the effect of the intervention varied with the parent's gender. No significant correlation was found to exist between the program's effectiveness and family income or type of handicap. These results are discussed in light of the goals of the intervention, various aspects of parental adaptation, and a number of factors that may be linked to the effectiveness of the intervention. PMID- 10030189 TI - Anticipating the adopted child: women's preadoptive experiences. AB - A phenomenological pilot study looked into the experiences of 3 women choosing to adopt internationally. The mothers of a total of 7 children from 4 different countries shared the journey leading to adoption: the desire to create a family, the labour of the adoption process, and the experience of bonding with their children. The preadoptive period was a time of preparation, generating the themes of taking control, creating a family, anticipating, celebrating the pictures, honouring the child's origins, investing personally, and bonding. This research validates and adds credibility to the experiences of adoptive mothers, thus contributing critical information to the knowledge base of the nursing professionals who work with these mothers. PMID- 10030190 TI - Telemedicine opportunities and challenges. PMID- 10030191 TI - The inadequacy of a duty-based approach to the moral problems of health care. AB - Moral beliefs commonly are thought to be eternal and not subject to change, a perspective frequently reinforced by religious authority and secular traditions. Yet an examination of morality shows that moral beliefs and actions have changed over time in response to various factors. Indeed, the point could be argued that one of the challenges to morality is responding to change--no less so in the domain of bioethics and health care than in society at large. PMID- 10030192 TI - Health care technology issues in home care. AB - Every 2 years the Federal Bureau of Labor Statistics updates its employment outlook for the next decade. In its publication, The Occupational Outlook Handbook, 1998-1999 edition, the agency projects that employment in home health care is expected to grow the fastest of all health care sectors in the next decade. One of the main reasons for this trend is advances in health care technology that have allowed health care activities once performed only in hospitals or physicians' offices to be performed in clients' homes. PMID- 10030193 TI - Health care providers riding the information superhighway. AB - Telehealth is the practice of providing health care services to people who are distant from the provider by the use of telecommunications and information technology. These services include client care, consultations, education, and research. Concerns include financial cost, reimbursement, liability, licensure, and confidentiality. Research to document treatment cost-effectiveness and efficacy is ongoing. PMID- 10030194 TI - ET, phone home: telehome care. AB - No doubt that advances in technology are making a substantial impact on the delivery of health care. The idea of using some of this high-tech equipment within the home setting can seem quite unusual, perhaps extraterrestrial, giving the phrase "Reach out and touch someone" a whole new meaning. This aspect of health care even has a new name--telehome care--and we are just at the threshold of this frontier. PMID- 10030195 TI - The risk of occupational exposure and infection with infectious diseases (Part I). AB - The variety of potentially infectious agents that frequent the health care environment is indeed large. As a result, health care workers are at some degree of risk for exposure to a variety of infectious diseases. However, as healthy individuals, we can protect ourselves quite successfully by following the guidelines that govern personal hygiene and immunization and adhering to accepted infection control standards of patient care, disinfection, antisepsis, and disease isolation. A clear understanding of the mechanisms of disease transmission is also important in this regard. PMID- 10030196 TI - Problems with herbal remedies in anticoagulated home care patients. AB - The increasing popularity of alternative therapies, including herbal remedies, poses new challenges for home health care providers. The cost of herbal remedy use now exceeds $1 billion annually in the United States and is expected to increase. The use of traditional medicine in combination with alternative therapy may lead to complications for patients and their caregivers as evidenced by the adverse effects of certain herbal products in patients who receive traditional anticoagulant or antiplatelet medication. PMID- 10030198 TI - A patient education notebook. Caregiver resources. PMID- 10030197 TI - Criminal background checks for home health employees. PMID- 10030199 TI - Is there a doctor in the house? Integrating medical education and home health care. AB - This article describes how one rural home health agency collaborated with a school of medicine to integrate medical education into the daily operations of the agency. Noteworthy aspects of this project include integration of home care concepts at all levels of the medical school curriculum, use of an advanced practice nurse to coordinate the program, collaboration between the home health agency and the schools of medicine and nursing, and reliance on telecommunication technology to minimize the barriers related to transportation to and scheduling of physician visits. PMID- 10030200 TI - Information technology as part of your home health care strategy. AB - Historically, home health care has been carried out by independent organizations that provide limited-scope services in a home-only setting. But as capitation takes hold throughout the country, the concept that home care is often the most beneficial way to deliver major portions of patient care finally is becoming clear to health care providers, payers, and patients. PMID- 10030201 TI - Through the eyes of a family caregiver. Part 2: Strategies to manage caregiver problems. AB - With the ever-increasing number of U.S. senior citizens, maintaining the health of care-givers for the chronically ill has become a major public concern. About 20% of older Americans need help getting out of bed and bathing. Millions more need help with finances, meals, and transportation. Overwhelmingly, their families provide that help; only about 5% of elderly Americans live in nursing homes. PMID- 10030202 TI - Joint Commission on Accreditation of Healthcare Organizations. Changes in the 1999-2000 Comprehensive Accreditation Manual for Home Care. PMID- 10030203 TI - The importance of home care for the very low birth weight infant. PMID- 10030204 TI - Neonatal intensive care in the home. AB - As the trend toward early discharge and home care of medically fragile neonates continues, parents find themselves thrust into a lifestyle for which they are unprepared. They must quickly adjust to a new daily routine and new home environment. They watch as part of their home is transformed into a mini intensive care unit with the kind of high-tech equipment and supplies once exclusively reserved for hospital settings. Parents also must learn to live with limited privacy because home care nurses and other providers become a visible presence and a daily reminder that their lives have been forever altered. PMID- 10030205 TI - Home care concerns for the normal newborn. AB - Four of the most common problems encountered with newborns in the home include feeding difficulties, jaundice, gastrointestinal problems, and inconsolable crying. This article suggests assessment measures and intervention strategies to deal with these problems and evaluate the home environment for safety. This article also includes suggestions to promote safe infant feeding, bathing, sleeping arrangements, car safety seats, firearm and poison storage, fall prevention, concerns about pets, pest control, heating and cooling, and a nonsmoking environment. PMID- 10030206 TI - Diabetic emergencies and sick day rules. AB - In home care, the health educator or staff development coordinator is responsible for providing current information on the chronic illnesses diagnosed within the geriatric populations serviced by the respective home care agencies. The in service provided in this column concerns updated information regarding diabetes mellitus, a common diagnosis of people who receive care by skilled home care nurses. PMID- 10030207 TI - Hospital discharge of the high-risk neonate. AB - The American Academy of Pediatrics (AAP) recently released a policy statement on the issue of hospital discharge of the high-risk neonate. The statement has been developed, to the extent possible, on the basis of published, scientifically derived information. PMID- 10030208 TI - The risk of occupational exposure and infection with infectious diseases: Part 2. AB - This article is the second of a series devoted to the epidemiology of selected infectious diseases known to be transmitted in health care settings. In subsequent issues, the relative risk of occupational exposure to and infection with these diseases will be discussed. Part 1 (October 1998 Home Care Provider) consisted of a brief review of general preventive measures associated with standard and transmission-based precautions. This article will address specific viral illnesses associated with blood-borne transmission. PMID- 10030210 TI - Congress approves minimal changes to Medicare home health benefit. PMID- 10030209 TI - A review of respiratory syncytial virus infection in infants and children. AB - By the age of 2, nearly every child becomes infected with the respiratory syncytial virus (RSV), the most common cause of lower respiratory tract infections (RTIs) in infants and children. Yearly epidemics occur from October to May. Most infections are mild, producing nothing more than a cold, and can be managed at home. Some cases, however, are more severe, leading to bronchiolitis, pneumonitis, pneumonia, and even death. PMID- 10030211 TI - Maintaining healthy boundaries in professional relationships: a balancing act. AB - For most people, the term boundary brings to mind an image of some physical barrier that keeps something in or out, such as a fence or a wall. These examples are physical, but boundaries also can be emotional or interpersonal. Just as physical boundaries keep some things in and others out, so do emotional ones. Emotional or interpersonal boundaries are the necessary space between people that allows a sense of individuality and separateness. This sense of uniqueness is essential for the development of a healthy person and ultimately the development of a professional identity. PMID- 10030212 TI - Recognizing patterns of child abuse in the home. PMID- 10030213 TI - 24-hour call centers and home health care. PMID- 10030214 TI - A look back at 10 years of home care accreditation at the Joint Commission. PMID- 10030215 TI - The year of our distractions PMID- 10030216 TI - Starting an HHNA local chapter. PMID- 10030217 TI - Downsizing: surviving and maybe thriving. PMID- 10030218 TI - The challenge of implementing OASIS. PMID- 10030219 TI - Writing manuscripts for clinical journals. AB - Publishing in clinical journals can be an exciting and rewarding opportunity for home care nurses to convey creative ways they address problems in their practice. This article provides strategies potential authors can use to select topics, develop content, adhere to appropriate format and style, and benefit from pre- and postsubmission manuscript critiques. An overview of the review and publication process is also discussed. PMID- 10030220 TI - Home care of high risk pregnant women by advanced practice nurses: nurse time consumed. AB - This study examined the time spent by advanced practice nurses (APNs) in providing prenatal care to women with high risk pregnancies. The results indicate that the overall mean APN time spent in providing prenatal care was 51.3 hours per woman. The greatest amount of time was spent in the clinic and women with pregestational diabetes consumed the most APN time and required the most contacts. Historically, home care services have been measured by number of visits or contacts. This study assists home care nurses and administrators to consider additional measurements including time spent. PMID- 10030221 TI - Implementation of the i.v. push method of antibiotic administration using the FOCUS/PDCA approach. AB - Home health agencies constantly seek ways to improve patient care as part of their performance improvement program. This includes revising and updating agency policies and procedures. Changing care processes, such as administering intravenous medications, requires input from pharmacy and nursing staff as well as administration. The authors describe how one agency used this process while adopting the i.v. push method of administering certain antibiotics to home care patients. PMID- 10030222 TI - A place to hide. PMID- 10030223 TI - Understanding Medicare reimbursement. PMID- 10030224 TI - Let's celebrate. PMID- 10030225 TI - Histopathology of congenital subglottic stenosis. AB - A precise delineation of each laryngeal abnormality is critical to planning rational therapy. Since congenital cricoid cartilage anomalies are easily overlooked, a systematic approach to their identification is as important as a clear concept of their classification. The purpose of this communication is to present the pathologic findings and classification of congenital cricoid cartilage deformities and to summarize updated information derived by the whole organ macrosection technique. The classification of congenital subglottic stenosis is based on study of the English-language literature and the collection in the Laryngeal Development Laboratory at The Children's Memorial Hospital in Chicago. Twenty-nine specimens with congenital cricoid abnormalities have been identified. Fourteen have an elliptical cricoid cartilage; 12, a laryngeal cleft; 5, a flattened shape: 1, a large anterior lamina; and 3, generalized thickening. Some specimens have more than 1 anomaly. Eight cases of fragmented or distorted cricoid cartilages are thought to be acquired lesions. An anterior submucous cricoid cleft has been identified and is presented for the first time. PMID- 10030226 TI - Effect of intravenous substance P on laryngeal adductor activity in young dogs. AB - Reflex laryngeal adduction is a component of both the laryngeal chemoreflex and the esophagolaryngeal adductor reflex, two life-threatening reflexes that occur in immature animals. These two reflex responses are also thought to exist in infants and may play a role in causing life-threatening laryngospastic events and perhaps sudden infant death syndrome. Identifying neurotransmitters that mediate laryngeal adduction is important to understanding the mechanism of reflex laryngeal responses and to identifying potential means of pharmacologic prevention. Substance P (SP), a tachykinin, putatively functions as a sensory neurotransmitter and may play a role in mediating laryngeal reflexes. Substance P immunoreactive-like fibers and receptors are present in the subepithelial tissues of the larynx, the vagus nerves, the nodose and jugular ganglia, and the vagal brain stem nuclei. In this investigation, the effect of SP infusion on laryngeal motor activity in an in vivo model is reported. Substance P was infused intravenously into 8 puppies (20 to 133 days of age, mean 81.2), on a mean of 3.0 occasions (range 1 to 6). Cardiovascular, respiratory, arterial blood gas, and cricothyroid (CT), thyroarytenoid (TA), and genioglossus electromyographic (EMG) responses to infusion of the tachykinin were recorded and subsequently analyzed. The SP infusion induced a marked increase in CT or TA EMG activity in 23 of 24 studies, and the increase was typically apparent within 60 seconds of the infusion. An increase in genioglossus EMG activity did not occur. An immediate, profound decrease in mean arterial pressure and an increase in respiratory rate and depth of chest wall excursion accompanied the laryngeal response. Arterial blood gas values remained unchanged (p > .05). The laryngeal adductor response to SP infusion was blocked when animals were pretreated with a systemic SP antagonist (Pfizer CP-96,345). This study demonstrates that peripheral infusion of the tachykinin SP induces a marked increase in laryngeal adductor activity. The response may be blocked by pretreatment of animals with a systemic SP antagonist. Because SP is thought to act primarily as a sensory neurotransmitter, these findings may be important in understanding the mechanism of reflex laryngeal adductor responses. PMID- 10030227 TI - Histomorphometric and laryngeal videostroboscopic analysis of the effects of corticosteroids on microflap healing in the dog larynx. AB - The histologic and functional effects of unilateral, layered corticosteroids on lateral microflap healing in 15 dogs were analyzed. Histologic sections of steroid-treated vocal folds (VFs) were studied with computer morphometry to examine differences in the tissue healing response. Paired analysis revealed increases in the inflammatory infiltrate around the microflap in the steroid treated VFs at 2, 4, and 6 weeks (6.3%, 30.6%, and 34.9%, all with p < .02). The neovascular response in the steroid-treated VFs was less at 2 weeks (-20.9%, p < .005) but greater at 4 and 6 weeks (16.3% and 4.3%, p < .005). To better characterize the effect of steroids on the healing process, a normal, time dependent distribution was applied to the histologic data and demonstrated a delay in the steroid-treated VF tissue response of 12 days for the inflammatory infiltrate and 21 days for the neovascular response. Qualitative and quantitative analysis of in vivo laryngeal videostroboscopy (LVS) samples taken preoperatively and at sacrifice could not identify significant differences in appearance, amplitude, mucosal wave, or suppleness between the 2 VFs. Therefore, although corticosteroids cause a delay in wound healing, LVS does not discern differences in microflap characteristics between healing steroid-treated and control VFs at 2, 4, or 6 weeks. If steroids are used, the surgeon should account for a probable delay in wound healing, but should not expect an overall difference in functional outcome. PMID- 10030228 TI - Radiotherapy followed by neck dissection for small head and neck cancers with advanced cervical metastases. AB - Patients with small or occult primary carcinomas of the head and neck with advanced cervical metastases present a difficult problem for the otolaryngologist. A retrospective review was performed of patients who presented to UCLA Medical Center between January 1986 and June 1996 with small or occult primary tumors of the head and neck with advanced cervical metastases. The treatment algorithm consisted of initial radiotherapy to the primary site and the neck, followed in 6 to 8 weeks with endoscopy and biopsy of the primary tumor site. As long as the repeat biopsy of the primary tumor site was negative by frozen section, an immediate neck dissection was performed, even if no residual neck disease was present. Almost 40% of patients with no clinical evidence of neck disease following radiotherapy had evidence of metastatic cancer on histopathologic examination. While some would consider a watchful waiting policy when there is no clinically detectable neck disease following radiotherapy, we believe it is preferable to perform immediate surgery in such patients, in light of the high incidence of microscopic metastatic disease. PMID- 10030229 TI - Clinical applications of transiently evoked otoacoustic emissions in the pediatric population. AB - Our objectives were 1) to determine whether transiently evoked otoacoustic emissions (TEOAEs) are affected by the status of the tympanic membrane (TM) and middle ear (ME) as determined by clinical examinations and tympanograms; 2) to determine the efficacy of TEOAEs in detecting hearing loss; and 3) to determine the relative effects of the ME status and hearing loss on TEOAEs. In a prospective observational study in a tertiary care children's hospital, 89 patients (169 ears; 9 ears eliminated from analyses) were examined by 2 attending pediatric otolaryngologists for otologic conditions and underwent audiologic evaluations including TEOAEs from August 1994 through May 1995. The main outcome measures were presence or absence of TEOAE whole reproducibility (WR) and reproducibility (R) at 2 kHz. Statistical analyses showed that of the 8 ME and TM conditions evaluated (normal, TM perforation, pressure equalization [PE] tube, TM retraction, tympanosclerosis, TM atrophy, ME effusion, surgery other than PE tube insertion), only the presence of ME effusion and normal examination findings had a significant effect on the results of WR and R at 2 kHz. Of the 6 different types of tympanograms evaluated (A, B, C, AD, As, B with large volume), type A, B, and C tympanograms had a significant effect on WR and types A and B had a significant effect on R at 2 kHz. Hearing losses > or = 25 dB hearing level (HL) at any of the 5 frequencies (0.25, 0.5, 1, 2, and 4 kHz) were well predicted by the absence of WR and R at 2 kHz. When clinical examination and impedance data were evaluated simultaneously with hearing status, hearing status had a greater effect on WR and R at 2 kHz. We conclude that type B and C tympanograms and the presence of ME effusion (which reflect abnormal ME status) have an adverse effect on TEOAEs. However, the presence of hearing loss is the most significant predictor of TEOAE results. The TEOAE WR and R at 2 kHz are effective in identifying patients with normal hearing and with hearing losses > or = 25 dB HL. PMID- 10030230 TI - Smoking increases facial skin flap complications. AB - This study was undertaken to determine whether smokers have a higher risk of complications after reconstruction of facial skin defects. Ninety-one patients with facial skin defects reconstructed with local flaps were reviewed retrospectively. Thirty-eight (42%) were active smokers, 12 (13%) had not smoked for at least 1 year prior to surgery, and the rest were nonsmokers. Complications occurred in 23 patients (25%; 37% in smokers, 17% in ex-smokers, and 17% in nonsmokers; p < .03). All full-thickness skin losses and all cellulitis occurred in active smokers. We conclude that active smokers are at a higher risk for complications in facial skin flap surgery. That ex-smokers had a complication rate similar to that of nonsmokers suggests that part of smoking's adverse effect on skin flaps may be an acute phenomenon, and that smoking cessation for shorter (<1 year) periods of time before surgery may have a beneficial effect. PMID- 10030231 TI - Autotransplantation of the trachea: experimental evaluation of a reconstructive technique for extended hemilaryngectomy defects. AB - Vascularized segments of trachea were used to repair extended hemilaryngectomy defects in a rabbit model. The cervical trachea was revascularized in a first stage by a fascia flap. In a second stage, the cervical trachea was isolated and transformed into a patch that could be autotransplanted on a vascular carrier. The patches were used for the reconstruction of hemilaryngectomy defects including half of the cricoid. Two months after transplantation, the vascular and morphologic characteristics of the tracheal patches were examined with silicone dye angiography and magnetic resonance imaging. The tracheal patches showed a reliable blood supply when wrapped in vascularized fascia. The patches provided a functional reconstruction of hemicricolaryngectomy defects. It is concluded that autotransplantation of the trachea should be further explored as a potential means for extending the limits of conservation laryngeal surgery. PMID- 10030232 TI - Transnasal endoscopic removal of an orbital cavernoma. AB - The approach to posterior and medial orbital tumors is still a challenge, since poor functional results are frequent. We report a case of cavernoma successfully removed by a modified transnasal endoscopic procedure. The patient, a 56-year-old woman, complained of a decrease in vision of the left eye. Magnetic resonance imaging evidenced a lesion in the posterior part of the orbital cavity, inferior to the optic nerve, extending to the sphenoidal cleft. The lesion was isodense on T1-weighted images and showed contrast enhancement. Because of the medial location of the tumor, the patient was referred to the otolaryngology department by the neurosurgeons, and a transnasal endoscopic approach was chosen. A large exposure of the operative field was obtained, and a cavernoma was removed. Rapid relief of the symptoms was obtained. In view of this good result, we advocate the transnasal endoscopic approach in cases of inferomedial and posterior intraconal lesions as an alternative and addition to the standard techniques of orbital surgery. PMID- 10030233 TI - Patients with CHARGE association: a model to study saccular function in the human. AB - The term CHARGE association refers to a combination of congenital malformations, the mnemonic CHARGE designating the most frequently occurring anomalies in the constellation. "C" indicates coloboma of the retina, "H" heart defects, "A" choanal atresia, "R" retarded growth and/or central nervous system anomalies, "G" genital hypoplasia, and "E" ear anomalies and/or deafness. The inner ear anomaly consists of a specific form of labyrinthine dysplasia that includes Mondini dysplasia of the pars inferior (cochlea and saccule) and complete absence of the pars superior (utricle and semicircular canals). We observed the development of a child with CHARGE association up to the age of 10 years. There was complete absence of nystagmic response to bithermal caloric and rotatory pendular stimuli. A nystagmic reaction was elicited by the off-vertical axis rotation test, indicating stimulation of the saccular macula, the sole remaining vestibular sense organ in this dysplasia. This reaffirms that the saccule is a vestibular organ, even though it is located in the pars inferior. In spite of the severe bilateral vestibular deficit and coloboma of the retina, the child was able to walk at the age of 2 years. The delay in the development of walking was not due to central nervous system anomalies, as suggested by the "R" of the acronym CHARGE, but rather, to the severe sensorineural visual and vestibular deficits. PMID- 10030234 TI - Carbon dioxide laser microsurgery of benign vocal fold lesions: indications, techniques, and results in 251 patients. AB - Two hundred fifty-one carbon dioxide laser-assisted cases of microphonosurgery are reported. Our series includes 167 women (66.5%) and 84 men (33.5%), with a mean age of 41 (+/-11) years. Single lesions represent 67.8% (n = 170) of the cases, with 20% (n = 50) being nodules, 18% (n = 44) Reinke's edema, 9% (n = 23) polyps, 8% (n = 19) sulci and related lesions, 6% (n = 16) mucosal cysts, 4% (n = 10) scars, 2% (n = 4) granulomas, and 2% (n = 4) vascular corditis. The cases with 2 or 3 lesions represented 32% (n = 81). Carbon dioxide laser-assisted microphonosurgery is efficient, provided the working parameters are strictly adhered to: micromanipulator micropoint providing a 250-microm laser beam for a 400-mm working distance; 0.1-second single pulses; and maximum power of 3 W with the superpulse wave. Glutaraldehyde-cross-linked collagen remains our filling material of choice in cases of vocal fold atrophy. Fibrin glue is useful for covering the resection area and for setting the microflaps. Microphonosurgery cannot be dissociated from speech therapy, the planning and duration of which, in relation to the procedure, depend on the nature of the initial lesion. Twenty to 30 sessions are usually adequate, but 6 months may be necessary in the case of sulcus vergetures. Our operating technique is derived from the microphonosurgery procedures with cold instruments. In addition to the classic advantage with regard to hemostasis, the carbon dioxide laser micropoint seems to make the dissection of microflaps easier. PMID- 10030235 TI - Telescopic video microlaryngeal surgery. AB - Although traditional microscopic laryngeal surgery has been well developed, we still may encounter some clinical problems, including exposure difficulty, blind areas during examination, and inadvertent cutting through lesions. These problems may lead to an increased risk of complications or protracted or even repeated operations. We have partially overcome these problems since October 1992 with a new telescopic endolaryngeal surgery technique. This technique was developed by combining and modifying the principles of bronchoscopic surgery and endoscopic sinus surgery. With this technique, it is not necessary to use a very slim laryngoscope or apply overpressure on the larynx when introducing and suspending the laryngoscope. Difficult-to-examine regions can be accessed more easily. We can also get a 3-dimensional impression of lesions and related structures, so it is easier to determine a proper cutting line to avoid cutting through lesions. We consider this telescopic method to be a useful alternative to conventional microscopic laryngeal surgery. PMID- 10030236 TI - Specific immunoglobulin E, interleukin-4, and soluble vascular cell adhesion molecule-1 in sera in patients with seasonal allergic rhinitis. AB - This study included 23 nonatopic volunteers and 84 patients with seasonal allergic rhinitis due to Japanese cedar pollen. Serum interleukin-4 (IL-4) and soluble vascular cell adhesion molecule-1 (sVCAM-1) in the patients were significantly higher than those in the nonatopic individuals, even outside of the pollen season. Both the good responders and the poor responders to antihistamine tablets showed significant increases in IL-4 and specific IgE during the pollen season, whereas such seasonal increases were not observed in the good responders to immunotherapy. Seasonal increases in IL-4 were significantly correlated with those of specific IgE. However, seasonal increases in sVCAM-1 were not significant. Seasonal increases in sVCAM-1 were not significantly different between the good responders and the poor responders to pharmacotherapy or immunotherapy. In conclusion, serum IL-4 and sVCAM-1 are increased in patients with seasonal allergic rhinitis, even outside of the pollen season; this finding might suggest underlying preponderant in vivo activation of T helper cell-2-like cells and inflammatory events in seasonal allergic rhinitis. A seasonal increase in IL-4 in sera might be at least partly involved in the seasonal increase in specific IgE in sera. Immunotherapy's inhibitory effect on IL-4 production and specific IgE response might be one of its working mechanisms. PMID- 10030237 TI - Diagnostic and therapeutic approach to migrating foreign bodies. AB - Ingested foreign bodies are the commonest otolaryngological emergency in Singapore and other parts of Southeast Asia. One of the uncommon complications of ingested foreign bodies is migration, which has the potential to cause morbidity and mortality. A retrospective study of 24 patients presenting from 1990 to 1996 at Singapore General Hospital was done to evaluate the presentation, investigation, and diagnosis of migrated foreign bodies. Of interest, most patients had ingested foreign bodies within 24 hours. All the migrated foreign bodies were linear, sharp fish bones. Migration is said to have occurred in the presence of positive neck radiography and negative rigid esophagoscopy. Computed tomography is the investigation of choice to confirm migration. All patients had neck exploration, and factors for successful outcome are discussed. This is the largest series in the literature to date. PMID- 10030238 TI - Astrocyte reaction in the rat vestibular nuclei after unilateral removal of Scarpa's ganglion. AB - Unilateral vestibular ganglionectomy (UVG) results in a complete degeneration of vestibular nerve fibers and terminals in the ipsilateral vestibular nuclear complex (VNC). A subsequent glial reaction may affect the activities of VNC neurons and thereby influence compensation for lesion-induced vestibular disorders. Expression of glial fibrillary acidic protein (GFAP), a specific marker for reactive astrocytes, was demonstrated immunohistochemically in the rat VNC at 7, 14, and 35 days after UVG. An increased GFAP-positive astrocytic response was evident at 7 days after lesion in all the VNC regions on the lesioned side and in some regions on the unlesioned side and remained through 35 days. The glial response included hypertrophy, which was more prominent at 7 days than at 14 days or 35 days, and proliferation, more prominent at the later times, of GFAP-positive astrocytes. Astrocytic projections around VNC neuron somata and proximal dendrites increased in number and became thicker and more elongated, especially at 14 days, in the lateral vestibular nucleus. It is suggested that UVG results in a bilateral astrocytic reaction in the VNC that would affect the subsequent compensation. PMID- 10030239 TI - Diagnostic and therapeutic management of bilateral carotid artery occlusion caused by near-suicidal hanging. AB - In cases of attempted suicide by hanging, a combination of mechanisms causing local destruction of the pharynx, larynx, vessels, and spine, as well as neurologic complications, has to be considered. We present a case of hanging in which a deeply unconscious patient without any palpaple pulsation of the carotid arteries was referred to our otolaryngology department. Computed tomography and angiography showed parapharyngeal air, complete obstruction of both common carotid arteries, and a compensatory circulation through the vertebral arteries. Three hours after the trauma, surgical exploration with resection of the enrolled intima of both carotid arteries and repair of the pharynx was performed. The patient awoke with an infarct of the right hemisphere with incomplete left hemiparesis the next day, but symptoms slowly declined during the following months, and the patient learned swallowing again perfectly. We conclude from our experience that in near-hanged patients a prompt onset of adequate diagnostic and therapeutic measures is mandatory, as good neurologic and functional results may occur even in cases with coma and severe destruction of the carotid arteries and pharyngeal and laryngeal structures. Surgical repair of blunt carotid lesions is recommended and may be crucial for a good outcome. PMID- 10030240 TI - Decrease of serum levels of soluble CD23 during immunotherapy in patients with perennial allergic rhinitis. AB - There is increasing in vitro evidence that soluble CD23 (sCD23) is capable of potentiating the synthesis of human IgE and is likely involved in the expression of allergic diseases. Our study has aimed at investigating whether serum sCD23 is elevated in patients with perennial allergic rhinitis as compared to nonatopic controls, whether sCD23 in perennial allergic rhinitis fluctuates during the natural course in untreated patients, and whether sCD23 is decreased by immunotherapy. This study included 139 patients with perennial allergic rhinitis due to Dermatophagoides farinae who gave informed consent to participation. They were divided into 2 groups--an untreated group and an immunotherapy group- according to their treatment background. Thirty-one nonallergic, healthy volunteers were included to serve as controls. Symptom scores and serum concentrations of IgE specific to D. farinae and sCD23 were examined twice in each patient: at enrollment (first evaluation) and on a variant time course after enrollment (second evaluation). Serum concentrations of sCD23 were measured by a sandwich enzyme-linked immunosorbent assay. The level of sCD23 in patients with perennial allergic rhinitis was significantly higher than that in nonatopic controls (p < .0001). The level of sCD23 in perennial allergic rhinitis was correlated with the level of specific IgE against D. farinae. The sCD23 level did not fluctuate during the natural course for a span of 2.8 +/- 2.7 years in untreated patients (p = .1337), but was significantly decreased in patients who received immunotherapy for 2.7 +/- 2.2 years (p < .0001). The rate of decrease in sCD23 was significantly correlated with the rate of decrease in specific IgE (rs = .523, p < .0001) and symptom scores (rs = .450, p < .0001). In conclusion, the reduction in sCD23 during immunotherapy is probably related to the decrease in specific IgE and also plays a role in mediating its clinical effect. PMID- 10030241 TI - Patulous eustachian tube in long-term survivors of nasopharyngeal carcinoma. AB - This article reports on 21 long-term (10 years) survivors of nasopharyngeal carcinoma, divided into 2 groups: those subjected to an inflation-deflation test and a clearance function test in a longitudinal study, and those receiving sonotubometry in a cross-sectional study. On the inflation-deflation test, 12 (55%) out of 22 ears had a patulous eustachian tube, and on sonotubometry, 10 (50%) out of 20 ears also revealed a patulous eustachian tube. Except for 4 ears with chronic otitis media, the ears had resolved to a normal eardrum appearance at 10 years postirradiation. The phenomenon might be attributed to both restoration of the impaired tubal function and the development of a patulous tube. PMID- 10030242 TI - Successful treatment of an invasive aspergillosis of the skull base and paranasal sinuses with liposomal amphotericin B and itraconazole. AB - Invasive aspergillosis and fulminant aspergillosis are rarities with a high mortality. In the literature there is no patient surviving an extended invasive aspergillosis of the paranasal sinuses and skull base after failure of operative intervention and of postoperative amphotericin B therapy. We report a complete remission of an invasive, partially fulminant aspergillosis. After an incomplete removal of the mycotic mass, we started postoperative drug therapy with amphotericin B. Under this treatment, the mycosis progressed. Additionally, the patient developed severe side effects, so that the treatment was interrupted. At this moment, we started a combined antimycotic drug therapy with liposomal amphotericin B and itraconazole. Within 10 weeks, clinically and radiologically, there was complete remission. The patient died 63 weeks after this treatment, due to a fulminant bacterial pneumonia. Postmortem histologic examination showed no aspergillosis in the skull base, paranasal sinuses, or lung. PMID- 10030243 TI - Vasomotor rhinitis following trauma to the nose. AB - Complaints of nasal obstruction following nasal trauma without any deformation have been noticed by rhinologists for many years. However, neither an epidemiologic nor a pathophysiologic connection has ever been established. The complaints and physical examination findings of these patients resemble those of vasomotor rhinitis. Only very few articles suggesting nasal trauma as a possible cause for vasomotor rhinitis have ever been published. We present a retrospective study that found 87 of 802 patients to suffer from vasomotor rhinitis following nasal trauma. No other factors known to cause vasomotor rhinitis were present in these patients. None had any previous nasal problems. We therefore suggest that nasal trauma was the causative factor in their vasomotor rhinitis. PMID- 10030244 TI - Multiple myeloma presenting as proptosis. PMID- 10030245 TI - Laryngeal pathology in the acquired immunodeficiency syndrome: diagnostic and therapeutic dilemmas. AB - The acquired immunodeficiency syndrome has produced a growing population of patients who, because of their associated immune system compromise, are prone to opportunistic infections and neoplastic diseases. The larynx, with its relatively inaccessible yet critical anatomic location, is a site in which these processes can produce clinical dilemmas, with respect to diagnosis as well as to therapy. By presenting 4 cases involving unusual laryngeal problems in patients infected with the human immunodeficiency virus (HIV), we emphasize these inherent diagnostic and therapeutic problems. Otolaryngologists must be familiar with the many diagnostic possibilities and therapeutic alternatives when HIV-infected patients present with laryngeal complaints. PMID- 10030246 TI - The employment experience of the graduates of 1996. PMID- 10030247 TI - In vivo dosimetry during external photon beam radiotherapy. AB - In this critical review of the current practice of patient dose verification, we first demonstrate that a high accuracy (about 1-2%, 1 SD) can be obtained. Accurate in vivo dosimetry is possible if diodes and thermoluminescence dosimeters (TLDs), the main detector types in use for in vivo dosimetry, are carefully calibrated and the factors influencing their sensitivity are taken into account. Various methods and philosophies for applying patient dose verification are then evaluated: the measurement of each field for each fraction of each patient, a limited number of checks for all patients, or measurements of specific patient groups, for example, during total body irradiation (TBI) or conformal radiotherapy. The experience of a number of centers is then presented, providing information on the various types of errors detected by in vivo dosimetry, including their frequency and magnitude. From the results of recent studies it can be concluded that in centers having modern equipment with verification systems as well as comprehensive quality assurance (QA) programs, a systematic error larger than 5% in dose delivery is still present for 0.5-1% of the patient treatments. In other studies, a frequency of 3-10% of errors was observed for specific patient groups or when no verification system was present at the accelerator. These results were balanced against the additional manpower and other resources required for such a QA program. It could be concluded that patient dose verification should be an essential part of a QA program in a radiotherapy department, and plays a complementary role to treatment-sheet double checking. As the radiotherapy community makes the transition from the conventional two-dimensional (2D) to three-dimensional (3D) conformal and intensity modulated dose delivery, it is recommended that new treatment techniques be checked systematically for a few patients, and to perform in vivo dosimetry a few times for each patient for situations where errors in dose delivery should be minimized. PMID- 10030248 TI - Enhancement of local control in locally advanced node-positive nasopharyngeal carcinoma by adjunctive chemotherapy. AB - PURPOSE: To determine the efficacy of chemotherapy adjunctive to radical radiotherapy (neoadjuvant +/- adjuvant) in patients with node-positive nasopharyngeal carcinoma (NPC). METHODS AND MATERIALS: All the node-positive patients given adjunctive chemotherapy between 1984-1989 (n = 209, CHEMO) were compared with all the node-positive patients treated by radical radiotherapy alone during the same period (n = 409, NCHEMO). The CHEMO group had significantly more bulky nodes, lower cervical/supraclavicular nodes, and more advanced overall stages than the NCHEMO group because nodal size (> or =24 cm) was used as a selection criterion for chemotherapy (1984-1988 departmental protocol and 1988 1989 prospective randomized trial). The chemotherapy consisted of two courses of neoadjuvant cisplatin (100 mg/m2 D1) and 5-fluorouracil (5-FU) (1 gm/m2 D1-D3) in 191 patients. In addition to the two courses of neoadjuvant, four courses of adjuvant chemotherapy, of the same combination, were given after radical radiotherapy in a further 18 patients. Radical radiotherapy delivered a nasopharyngeal dose of 60-62.5 Gy. In addition, parapharyngeal booster external radiotherapy (20 Gy) was given in the presence of parapharyngeal involvement, and intracavitary brachytherapy (24 Gy) was used to treat any local residual tumor diagnosed at 4-6 weeks after external radiotherapy. Both crude and actuarial rates were compared (survival, distant metastases, and local failures) between CHEMO and NCHEMO for all patients, for individual Ho's overall stage, for patients with nodes of different sizes (< or =3 cm, >3-< or =6 cm, >6 cm), for individual T-stage and individual N-stage, and for patients belonging to different gender and different age groups (<40 years, > or =40 years). Multivariate analyses using the Cox Regression Model were performed to identify significant prognostic factors. RESULTS: With a median follow-up of 5.5 years (range 0.7 to 10 years), CHEMO had significantly less local failures overall than NCHEMO; this was especially true for patients with advanced stages (III + IV). Additionally, in all nodal-size subgroups, in all node-positive T3, and in node positive T3-Stage IV, there was a significant reduction in local failures after chemotherapy. There was a trend toward fewer local failures in favor of chemotherapy in Stage III, Stage IV, and T3-Stage III (0.05 or =14.1 cm3, respectively. RESULTS: Median follow-up was 2.3 years (range 0.1-6) for 80 of 82 patients. The actuarial incidence (Kaplan-Meier) of facial neuropathy at 2 years was 38% (95% confidence interval [CI], 23-53%) for the standard-dose protocol and 8% (95% CI, 0-17%) for the reduced-dose protocol (p = 0.006). Univariate analysis revealed an association between risk of facial neuropathy and use of CT planning, higher radiosurgical dose, and neurofibromatosis, type 2. Multivariate analysis revealed that the only factor associated with increased risk of post-treatment facial neuropathy was a tumor margin dose > or =18 Gy. The incidence of trigeminal neuropathy at 2 years was 29% (95% CI, 15-43%) for the standard-dose protocol and 15% (95% CI, 3-27%) for the reduced-dose protocol (p = 0.17). Univariate analysis revealed an association between maximal tumor diameter and increased risk of trigeminal neuropathy; multivariate analysis revealed no additional statistically significant associations between tumor and dosimetric and patient characteristics and risk of trigeminal neuropathy. Two tumors in the standard-dose protocol required salvage surgery for progression. To date, no tumor in the reduced-dose protocol has shown progression. CONCLUSION: Our analysis suggests that a tumor margin dose of > or =18 Gy is the most significant risk factor for facial nerve complications after acoustic neuroma radiosurgery. Patients receiving a minimal tumor dose of < or =16 Gy are at significantly lower risk for permanent facial neuropathy after radiosurgery. Longer follow-up is required before definitive conclusions can be made about the ultimate rate of tumor control using reduced radiosurgical doses. PMID- 10030256 TI - Linac radiosurgery for benign meningiomas. AB - PURPOSE: To review outcomes for patients treated with linac radiosurgery for benign meningiomas. METHODS AND MATERIALS: Between January 1989 and July 1997, 70 patients with 76 meningiomas were treated with LINAC-based radiosurgery. In 38 patients, radiosurgery was the initial treatment. In 32 patients, radiosurgery followed surgery or conventional radiotherapy. The average treatment volume was 10.0 cm3 (range, 0.6 to 28.6 cm3). The mean peripheral dose was 12.7 Gy (range, 10 to 20 Gy). The mean clinical follow-up period was 23 months. No patient was lost to follow-up. RESULTS: No lesions enlarged during the follow-up period; of 48 lesions in patients who had follow-up for at least one year and hence had follow-up imaging, 27 tumors remained unchanged and 21 tumors were reduced in size. Two patients experienced transient radiation-induced neurological deficits. One was treated with surgical excision of the tumor; the other responded to prolonged steroid therapy. Both patients, treated early in our experience, received doses higher than we would currently recommend. CONCLUSIONS: Early results suggest that stereotactic radiosurgery is an effective treatment for meningiomas. Long-term follow-up will be necessary to fully evaluate its efficacy. PMID- 10030257 TI - Hodgkin's disease with lymphocyte predominance: long-term results based on current histopathologic criteria. AB - PURPOSE: To define the disease course, therapeutic strategies, patterns and rates of relapse and causes of death for patients with Hodgkin's disease with lymphocyte predominance (LPHD) and to assess prognostic factors including nodular and diffuse histologic patterns. PATIENTS AND METHODS: The records of all previously untreated patients with LPHD who received initial treatment at the University of Texas M. D. Anderson Cancer Center (UTMDACC) from 1960 through 1992 were reviewed. Clinical and histopathologic characteristics, specifically nodular and diffuse LPHD, and treatment groups were assessed by overall and relapse-free survival, patterns of relapse, and causes of death. RESULTS: Of 70 patients, 58 (83%) had nodular LPHD and 12 (17%) had a diffuse pattern: clinical characteristics were similar between the two subtypes. The median age of all patients was 25 years, 79% were male, 96% presented with stage I or II disease and 93% were free of B symptoms. Laparotomy (23 patients) failed to upstage any patient with a negative lymphogram. With a median follow-up of 12.3 years for alive patients, 19 (27%) patients have relapsed. All 3 relapses among the patients with diffuse subtype occurred within 3 years while 9 of 16 relapses occurred after 5 years with nodular subtype. However, we did not detect any statistically significant difference in relapse free survival or survival between the subtypes in our patient population. There was some suggestion that patients aged 40 and older experienced shorter survival; no other pretreatment characteristics were noted to be associated with relapse free survival or survival. Though there were no relapses within the radiation fields, no effect of extent of radiation therapy on relapse rate was observed. Thirteen (19%) patients have died, 6 (8.6%) of whom succumbed to LPHD. Two patients developed diffuse large cell lymphoma. CONCLUSIONS: Patients with LPHD usually present with localized and asymptomatic disease. Laparotomy is unnecessary if the lymphogram is negative. Nodular histology occurred in the majority of patients. Though all relapses from diffuse subtype occurred within 3 years in contrast to some late relapses observed for nodular subtype, there was no statistically significant difference in relapse free survival or survival between the subtypes. The extent of irradiation had no effect on relapse free survival or survival. We could not find any evidence that LPHD should be treated any different from the classical Hodgkin's disease at this point despite suggestions that it be classified as a non-Hodgkin's B-cell lymphoma. PMID- 10030258 TI - Results of the 1988-1989 Patterns of Care Study process survey for Hodgkin's disease. AB - PURPOSE: To document national standards of care for patients receiving radiotherapy as part of curative treatment for Hodgkin's disease. MATERIALS AND METHODS: A national survey was conducted of 61 institutions treating 275 patients with Stages I-III Hodgkin's disease and representing six facility type strata. Pretreatment evaluation, radiotherapy treatment parameters, and use of combined modality therapy were assessed. RESULTS: Ann Arbor stage for the 275 patients was as follows: IA, 69 (25%); IB, 7 (3%); IIA, 123 (45%); IIB, 36 (13%); IIIA 23 (8%), IIIB, 14 (5%); unknown, 3 (1%). Pretreatment evaluation included complete blood count for 93%, sedimentation rate in 29%, chest CT in 88%, abdominal CT scan in 87%, and bone marrow biopsy in 81%. Lymphangiograms were obtained in 50% of cases; laparotomy was performed in 46%. The yield of positive findings in the spleen at laparotomy was 6.5 % overall. Facility differences with respect to staging were seen only for the use of gallium scans, which were more commonly used in academic centers (44% vs. 15-23% elsewhere, p<0.001). Radiotherapy was delivered with a linear accelerator in 94% of cases. Treatment simulation was performed for 94% and individualized blocks constructed for 95% overall; however, freestanding facilities had a lower rate of performance of these procedures (78% vs. 98-99% for simulation and 88% vs. 96-99% for customized blocking, p<0.001). The mean supradiaphragmatic dose was 36.74 Gy and the mean subdiaphragmatic dose was 33.81 Gy. Planned combined modality therapy was given in 36% of patients. The use of combined modality therapy by stage was as follows: IA, 11%; IB, 43%; IIA, 30%; IIB, 68%; IIIA, 57%; IIIB, 100%. Chemotherapy was completed prior to radiation in 80% of cases and generally consisted of ABVD (32%), an alternating regimen (25%), or MOPP (22%). Among Stage I/II patients, use of chemotherapy was associated with reduced radiation doses (mean supradiaphragmatic dose 34.53 Gy vs. 38.43 Gy and mean subdiaphragmatic dose 31.27 Gy vs. 34.51 Gy), and reduced volumes of treatment (87% vs. 28% treated to one side of the diaphragm only). Laparotomy was not associated with decreased supra- or subdiaphragmatic radiation doses or decreased volumes of treatment. CONCLUSIONS: With the exception of gallium scans, pretreatment evaluation is relatively uniform across facility strata. Increased understanding of prognostic factors in Hodgkin's disease and greater use of planned combined modality therapy for higher risk patients appears to have contributed to a decreased use of and low yield of positive findings for laparotomy. Laparotomy was not associated with reduced radiation volumes or doses. Freestanding radiation facilities had a lower rate than other facility types for the performance of treatment simulation and customized patient blocking. PMID- 10030259 TI - Mammographic, pathologic, and treatment-related factors associated with local recurrence in patients with early-stage breast cancer treated with breast conserving therapy. AB - BACKGROUND: We retrospectively reviewed our institution's experience treating early-stage breast cancer patients with breast conserving therapy (BCT) to determine clinical, pathologic, mammographic, and treatment-related factors associated with outcome. METHODS: Between January 1980 and December 1987, 400 cases of Stage I and II breast cancer were managed with BCT at William Beaumont Hospital, Royal Oak, Michigan. All patients underwent at least an excisional biopsy. Radiation treatment consisted of delivering 45-50 Gy to the whole breast, followed by a boost to the tumor bed to at least 60 Gy in all patients. The median follow-up in the 292 surviving patients is 118 months. Multiple clinical, pathologic, mammographic, and treatment-related factors were analyzed for an association with local recurrence and survival. RESULTS: A total of 37 local recurrences developed in the treated breast, for a 5- and 10-year actuarial rate of 4% and 10%, respectively. On univariate analysis, patient age < or =35 years (25% vs. 7%, p = 0.004), and positive surgical margins (17% vs. 6%, p = 0.018) were associated with an increased risk of local recurrence at 10 years. On multivariate analysis, only age < or = 35 years remained significant. A subset analysis of 214 patients with evaluable mammographic findings was performed. On univariate analysis, age < or = 35 years (38% vs. 8%, p = 0.0029) and the presence of calcifications on preoperative mammography (22% vs. 6%, p = 0.0016) were associated with an increased risk of local recurrence. On multivariate analysis, both of these factors remained significant. The presence of calcifications on preoperative mammography did not affect the rates of overall survival, disease-free survival, and cause-specific survival. CONCLUSION: In patients with early-stage breast cancer treated with BCT, age < or = 35 years and calcifications on preoperative mammography appear to be associated with an increased risk of local recurrence. PMID- 10030260 TI - The importance of surgical clips for adequate tangential beam planning in breast conserving surgery and irradiation. AB - PURPOSE: To evaluate the role of surgical clips in the planning of tangential beams in patients undergoing breast conserving surgery and adjuvant radiotherapy. METHODS AND MATERIALS: Between September 1996 and April 1998, 25 consecutive female patients with ductal carcinoma in situ, Stage I and II cancer of the breast, underwent lumpectomy with the excision cavity marked by the surgical clips. Subsequently, tangential fields were planned using clinical and radiologic information obtained during simulation without the clips position being visible. RESULTS: When measured from the center of the deepest clip to the posterior field border of the tangential fields in 6/25 patients (24%) the distance was less than 2 cm, with the closest being only 0.5 cm. Respective measurements for the distal end of the clip and the posterior border were: 9/25 patients (36%); less than 2 cm, with the closest distance of 0.3 cm. There was a positive correlation between the distance from the scar to the palpable breast border and the distance between the deepest clip and the posterior border of the tangential beams. CONCLUSION: The lumpectomy scar is often a poor indicator of the excision cavity as demarcated by surgical clips. Without the clips, part of the cavity may be underdosed by the tangential radiation beams. This is more likely for the cavities located close to the lateral or medial border of the breast tissue. PMID- 10030261 TI - Patterns of radiotherapy practice for patients with squamous carcinoma of the uterine cervix: patterns of care study. AB - PURPOSE: To determine the impact of research findings and evolving technology on the patterns of radiotherapy practice for patients with carcinoma of the uterine cervix. METHODS AND MATERIALS: Sixty-two radiation therapy facilities participated in the study after having been selected from a random sample, proportionally stratified according to practice type, of all United States facilities. Each facility submitted a list of patients treated during 1992-1994 with radiation for squamous carcinoma of the cervix. Cases for review were randomly selected from each institution after excluding those of patients who had distant metastases or initial hysterectomy. A total of 471 patients' records were reviewed in the treating institutions to obtain information about patients' characteristics, diagnostic evaluation, tumor extent, treatment approach, and radiotherapy techniques. RESULTS: Of the 61 facilities that treated eligible cases of intact cervical cancer during the 3-year survey period, 35 (57%) treated fewer than three eligible patients per year. Thirty-four (83%) of 41 non-academic facilities vs. 1 (5%) of 20 academic facilities treated fewer than three patients per year. FIGO stages were I, II, III, and IV in 32%, 40%, 24%, and 3% of patients, respectively. Computed tomography (CT) was the most common method of lymph node evaluation, but surgical evaluation, which was performed in 76 (16%) patients, had increased from previous surveys. Fields were designed using a dedicated simulator in 95% of patients; a dedicated CT unit was used for treatment planning in 119 (30%) cases. External beam irradiation was most often given using a four-field technique at 180 cGy per day on a 10-20 MV linear accelerator. The average daily fraction size had decreased from previous surveys, and 13% of patients were treated with daily doses of 170 cGy or less. Most patients were treated with a combination of external beam and low dose-rate (LDR) intracavitary irradiation. Of 425 patients who had treatment with curative intent that included brachytherapy, 362 (85%) had LDR brachytherapy, 45 (11%) had high dose-rate (HDR) brachytherapy, 3 had a combination of HDR and LDR, and 15 had incomplete information about the brachytherapy dose-rate. Forty-six (23%) of 197 patients with Stages I-IIA disease were treated with radiation followed by extrafascial hysterectomy. Of 111 patients treated with curative intent for Stage III-IV disease, 72 (65%) had a combination of external beam and intracavitary radiation therapy, 22 (20%) had external beam plus interstitial brachytherapy, and 17 (15%) were treated with external beam irradiation only. For patients who completed treatment with curative intent and did not have adjuvant hysterectomy or HDR brachytherapy, the median total dose at point A was 82.5 Gy. For all patients who completed treatment with radiation alone, the median total duration of treatment was 63 days; more than 70 days were taken to complete treatment in 33% of cases. Twenty-nine percent of patients received chemotherapy, usually concurrent with their radiation therapy. Only 27% of these patients were on investigational protocols. CONCLUSIONS: Greater participation in well-designed prospective trials might help clinicians address important clinical questions and reduce current inconsistencies in the use of adjuvant treatments. Radiation oncologists should take steps to avoid unnecessary treatment protraction and to improve patient compliance. Future studies will be needed to determine whether the small number of cases being treated in most nonacademic facilities will influence the outcome for patients with invasive cervical carcinoma. PMID- 10030262 TI - Literature analysis of high dose rate brachytherapy fractionation schedules in the treatment of cervical cancer: is there an optimal fractionation schedule? AB - PURPOSE: A literature review and analysis was performed to determine whether or not efficacious high dose rate (HDR) brachytherapy fractionation schedules exist for the treatment of cervical cancer. METHODS AND MATERIALS: English language publications from peer reviewed journals were assessed to calculate the total contribution of dose to Point A from both the external and intracavitary portions of radiation for each stage of cervical cancer. Using the linear quadratic formula, the biologically effective dose to the tumor, using an alpha/beta = 10, was calculated to Point A (Gy10) in order to determine a dose response relationship for local control and survival. Significant complications were assessed by calculating the dose to the late-responding tissues at Point A using an alpha/beta = 3 (Gy3) as a surrogate for normal tissue tolerance, since few publications list the actual bladder and rectal doses. RESULTS: For all stages combined, the median external beam fractionation schedule to Point A was 40 Gy in 20 fractions, while the median HDR fractionation schedule was 28 Gy in 4 fractions. For stages IB, IIB, and IIIB the median biologically effective dose to Point A (Gy10) was 96, 96 and 100 Gy10s, respectively. No correlation was identified between Point A BED (Gy10s) to either survival or pelvic control. A dose response relationship could also not be identified when correlating Point A Gy3s to complications. CONCLUSION: A dose response relationship could not be identified for either tumor control nor late tissue complications. These findings do not necessarily question the validity of the linear quadratic model, as much as they question the quality of the current HDR brachytherapy literature as it is currently presented and reported. Most of the HDR publications report inadequate details of the dose fractionation schedules. Only a minority of publications report significant complications using the actuarial method. In the future, all HDR publications for the treatment of cervical cancer should provide accurate fractionation details for each stage of disease, while reporting actuarial complication rates. The optimal fractionation schedule for treating cervical cancer using HDR brachytherapy is still unknown, and presently can be based only on single institutions with significant experience. PMID- 10030263 TI - Oxygenation of cervical cancers during radiotherapy and radiotherapy + cis retinoic acid/interferon. AB - PURPOSE: We have evaluated the tumor tissue pO2 in cervical cancers during radiotherapy with special emphasis on the course of the pO2 in primarily hypoxic tumors and in patients treated with radiotherapy plus 13-cis-retinoic acid/interferon-alpha-2a. METHODS AND MATERIALS: From June 1995 through April 1997, 49 patients with squamous cell carcinoma FIGO IIB-IVA of the cervix who were treated with definitive radiotherapy with curative intent underwent polarographic measurement of tumor tissue pO2 with an Eppendorf pO2-histograph prior to and during radiation treatment. Radiotherapy consisted of external irradiation with 50.4 Gy in 28 fractions of 1.8 Gy plus high dose rate (HDR) brachytherapy. Twenty-two patients had additional treatment with 13-cis-retinoic acid (cRA, isotretinoin) and interferon-alpha-2a (IFN-alpha-2a). Therapy with cRA/IFN in these patients started 2 weeks before radiotherapy; during this induction period, cRA was administered in a dosage of 1 mg per kilogram body weight orally daily and IFN-alpha-2a in a dosage of 6x10(6) I.U. subcutaneously daily. After start of external radiotherapy (XRT), cRA/IFN was continued concomitantly with radiotherapy in reduced doses (0.5 mg cRA per kg body weight orally daily plus 3x10(6) I.U. IFN-alpha-2a subcutaneously three times weekly until the end of the radiation treatment). PO2 measurements were performed prior to radiotherapy, at 20 Gy, and at the end of radiotherapy. RESULTS: A poor oxygenation defined as a median pO2 of 10 mm Hg or less was present in 15/38 tumors (39%) in which measurements prior to any treatment were done. Low pO2 readings below 5 mm Hg were present in 70% of all tumors prior to treatment. In 13 of 15 hypoxic tumors, pO2 measurements at 19.8 Gy were performed. In these tumors, a significant increase of the median pO2 from 6.0+/-3.1 mm Hg to 20.7+/ 21.2 mm Hg was found, p<0.01. The increase in the median pO2 was more pronounced in patients with radiotherapy plus additional cRA/IFN treatment as compared to patients treated with irradiation alone (median pO2 raised from 7.0+/-3.5 mm Hg to 40.9+/-21.3 mm Hg versus 5.7+/-3.1 mm Hg to 14.7+/-17.9 mm Hg). In a multivariate analysis, both the effect of radiation dose (pretreatment versus 19.8 Gy) and the type of treatment (XRT alone versus XRT plus cRA/IFN) had significant impact on the pO2 (P = 0.003 and p = 0.04). In patients with well oxygenated tumors (pretreatment median pO2>10 mm Hg), 20/23 (87%) achieved a clinically complete response. In patients with primarily hypoxic tumors, 6/6 patients whose primarily hypoxic tumors showed an increase of the median pO2 above 10 mm Hg at 19.8 Gy achieved a complete remission (CR). In contrast, only 4/7 patients with a low pretreatment and persisting low median pO2 achieved a CR. CONCLUSIONS: There are evident changes in the oxygenation of cervical cancers during a course of fractionated radiotherapy. In primarily hypoxic tumors, a significant increase of the median pO2 was found. An additional treatment with cis-retinoic acid/interferon further improved the oxygenation. An impact of the different patterns of oxygenation on local control is to be evaluated. PMID- 10030264 TI - Comparability of CT-based and TRUS-based prostate volumes. AB - PURPOSE: To compare the prostate volumes defined by transrectal ultrasound (TRUS) versus computed tomographic (CT) scans used for brachytherapy planning. METHODS AND MATERIALS: Ten unselected patients underwent evaluation for prostate brachytherapy with TRUS and CT imaging. Axial prostate contours were obtained at 5-mm intervals in both studies. The CT images were photographed, scanned into a commercial software program, and reprinted from a laser printer at 600 dots per inch to provide individual images that were interpreted independently by the three physician authors (BK, KW, and JB). An effort was made to exclude pelvic floor muscles from the defined prostate contour. Volumes were calculated in cubic centimeters. The prostate volume and maximum dimension in each plane were compared for each imaging modality. RESULTS: The CT-based prostate volumes ranged from 31.1 cc to 48.1 cc. The TRUS-based volumes ranged from 26.6 cc to 46.4 cc. There was close agreement between imaging modalities (r = 0.9). The anterior posterior, lateral, and craniocaudal prostatic dimensions were similar between modalities. To test for consistency between observers, the CT volumes were drawn independently by KB, KW, and JB. The prostatic measurements were consistent in all dimensions between observers. CONCLUSION: CT scan volumes and measurements correlate well with those obtained by TRUS, and are appropriate for pre- or postimplant dosimetry. PMID- 10030265 TI - Familial prostate cancer: outcome following radiation therapy with or without adjuvant androgen ablation. AB - PURPOSE: To compare the outcome of familial versus sporadic prostate carcinoma after definitive external radiation. METHODS AND MATERIALS: Between 1987 and 1996, 1214 men with clinically localized prostate cancer (T1-T4, N0/NX, M0) received definitive radiation therapy in our department. By retrospective review of charts and questioning of patients, a record on the presence or absence of prostate cancer in a first degree relative was obtained in 1164 men. Univariate and multivariate analysis was performed on these cases with relapse or rising prostate-specific antigen (PSA), local recurrence, metastasis, and survival as endpoints. RESULTS: Familiar prostate cancer was present in 148 of 1164 men (13%). Men with familial disease were slightly but significantly younger (mean 66 years) at diagnosis than those with sporadic disease (mean 68 years) (p = 0.02). Apart from this there were no significant differences between the two groups in T stage, Gleason score, pretreatment PSA levels, DNA ploidy, or serum testosterone levels. There were no significant differences in treatment parameters including radiation dose and the use of adjuvant androgen ablation. With a median follow-up of 42 months, there was no difference in freedom from relapse or rising PSA at 6 years between those with a family history (54%) and those without a family history (58%) (p = 0.171). Likewise there was no difference between the two groups when local recurrence or metastasis was the endpoint. Multiple subgroup analyses (younger and older; T1/T2 and T3; low Gleason and high Gleason; no androgen ablation and androgen ablation; race) failed to reveal any differences in outcome in any category between familial and sporadic disease. Among patients with a rising post-treatment PSA profile, PSA doubling times were similar in those with sporadic and familial disease. CONCLUSIONS: This study provides no evidence for any substantial difference between familial and sporadic prostate cancer either in clinicopathological features, in response to treatment, or in ultimate outcome. PMID- 10030266 TI - Normal tissue complication probabilities correlated with late effects in the rectum after prostate conformal radiotherapy. AB - PURPOSE: Radiation therapy of deep-sited tumours will always result in normal tissue doses to some extent. The aim of this study was to calculate different risk estimates of late effects in the rectum for a group of cancer prostate patients treated with conformal radiation therapy (CRT) and correlate these estimates with the occurrences of late effects. Since the rectum is a hollow organ, several ways of generating dose-volume distributions over the organ are possible, and we wanted to investigate two of them. METHODS AND MATERIALS: A mathematical model, known as the Lyman-Kutcher model, conventionally used to estimate normal tissue complication probabilities (NTCP) associated with radiation therapy, was applied to a material of 52 cancer prostate patients. The patients were treated with a four field box technique, with the rectum as organ at risk. Dose-volume histograms (DVH) were generated for the whole rectum (including the cavity) and of the rectum wall. One to two years after the treatment, the patients completed a questionnaire concerning bowel (rectum) related morbidity quantifying the extent of late effects. RESULTS: A correlation analysis using Spearman's rank correlation coefficient, for NTCP values calculated from the DVHs and the patients' scores, gave correlation coefficients which were not statistically significant at the p<0.01 level. The correlation coefficients based on histograms of the whole rectum were larger than those derived from histograms of the rectum wall. Also, simpler descriptive measures as Dmax, of the whole rectum, correlated better to observed late toxicity than Dmax derived from histograms of the rectum wall. Correlation coefficients from "high dose" measures were larger than those calculated from the NTCP values. Accordingly, as the volume parameter of the Lyman-Kutcher model was reduced, raising the impact of small high-dose volumes on the NTCP values, the correlation between observed effects and NTCP values became significant at p<0.01 level. CONCLUSIONS: 1) High-dose levels corresponding to small volume fractions of the cumulative dose-volume histograms were best correlated with the occurrences of late effects in the rectum as measured with questionnaires. This is compatible with a more serial organisation of the rectal tissue architecture than previously reported. 2) Reducing the Lyman-Kutcher model's volume parameter, thus allowing small high-dose regions to determine the NTCP, improved the correlation, but not beyond that of high-dose levels corresponding to small volume fractions of the cumulative dose-volume histograms. PMID- 10030267 TI - Combined transcatheter arterial chemoembolization and local radiotherapy of unresectable hepatocellular carcinoma. AB - PURPOSE: The best prognosis in hepatocellular carcinoma (HCC) can be achieved with surgical resection; however, the number of resected cases are limited due to advanced lesions or associated liver disease. The purpose of this study was to investigate the efficacy and toxicity of a prospective trial of combined transcatheter arterial chemoembolization (TACE) and local radiotherapy (RT) in unresectable HCC. METHODS AND MATERIALS: Patients with histologically proven unresectable HCC due to either advanced lesions or associated cirrhosis were eligible. From March 1992 to August 1994, 30 patients were entered into this study. TACE was performed with Lipiodol (5 ml) and doxorubicin (Adriamycin ; 50 mg), followed by gelatin sponge particle (Gelfoam) embolization. Local RT was started within 7-10 days following TACE. Mean tumor dose was 44.0+/-9.3 Gy in daily 1.8 Gy fractions. Response was assessed by computerized tomography (CT) scan 4-6 weeks following completion of the treatment and then at 1-3-month intervals. Survival was calculated from the start of TACE using the Kaplan-Meier method. RESULTS: An objective response was observed in 19 patients, giving a response rate of 63.3%. Distant metastasis occurred in 10 patients, with 8 in the lung only and 2 in both lung and bone. Survival rates at 1, 2, and 3 years were 67%, 33.3%, and 22.2%, respectively. Median survival was 17 months. There were 6 patients surviving more than 3 years. Toxicity included transient elevation of liver function tests in all patients, fever in 20, thrombocytopenia in 4, and nausea and vomiting in 1. There was no treatment-related death. CONCLUSION: Combined TACE and local RT is feasible and tolerable. It gives a 63.3% response rate with median survival of 17 months. We feel that this regimen would be a new promising modality in unresectable HCC. Further study is required to compare the therapeutic efficacy of this regimen to TACE alone. PMID- 10030268 TI - p53 function influences the effect of fractionated radiotherapy on glioblastoma tumors. AB - PURPOSE: Glioblastoma multiforme brain tumors (GM) are treated with a spectrum of fractionation regimens based on the clinical and anatomical characteristics of the tumor but rarely based on the molecular characteristics of the individual neoplasm. This study tests the hypothesis that the response of cell lines derived from GM to fractionated radiotherapy depends on the function of wild-type p53 (wt p53), a tumor suppressor gene frequently mutated in GM tumors. METHODS & MATERIALS: Isogenic derivatives of glioblastoma cells differing only in p53 function were prepared using a retroviral vector expressing a dominant negative mutant of p53 (mt p53). Radiation survival in vitro was quantitated using linear quadratic and repair-saturation mathematical models. Apoptosis was assayed by a terminal deoxynucleotide transferase-labeling technique and chromatin morphology. RESULTS: We have previously reported the generation of isogenic GM cell lines differing only in p53 function. U87-175.4, lacking wt p53 function, had a significantly lower alpha/beta value than U87-LUX.8, expressing functional wt p53, leading us to hypothesize that fractionated irradiation would preferentially spare GM cells harboring mt p53 compared with those expressing functional, wt p53. Survival curves following either 2.0 Gy or 3.5 Gy/fraction demonstrated that lack of functional wt p53 was associated with resistance to fractionated irradiation. Radiation-induced apoptosis could not account for the observed differences in clonogenic survival. Rather, our data suggested that a deficit in the G1-checkpoint contributed to increased resistance to fractionated irradiation of cells expressing mutant p53. CONCLUSIONS: The effect of fractionated radiotherapy in GM may depend on the function of the tumor suppressor gene p53. A potential clinical consequence of these findings is that hyperfractionation regimens may provide a therapeutic advantage specifically for tumors expressing wt p53 whereas a radiotherapy course of fewer, larger fractions may be appropriate for the treatment of tumors carrying p53 mutations. Further studies are needed to confirm our proposal that the p53 status of GM tumors can be used to guide our choice of fractionation schemes. PMID- 10030269 TI - The combined effect of interferon beta and radiation on five human tumor cell lines and embryonal lung fibroblasts. AB - PURPOSE: The combined effect of natural Interferon-beta (n-IFN-beta) and ionizing radiation was tested in vitro on 5 different tumor cell lines and 1 embryonal lung fibroblast cell line. MATERIALS AND METHODS: The following cell lines were used: A549 (lung cancer), MCF-7 (breast cancer), CaSki (cervical cancer), WiDr (colon cancer), ZMK-1 (head and neck cancer), and MRC-5 (embryonal lung fibroblast line). Cells were incubated with n-IFN-beta (30 I.U./ml to 3000 I.U./ml) 24 h before irradiation. Irradiation was given as single dose between 1 and 6 Gy. Cell survival was evaluated using a standard colony-forming assay. RESULTS: Incubation with n-IFN-beta enhanced the effect of radiation in all tumor cell lines tested. The maximum sensitizing enhancement ratios (SER) at the 37% survival level were: 1.66 for A549 cells, 1.47 for CaSki cells, 1.56 for MCF-7 cells, 1.40 for WiDr cells, and 1.57 for ZMK-1 cells. In the nonneoplastic MRC-5 cell line, no radiosensitizing effect of n-IFN-beta could be demonstrated. The linear quadratic fit of the survival curves showed an increase of the alpha component for all tumor cell lines treated with n-IFN-beta. CONCLUSIONS: IFN-beta enhanced the effect of radiation in the tumor cell lines, but not in the nonmalignant lung fibroblasts. The increase of the alpha component in the survival curves indicates that impaired radiation repair or the accumulation of sublethal damage might play a role for the radiosensitizing effect of n-IFN-beta. PMID- 10030270 TI - Diltiazem enhances tumor blood flow: MRI study in a murine tumor. AB - PURPOSE: Diltiazem, a calcium-channel blocker, is known to differentially influence the radiation responses of normal and murine tumor tissues. To elucidate the underlying mechanisms, the effects of diltiazem on the radiation response of Ehrlich ascites tumor (EAT) in mice have been investigated, and the hemodynamic changes induced by diltiazem in tumor and normal muscle have been studied using magnetic resonance imaging (MRI) techniques. METHODS AND MATERIALS: Ehrlich ascites tumors were grown subcutaneously in Swiss albino strain A mice. Dynamic gadodiamide and blood oxygen level dependent (BOLD) contrast enhanced 1H MR imaging studies of EAT and normal muscle were performed after administration of diltiazem in mice using a 4.7 Tesla MR scanner. Tumor radiotherapy experiments (total dose = 10 Gy, 0.4-0.5 Gy/min, single fraction) were carried out with 30 min preadministration of diltiazem (27.5 or 55 mg/kg i.p.) to EAT-bearing mice using a teletherapy machine. RESULTS: The diltiazem+ radiation treated group showed significant tumor regression (in approximately/= 65% of the animals) and enhanced animal survival. MR-gadodiamide contrast kinetics revealed a higher magnitude of signal enhancement in diltiazem treated groups as compared to the controls. The observed changes in the magnitude of kinetic parameters were the same for both tumor and normal muscle. BOLD-MR images at 30 min after diltiazem administration showed a 25% and 8% (average) intensity enhancement from their basal values in tumor and normal muscle regions, respectively. The control group showed no significant changes. CONCLUSION: The present studies demonstrate the radiosensitization potential of diltiazem in the mice EAT model. The enhanced radiation response observed with diltiazem correlates with the diltiazem-induced increase in tumor blood flow (TBF) and tumor oxygenation. The present results also demonstrate the applications of BOLD-MR measurements in investigating the alterations in tumor oxygenation status. PMID- 10030271 TI - 'Loop' domain deletional mutant of Bcl-xL is as effective as p29Bcl-xL in inhibiting radiation-induced cytosolic accumulation of cytochrome c (cyt c), caspase-3 activity, and apoptosis. AB - PURPOSE/OBJECTIVE: To investigate the effect of the enforced expression of p29Bcl xL or its loop deletional mutant, p18Bcl-xLdelta, on irradiation-induced apoptosis and cell-cycle distribution of HL-60 cells. MATERIALS & METHODS: We compared the irradiation-induced molecular cascade of apoptosis in control human AML HL-60/neo versus Bcl-xL overexpressing (approximately 8-fold) (HL-60/Bcl-xL) and HL-60/Bcl-XLdelta cells that express the loop domain deletional mutant construct (delta26-83 AA) of Bcl-xL. The three cell lines were irradiated with 6MV photons to varying doses up to 20 Gy. Following this, cytosolic cyt c levels, caspase-3 activity, and the Bcl-2 family of proteins were evaluated utilizing Western blot analysis (whole cell lysate or cytosolic S-100 fraction). Apoptosis was assessed by internucleosomal DNA fragmentation, Annexin-V staining and FACS analysis, as well as by morphologic criteria. The cell-cycle effects of radiation were analyzed by flow cytometry. RESULTS: Eight hours following irradiation (12 Gy) of HL-60/neo cells, a marked increase (approximately 8-fold) in the cytosolic accumulation of cyt c in the S-100 fraction was observed. This was associated with the cleavage of caspase-3, as well as the generation of its poly (ADP ribose) polymerase (PARP) and DFF (DNA fragmentation factor)-45 cleavage activity. Twenty-four to forty-eight hours after irradiation, internucleosomal DNA fragmentation and positive Annexin-V staining (32.3+/-3.3%) was detected in HL-60/neo cells. In contrast, in both HL-60/Bcl-xL and HL-60/Bcl-xLdelta cells, a significantly lower percentage of apoptotic cells (p<0.05) were detected and internucleosomal DNA fragmentation was not induced. Following irradiation, Western analysis neither demonstrated any significant alteration in Bcl-2, p29Bcl xL, p18Bcl-xLdelta, or Bax; nor induced CD95 (Fas receptor) or Fas ligand expression in any cell type. However, in all cell types, irradiation produced approximately a 2-fold increase in the percentage of cells in the G2/M phase of the cell cycle. CONCLUSION: These results demonstrate that an intact loop domain is not necessary for the full antiapoptotic function of Bcl-xL against irradiation-induced cytosolic accumulation of cyt c, caspase activation, and apoptosis of HL-60 cells. Additionally, the cell-cycle effects of ionizing radiation in HL-60 cells are not affected by enforced expression of Bcl-xL or Bcl xLdelta. PMID- 10030272 TI - The combined effect of boronophenylalanine and borocaptate in boron neutron capture therapy for SCCVII tumors in mice. AB - PURPOSE: To increase the effect of boron neutron capture therapy (BNCT) on tumors in vivo, the combined effects of para-boronophenylalanine (BPA) and borocaptate sodium (BSH) were investigated. METHODS AND MATERIALS: 10B-enriched BPA and BSH were administered to C3H/He mice bearing SCCVII tumors by intragastric and intravenous injections, respectively. The colony formation and tumor control assays were employed for investigating antitumor effects of BNCT. The extent of homogeneity of tumor cell killing effect was examined by the distribution of frequencies of binuclear cells (BNC) producing a certain number of micronuclei (0,1,2,--,> or =5) to total number of BNC and by the comparison between surviving cell fraction (SF) in colony formation assay and the normal nuclear division fraction (NNDF) at first mitosis following BNCT. RESULTS: The relationships between SF and radiation dose in Gy (D) at around 10 ppm of 10B in tumors were as follow: -InSF = -0.101 + 0.648 Gy(-1) x D, 0.0606+0.435 Gy(-1) x D, and -0.0155 + 0.342 Gy(-1) x D for BPA, BPA + BSH, and BSH, respectively. In tumor control assay, BPA was also more effective than BSH, but the difference of effectiveness significantly decreased: 1.9 times more effective in colony assay vs. 1.2 times in tumor control assay. The most effective treatment to achieve tumor cure was BNCT using BPA + BSH, and it was 1.9 times more effective than BSH-BNCT. In BSH BNCT, NNDF decreased exponentially with radiation dose and was equal to SF. However, NNDF following BPA-BNCT showed a biphasic decrease with radiation dose, and SF was much lower than NNDF. In the combination of BPA and BSH, the discrepancy between NNDF and SF decreased in comparison with BPA-BNCT. The distribution of frequency of BNC with a certain number of micronuclei to total BNC was very close to Poisson distribution in BSH-BNCT tumors; however, it deviated from the Poisson in BPA-BNCT tumors. In combination with BPA and BSH, the distribution showed an intermediate pattern. These findings indicate that BSH distributes homogeneously with a heterogeneous distribution of BPA in tumors, and the heterogeneous effect of BPA-BNCT was improved by the combination of two boron compounds. CONCLUSION: The heterogeneous cell killing effect of BPA-BNCT was improved by the combination of BSH, and increased tumor control rates. Therefore, this combination may improve clinical outcome of BNCT although the effects on normal tissues have to be examined before clinical application. PMID- 10030273 TI - Computerized design of target margins for treatment uncertainties in conformal radiotherapy. AB - PURPOSE: We describe a computerized method of determining target margins for beam aperture design in conformal radiotherapy plans. MATERIALS AND METHODS: The method uses previously measured data from a population of patients to simulate setup error and organ motion in the patient currently being planned. Starting with a clinical target volume (CTV) and nontarget organs from the patient's planning CT scan, the simulation is repeated many times to produce a spatial probability distribution for each organ in the treatment machine coordinate system. This is used to determine a prescribed dose volume (PDV), defined as the volume to receive the prescribed dose, which encompasses the CTV while restricting the volume of nontarget organs within it, according to planner specified values. The PDV is used to design beam apertures using a conventional margin for beam penumbra. RESULTS: The method is applied to 6-field prostate conformal treatment plans, in which the PDV encloses the prostate and seminal vesicles while limiting the enclosed rectal wall volume. The effect of organ motion is assessed by applying the plans on subsequent CT scans of the same patients, calculating probabilities for tumor control (TCP) and normal tissue complication (NTCP), and comparing with plans designed from a physician-drawn planning target volume (PTV). Although prostate TCP and rectal wall NTCP are found to be similar in the two sets of plans, TCP for the seminal vesicles is significantly higher in the PDV-based plans. CONCLUSIONS: The method can improve the dose conformality of treatment plans by incorporating population-based measurements of treatment uncertainties and consideration of nontarget tissues in the design of nonuniform target margins. PMID- 10030274 TI - A dynamic model for the estimation of optimum timing of computed tomography scan for dose evaluation of 125I or 103Pd seed implant of prostate. AB - PURPOSE/OBJECTIVE: The dosimetric evaluation of permanent 125I or 103Pd prostate implant is based on the assumption that both prostate and seeds are static throughout the entire treatment time which lasts months. However, the prostate is often edematous after the surgical implantation of seeds. Therefore, both the volume of the prostate and the seed locations change dynamically as the edema resolves. This effect has impact on the validity of postimplant analysis based upon a CT scan. If a CT scan is taken too early after implantation while there is edema in the prostate, the dose delivered by the implant may be underestimated. If the imaging is delayed too long, the dose may be overestimated. The magnitude of this effect depends on both of the half-life of the isotope used and the half life and magnitude of the edema. This study describes a dynamic biomathematical model which takes edema into account in calculating the dose delivered by the implant and is used to investigate the optimum time to obtain the postimplant CT scan. MATERIALS AND METHODS: The dynamic biomathematical model is a numerical integration of the accumulated dose in which the prostate dimensions, the seed locations, and the source strength are all functions of time. The function which describes the change in prostate dimensions and seed locations as a function of time was determined in a separate study by analysis of serial postimplant CT scans. Dose-volume histograms (DVH) of the prostate for the total dose generated by the dynamic model are compared to DVHs generated by CT scans simulated for postimplant intervals ranging from 0 to 300 days after the implantation for 30 different combinations of the magnitude and duration of edema. RESULTS: DVHs of the prostate calculated by taking edema into account show that the time of obtaining a CT scan for postimplant analysis is critical to the accuracy of dose evaluations. The comparison of the DVHs generated by the dynamic model to those generated by the CT scans simulated for a range of postimplant intervals show that obtaining the CT scan too early tends to underestimate the total dose while obtaining the CT scan after the edema is resolved tends to overestimate it. The results show that the optimum timing of the CT scan depends upon the duration of the edema and the half-life of the radioisotope used. It is almost independent of the magnitude of the edema. Thus, a unique optimum time window for the imaging study cannot be defined for either 125I or 103Pd implants. However, an optimum time window can be identified for which the calculated dose, on the average, will generally differ from the actual dose by less than 5%, with a maximum error not exceeding 15%. Such a window is 4 to 10 weeks after the implantation for an 125I implant, and 2 to 4 weeks for a 103Pd implant. CONCLUSIONS: A dynamic biomathematical model to correct for the effects of edema in calculating the total dose delivered by an 125I or 103Pd seed implant has been developed. The model has been used to investigate the optimum time window during which the postimplant CT scans for analysis should be obtained. PMID- 10030275 TI - A non-invasive immobilization system and related quality assurance for dynamic intensity modulated radiation therapy of intracranial and head and neck disease. AB - PURPOSE: To develop and implement a non-invasive immobilization system guided by a dedicated quality assurance (QA) program for dynamic intensity-modulated radiotherapy (IMRT) of intracranial and head and neck disease, with IMRT delivered using the NOMOS Corporation's Peacock System and MIMiC collimator. METHODS AND MATERIALS: Thermoplastic face masks are combined with cradle-shaped polyurethane foaming agents and a dedicated quality assurance program to create a customized headholder system (CHS). Plastic shrinkage was studied to understand its effect on immobilization. Fiducial points for computerized tomography (CT) are obtained by placing multiple dabs of barium paste on mask surfaces at intersections of laser projections used for patient positioning. Fiducial lines are drawn on the cradle along laser projections aligned with nasal surfaces. Lateral CT topograms are annotated with a crosshair indicating the origin of the treatment planning and delivery coordinate system, and with lines delineating the projections of superior-inferior field borders of the linear accelerator's secondary collimators, or with those of the fully open MIMiC. Port films exposed with and without the MIMIC are compared to annotated topograms to measure positional variance (PV) in superior-inferior (SI), right-left (RL), and anterior posterior (AP) directions. MIMiC vane patterns superposed on port films are applied to verify planned patterns. A 12-patient study of PV was performed by analyzing positions of 10 anatomic points on repeat CT topograms, plotting histograms of PV, and determining average PV. RESULTS AND DISCUSSION: A 1.5+/-0.3 mm SD shrinkage per 70 cm of thermoplastic was observed over 24 h. Average PV of 1.0+/-0.8, 1.2+/-1.1, and 1.3+/-0.8 mm were measured in SI, AP, and RL directions, respectively. Lateral port films exposed with and without the MIMiC showed PV of 0.2+/-1.3 and 0.8+/-2.2 mm in AP and SI directions. Vane patterns superimposed on port films consistently verified the planned patterns. CONCLUSION: The CHS provided adequately reproducible immobilization for dynamic IMRT, and may be applicable to decrease PV for other cranial and head and neck external beam radiation therapy. PMID- 10030276 TI - Brain death and its influence on donor organ quality and outcome after transplantation. PMID- 10030277 TI - Transalveolar fluid absorption ability in rat lungs preserved with Euro-Collins solution and EP4 solution. AB - BACKGROUND: Pulmonary reimplantation response, presenting lung edema, is a major obstacle of lung transplantation. Transalveolar fluid absorption mechanism, regulated by active transalveolar Na+ transport via Na+ channel and Na+-K+ ATPase, is considered to be essential for resolution of lung edema. We investigated the effect of lung preservation on this fluid transport mechanism. METHODS: The rat lungs were flushed and preserved with either EP4 solution (EP4) or Euro-Collins solution (EC). First, we determined the basal transalveolar fluid movement by calculating alveolar fluid clearance (AFC) after pulmonary flushing, 24- and 72-hr preservation. Then, we assessed the effects of Na+ channel blocker, amiloride, and Na+-K+-ATPase inhibitor, ouabain, on AFC after 24-hr preservation. We further measured lung ATP content and Na+-K+-ATPase activity after 24-hr preservation to evaluate cellular metabolism and enzymatic activity during preservation. RESULTS: We found that the lungs preserved with EC showed significantly lower AFC and less inhibitory effects of both blockers than with EP4 after 24-hr preservation. Na+-K+-ATPase activity was significantly lower with EC than with EP4, even though lung ATP content was not affected by preservation solution. CONCLUSIONS: EP4 preservation provides a better environment for maintaining transalveolar fluid absorption mechanism than EC preservation. Therefore, lung preservation with EP4 may ensure more reliable ability in resolving pulmonary edema. PMID- 10030278 TI - Potentiation of immunosuppressive efficacy by combining the novel leflunomide analog, HMR 279, with microemulsion cyclosporine in a rat lung transplant model. AB - BACKGROUND: The novel leflunomide (LFM) analog, HMR 279, potentiates the immunosuppressive efficacy of microemulsion cyclosporine (Neoral) in rodent heart transplantation. The present study was designed to evaluate the immunosuppressive efficacy of this combination in comparison to the combination of Neoral and LFM in a stringent allogeneic rodent lung transplant model. METHODS: Donor lungs from Brown Norway rats were implanted into Lewis recipients and were followed for 21 days. Postoperative monitoring included daily weight assessment, chest radiographs, drug trough levels measured by high-performance liquid chromatography (LFM/HMR 279) and high-performance liquid chromatography/mass spectrometry (Neoral), and blinded histology assessment of the transplanted lung on the day of death based on the International Society for Heart and Lung Transplantation working formulation. Untreated lung recipients served as controls (group I, n=5). Rats were assigned to the following treatment groups: II, 7.5 mg/kg/day Neoral (n=6); III, 10 mg/kg/day LFM (n=6); IV, 10 mg/kg/day HMR 279 (n=6); V, 10 mg/kg/day LFM plus 7.5 mg/kg/day Neoral given simultaneously (n=13); and VI, 10 mg/kg/day HMR 279 plus 7.5 mg/kg/day Neoral given simultaneously (n=6). Drugs were given daily by oral gavage. RESULTS: All rats except for one in the HMR 279 monotherapy group survived the follow-up period. The chest radiographs in the control, LFM, and HMR 279 monotherapy groups showed moderate to complete opacification of the left chest by postoperative day 7 (controls) and day 14 (LFM, 279). At postoperative day 21, the Neoral monotherapy and the combination groups showed no signs of opacification in the radiographs. Combination therapies of Neoral plus HMR 279 or Neoral plus LFM were most successful in preventing histologic allograft rejection. Combining Neoral and HMR 279 resulted in a significant decrease in the cyclosporine trough levels. Co administration of LFM plus Neoral resulted in significantly higher LFM trough levels when compared to LFM monotherapy. Of all treatments studied, the combination of HMR 279 plus Neoral was tolerated best as assessed by percentage of weight change. CONCLUSIONS: This study showed for the first time in a stringent rodent lung transplant model that combined treatment of LFM or HMR 279 plus Neoral potentiates the immunosuppressive efficacies of these drugs and successfully prevents allograft rejection. PMID- 10030279 TI - Mouse-to-rabbit xenotransplantation: a new small animal model of hyperacute rejection mediated by the classical complement pathway. AB - BACKGROUND: Hyperacute rejection of porcine organs transplanted into primate recipients is initiated by the binding of preformed xenoreactive natural antibodies to the vascular endothelium of the graft and activation of the classical complement pathway. Several small animal models are currently employed to study various aspects of xenograft rejection; however, none has been shown to manifest hyperacute rejection mediated by the classical pathway of complement activation. METHODS: We performed heterotopic mouse heart transplants into weanling rabbits, adult rabbits, and C6-deficient rabbits. The recipients received no immunosuppression. Rejected grafts were subjected to histologic analysis and immunofluorescence staining for rabbit IgG, IgM, and C3. Levels of preexisting cytotoxic antibodies as well as classical and alternative complement pathway activities were determined in rabbit serum using mouse red cells as targets. RESULTS: Mean graft survival was 37+/-9.6 min for mouse-to-weanling rabbit transplants (n=10), and 40+/-11.1 min for mouse-to-adult rabbit transplants (n=5). Rejected grafts showed diffuse interstitial hemorrhage, endothelial cell damage, myocyte necrosis, moderate diffuse deposition of rabbit IgG, and dense deposition of rabbit IgM and C3 on the vascular endothelium of the graft, consistent with hyperacute rejection. One mouse-to-C6-deficient rabbit transplant was rejected at 21 hr with severe interstitial hemorrhage, cellular necrosis and a moderate cellular infiltrate consisting primarily of neutrophils and some mononuclear cells. A second transplant in a C6-deficient rabbit was functioning when the recipient died at 6.5 hr as a result of complications of surgery; the graft had normal myocytes and vasculature with minimal spotty interstitial hemorrhage. Both weanling and adult rabbit serum were found to have high titers of cytotoxic IgM anti-mouse antibodies and strong classical complement pathway activity with minimal alternative pathway activity towards mouse red cells. CONCLUSIONS: The mouse-to-rabbit species combination manifests hyperacute xenograft rejection. In vitro studies suggest that this process is mediated by IgM anti-mouse natural antibodies and activation of the classical pathway of complement. PMID- 10030280 TI - Carotid atherosclerosis in renal transplant recipients: relationships with cardiovascular risk factors and plasma lipoproteins. AB - BACKGROUND: Renal transplant recipients have an increased incidence of cardiovascular disease, but less data exist about cerebrovascular atherosclerosis. In this study, we assessed the prevalence of carotid lesions as evaluated by B-mode ultrasonography in a group of renal transplant recipients, and we evaluated univariate and multivariate relationships between common risk factors and plasma lipoproteins and carotid lesions. METHODS: Fifty-seven renal transplant recipients and 113 age- and gender-matched controls underwent a complete clinical visit for the evaluation of risk factors present. In all subjects, a blood sample was collected for lipoprotein determination, and an ultrasound high-resolution B-mode imaging examination of the common carotid arteries was performed. RESULTS: We found that among renal transplant recipients, there was a significantly increased prevalence of subjects with plaque in comparison with controls (24.6% vs. 6.2%, P<0.001). At multiple analysis, carotid lesions were independently associated with age, hypertension, diabetes, smoking habit, and the presence of cardiovascular disease in controls and with age and hypertension in renal transplant recipients. Neither the lipid profile nor the presence of dyslipidemias was related to carotid score in renal transplant recipients, whereas a nonsignificant trend was observed in controls. Finally, in transplant patients, we did not find any association between carotid lesions and high-density lipoprotein subfractions. CONCLUSIONS: Age and hypertension are the main predictors of extracranial cerebrovascular atherosclerosis after renal transplantation. Because carotid lesions may represent a useful predictive marker of clinical events in nontransplant subjects, carotid artery evaluation by B-mode ultrasound might be routinely included in the management of renal transplant patients. PMID- 10030281 TI - Immunoregulatory role of CD8alpha in the veto effect. AB - BACKGROUND: Allogeneic bone marrow cell (allo-BMC) infusion induces tolerance to incompatible renal allografts in rhesus macaques after depletion of peripheral T lymphocytes with cytolytic anti-T cell antibodies. The tolerogenic effect of allo BMC, ascribed to a veto mechanism, associates with specific functional deletion of antidonor cytotoxic T lymphocyte precursor (CTLp), and is dependent on a CD8+ donor BMC subset. In previous studies, the CD8 molecule was implicated by loss of suppression after blocking interaction between CD8 on allo-BMC and major histocompatibility complex class Ialpha3 domain on CTLp. CD8 cross-linking on BMC induced secretion of active transforming growth factor-beta1 (TGF-beta1), suggesting a regulatory mechanism(s) operating via a CD8-mediated signaling pathway. METHODS: CD8 on rhesus cells was cross-linked using IgG-conjugated beads, and TGF-beta1 mRNA and protein were quantified. CD8+ cells were tested for veto activity by mixed lymphocyte reaction (MLR)-induced cell-mediated lymphocytotoxicity (CML) assay. Activated rhesus T cells exposed to TGF-beta1 were examined for apoptosis by TdT-mediated end-labeling and annexin staining. RESULTS: CD8 cross-linking induces accumulation of TGF-beta1 mRNA and protein. Both CD3- CD8+CD16+ and CD3+ CD8+CD16- subsets of allo-BMC up-regulate TGF-beta1 mRNA after CD8 cross-linking, and exhibit veto activity. The CD3-CD8+CD16+ subset expresses more TGF-beta1 mRNA and increased veto activity at low BMC/CTLp ratios. Exposure of activated T cells to TGF-beta1 induces apoptosis. CONCLUSIONS: CD8+ allo-BMC are enriched for veto activity and activation via CD8 induces TGF-beta1 mRNA and protein accumulation. These results agree with the hypothesis that paracrine TGF-beta1 may be involved in peripheral deletion of alloreactive CTLp by CD8+ allo-BMC. We suggest that TGF-beta1 overexpression by donor lymphohematopoietic cells may enhance tolerance induction. PMID- 10030282 TI - The significance of bronchus-associated lymphoid tissue in human lung transplantation: is there an association with acute and chronic rejection? AB - BACKGROUND: In animal models of acute rejection in lung allografts, bronchus associated lymphoid tissue (BALT) plays a major role in the induction and persistence of the alloreactive response. We undertook a study of the clinical and histologic associations with BALT identified on transbronchial biopsy in human lung allograft recipients. METHODS: Transbronchial biopsies of patients receiving single lung, double lung, and combined heart-lung transplantation from 1984 to 1997 at the University of Pittsburgh Medical Center were reviewed. Seventy-seven patients had transbronchial biopsies demonstrating BALT. We examined all pathologic reports and slides, and graded rejection utilizing the Revised Working Formulation for the Classification of Pulmonary Allograft Rejection. Twenty-nine of 77 patients were selected at random to evaluate the distribution of BALT lymphocyte subsets immunohistochemically. RESULTS: There was no relationship between native disease or the transplant procedure and the identification of BALT. BALT was found from 9 days to 2431 days after transplant (average: 440 days; median: 157 days) in association with clinically insignificant acute cellular rejection (A0, A1) in 75% of cases. Bronchiolitis obliterans developed in 29% of patients with a BALT-positive biopsy, a percentage not different from that of our overall lung transplant population. Immunohistochemical examination of BALT showed helper T cells predominated over cytotoxic T cells in zones surrounding B cell-rich follicular center cells. CONCLUSIONS: The association of BALT with high-grade acute cellular rejection and with the development of bronchiolitis obliterans could not be confirmed in human lung allografts. BALT most often accompanied A0 or A1 rejection. This raises the possibility that the presence of BALT on transbronchial biopsy may be part of the evolution of immunologic tolerance in human pulmonary allografts. PMID- 10030283 TI - The clinical significance of antibodies to human vascular endothelial cells after cardiac transplantation. AB - BACKGROUND: Vascular endothelial cells are primary targets for injury during both cellular and humoral allograft rejection (AR). In cardiac transplantation, the role of humoral immunity in mediating AR has not been extensively characterized. METHODS: Antibodies against human vascular endothelial cells (AECA) were measured using a cellular ELISA developed from human umbilical vein endothelial cells in 80 consecutive patients after cardiac transplantation. The aim was to determine the incidence of AECA formation after transplantation and their association with different types of AR, graft survival, and development of cardiac allograft vasculopathy (CAV). At least eight serum samples obtained from each patient were examined for AECA and an endomyocardial biopsy was performed at regular intervals during the first year after transplantation. RESULTS: Of the 80 patients examined, 31 were AECA (+) and 49 patients were AECA (-). There were no significant differences between the AECA (+) and (-) groups when examined for age, sex, and pretransplantation ischemia time. A significant correlation was found between the presence of AECA and humoral AR (P<0.015). AECA positivity did not correlate with the presence of cellular AR or the number of rejection episodes. In addition, allograft survival at 2 years after transplantation was significantly better in the AECA (-) group compared with that in the AECA (+) group (89.8% vs. 71.0%, P<0.0004). The persistence of AECA positivity during the first year after transplantation was also associated with a significantly greater incidence of CAV when compared with the patients who were AECA (-) (25.8% vs. 14.3%, P<0.004). CONCLUSIONS: AECA may be important in the mediation of humoral AR, may decrease allograft survival, and may identify a high-risk group for CAV. PMID- 10030284 TI - Prolonged allograft survival but no tolerance induction by modulating CD28 antibody JJ319 after high-responder rat heart transplantation. AB - BACKGROUND: Allograft rejection depends on T cell immune responses requiring antigen recognition and costimulatory signals through accessory T cell receptors, including CD28. Inhibition of CD28 signaling with a CTLA-4-immunoglobulin (Ig) fusion protein has resulted in immunosuppression and occasional T cell anergy in mouse transplant models, but not in rats. Because this approach also inhibits a potentially tolerizing signal through CTLA-4, selective blockade of CD28 ligation might induce more profound immunosuppression and transplant tolerance. METHODS: The effects of escalating doses of the rat CD28 monoclonal antibody JJ319 on allograft survival were studied after vascularized heterotopic heart transplantation in a high responder strain combination (DA to Lewis). CD28 antigen modulation and circulating antibody levels were monitored by flow cytometry. RESULTS: CD28 antibody JJ319 markedly prolonged cardiac graft survival compared with untreated controls (7 days, range: 6-8). A strictly dose-dependent increase in median graft survival time was demonstrated with a maximum of 36 days (range: 30-40; p <0.001) after the administration of 8 x 1 mg JJ319 i.p. (days -1 to +6 before/after transplantation). However, indefinite graft survival and tolerance could not be induced by JJ319 treatment. At the maximal dose, flow cytometry showed complete down modulation of the CD28 receptor for 10-14 days without T cell depletion in close temporal relation to antibody presence in serum. In vitro, CD28-modulated T cells showed significantly reduced responses to activation. CONCLUSIONS: CD28 antibody JJ319 induces profound immunosuppression after rat heart transplantation, however without development of transplant tolerance. The underlying mechanism seems to be receptor modulation during primary alloantigen recognition. While still potentially applicable clinically, there are no qualitative or quantitative differences to the treatment with CTLA 4/lg or the blockade of CD2 or LFA-1, as reported elsewhere. Thus, a CD28 modulating approach seems not to allow therapeutic exploitation of a tolerizing signal delivered by CTLA-4 but may still be clinically applicable, especially in combined immune interventions. PMID- 10030285 TI - Human herpesvirus 6 seronegativity before transplantation predicts the occurrence of fungal infection in liver transplant recipients. AB - BACKGROUND: Invasive fungal infection has a major impact on the morbidity and mortality of liver transplant recipients. Human herpesvirus (HHV)-6 infection after transplantation is associated with an immunosuppressive state and the development of cytomegalovirus disease. Because cytomegalovirus infection is a risk factor for invasive fungal infection after transplantation, we have examined whether HHV-6 and fungal infection are associated after transplantation. METHODS: Pretransplantation sera from 247 consecutive liver transplant recipients were analyzed for IgG to HHV-6. Thirty-three (13%) HHV-6-seronegative recipients were identified. Six of 33 (18%) seronegative recipients experienced fungal infection as compared with 15 of 214 (7%) seropositive recipients (P=0.034). RESULTS: In a univariate analysis of risk factors for fungal infection, pretransplantation seronegativity to HHV-6 (P=0.034), intraoperative cryoprecipitate requirements greater than the 75th percentile (P=0.035), reoperation (P=0.005), biliary stricturing postoperatively (P=0.046), and gastrointestinal or vascular complications postoperatively (P=0.030) were identified as significant risk factors. Moreover, in pairwise multivariate analysis, pretransplantation HHV-6 seronegativity remained a significant variable even in the presence of each of the other variables. CONCLUSIONS: These results suggest that HHV-6 seronegativity before transplantation is a valuable clinical marker that identifies patients at risk for developing fungal infection after transplantation. PMID- 10030286 TI - Factors affecting growth after pediatric liver transplantation. AB - BACKGROUND: Poor linear growth after pediatric orthotopic liver transplantation (OLT) is a well-described phenomenon. We have undertaken a bivariate and multivariate analysis of multiple factors that might effect postOLT growth in all children who underwent transplantation at a single center, with survival > 1 year and adequate follow-up. METHODS: Standardized height score (Z score) and height deficit (centimeters below the 50th percentile) were computed for each patient over time. The variables assessed were (i) age at OLT, (ii) gender, (iii) pretransplantation diagnosis, (iv) Z score and height deficit at OLT, (v) tacrolimus versus cyclosporine as primary immunosuppressive therapy, (vi) retransplantation, (vii) graft disease, (viii) chronic illness, (ix) posttransplant lymphoproliferative disease, (x) intractable rejection, and (xi) prednisone withdrawal. RESULTS: A total of 236 children met the inclusion criteria, with a mean follow-up of 3.8+/-1.9 years. For the population as a whole, the baseline Z score was -1.72 (fourth percentile) with a significant improvement to - 1.37 (ninth percentile) at 2 years, but with no additional gain at 5 years (Z score -1.4). The baseline height deficit was -6.4 cm, with no improvement at 2 years (-6.52 cm), and was significantly worse at 5 years (-7.87 cm). In the bivariate analysis, the most important variables affecting growth were age at OLT, Z score at OLT, and diagnosis. In general, children <2 years with biliary atresia and those with the most growth delay at OLT showed the best posttransplantation growth. In the multivariate analysis, 18 factors were considered, of which 9 were significant. These were (i) Z score at baseline, (ii) follow-up time, (iii) age at OLT, (iv) diagnosis of tumor, (v) diagnosis of fulminant hepatic failure, (vi) retransplantation, (vii) graft disease, (viii) posttransplant lymphoproliferative disease, and (ix) stoppage of prednisone. Multivariate models using these nine variables accounted for 84% of the variation in standardized height. CONCLUSION: In general, children after OLT show some potential for catch-up growth but do not achieve normal height compared with their age and sex-matched peers. A multivariate analysis was necessary to investigate the interdependent effects of the many variables that can affect growth after OLT. The most important detrimental affects were older age at time of OLT, Z scores greater than -2.0 at OLT, fulminant hepatic failure, tumor, and postOLT complications causing graft dysfunction. PMID- 10030287 TI - A prospective, randomized trial of tacrolimus/prednisone versus tacrolimus/prednisone/mycophenolate mofetil in renal transplant recipients. AB - BACKGROUND: Between September 20, 1995 and September 20, 1997, 208 adult patients undergoing renal transplantation were randomized to receive tacrolimus/prednisone (n=106) or tacrolimus/prednisone/mycophenolate mofetil (n=102), with the goal of reducing the incidence of rejection. METHODS: The mean recipient age was 50.7+/ 13.7 years. Sixty-three (30.3%) patients were 60 years of age or older at the time of transplantation. The mean donor age was 34.5+/-21.7 years. The mean cold ischemia time was 30.5+/-9.2 hr. The mean follow-up is 15+/-7 months. RESULTS: The overall 1-year actuarial patient survival was 94%; the overall 1-year actuarial graft survival was 87%. When the patient and graft survival data were stratified to recipients under the age of 60 who did not have delayed graft function, the overall 1-year actuarial patient survival was 97%, and the corresponding 1-year actuarial graft survival was 93%. There were no differences between the two groups. The overall incidence of rejection was 36%; in the double therapy group, it was 44%, whereas in the triple therapy group, it was 27% (P=0.014). The mean serum creatinine was 1.6+/-0.8 mg/dl. A total of 36% of the successfully transplanted patients were taken off prednisone; 32% of the patients were taken off antihypertensive medications. The incidence of delayed graft function was 21%, the incidence of cytomegalovirus was 12.5%, and the initial and final incidences of posttransplant insulin-dependent diabetes mellitus were 7.0% and 2.9%; again, there was no difference between the two groups. CONCLUSIONS: This trial suggests that the combination of tacrolimus, steroids, and mycophenolate mofetil is associated with excellent patient and graft survival and a lower incidence of rejection than the combination of tacrolimus and steroids. PMID- 10030288 TI - Unsuspected bile duct paucity in donors for living-related liver transplantation: two case reports. AB - Alagille's syndrome is a common cause of liver disease in children and may lead to the need for orthotopic liver transplantation. Alagille's syndrome is inherited in an autosomal dominant manner, with variable penetration, and may also be present in patients' parents, who may be considered potential donors for living-related transplantation. We report here on two cases in which the living related donors for children with Alagille's syndrome had no liver function abnormalities or characteristic features of Alagille's syndrome. In both cases, the operation for living-related donation had to be aborted because of a paucity of bile ducts discovered intraoperatively. Given the variable presentation of Alagille's syndrome, we believe that it is necessary preoperatively to evaluate the biliary system of family members who are potential living-related donors for patients with this condition. PMID- 10030289 TI - Increased incidence of oropharyngeal squamous cell carcinomas after liver transplantation for alcoholic cirrhosis. AB - BACKGROUND: THE aim of this study was to describe the features of posttransplantation tumors observed in a series of liver transplant recipients with special reference to patients receiving a transplant for alcoholic cirrhosis. METHODS: Among 171 consecutive liver transplant recipients, 90 patients who had received a first liver allograft for cirrhosis were studied. After liver transplantation, detection of de novo malignancies was prospectively undertaken and the characteristics of the patients in whom tumors occurred were compared with those in whom tumors did not develop. RESULTS: With a follow-up of 45.2+/-21.2 months, 11 tumors were observed in 90 patients (overall incidence of 12.2%). The incidence of tumors was higher in patients receiving a transplant for alcoholic cirrhosis than in patients receiving a transplant for nonalcoholic cirrhosis (26.7% vs. 5.0%, P<0.01). Squamous cell carcinoma (SCC) of the oropharynx or esophagus and posttransplant lymphoproliferative disorders were mainly observed. SCC (uvula in two cases, tongue in one case, esophagus in one case, pharynx in one case) occurred exclusively in patients transplanted for alcoholic cirrhosis (16.7% vs. 0%, P=0.001). The incidence of posttransplant lymphoproliferative disorders was similar in alcoholics and nonalcoholics (6.7% vs. 5%, NS). Survival was not influenced by the occurrence of SCC. CONCLUSION: The incidence of oropharyngeal SCC could be high in patients receiving a transplant for alcoholic cirrhosis. This could be due to an additional effect of posttransplantation immunosuppression in patients exposed to alcohol and tobacco before transplant. Careful posttransplantation screening of oropharyngeal SCC is warranted after liver transplantation for alcoholic cirrhosis. PMID- 10030290 TI - A simple model to estimate survival after retransplantation of the liver. AB - To formulate a model predicting survival after liver retransplantation, we analyzed in detail the last 150 cases of hepatic retransplantation at UCLA. Cox proportional hazards regression analysis identified five variables that demonstrated independent simultaneous prognostic value in estimating patient survival after retransplantation: (1) age group (pediatric or adult), (2) recipient requiring preoperative mechanical ventilation, (3) donor organ cold ischemia > or =12 hr, (4) preoperative serum creatinine, and (5) preoperative serum total bilirubin. The Cox regression equation that predicts survival based on these covariates was simplified by assigning individual patients a risk classification based on a 5-point scoring system. We demonstrate that this system can be employed to identify a subgroup of patients in which the expected outcome is too poor to justify retransplantation. These findings may assist in the rational selection of patients suitable for retransplantation. PMID- 10030291 TI - Histological outcome of acute cellular rejection in kidney transplantation after treatment with methylprednisolone. AB - BACKGROUND: Several studies comparing the response of acute cellular rejection (ACR) episodes to different corticosteroid regimens have been conducted. However, in most of them, the histological evaluation of the infiltrate and its correlation with clinical response was not studied. The clinical and histological outcomes of 37 episodes of ACR treated with methylprednisolone (MP) were studied, with the aim to determine how long the infiltrate takes to be cleared after therapy. METHODS: A total of 37 patients with biopsy-proven ACR were treated with 8 or 16 mg of MP/kg/day. Allograft biopsies were repeated at 5 and 10 days after the end of corticotherapy. Clinical and histological outcomes were compared. RESULTS: Six patients were excluded; 15 (48.4%) patients responded to therapy; the mean serum creatinine of these patients reached normal levels in the 2 weeks that followed treatment. Nine patients (60%) of this group had signs of ACR on biopsies done 5 days after corticotherapy, and four (26.7%) maintained them on the 10th day. Among 16 patients with no clinical response, none reached normal serum creatinine levels; 15 (93.7%) had signs of rejection 5 days after treatment and maintained them on the 10th day. Histological signs of ACR disappeared in 73.3% of patients with clinical response 10 days after therapy, but in only 6.3% of patients with no response (P=0.001). CONCLUSIONS: Biopsies performed 5 days after treatment show a high incidence of features of ACR; such features take on average 10 days to disappear in nearly 75% of cases with successful therapy with MP. PMID- 10030292 TI - CD4+ cells play a major role in xenogeneic human anti-pig cytotoxicity through the Fas/Fas ligand lytic pathway. AB - BACKGROUND: In this study, the role of cell-mediated cytotoxicity by human leukocytes against pig endothelial cells was examined in vitro. The aim was to determine which cell subsets were responsible for this phenomenon and which pathways were involved in cell lysis. METHODS: Primed human peripheral blood mononuclear cells (PBMC) or purified CD4+ or CD8+ T cells were used in a cell mediated cytotoxicity assay in which cytotoxicity of an SV40 transformed porcine endothelial cell (EC) line (SVAP) was determined by Annexin V binding. RESULTS: Human PBMC demonstrated specific lysis of porcine EC that was proportional to the effector: target ratio. CD4+ T cells accounted for >60% of this lysis, whereas CD8+ T cells accounted for <20%. CD4+ T cell-mediated lysis depended on direct recognition of porcine major histocompatibility complex class II molecules as inhibition of swine leukocyte antigen class II on porcine EC-inhibited CD4+ T cell cytotoxicity. This lysis was mediated through the Fas/FasL pathway as addition of anti-Fas and/or anti-FasL antibody profoundly inhibited antiporcine lysis. In addition, FasL gene expression was detected in primed PBMC and CD4+ T cells by RT-PCR, whereas granzyme B gene expression was not. Primed CD4+ T cells demonstrated high level FasL protein by Western blotting and two-color FACS analysis, whereas NK cells and CD8+ T cells did not. Finally, recombinant human FasL induced apoptosis in Fas expressing porcine EC cells, demonstrating that human FasL interacted with and activated Fas on porcine EC cells. CONCLUSIONS: In conclusion, human to pig cell-mediated cytotoxicity was mediated predominantly by CD4+ T cells through the Fas/FasL pathway of apoptosis. These results suggest that direct cytotoxicity by xenoreactive CD4+ T cells may be one of several effector mechanisms involved in cellular xenograft rejection. PMID- 10030293 TI - Prevention and restoration of second-set liver allograft rejection in presensitized mice: the role of "passenger" leukocytes, donor major histocompatibility complex antigens, and host cytotoxic effector mechanisms. AB - BACKGROUND: The aim was to determine whether sublethal donor total body irradiation (TBI) might be as effective as lethal TBI in preventing mouse second set liver allograft rejection, and to evaluate the role of passenger leukocytes, donor major histocompatibility complex (MHC) antigens, and host effector mechanisms in the response to livers from sublethally irradiated donors. METHODS: B10 (H2b) donors received various doses of TBI at different times before their livers were transplanted orthotopically into normal or donor skin-presensitized C3H (H2k) recipients. The influence of irradiation on graft non-parenchymal cells (NPC) was determined by monoclonal antibody staining, and flow cytometric analysis. Hematopoietic cells within the grafts were reconstituted by intravenous infusion of syngeneic or third-party bone marrow cells. Allograft survival was determined in recipients that received no treatment, or that were given spleen cells from either normal B10 donors, or MHC class I - or class II-deficient mice syngeneic with the donors. Cytotoxic activity of graft-infiltrating cells and host spleen cells, and complement-dependent cytotoxic alloantibody titers were determined by isotype release assays. RESULTS: The protective effect of donor TBI was observed both at lethal (9.5 Gy) and sublethal doses (5 and 3 Gy; graft median survival time: >100 days). Extended delay in liver transplantation, allowing hematopoietic recovery and graft reconstitution eliminated the effect. Liver NPC were reduced about 80% within 24 hr of 3 Gy TBI, with a selective reduction in the incidence of B cells. The NPC-depleted livers underwent accelerated rejection when donor (but not third-party) spleen cells (5 x 10(7) were administered systemically to the recipient immediately after graft revascularization. Spleen cells from MHC class I-deficient (but not MHC class II deficient) mice failed to fully restore accelerated rejection of TBI liver grafts. Freshly isolated graft NPC, or spleen cells from TBI liver recipients, harvested 4 days after transplantation, exhibited lower, donor-specific cytotoxic activity than cells from mice given normal livers. Recipients of TBI livers also showed much lower serum complement-dependent cytotoxic alloantibody titers. CONCLUSIONS: By substantially depleting "passenger leukocytes," sublethal donor TBI undermines anti-donor cell-mediated and humoral immune reactivity and inhibits second-set liver allograft rejection in presensitized recipients. The interval between irradiation and transplantation is important in conferring resistance to rejection. Expression of MHC class I on donor leukocyte infusions is important for overcoming resistance to second-set rejection induced by donor irradiation. PMID- 10030294 TI - A synergistic effect of extracellular hypocalcemic condition for hyperoxic reoxygenation injury in rat hepatocytes. AB - BACKGROUND: Calcium accumulation of cells and mitochondria during reperfusion or reoxygenation has been implicated as a potential factor in cell injury as the result of mitochondrial damage. The objective of this study was to disclose whether or not low extracellular calcium ion concentration ([Ca2+]ex) in the medium at the time of reoxygenation might prevent calcium accumulation and attenuate hepatocytes injury after severe hypoxia. METHODS: Isolated rat hepatocytes were incubated under a hyperoxic or hypoxic atmosphere for 60 min. During the ensuing 60-min hyperoxic reoxygenation, medium [Ca2+]ex was varied from 0.6 microM to 2.0 mM by altering total calcium and addition of chelators. RESULTS: Incubation in low [Ca2+]ex reduced total cellular calcium and mitochondrial calcium in both the hyperoxic and hypoxic group. Under hyperoxic/hyperoxic incubation (control), hepatocytes were able to maintain potassium balance when [Ca2+]ex was >3.0 microM (pCa=5.5) and cellular viability (% lactate dehydrogenase release) at all levels of extracellular calcium. Under hypoxic/hyperoxic incubation (reoxygenation), however, loss of the ability to restore potassium balance as well as apparent increase in lactate dehydrogenase release were observed at severely low [Ca2+]ex (<30 microM; pCa=4.5). This low [Ca2+]ex-induced exacerbation of hepatocytes viability could not be generated under mild reoxygenation such as normoxia. CONCLUSIONS: In normal isolated hepatocytes, very low [Ca2+]ex levels produce only very subtle changes in membrane permeability of isolated hepatocytes. After hypoxia, however, hypocalcemia acts synergistically with hyperoxic reoxygenation to produce more severe damage. These results suggested that [Ca2+]ex should be maintained on the physiological level to attenuate hepatocytes injury after severe hypoxia. PMID- 10030295 TI - Role of the thymus in transplantation tolerance in miniature swine: II. Effect of steroids and age on the induction of tolerance to class I mismatched renal allografts. AB - BACKGROUND: Recent studies in young (5-7 months) miniature swine have demonstrated that the thymus is involved in the rapid induction of stable tolerance to class I mismatched renal allografts after a 12-day course of Cyclosporine (CyA). Because both steroids and age are known to influence the structure and function of the thymus, we have now studied the effects of these two parameters on tolerance induction in this model. MATERIALS AND METHODS: In young swine, the administration of methylprednisolone (MP) during the standard tolerance-inducing regimen (a 12-day course of CyA) produced severe renal dysfunction and acute cellular rejection histologically. However, the renal allografts recovered and were accepted for >100 days with histological evidence of chronic rejection. To test the effect of age, two relatively old swine (55 and 71 months) received transplants of class I mismatched renal allografts and the standard 12-day course of CyA. One animal rejected the allograft acutely on postoperative day 22, and the second also rejected, but more slowly, with manifestations of chronic rejection. CONCLUSION: These findings suggest that both MP and old age interfere with the induction of stable tolerance in a fashion similar to the previously described effect of thymectomy. These results may have important implications for the mechanism of thymic-dependent tolerance, for the use of steroids in clinical protocols for the induction of allograft tolerance, and for the application of such protocols to adult patients. PMID- 10030296 TI - Inhibition of tissue factor-dependent and -independent coagulation by cell surface expression of novel anticoagulant fusion proteins. AB - BACKGROUND: Thrombotic vascular occlusion occurs in disorders of diverse etiology, including atherosclerosis, vasculitis, and disseminated intravascular coagulation. The same process results in hyperacute rejection of renal allografts transplanted into sensitized patients and remains a major problem in experimental xenotransplantation. METHODS: We have previously described the design and expression of several genetic constructs encoding novel fusion proteins with anticoagulant properties. They are based on two naturally occurring soluble anticoagulant proteins, human tissue factor pathway inhibitor (hTFPI) and the leech protein hirudin, which act early and late in the clotting cascade, respectively. We report the expression of human hTFPI-CD4 on the surface of immortalized porcine endothelial cells (IPEC), and show that it functions across the species divide as evidenced by the binding of membrane-expressed porcine tissue factor (pTF)-human factor VIIa complexes. RESULTS: Using a human plasma recalcification clotting assay, we distinguished between pTF-dependent and pTF independent fibrin generation, and we have demonstrated that expression of hTFPI CD4 on IPEC effectively prevented pTF-dependent clotting. Moreover, we show that when hTFPI-CD4 was co-expressed with the hirudin construct, the procoagulant properties of in vitro cultured, activated IPEC were almost completely abolished. CONCLUSIONS: These results suggest that these novel anticoagulant molecules may prove useful therapeutic agents for gene therapy or for transgenic expression in animals whose organs may be used for cliniCal xenotransplantation. PMID- 10030297 TI - Successful donation and transplantation of multiple organs after fatal poisoning with brodifacoum, a long-acting anticoagulant rodenticide: case report. AB - BACKGROUND: Successful organ donation has been reported after death from poisonings with cyanide, carbon monoxide, methanol, benzodiazepines, and tricyclic antidepressants. In this report, we describe a case of multiple organ donation from a previously healthy individual who died from poisoning with the long-acting anticoagulant rodenticide, brodifacoum. METHODS: Case report and review of the literature. RESULTS: All organs procured from the poisoned donor functioned adequately, and there were no hemorrhagic complications in any of the recipients. CONCLUSION: This case demonstrates that brodifacoum poisoning is not an absolute contraindication to organ donation from brain-dead patients who have sustained a fatal ingestion. PMID- 10030298 TI - Idiopathic thrombocytopenic purpura after a living-related liver transplantation. AB - BACKGROUND: Idiopathic thrombocytopenic purpura (ITP) is a rare complication after liver transplantation. We describe three cases of ITP in pediatric patients after a living-related liver transplantation (LRLT). METHODS: Of 266 patients who underwent an LRLT between June 1990 and June 1996, severe thrombocytopenia developed in three pediatric patients after transplantation, and ITP was also diagnosed. The original disease was biliary atresia in all cases, and the patients were given a partial liver graft from a living-related mother and subsequently treated with tacrolimus and low-dose steroids as an immunosuppressive regimen. RESULTS: The duration until the onset of ITP after transplantation in the three cases was 1 day, 3 months, and 13 months, respectively. The platelet-associated IgG levels increased in all cases. A preceding viral infection was suspected in two of the three cases. All patients were treated with intravenous gamma globulin with a transient recovery of thrombocytopenia in two cases and a sustained recovery in another. CONCLUSIONS: Transplant clinicians need to be aware of the possibility of ITP complication because a sudden onset of severe thrombocytopenia can occur even in patients who are apparently doing well after undergoing an LRLT. PMID- 10030299 TI - Microsporidia infection in transplant patients. AB - BACKGROUND: Microsporidia are the most common cause of chronic diarrhea in patients infected with human immunodeficiency virus. Patients who have undergone organ transplantation may also be infected. The precise immune defect and the clinical picture in transplant patients have not been studied. METHODS: We report a case of microsporidia infection in a heart transplant patient and review three other cases reported in the literature. RESULTS: Infection in three solid organ transplant patients occurred when the patients were receiving immunosuppressive therapy for rejection 1.5-3 years after transplantation. Patients had chronic diarrhea, vomiting, dyspepsia, and weight loss for 1 month to 3 years. CONCLUSIONS: Microsporidia may be the cause of chronic unexplained diarrhea and gastrointestinal disturbances in transplant patients. Defects in cell-mediated immunity probably play a role in maintaining the chronicity of this infection. Specific screening requests should be made to the microbiology laboratory when microsporidia infection is suspected. PMID- 10030300 TI - "Striped" pattern of medullary ray fibrosis in allograft biopsies from kidney transplant recipients maintained on tacrolimus. AB - BACKGROUND: A striped pattern of fibrosis has been described in the kidneys of patients undergoing long-term cyclosporine or tacrolimus therapy. This lesion is frequently misconstrued as being specific for drug toxicity. METHODS: We performed clinicopathologic correlation on 18 patients with striped fibrosis identified by reviewing 61 biopsies from kidney transplant recipients maintained with tacrolimus. RESULTS: Acute rejection was identified in 14 of 18 patients, chronic rejection in 9 of 18 patients, potential diabetic microvascular injury in 8 of 18, and pre-existing donor disease in 2 of 18. In only one patient could striped fibrosis be ascribed primarily to tacrolimus. Striped fibrosis could also be demonstrated in 6 of 10 late allograft biopsy specimens from patients maintained with only azathioprine, and 8 of 10 native biopsies from patients with advanced diabetes mellitus. CONCLUSION: Multiple insults contribute to the pathogenesis of striped fibrosis in the kidney. This lesion can be attributed entirely to chronic drug toxicity in only a minority of allografts. PMID- 10030301 TI - Acute torsion of the renal transplant after combined kidney-pancreas transplant. AB - BACKGROUND: Surgical complications after combined kidney and pancreas transplantation are a major source of morbidity and mortality. Complications related to the pancreas occur with greater frequency as compared to renal complications. The occurrence in our practice of two cases of renal infarction resulting from torsion about the vascular pedicle led to our retrospective review of similar vascular complications after combined kidney and pancreas transplantation. METHODS: Charts were reviewed retrospectively, and two patients were identified who experienced torsion about the vascular pedicle of an intra abdominally placed renal allograft. RESULTS: Two patients who had received combined intraperitoneal kidney and pancreas transplantation presented at 16 and 11 months after transplant, respectively, with abdominal pain and decreased urine output. One patient had radiological documentation of abnormal rotation before the graft loss; unfortunately, the significance of this finding was missed. Diagnosis was made in both patients at laparotomy, where the kidneys were infarcted secondary to torsion of the vascular pedicle. Both patients underwent transplant nephrectomy and subsequently received a successful second cadaveric renal transplant. CONCLUSIONS: The mechanism of this complication is a result of the intra-abdominal placement of the kidney, length of the vascular pedicle, excess ureteral length, and paucity of adhesions secondary to steroid administration. These factors contribute to abnormal mobility of the kidney. Technical modifications such as minimizing excess ureteral length and nephropexy may help to avoid this complication. PMID- 10030302 TI - Liver transplantation for metastatic hemangiopericytoma associated with hypoglycemia. AB - We report a case of successful liver transplantation in a young man with metastatic hemangiopericytoma confined to the liver. He had a primary retroperitoneal hemangiopericytoma removed in 1982 and was diagnosed as having liver metastases 8 years later. Subsequently, he developed hypoglycemia, which did not respond to chemotherapy. Hepatectomy and transplantation resolved his hypoglycemic attacks. He remained well and symptom free for 4 years. Liver transplantation can provide effective palliation and should be considered in carefully selected patients with localized metastatic cancer. PMID- 10030303 TI - Outcome of twin pregnancy in a renal transplant recipient treated with tacrolimus. AB - Our report describes the outcome of a twin pregnancy in a woman who was maintained on tacrolimus after a living related renal transplant. Both babies born at 32 weeks of gestation developed severe respiratory distress requiring ventilator assistance and went on to develop congestive heart failure. Echocardiograms on both babies showed dilated heart chambers. Twin A succumbed to complications, but twin B, who was treated more aggressively with vasopressors, recovered. Autopsy findings on twin A revealed a thrombotic cardiomyopathy with degeneration of cardiac muscle. We believe that the unusual outcome in this set of twins may have been a result of cardiomyopathy secondary to tacrolimus used by the mother during her pregnancy. PMID- 10030304 TI - Successful renal transplantation with ipsilateral femoral arteriovenous grafts. AB - BACKGROUND: The choice of location for revascularization of a renal allograft is frequently influenced by the presence of previous pelvic surgery or failed allografts that remain in situ. The presence of polytetrafluoroethylene (PTFE) loop grafts in the femoral vessels may potentially result in iliac venous hypertension, thereby compromising the function of a renal allograft placed nearby. The purpose of this study is to report the hemodynamic changes within the iliac veins as a result of PTFE femoral grafts and report the outcome of renal allografts placed ipsilateral to such grafts. METHODS: THREE patients with a failed renal allograft in the right iliac fossa and functioning left groin PTFE loop grafts underwent left iliac venography and hemodynamic measurements of the iliac venous system. All three patients underwent renal transplantation in the left iliac fossa without ligation or alteration of the loop graft. Standard clinical data were collected after transplantation. RESULTS: All three patients demonstrated widely patent external iliac and common iliac veins ipsilateral to the loop graft. Elevated pressures measured within the venous limb of the loop graft dissipated rapidly within the common femoral and external iliac veins. All three kidneys were well perfused, as documented by posttransplant technetium 99m diethylenetriaminepentaacetic acid nuclear renography. All three patients have normal renal function past 7 months after transplant, and all three femoral loop grafts are still functioning. CONCLUSIONS: PTFE loop grafts to the femoral vessels are not associated with local venous hypertension in the ipsilateral external iliac veins. Revascularization of a renal allograft may be performed ipsilateral to a femoral loop graft provided other venous diseases, such as strictures, have been excluded. PMID- 10030305 TI - Hyponatremia, hyposmolality, and hypotonicity: tables and fables. AB - The difficulty that nonnephrologists sometimes have with the differential diagnosis of hyponatremic patients often results from misinterpreting the significance of measured and calculated serum osmolalities, effective serum osmolalities (tonicities), and the influence of various normal (eg, serum urea nitrogen) and abnormal (eg, ethanol) solutes. Among the more commonly held misconceptions are that high serum urea or alcohol levels will, by analogy with glucose, cause hyponatremia, and that a normal (or elevated) measured serum osmolality in a hyponatremic patient excludes the possibility of hypotonicity. This article describes typical and deliberately comparative data of the serum levels of sodium, glucose, urea nitrogen, and mannitol and/or ethanol (if present); calculated and measured osmolality; effective osmolality; and the potential risk of hypotonicity-induced cerebral edema for each of 6 prototypical hyponatremic states. This provides a helpful educational tool for untangling these interrelationships and for clarifying the differences among various hyponatremic conditions. PMID- 10030306 TI - Treatment of intermittent claudication with physical training, smoking cessation, pentoxifylline, or nafronyl: a meta-analysis. AB - BACKGROUND: There is no consensus on the efficacy of physical training, smoking cessation, and pharmacological therapy (pentoxifylline or nafronyl oxalate) in the treatment of patients with intermittent claudication at Fontaine stage II of disease. METHODS: A MEDLINE and manual search was used to identify relevant publications. Uncontrolled or retrospective studies, double reports, and trials without clinically meaningful outcomes were excluded. Included studies were graded level 1 (randomized and double- or assessor-blind), level 2 (open randomized), or level 3 (nonrandomized). Pain-free and total walking distance were the main outcomes considered; when feasible, end-of-treatment results were combined with appropriate meta-analytical procedures. RESULTS: In 5 level 2 studies, physical training increased pain-free and total walking distance significantly (139.0 m [95% confidence interval {CI}, 31.0 to 246.9 m] and 179.1 m [95% CI, 60.2 to 298.1 m], respectively). In a level 3 study, smoking cessation resulted in a nonsignificant increase in total walking distance of 46.7 m (95% CI, -19.3 to 112.7 m). In 6 level 1 studies, pentoxifylline increased both pain free and total walking distance by 21.0 m (95% CI, 0.7 to 41.3 m) and 43.8 m (95% CI, 14.1 to 73.6 m), respectively. In 4 level 1 trials, nafronyl significantly increased pain-free walking distance (58.6 m [95% CI, 30.4 to 86.8 m]) and total walking distance (71.2 m [95% CI, 13.3 to 129.0 m]). CONCLUSIONS: Physical training increased pain-free and total walking distance in level 2 studies. Only level 3 studies support the usefulness of smoking cessation. In level 1 studies, pentoxifylline and nafronyl increased pain-free and total walking distance, but the average effects were relatively small. PMID- 10030307 TI - Review of 6-month mortality following low-probability lung scans. AB - BACKGROUND: Ventilation perfusion lung scanning is widely used as a diagnostic method for evaluating patients suspected of having pulmonary embolism (PE). While lung scan interpretation is traditionally performed in terms of probability of PE (usually low, moderate or intermediate, and high), in recent years concern has been raised that the term low probability may be misleading because adverse and even fatal sequelae of PE occasionally occur in such patients. To assess these concerns, a review of mortality in a large series of patients following low probability lung scans was performed. OBJECTIVE: To determine the 6-month mortality in a consecutive series of patients following low-probability ventilation perfusion (V/Q) lung scans. METHODS: Records of all patients who had low-probability V/Q scans during a 9-year period (1987-1995) were reviewed. Causes of mortality for those patients who died during the 6-month period after the index scan were established from patients' charts, autopsy reports, and computer record data. RESULTS: Of the total 536 evaluable patients, 83 (15%) died within 6 months of the date of the lung scan; 73 (88%) died while inpatients at the Seattle Veterans Affairs Medical Center, Seattle, Wash, and the other 10 (12%) died at other facilities or at home. Pulmonary embolism was not reported as a suspected or probable contributing factor in any of the 83 deaths. Sixty-three patients (76%) who died had a diagnosis of either cancer (n = 32) or advanced cardiovascular disease (n = 31) at the time of their lung scans. Twenty-six patients (31%) underwent autopsies, and PE was not identified on examination of the lungs in any of them. Of the 27 patients who died within 1 month of the scan date, 17 (63%) underwent autopsies. CONCLUSION: Review of data from all patients with low-probability V/Q scans and a follow-up of 6 months showed no documentation to attribute any deaths to PE. PMID- 10030308 TI - Validation in a community hospital setting of a clinical rule to predict preserved left ventricular ejection fraction in patients after myocardial infarction. AB - BACKGROUND: A previous study showed that patients with previous myocardial infarction (MI) who meet 4 simple clinical and/or electrocardiographic criteria have a left ventricular ejection fraction (LVEF) of 40% or greater, with a positive predictive value of 98%. The objective of this study was to validate this clinical rule in the community hospital setting. METHODS: Retrospective chart review in a 330-bed community hospital. Two hundred thirteen consecutive patients with MI were identified between June 1, 1993, and March 31, 1995. Left ventricular ejection fraction was predicted in a blinded fashion by means of the clinical rule before the actual LVEF test was reviewed. RESULTS: We identified 213 patients admitted with the primary discharge diagnosis of acute MI. All patients met standard clinical and enzymatic definitions for acute MI and had at least 1 measure of LVEF, such as echocardiography, ventricular angiography, or gated blood pool scan. The clinical rule predicted that 83 patients (39.0%) would have an LVEF of 40% or greater. Of these 83 patients, 71 had an ejection fraction of 40% or greater, for a positive predictive value of 86%. Of the 12 patients who were incorrectly predicted to have a preserved LVEF, 6 (50%) had an index non-Q wave anterior MI (P<.001). Reanalyzing the patient population with a fifth variable (anterior non-Q-wave MI) added to the original 4 variables increased the positive predictive value to 91%. CONCLUSION: This simple clinical prediction rule has a positive predictive value of 86% when applied in the community hospital setting. Patients with anterior non-Q-wave MI may be 1 group in whom the rule is inaccurate, and expanding the clinical rule to 5 variables may increase the positive predictive value. When a technology-based assessment of left ventricular function is considered in patients after an MI, this prediction rule may allow for a more cost-effective patient selection, and as many as 40% of patients who have had acute MIs may require no testing at all. PMID- 10030309 TI - Evaluating the appropriateness of digoxin level monitoring. AB - BACKGROUND: Digoxin level determinations can be useful clinically in patients receiving digoxin therapy but are sometimes misused. METHODS: Explicit appropriateness criteria were adapted from previously published criteria and revised using local expert opinion. They were then used to evaluate the appropriateness of random samples of inpatient and outpatient serum digoxin levels. Overall agreement between reviewers regarding appropriateness was good (K = 0.65). Patients in the study included 162 inpatients in whom 224 digoxin levels were measured and 117 outpatients in whom 130 digoxin levels were measured during a 6-month period. The main outcome measure was the proportion of digoxin levels with an appropriate indication. RESULTS: Among inpatient levels, only 16% (95% confidence intervals [CI], 11%-20%) were appropriate. Of the 189 digoxin levels considered inappropriate, only 26 (14%) had a result of 2.3 nmol/L or more (> or =1.8 ng/ mL). None of these levels resulted in an important change in therapy, and no patient had a toxic reaction to the therapy. Among inappropriate levels, daily routine monitoring accounted for 78%. Of the 130 outpatient levels, 52% (95% CI, 44%-61%) were appropriate. Of 62 inappropriate levels, only 4 (6%) had a result of 2.3 nmol/L or more (> or =1.8 ng/mL). One result led to a change in therapy, but none of the patients were believed to experience a toxic reaction. Among the inappropriate levels, 87% of patients underwent early routine monitoring before a steady state was achieved. CONCLUSIONS: A high proportion of digoxin levels were inappropriate, particularly among inpatients. In both groups, the primary reason tests were judged inappropriate was early routine monitoring. Few inappropriate tests resulted in important data. Interventions to improve the use of digoxin levels could potentially save substantial resources without missing important clinical results. PMID- 10030310 TI - A population-based case-cohort study of drug-associated agranulocytosis. AB - BACKGROUND: Agranulocytosis is a life-threatening disorder, often caused by drugs. Incidences or risks of drug-induced agranulocytosis are not well known, since it is rare. METHODS: To determine the risk of drug-associated agranulocytosis as a reason for admission to Dutch hospitals, we performed a population-based case-cohort study. Hospital discharge data came from the Dutch Centre for Health Care Information, Utrecht, which contains data on all general and university hospitals in the Netherlands. The reference cohort consisted of all persons in the catchment area of the Pharmaco Morbidity Record Linkage System (PHARMO RLS) in the Netherlands, composing a population of approximately 220 000 to 484 000 persons from 1987 through 1990. All admissions during that period with agranulocytosis or related diagnoses were included in the study (n = 923). The potential causes of agranulocytosis were assessed in all cases classified as probable or possible agranulocytosis. RESULTS: Discharge summaries were received of 753 admissions, of which 678 contained enough information for analysis. Of the 678,108 were classified as "agranulocytosis probable" or as "agranulocytosis possible." In 75 of these 108 cases, agranulocytosis had been the reason for admission. Fifteen patients had used methimazole within 10 days before developing agranulocytosis; 2, carbimazole; 9, sulfasalazine; 8, sulfamethoxazole trimethoprim; 4, clomipramine hydrochloride; and 2, dipyrone with analgesics, yielding adjusted relative risks of agranulocytosis of 114.8 (for thyroid inhibitors combined) (95% confidence interval [CI], 60.5-218.6), 74.6 (95% CI, 36.3-167.8), 25.1 (95% CI, 11.2-55.0),20.0 (95% CI, 6.1-57.6), and 26.4 (95% CI, 4.4-11.1), respectively. CONCLUSIONS: The highest relative risks were found for thyroid inhibitors, sulfamethoxazole-trimethoprim, sulfasalazine, clomipramine, and dipyrone combined with analgesics. PMID- 10030311 TI - Do symptoms predict cardiac arrhythmias and mortality in patients with syncope? AB - BACKGROUND: Patients with syncope frequently present with multitude of other symptoms but their significance in predicting morbidity or mortality has not been previously studied. OBJECTIVE: To determine if certain symptoms can be used to identify syncope patients at risk for cardiac arrhythmias, mortality, or recurrence of syncope. PATIENTS AND METHODS: From August 1987 to February 1991, we prospectively evaluated patients with syncope from outpatient, inpatient, and emergency department services of a university medical center. These patients were interviewed, charts were reviewed, and detailed information on 19 symptoms and comorbidities was obtained. A cause of syncope was assigned using standardized diagnostic criteria. All patients were followed up at 3-month intervals for at least 1 year for recurrence of syncope and mortality. Patients in whom the cause of syncope was determined by medical history and physical examination alone were not included in our analysis. RESULTS: History and physical examination led to the cause of syncope in 222 of 497 patients enrolled. In the remaining 275 patients, the absence of nausea and vomiting before syncope (odds ratio, 7.1) and electrocardiographic abnormalities (odds ratio, 23.5) were predictors of arrhythmic syncope. Underlying cardiac disease was the only predictor of 1-year mortality. No symptom remained as independent predictor for 1-year mortality or syncope recurrence. CONCLUSIONS: Symptoms, although important in assigning many noncardiac causes, are not useful in risk-stratifying patients whose cause of syncope cannot be identified by other history and physical examination. Triage decisions and management plans should be based on pre-existing cardiac disease or electrocardiographic abnormalities, which are important predictors of arrhythmic syncope and mortality. PMID- 10030312 TI - Serum beta-hydroxybutyrate measurement in patients with uncontrolled diabetes mellitus. AB - OBJECTIVE: To assess whether routinely measuring serum beta-hydroxybutyrate (beta OHB) concentration might help judge the severity of or assist in treating patients with suspected ketoacidosis. METHODS: Serum beta-OHB level was estimated by a standard enzymatic method in 64 episodes in adults admitted to a municipal hospital. Of the 85 specimens analyzed, 60 were taken before treatment from a nearly consecutive group of diabetic patients with ketosis, 21 were follow-up specimens, and 4 were from nondiabetic patients with ketosis. RESULTS: In the 85 specimens, the correlation between serum carbon dioxide and beta-OHB levels was 0.69, and that between anion gap and beta-OHB level was 0.75. For just the initial specimens, the respective correlation coefficients were -0.60 and 0.52. CONCLUSIONS: The correlations between serum beta-OHB and carbon dioxide levels and the anion gap were close, but not sufficiently so for the beta-OHB measurements to be routinely useful alone to assess the severity of the ketoacidosis. Full laboratory assessment of the severity and characteristics of ketoacidosis also requires knowledge of serum carbon dioxide level, anion gap, often blood pH, and ideally serum acetoacetate and lactate concentrations as well as serum beta-OHB concentration. PMID- 10030313 TI - Exertional leg symptoms other than intermittent claudication are common in peripheral arterial disease. AB - BACKGROUND: Epidemiological data show that most community-dwelling men and women with lower-extremity peripheral arterial disease (PAD) do not have typical symptoms of intermittent claudication. We compared the prevalence of intermittent claudication, leg symptoms other than intermittent claudication, and absence of exertional leg symptoms between patients with PAD identified from a blood flow laboratory (group 1), patients with PAD in a general medicine practice (group 2), and control patients without PAD (group 3). METHODS: Numbers of participants in groups 1, 2, and 3 were 137, 26, and 105, respectively. Patients with previously diagnosed PAD were excluded from groups 2 and 3. All participants underwent ankle brachial index measurement and were administered the San Diego claudication questionnaire to assess leg symptoms. RESULTS: Within groups 1, 2, and 3, prevalences of intermittent claudication were 28.5% (n = 39), 3.8% (n = 1), and 3.8% (n= 4), respectively. Prevalences of exertional leg symptoms other than intermittent claudication were 56.2% (n= 77), 42.3% (n= 11), and 19.0% (n = 20), respectively. Absence of exertional leg symptoms was reported by 15.3% (n= 21), 53.8% (n= 14), and 77.1% (n=81), respectively. Among patients with PAD, older age, male sex, diabetes mellitus, and group 2 vs group 1 status were associated independently with absence of exertional leg symptoms in multivariable regression analysis. Lower ankle-brachial index levels and group 1 vs group 2 status were associated with intermittent claudication. CONCLUSIONS: Clinical manifestations of PAD are diverse, particularly among patients identified by ankle-brachial index screening. Exertional leg symptoms other than intermittent claudication are common in PAD. Patients with PAD who are older, male, diabetic, or identified with ankle-brachial index screening in a primary care setting are more likely to have asymptomatic PAD. PMID- 10030314 TI - Impact of same-day screening mammography availability: results of a controlled clinical trial. AB - BACKGROUND: We conducted a prospective controlled clinical trial in an urban academic general medicine practice to test the effect of same-day mammography availability on adherence to physicians' screening mammography recommendations. PATIENTS AND METHODS: Participants were a consecutive sample of 920 female patients aged 50 years or older who had received a physician's recommendation for screening mammography at an office visit and had no active breast symptoms, history of breast cancer, or a mammogram within the previous 12 months. Women were assigned to same-day screening mammography availability (intervention group) or usual screening mammography scheduling (control group). MAIN OUTCOME MEASURES: Three-, 6-, and 12-month rates of adherence to physicians' recommendations for screening mammography. RESULT: Twenty-six percent of women in the intervention group obtained a same-day screening mammogram. At 3 months, 58% of the women in the intervention group underwent the recommended screening mammography compared with 43% of the women in the control group (P<.001), increasing to 61% and 49% at 6 months (P<.001), and 268 (66%) of 408 vs 287 (56%) of 512 at 12 months (P = .003). The difference between the intervention and control groups 3-month adherence rates was most marked among women aged 65 years or older (58% vs 34%; P<.001), women who were not employed (54% vs 36%; P<.001), and women with a history of having had either no mammograms (39% vs 20%; P = .02) or only 1 to 2 mammograms (57% vs 38%; P<.001) within the last 5 years. CONCLUSIONS: Same-day mammography availability increased 3-, 6-, and 12-month screening mammography adherence rates in this urban academic general medicine practice. The effect was most marked among women aged 65 years or older, women who were not employed, and those who had had fewer than 3 mammograms in the last 5 years. The efficacy of this intervention in other settings still needs to be demonstrated. PMID- 10030315 TI - Mastocytosis: diverse presentations and outcomes. AB - Within the general category of mastocytosis lies an array of clinical presentations with differing prognostic implications. We report 3 cases of systemic mastocytosis distinguished by novel aspects of the disease. Case 1 documents the first successful orthotopic liver transplantation in a patient with mastocytosis; case 2 depicts a potential hereditary component of mastocytosis; and case 3 documents the progression of mastocytosis with hematologic abnormality to mast cell leukemia. Future investigations, such as the early definition of c kit receptor mutations, may provide additional insight as to the molecular basis for this heterogeneous disease and guidance for prognostic implications and targeted therapies. PMID- 10030316 TI - Prevalence of subtle cobalamin deficiency. PMID- 10030317 TI - Causes of peptic ulcers. PMID- 10030318 TI - Evaluation of a blood pressure monitoring device. PMID- 10030319 TI - An African solution. PMID- 10030320 TI - Which drug for treatment of hypertension? PMID- 10030321 TI - Keeping watch over genetically modified crops and foods. PMID- 10030322 TI - Preventive medicine in a diabetes clinic: an opportunity to make a difference. PMID- 10030323 TI - Buccal route for benzodiazepines in treatment of seizures? PMID- 10030324 TI - Evidence and primary care. PMID- 10030325 TI - Effect of angiotensin-converting-enzyme inhibition compared with conventional therapy on cardiovascular morbidity and mortality in hypertension: the Captopril Prevention Project (CAPPP) randomised trial. AB - BACKGROUND: Angiotensin-converting-enzyme (ACE) inhibitors have been used for more than a decade to treat high blood pressure, despite the lack of data from randomised intervention trials to show that such treatment affects cardiovascular morbidity and mortality. The Captopril Prevention Project (CAPPP) is a randomised intervention trial to compare the effects of ACE inhibition and conventional therapy on cardiovascular morbidity and mortality in patients with hypertension. METHODS: CAPPP was a prospective, randomised, open trial with blinded endpoint evaluation. 10,985 patients were enrolled at 536 health centres in Sweden and Finland. Patients aged 25-66 years with a measured diastolic blood pressure of 100 mm Hg or more on two occasions were randomly assigned captopril or conventional antihypertensive treatment (diuretics, beta-blockers). Analysis was by intention-to-treat. The primary endpoint was a composite of fatal and non fatal myocardial infarction, stroke, and other cardiovascular deaths. FINDINGS: Of 5492 patients assigned captopril and 5493 assigned conventional therapy, 14 and 13, respectively, were lost to follow-up. Primary endpoint events occurred in 363 patients in the captopril group (11.1 per 1000 patient-years) and 335 in the conventional-treatment group (10.2 per 1000 patient-years; relative risk 1.05 [95% CI 0.90-1.22], p=0-52). Cardiovascular mortality was lower with captopril than with conventional treatment (76 vs 95 events; relative risk 0.77 [0.57-1 04], p=0.092), the rate of fatal and non-fatal myocardial infarction was similar (162 vs 161), but fatal and non-fatal stroke was more common with captopril (189 vs 148; 1.25 [1-01-1-55]. p=0.044). INTERPRETATION: Captopril and conventional treatment did not differ in efficacy in preventing cardiovascular morbidity and mortality. The difference in stroke risk is probably due to the lower levels of blood pressure obtained initially in previously treated patients randomised to conventional therapy. PMID- 10030326 TI - Intensified multifactorial intervention in patients with type 2 diabetes mellitus and microalbuminuria: the Steno type 2 randomised study. AB - BACKGROUND: In type 2 diabetes mellitus the aetiology of long-term complications is multifactorial. We carried out a randomised trial of stepwise intensive treatment or standard treatment of risk factors in patients with microalbuminuria. METHODS: In this open, parallel trial patients were allocated standard treatment (n=80) or intensive treatment (n=80). Standard treatment followed Danish guidelines. Intensive treatment was a stepwise implementation of behaviour modification, pharmacological therapy targeting hyperglycaemia, hypertension, dyslipidaemia, and microalbuminuria. The primary endpoint was the development of nephropathy (median albumin excretion rate >300 mg per 24 h in at least one of the two-yearly examinations). Secondary endpoints were the incidence or progression of diabetic retinopathy and neuropathy. FINDINGS: The mean age was 55.1 years (SD 7.2) and patients were followed up for 3.8 years (0.3). Patients in the intensive group had significantly lower rates of progression to nephropathy (odds ratio 0.27 [95% CI 0-10-0.75]), progression of retinopathy (0.45 [0.21-0.95]), and progression of autonomic neuropathy (0.32 [0.12-0.78]) than those in the standard group. INTERPRETATION: Intensified multifactorial intervention in patients with type 2 diabetes and microalbuminuria slows progression to nephropathy, and progression of retinopathy and autonomic neuropathy. However, further studies are needed to establish the effect of intensified multifactorial treatment on macrovascular complications and mortality. PMID- 10030327 TI - Buccal midazolam and rectal diazepam for treatment of prolonged seizures in childhood and adolescence: a randomised trial. AB - BACKGROUND: Convulsive status epilepticus is the most common neurological medical emergency and has high morbidity and mortality. Early treatment before admission to hospital is best with an effective medication that can be administered safely. We aimed to find out whether there are differences in efficacy and adverse events between buccal administration of liquid midazolam and rectal administration of liquid diazepam in the acute treatment of seizures. METHODS: At a residential school with on-site medical facilities 42 young people with severe epilepsy were enrolled. Continuous seizures of more than 5 min duration were randomly treated with buccal midazolam or rectal diazepam. If the seizure did not stop within 10 min additional medication chosen by the attending physician was administered. We monitored oxygen saturation and blood pressure for 30 min after treatment. The main outcome measures were efficacy, time from arrival of the nurse to drug administration, time from drug administration to end of seizure, and incidence of adverse cardiorespiratory events. FINDINGS: Buccal midazolam was used to treat 40 seizures in 14 students, and rectal diazepam 39 seizures in 14 students. Midazolam stopped 30 (75%) of 40 seizures and diazepam 23 (59%) of 39 (p=0.16). The median time from arrival of the nurse to administration of medication was 2 min. Time from administration to end of seizure did not differ significantly between the two treatments. No clinically important adverse cardiorespiratory events were identified in the two groups. Buccal midazolam was universally acceptable to the nursing and care staff. INTERPRETATION: Buccal midazolam is at least as effective as rectal diazepam in the acute treatment of seizures. Administration via the mouth is more socially acceptable and convenient and may become the preferred treatment for long seizures that occur outside hospital. PMID- 10030328 TI - Chronic stress in elderly carers of dementia patients and antibody response to influenza vaccination. AB - BACKGROUND: There are many reports of psychological morbidity in spousal carers of patients with dementia. The consequences of this increased stress on the immune system are unclear. We investigated whether antibody responses to influenza vaccination differed between carers and a control group, and the relation of the antibody response to the hypothalamic-pituitary-adrenal (HPA) axis. METHODS: 50 spousal carers of dementia patients, median age 73 years (IQR 66-77), and 67 controls (68 years [66-71]) of similar socioeconomic status were enrolled. Anxiety and depression were measured by the Savage Aged Personality Screening Scale and stress by the Global Measure of Perceived Stress scale. Principal-component analysis was used to yield a summary score of emotional distress from these two scales. Salivary cortisol concentrations were measured over a single day at three times (0800-1000, 1100-1300, and 2000-2200). Participants received a trivalent influenza vaccine and IgG antibody titres to each strain were measured on days 0, 7, 14, and 28. FINDINGS: Mean scores of emotional distress were significantly higher in carers at each time point than in controls (all p<0.0003). Mean (SD) salivary cortisol concentrations, calculated as area under the curve (AUC), were higher in carers than controls at all three assessments (6 months 16.0 [8.0] vs 11.2 [4.4], p=0.0001; respectively). Eight (16%) of 50 carers and 26 (39%) of 67 controls had a four-fold increase in at least one of the IgG titres (p=0.007). There was an inverse relation between AUC cortisol and IgG antibody titre to the Nanchang strain that was significant on day 14 (r=-0.216, p=0.039). INTERPRETATION: Elderly carers of spouses with dementia have increased activation of the hypothalamic-pituitary-adrenal axis and a poor antibody response to influenza vaccine. Carers may be more vulnerable to infectious disease than the population of a similar age. PMID- 10030330 TI - Familial papillary thyroid microcarcinoma: a new clinical entity. AB - BACKGROUND: Familial, non-medullary thyroid carcinoma is clinically more aggressive than the sporadic form. We wanted to find out whether papillary thyroid microcarcinoma also occurs in a familial pattern, and, if so, to identify specific clinical and prognostic features. METHODS: We reviewed the clinical records of 119 patients with papillary thyroid microcarcinoma. Familial occurrence, together with clinical presentation, surgical treatment, pathological characteristics, and follow-up were recorded. FINDINGS: We identified a family history of thyroid carcinoma in seven patients. The tumour was multifocal in five patients, bilateral in three, and vascular invasion occurred in three of the seven patients. Lymph-node metastases were found in four patients. Three patients had a recurrence and one patient with pulmonary metastases died within 11 months. INTERPRETATION: We identified familial occurrence in 5.9% of cases of papillary thyroid microcarcinoma. The unfavourable behaviour in the familial form of papillary thyroid microcarcinoma suggests that radical treatment and careful follow-up are warranted. PMID- 10030329 TI - Intermittent sulphadoxine-pyrimethamine to prevent severe anaemia secondary to malaria in pregnancy: a randomised placebo-controlled trial. AB - BACKGROUND: In areas of endemic transmission, malaria in pregnancy is associated with severe maternal anaemia and low-birthweight babies. We studied the efficacy of intermittent treatment doses of sulphadoxine-pyrimethamine in preventing malaria and severe anaemia in pregnancy in a double-blind placebo-controlled trial among primigravid women living in Kilifi District, Kenya. METHODS: Between January, 1996, and April, 1997, 1264 primigravid women were recruited when they attended for antenatal care, and randomly assigned sulphadoxine-pyrimethamine (640) or placebo (624). Women received one, two, or three doses of study medication depending on the duration of gestation at enrolment. Primary outcome measures were severe anaemia (haemoglobin <8 g/dL) and malaria parasitaemia, assessed at 34 weeks of gestation. Analyses were based on intention to treat among women who had study blood tests at 34 weeks. FINDINGS: 30 (5.3%) of 567 women in the sulphadoxine-pyrimethamine group and 199 (35.3%) of 564 in the placebo group had peripheral parasitaemia (protective efficacy 85% [95% CI 78 90], p<0.0001). 82 (14.5%) and 134 (23.7%) had severe anaemia (protective efficacy 39% [22-52], p<0.0001). Even women who booked late and received only one dose of sulphadoxine-pyrimethamine benefited significantly from the intervention. The effects were seen both in women who owned insecticide-treated bednets and in women who did not. INTERPRETATION: Intermittent presumptive treatment with sulphadoxine-pyrimethamine is an effective, practicable strategy to decrease the risk of severe anaemia in primigravidae living in malarious areas. PMID- 10030331 TI - Gynaecomastia and raised oestradiol concentrations. PMID- 10030332 TI - Successful combined kidney-liver right lobe transplant from a living donor. PMID- 10030333 TI - Autologous patient serum for the culture of keratinocyte transplants reduces risk of transmittable disease. PMID- 10030334 TI - Plasma lipoprotein responses to enzyme-replacement in Gaucher's disease. PMID- 10030335 TI - Circadian variation in spontaneous rupture of abdominal aorta. PMID- 10030336 TI - Spatial and temporal mapping of neural activity associated with auditory hallucinations. PMID- 10030337 TI - Patients' ability to recall risk associated with treatment options. PMID- 10030338 TI - Analysis of the monoamine oxidase genes and the Norrie disease gene locus in narcolepsy. PMID- 10030339 TI - A 61-year-old man with Holmes' heart. PMID- 10030340 TI - UK psychiatrists refuse to treat the untreatable. PMID- 10030341 TI - The application of cell biology to broken bones. PMID- 10030342 TI - A quiet clinical guideline revolution begins. PMID- 10030343 TI - Big health threat from drug abuse in south Asia. PMID- 10030344 TI - Former French ministers on trial for infected blood-products scandal. PMID- 10030345 TI - South African faces an AIDS crisis as government health campaigns fail. PMID- 10030346 TI - Leprosy. AB - Leprosy is an ancient disease which is still poorly understood and often feared by the general public and even by some healthcare professionals. Fortunately, improvements in the management of leprosy over the past three decades have diminished the stigma and greatly altered the outlook for patients. Public understanding of the disease has benefited from WHO's goal of eliminating leprosy as a public health problem by the year 2000. Unfortunately that goal has also led many to believe that leprosy has been or will soon be eradicated. This will not happen in the near future because, despite a fall in registered cases, the incidence of the disease has changed very little, and eradication of a bacterial infectious disease such as this is unlikely with chemotherapy alone. Nevertheless, as a result of the WHO's efforts, patients nearly everywhere should have access to care, and the incidence may begin to diminish if adequate control efforts are maintained beyond the year 2000. Given the mobility of patients today a physician anywhere may occasionally see a case or be asked about the disease so a basic understanding of leprosy and its management should prove useful. PMID- 10030347 TI - Application of evidence from randomised controlled trials to general practice. PMID- 10030348 TI - Religion, spirituality, and medicine. PMID- 10030349 TI - Treating influenza with zanamivir. PMID- 10030350 TI - Treating influenza with zanamivir. Management of Influenza in the Southern Hemisphere Trialists. PMID- 10030351 TI - Circumcision of newborn boys. PMID- 10030352 TI - Circumcision of newborn boys. PMID- 10030353 TI - Circumcision of newborn boys. PMID- 10030354 TI - Corpses and the spread of cholera. PMID- 10030355 TI - Classification of inflammatory arthritis. PMID- 10030356 TI - A specific treatment for hypochondriasis? PMID- 10030357 TI - A specific treatment for hypochondriasis? PMID- 10030358 TI - Cranberry juice and prevention of recurrent urinary tract infection. PMID- 10030359 TI - Childhood mortality in sub-Saharan Africa. PMID- 10030360 TI - Appendicectomy in ulcerative colitis. PMID- 10030361 TI - Appendicectomy in ulcerative colitis. PMID- 10030362 TI - Oestrogen replacement therapy in postmenopausal women. PMID- 10030363 TI - Diagnosis of molybdenum cofactor deficiency. PMID- 10030364 TI - Diagnosis of molybdenum cofactor deficiency. PMID- 10030365 TI - Aspirin, myocardial infarction, and gastrointestinal bleeding. PMID- 10030366 TI - Aspirin, myocardial infarction, and gastrointestinal bleeding. PMID- 10030367 TI - Antioxidant effects of herbs. PMID- 10030368 TI - Pain relief in India. PMID- 10030369 TI - Pain relief in India. PMID- 10030370 TI - Alice C is poor evidence against age-based rationing. PMID- 10030371 TI - Pagers to test vibratory sense. PMID- 10030372 TI - Soranus of Ephesus on migraine. PMID- 10030373 TI - A doctor's guide to keeping your head above the hogwash. PMID- 10030374 TI - The Nobel chronicles. 1939: Gerhard Domagk (1895-1964). PMID- 10030375 TI - Heart allograft vascular disease: an obliterative vascular disease in transplanted hearts. AB - More than 30 years have passed since the first human heart transplantation was performed. Since then, short-term survival after heart transplantation has been markedly improved, but this development has not been paralleled with a similar improvement in long-term survival. One of the major reasons for this is the subsequent development of heart allograft vascular disease, an obliterative disease in the coronary arteries of the transplanted heart. The dubious effect of re-vascularization in this disease, the less favorable outcome after repeat heart transplantation, and the low donor supply have called for intensified research for new and efficient prophylactic therapies against heart allograft vascular disease. This research has lead to improved knowledge about diagnosis, etiology, pathogenesis, prophylaxis, and treatment possibilities. The most important among these seem to be: (i) the introduction of intravascular ultrasound for early detection of the disease; (ii) evidence to suggest that hyperlipidemia, insufficient immunosuppressive therapy, human leukocyte antigen (HLA)-mismatch, and infection with cytomegalovirus (CMV) all may promote allografts vascular disease; and (iii) the introduction of at least two promising prophylactic therapies in humans namely 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors and calcium entry blockers, and others potentially promising e.g. angiotensin-converting enzyme-inhibitors, angiopeptin, mycophenolate mofetil and rapamycin. This review summarizes present knowledge on the possibilities of inhibiting or treating heart allograft vascular disease incorporating evidence from both human and experimental studies. PMID- 10030376 TI - A critical analysis of the role of cholesterol in atherogenesis. AB - Serum hypercholesterolemia is theorized to accelerate atherogenesis by augmenting cholesterol accumulation (insudation) in the arterial intima. The author views this theory as an example of what the noted philosopher of science Imre Lakatos called 'degenerative science', because data have forced several modifications of the theory. Although the theory that some fraction of intimal cholesterol causes atherosclerosis is not yet disproved, the author favors the hypothesis that serum hypercholesterolemia accelerates atherogenesis and contributes to symptomatic atherosclerosis by increasing blood viscosity and the mechanical fragility of atherosclerotic plaques, making them vulnerable to rupture and thrombosis. PMID- 10030377 TI - Immunolocalization of high-density lipoproteins in arterial walls of rats. AB - The inverse correlation between serum high-density lipoprotein (HDL) levels and coronary heart disease in humans suggests that HDL has a protective effect against the development of atherosclerosis. However, there is a lack of data concerning its distribution across the arterial wall. In order to detect this lipoprotein, we performed immunogold labeling on ultrathin sections of L.R. White embedded rat arterial tissue. Electron microscopic examination revealed that HDL was localized in the cytoplasm of the endothelial cells and the smooth muscle cells, but not in the nucleus or other organelles. The HDL was also present in the subendothelial space, the extracellular matrix as well as the intercellular clefts between the endothelial cells. Quantitative study revealed that rats on a high cholesterol diet for one month have more immunogold labeling (P < 0.05) in the subendothelial space, the smooth muscle cells and the extracellular matrix as compared to rats on a normal diet. After 12 months of normal diet, the intracellular labeling was significantly increased (P < 0.05) in the endothelial cells and the smooth muscle cells as compared to 1 month on the normal diet. The increase was greater (P < 0.05) for the high-cholesterol diet than for the normal diet treatment. PMID- 10030378 TI - Differences in biological risk factors for cardiovascular disease between three ethnic groups in the Whitehall II study. AB - This study compares risk factors for cardiovascular disease in civil servants of three ethnic groups screened as part of the Whitehall II cohort study. Previously identified risk factors for cardiovascular disease in 360 Afro-Caribbean and 577 South Asian subjects are compared with the 8973 white Caucasian subjects. Controlling for socio-economic status is more precise than in most previous studies of cardiovascular differences between ethnic groups. After controlling for socio-economic confounding factors, age and sex, South Asian subjects were found to have increased prevalence of hypertension (defined as either having systolic pressure of > 160, diastolic pressure of > 95 or being on antihypertensives) OR 2.3 (95% CI 1.6-3.3), diabetes OR 4.2 (95%, CI 3.0-5.8) and a high risk lipid profile, although total cholesterol was lower than in the white population. Afro-Caribbean subjects had more hypertension OR 4.0 (95% CI 2.8-5.7) and diabetes OR 2.8 (95% CI 1.7-4.6), but this was accompanied by a favourable lipid profile with low cholesterol and high HDL. Afro-Caribbean alcohol and smoking habits were low-risk. Socio-economic status was found to be an important confounding factor for ethnic differences in biochemical risk factors for cardiovascular disease. However, adjusting for socioeconomic class only attenuates observed differences; it does not abolish them. PMID- 10030379 TI - Monocyte prostaglandins inhibit procollagen secretion by human vascular smooth muscle cells: implications for plaque stability. AB - Extracellular matrix remodelling occurs during atherosclerosis dictating the structure of the plaque and thus the resistance to rupture. Monocytes and macrophages are believed to play a role in this remodelling. In the present study, filter-separated co-culture has been used to study the effect of monocytes on procollagen turnover by human vascular smooth muscle cells (VSMC). In this system, freshly isolated human peripheral blood monocytes inhibited procollagen secretion from VSMC without affecting either degradation of procollagen, or DNA synthesis by the VSMC. Insertion of a 12 kDa dialysis membrane between the two cell types and treatment with indomethacin showed that the inhibitory factor was of low molecular weight and was cyclooxygenase-dependent. Pre-incubation of each cell type with indomethacin demonstrated that monocyte, but not VSMC cyclooxygenase was required. Thus, the inhibitory effect on procollagen secretion was due, most likely, to monocyte prostaglandins. Neither inhibition of thromboxane synthetase, nor blocking IL-1 activity, reduced the inhibitory activity. Addition of prostaglandins PGE1, PGE2 and PGF2alpha to VSMC cultures caused a reduction in procollagen secretion which was equivalent to, but was not additive with, the maximal effect achieved by monocytes. Monocytes and macrophages are a major source of prostaglandins and these molecules are likely to play an important role in collagen turnover within lesions. PMID- 10030380 TI - Association of FXIII Val34Leu with decreased risk of myocardial infarction in Finnish males. AB - Factor XIII is a transglutaminase that crosslinks fibrin in the last steps of the coagulation process. A few polymorphic sites have been identified in this gene, one of them being a point mutation (FXIII Val34Leu), leading to an amino acid change of valine to leucine. Recently, in British patients, FXIII 34Leu allele was suggested to be associated with a decreased incidence of myocardial infarction (MI). PAI-1 4G/4G genotype seemed to lessen the beneficial effect of FXIII 34Leu allele. The aim of our study was to further investigate the possible protective role of the FXIII 34Leu allele against MI and its suggested interaction with the PAI-1 4G/5G polymorphism. We carried out genotype analyses for FXIII Val34Leu using solid-phase minisequencing in two independent Finnish study groups. In our study, the FXIII 34Leu allele was associated with a lower risk of MI (P = 0.009), however, the PAI-1 4G allele showed no interaction with this polymorphism. To establish the population frequency of the FXIII 34Leu allele and to study the possible variations in Finland four DNA pools from different geographical areas of Finland were genotyped. No significant differences in the allele frequencies were observed (21-28%) except in the Eastern Kainuu area (13%), an area with an increased risk of mortality from coronary artery disease (CAD), supporting the results presented above. The association of FXIII 34Leu variant with a lower incidence of myocardial infarction suggests a new role for FXIII in a polygenic thrombotic disease. PMID- 10030381 TI - Cholesteryl ester transfer protein gene expression during differentiation of human preadipocytes to adipocytes in primary culture. AB - The expression pattern of the CETP gene in relationship to that of LPL, adipsin, PPARgamma, C/EBPalpha, ADD1/SREBPI and actin was examined by RT-PCR during differentiation of human fibroblastic preadipocytes to adipocytes in primary culture. Preadipocytes were isolated from subcutaneous fat obtained from healthy female subjects undergoing mammary reduction procedures, and induced to differentiate in culture. Morphologically, adipogenesis was confirmed by the accumulation of lipid droplets in cells. We show that the gene encoding CETP is expressed in preadipocytes and is present throughout differentiation as compared to LPL and adipsin which were detected in the majority of samples by day 2 or 3 of adipogenesis. The transcription factors, PPARgamma, ADD1/SREBP1 and C/EBPalpha were expressed by day 2, concomitant with the appearance of LPL and adipsin but subsequent to the appearance of CETP. CETP mRNA was not detectable in human skin fibroblasts. These studies demonstrate that CETP. expression is induced at an early stage of commitment to the adipocyte lineage and may be activated by transcription factor(s), which are not members of the PPAR, ADD1/SREBP1 or C/EBP families. PMID- 10030382 TI - Association of plasma triglyceride-rich lipoprotein remnants with coronary atherosclerosis in cases of sudden cardiac death. AB - Among the risk factors for coronary atherosclerosis, elevated LDL-C level is best known. The action of lipoprotein lipase on triglyceride-rich lipoproteins produces remnant lipoprotein particles enriched in cholesterol and apolipoprotein E (apo E). Apo E serves as the ligand for uptake of remnant lipoproteins via the LDL-receptor or the remnant receptor. In this study, postmortem plasma total cholesterol, triglycerides (TG), VLDL-C, HDL-C, lipoprotein (a) [Lp(a)] and remnant-like lipoprotein particles (RLP)-cholesterol, RLP-TG, apolipoproteins B, C III and E were measured, together with LDL-C to assess their potential contribution to the severity of coronary and aortic atherosclerosis of the 197 cases of sudden death (132 cardiac death and 65 non-cardiac death). In all cases, the severity of coronary atherosclerosis was determined at postmortem pathological examination. RLP-cholesterol (RLP-C) and LDL-C concentrations were significantly higher in cases with advanced coronary atherosclerosis compared with those without coronary atherosclerosis; respective median values were 13.5 vs 8.4 mg/dl (P < 0.001) and 140 vs 115 mg/dl (P < 0.05). RLP-C levels were more strongly correlated with the severity score of coronary atherosclerosis than LDL C. PMID- 10030383 TI - Coronary artery apoptosis in experimental hypercholesterolemia. AB - The altered coronary vasoactivity detected in experimental hypercholesterolemia before lesion formation is presumably due to an imbalance between vasodilating and vasoconstricting factors. Apoptosis, which has been previously described in advanced atherosclerosis, is modulated by vascular derived peptides with vasoactive properties. We hypothesized that coronary apoptosis occurs in experimental hypercholesterolemia prior to lesion formation. Pigs were sacrificed after being on either a high-cholesterol diet for 10-16 weeks (n = 17) or a normal diet (n = 9). Identification of apoptosis in each layer of coronary arteries and arterioles was performed by terminal deoxynucleotidyl transferase (TdT)-mediated dUTP-biotin nick end-labeling (TUNEL). In additional animals, ligation-mediated polymerase chain reaction (PCR) and transmission electron and confocal microscopy were done. Plasma cholesterol levels were higher in the cholesterol-fed animals (86+/-9 mg/dl versus 342+/-20 mg/dl, P < 0.001). Atheromatous plaques were not evident in the high-cholesterol group. TUNEL was positive in 11 of 17 hypercholesterolemic animals, primarily in the intima (1-2% of cells) and adventitia (3% of cells), but not in control vessels. A similar distribution was detected in arterioles. DNA bands were detected only in experimental animals, as were morphological features of apoptosis by transmission electron and confocal microscopy. In experimental hypercholesterolemia, apoptosis occurred in coronary arteries and arterioles before lesion formation. Apoptosis may be an integral process of early coronary atherosclerosis. PMID- 10030384 TI - Cholesterol and omega-3 fatty acids inhibit Na, K-ATPase activity in human endothelial cells. AB - We have investigated the effects of cholesterol and omega-3 fatty acids eicosapentaenoic acid (EPA) and docosahexenoic acid (DHA) on Na, K-ATPase activity in human endothelial cells (HUVEC). Cultured HUVEC were incubated for 18 h with pure egg phosphatidylcholine (PC), or cholesterol-enriched liposomes (4 mg PC/ml). EPA and DHA alpha-tocopherol-acetate were emulsified with PC and incubated with HUVEC (10 mM). Na, K-ATPase and 5'-nucleotidase activities were determined using the coupled assay method on microsomal fractions obtained from cultured cells using non treated cells as control. Cholesterol enrichment significantly reduced both Na, K-ATPase and 5'-nucleotidase activities by a similar level (- 40%), whereas pure phospholipid liposomes inhibited this activity only by 22%. The dose-response curves of Na, K-ATPase activity were all biphasic assuming the presence of two independent sites exhibiting different affinities for ouabain of nM and microM respectively. The cholesterol induced inhibitory effect was greater for low affinity sites (-54%) as compared to that of the high affinity sites (-24%) whereas omega-3 fatty acids reduced the activity of both sites by 22%. Short term effects of EPA and DHA on Na, K-ATPase activity were determined by incubating microsomal fractions from untreated cells with various concentrations of free fatty acids (from 1 to 200 microM) for 20 min. Both EPA and DHA significantly reduced Na, K-ATPase activity but inhibition by EPA seems to be more effective than DHA. These results suggest that cholesterol and omega-3 fatty acids reduce Na, K-ATPase activity in HUVEC. PMID- 10030385 TI - Distribution and prevalence of inducible nitric oxide synthase in atherosclerotic vessels of long-term cholesterol-fed rabbits. AB - The expression of inducible nitric oxide synthase (iNOS) as well as its functional activity has recently been reported in atherosclerotic lesions. The aim of the present study was to evaluate the expression of iNOS in various arteries of rabbits fed a long-term but low-level cholesterol-enriched diet which promotes different types of atherosclerotic lesions resembling human diseased vessels. No iNOS expression was revealed in arteries from control rabbits and in fatty streaks found in carotid and femoral arteries from hypercholesterolemic rabbits. In transitional lesions from the thoracic and abdominal aortas, the coronary and pulmonary arteries, a punctiform iNOS staining was detected in the intima. When lesions were more advanced, iNOS expression was found more intense and diffuse and localized in the subendothelial layer as well as in the media. Smooth muscle cell accumulation in intimal layers of the arteries is a marker of the degree of evolution of the atherosclerotic lesion; since we found a correlation between the smooth muscle cell infiltration in the intima and the iNOS expression in the intima and the subendothelial layer, our results suggest a link between the severity of the lesion and the iNOS expression. PMID- 10030386 TI - Combination treatment with troglitazone, an insulin action enhancer, and pravastatin, an inhibitor of HMG-CoA reductase, shows a synergistic effect on atherosclerosis of WHHL rabbits. AB - We examined whether improving insulin resistance augments the antiatherosclerotic effect of LDL reduction. Since WHHL rabbits show hyperinsulinemia and insulin resistance, we administered troglitazone (100 mg/kg), an insulin action enhancer, pravastatin sodium (50 mg/kg), an HMG CoA reductase inhibitor, and a combination of both drugs to 2-month-old WHHL rabbits for 32 weeks. As compared to the control, total cholesterol levels in the plasma and LDL were decreased significantly by 20% in the pravastatin and combination groups. Basal immunoreactive insulin levels and insulin index were decreased significantly by approximately 50% in the troglitazone and combination groups. Surface lesion area of atherosclerosis on the thoracic aorta was decreased significantly by 36% in the combination group and was less in the troglitazone group. Coronary atherosclerosis was decreased significantly by 39% in the combination group and was less in the pravastatin and troglitazone groups. The collagen content in the plaques was decreased in the troglitezone and combination groups and the extracellular lipid deposits were decreased in the pravastatin and combination groups. The incidence and severity of xanthomata in the digital joints were also decreased significantly in the three treated groups. In conclusion, the antiatherogenic effect of the combination treatment is stronger than that of the monotherapy. PMID- 10030387 TI - Activation of monocytes in vivo causes intracellular accumulation of lipoprotein derived lipids and marked hypocholesterolemia--a possible pathogenesis of necrobiotic xanthogranuloma. AB - Necrobiotic xanthogranuloma (NXG) is a rare histiocytic disease with generalized xanthomatosis. However, most cases with NXG are normolipidemic or hypolipidemic. The mechanism for the formation of xanthoma in NXG has not yet been clarified. We observed a case of NXG with severe hypocholesterolemia (total cholesterol: 1.69 mmol/l) and analyzed the function of monocytes in this case. Histological examinations by light microscopy revealed a large amount of lipid deposition in the patient's freshly isolated monocytes. The patient's monocytes showed a 3-fold increase in cholesteryl ester content and a 3-fold enhancement of acetyl low density lipoprotein (LDL) uptake compared with the control monocytes. However, no significant difference was noted in the expression of CD36 protein and the mRNA levels of scavenger receptor-class A (SR-A) between the monocytes of the patient and the control. The phagocytotic ability of the patient's monocytes was enhanced 1.5-fold compared with that of the control monocytes. These findings suggest that the activated monocytes may have degraded the modified LDL via a pathway other than CD36 or SR-A, and accumulated a great amount of lipids in vivo. In conclusion, the present study has demonstrated a possible pathogenesis of NXG that the activation of monocytes in vivo may contribute to the intracellular accumulation of lipoprotein-derived lipids leading to non-inherited xanthomatosis and the marked hypocholesterolemia. PMID- 10030388 TI - Significance of skeletal muscle properties on fitness, long-term physical training and serum lipids. AB - The percentage of slow-twitch (ST) fibers in a person's skeletal muscle, e.g. muscle fiber composition (ST-%), may have a significant impact on physical activity, fitness level, serum high density lipoprotein cholesterol (HDL-C) concentration, and ultimately, on the risk of coronary heart disease (CHD). We studied the effect of a 12 month home-based exercise training program on skeletal muscle metabolic activity, serum lipids, and hormones in 12 healthy middle-aged men (sedentary men) with a low level of fitness and leisure-time physical activity (LTPA). Their parameters and changes in them were compared with 12 men of the same age with defined CHD and with two groups (15 each) of physically active men, who had either a high ST-% (high-ST-men) or a low ST-% (low-ST-men). In the sedentary men, CHD-patients and low-ST-men, the mean ST-% (42, 44, and 49%, respectively) was similar but was significantly higher in the high-ST-men (73%). The sedentary men whose LTPA mean was 34 and 19% of the mean of low-ST-men (mean of 2137 kcal/week) and high-ST-men (mean of 3845 kcal/week), respectively, increased their LTPA from a mean of 728-1526 kcal/week (P < 0.01). After training, we found an increase in serum HDL-C by 21%, (P < 0.01) and apo A-I by 36% (P < 0.01), and a decrease in serum LDL-C by 8%. The cholesterol/HDL-C ratio decreased by 17(% (P < 0.01) and the LDL-C/HDL-C ratio decreased by 22% (P < 0.01). Skeletal muscle lipoprotein lipase (LPL) activity increased by 65% (P < 0.001). Moreover, the increase in LPL as well as in HDL-C concentration tended to be more pronounced the higher the level was before training. The oxidative enzyme activity of alpha-ketoglutarate dehydrogenase (KGDH) in skeletal muscle and the activity of carnitine palmitoyltransferase (CPT) in lipid metabolism increased, whereas glycolytic phosphofructokinase (PFK) did not change but the PFK to CPT ratio decreased, which was reflected as a decrease of lactate accumulation during exercise. Increase in CPT activity correlated significantly (r(s) = 0.81, P < 0.01) with the increase in HDL-C concentration. In all men (n = 54), the CPT activity correlated negatively with serum triglyceride concentration (r(s) = 0.34, P < 0.05) but positively with serum HDL-C concentration and ST-% (r(s) = 0.34, P < 0.05 and r(s) = 0.47, P < 0.01, respectively). In all healthy men, (n = 42) LTPA correlated with both Vo2max, and ST-% (r(s) = 0.76, P < 0.001 and r(s) = 0.54, P < 0.001, respectively) and with serum HDL-C and apo A-I concentrations (r(s) = 0.35, P < 0.05 and r(s) = 0.54, P < 0.001, respectively). Serum sex hormones did not show significant associations with serum lipids, but in sedentary men, serum total and free testosterone as well as the ratio of free testosterone to free estradiol decreased significantly after training. These findings confirm the pronounced effects of a home-based exercise training program on CHD risk factors and they underline the importance of considering skeletal muscle properties when studying serum lipids and lipoproteins and their modifications in the field of health-related fitness and physical activity. PMID- 10030389 TI - Endotoxin and interleukin-1 decrease hepatic lipase mRNA levels. AB - The acute phase response induces a multitude of changes in lipoprotein metabolism including hypertriglyceridemia, triglyceride enriched LDL, and decreased HDL levels accompanied by changes in HDL composition including increased free cholesterol and triglycerides and a decrease in esterified cholesterol. Here we demonstrate that endotoxin (LPS) induces a 56% decrease in hepatic lipase activity in liver and a 45% decrease in hepatic lipase activity in post heparin plasma in Syrian hamsters. LPS treatment also produces a marked decrease in hepatic lipase mRNA levels in the liver. Half maximal reduction in hepatic lipase mRNA levels occurred at approximately 0.2 microg LPS/100 g BW with a maximal decrease at 1.0 microg/100 g BW ( > 90% decrease), indicating that inhibition of hepatic lipase is a sensitive host response to LPS. Additionally, IL-1 produced a marked decrease in hepatic lipase mRNA levels while TNF had no effect. Moreover, IL-1 treatment of HepG2 cells in vitro also decreased hepatic lipase mRNA levels suggesting that IL-1 can directly regulate hepatic lipase expression in liver cells. LPS decreased hepatic lipase mRNA levels in control as well as IL-1 type 1 receptor deficient mice indicating that IL-1 action is not absolutely essential and that several cytokines and/or small molecular mediators can regulate hepatic lipase during the acute phase response. The LPS and IL-1 induced decrease in hepatic lipase could have several consequences including decreasing the clearance of triglyceride rich lipoprotein particles and producing an increase in triglyceride rich HDL. The decrease in hepatic lipase activity and mRNA levels may be part of a series of coordinated changes in lipoprotein metabolism that occur during the acute phase response. These changes may be initially beneficial to the host but if present for an extended period may be proatherogenic. PMID- 10030390 TI - Upregulation of cholesterol synthesis after acute myocardial infarction--is cholesterol a positive acute phase reactant? AB - Acute myocardial infarction is associated with profound alterations in the plasma lipoprotein profile. The mechanism of these alterations is not clear, and both cholesterol biosynthesis up- and downregulation could possibly be a consequence of acute myocardial infarction. We determined plasma lipids, lipoproteins, apolipoproteins, and lathosterol-which is regarded as an estimate of whole body cholesterol biosynthesis in humans-concentrations in 34 patients (age 68+/-10 years, 24 male, 10 female) admitted to our hospital with acute MI and with onset of symptoms within the last 12 h. Samples were taken immediately after admission to the hospital, and 1, 2, and 10 days after admission. On the first day after admission there was a decrease in total cholesterol (C) by 14.1%, (P = 0.01), in LDL-C by 14.4% (P = 0.03), in HDL-C by 9.3% (NS), and in triglycerides by 19.5% (NS). Apolipoprotein B100 was reduced by 18.3% (P = 0.008), and apolipoprotein AI by 12.3% (NS). The lathosterol/cholesterol ratio was increased by 23.1% after 1 day, and by 28.7% after 2 days (P = 0.05). After 10 days, all variables except the apolipoproteins had essentially returned to baseline values. In conclusion, the changes in the plasma lipid profile after acute myocardial infarction are associated with a profound increase of whole body cholesterol biosynthesis as judged by the lathosterol/cholesterol ratio. These changes may possibly enhance the delivery of cholesterol to cells involved in tissue repair mechanisms after acute myocardial infarction. PMID- 10030391 TI - Variations in serum cholesteryl ester transfer and phospholipid transfer activities in healthy women and men consuming diets enriched in lauric, palmitic or oleic acids. AB - Cholesteryl ester transfer protein (CETP) and phospholipid transfer protein (PLTP) activities were measured in sera from 32 normolipidemic women and men consuming diets enriched in lauric, palmitic, or oleic acids. Serum CETP activity, measured as the rate of radiolabeled cholesteryl esters transferred from HDL toward serum apo B-containing lipoproteins, was higher with the palmitic acid diet (25.1+/-2.5%) than with the lauric acid (23.7+/-2.4%) and the oleic acid (24.0+/-2.7%) diets (P = 0.0028 and 0.0283, respectively). CETP mass concentrations, as measured with an enzyme-linked immunosorbent assay were increased after the lauric acid diet (2.57+/-0.63 mg/l) and the palmitic acid diet (2.49+/-0.64 mg/l) as compared with the oleic acid diet (2.34+/-0.45 mg/l) (P = 0.0035 and 0.0249, respectively). In contrast with CETP, serum PLTP activity, as measured as the rate of radiolabeled phosphatidylcholine transferred from liposomes toward serum HDL, was significantly higher with the lauric acid diet (23.5+/2.6%) than with the palmitic acid diet (22.5+/-2.5%) (P = 0.0013), while no significant differences were noted when comparing the saturated diets versus the oleic acid diet (23.0+/-2.3%). No significant alterations in the mean apparent diameter of LDL, and in the relative proportions of individual HDL subpopulations were observed from one dietary period to another. Nevertheless, lipid transfer activities correlated significantly with the relative abundance of HDL2b, HDL2a, HDL3b, and HDL3c, with opposite tendencies being observed for cholesteryl ester transfer and phospholipid transfer activities. In general, serum CETP activity correlated negatively with HDL cholesterol, but positively with triglyceride concentrations after the dietary interventions, and the relations with serum lipids were just the opposite for PLTP activity. In addition, CETP and PLTP activities correlated negatively when subjects consumed the standardized diets (P < 0.05 in all cases), but not when subjects consumed their habitual diet. It is concluded that serum lipid transfer activities in normolipidemic subjects can be significantly affected by the fatty acid content of the diet, with differential effects on CETP and PLTP activities. PMID- 10030392 TI - Symptoms of chronic bronchitis, haemostatic factors, and coronary heart disease risk. AB - Positive association has been suggested between a variety of infections and coronary heart disease. Disturbances in blood coagulation system may form a link between infections and coronary heart disease. The aim of this study was to analyze whether chronic bronchitis, defined by the occurrence of symptoms, is associated with selected haemostatic factors in a cross-sectional population study of 2379 Finnish men and women aged between 45 and 64 years. Plasma fibrinogen level was significantly higher, 3.70 versus 3.35 g/l (P < 0.001) in men and 3.64 versus 3.44 g/l (P < 0.001) in women, among subjects with symptoms of chronic bronchitis than among those without symptoms. The association was independent of age, smoking, body mass index, physical exercise, and alcohol consumption. Also plasminogen was higher among men with symptoms than among those without but the difference disappeared after adjustment for age and smoking. Factor VII coagulant activity and factor VII antigen level did not differ between subjects with and without symptoms. Thus, fibrinogen may be associated with a possible mechanism to link chronic bronchitis to coronary heart disease risk, even though the causality of the association cannot be verified in a cross sectional study. PMID- 10030393 TI - The apolipoprotein E4 allele is not associated with an abnormal lipid profile in a Native American population following its traditional lifestyle. AB - The apolipoprotein E4 allele is associated in industrialized countries with an elevated LDL cholesterol concentration and an increased cardiovascular risk. Our purpose in this study was to assess the influence of the genetic variation at the APOE gene locus on the lipid profile of a Native American rural population. We examined plasma lipid levels and the common apo E alleles in 142 healthy randomly selected adults living in their native communities in western Mexico. Their age was 38+/-17 years and the BMI 25.7+/-4.5 kg/m2. Plasma cholesterol, triglycerides, LDL C and HDL C were 165+/-29.6, 126+/-83, 98+/-26 and 42+/-12.7 mg/dl respectively. Ninety-one per cent of the subjects had Lp(a) concentrations below 20 mg/dl and 30% had levels lower than 2 mg/dl. The most common APOE genotype was E3/3 (63%), followed by E3/4 (30.1%). The prevalence of the E2 allele was very low (2.3%). No difference was observed in LDL C concentrations between the E3/E3 and E3/E4 subjects; however carriers of the E2/3 genotype had lower LDL C levels. Similar results were obtained for cholesterol and apo B levels. In summary, the increased LDL C levels associated with the E4 allele in previous studies were not observed in a population with non-westernized habits. Environmental factors, such as diet and lifestyle, could outweigh the hypercholesterolemic predisposition resulting from the presence of the apo E4 allele. PMID- 10030394 TI - Coronary heart disease risk factors and menopause: a study in 1684 French women. AB - This study aimed to assess the relationship between menopause and various risk factors for coronary heart diseases (CHD) in a large sample of French women aged 45 65 years. One thousand six hundred and eighty-four consecutive healthy women who received a systematic check-up in our Menopause Unit were included in this study. All the women answered a computer-assisted questionnaire which comprised 156 items, 72 questions being exclusively related to the identification of familial and personal cardio-vascular risk factors. Biological measurements were performed to evaluate lipid-lipoprotein profile and fasting glucose levels. Women, none of whom were treated with hormonal replacement therapy, were classified as postmenopausal according to the date of their last menses and levels of serum FSH and estradiol (n = 1200). Perimenopausal women were further subdivided into two subgroups according to the regularity of their menstrual cycles and FSH levels (early (n = 143) and late (n = 341) perimenopause). 12% (n = 205) of the women were currently receiving lipid-lowering drugs (84.4% postmenopausal vs. 15.6% perimenopausal). When all women were considered, menopause was associated with a higher prevalence of hypertension and hypercholesterolemia (serum total cholesterol level > 250 mg/dl + LDL cholesterol level > 160 mg/dl). This higher prevalence in postmenopausal women was also found when the analysis was restricted to women aged 45 55 years, which rather suggests an effect of menopause than of age. Of the women not receiving hypolipidemic treatments, postmenopausal women had significantly higher serum levels of total cholesterol, LDL , VLDL cholesterol, triglycerides and apolipoprotein B and lower levels of HDL cholesterol than perimenopausal women. Multivariate analysis indicated that these effects were independent of age, body mass index and years since menopause. The prevalence of other metabolic disturbances was much more lower. On average, perimenopausal women had significantly less CHD risk factors than postmenopausal women (P < 0.0001). Fifty-two per cent of the perimenopausal women had none of the risk factors studied as compared with 39% of the postmenopausal women (P < 0.0001). This study shows that menopause was associated with a higher prevalence of risk factors for CHD. PMID- 10030395 TI - Infection-associated intimal thickening in the coronary arteries of children. AB - OBJECTIVES: based on autopsy material from children this study investigated the possible relationship of clinically evident infection prior to death with intimal thickening of the coronary arteries. BACKGROUND: viral infections are suggested to be associated with intimal thickening in the coronary arteries both in animals and man. METHODS: the coronary arteries were examined in 175 autopsied children 0 15 years of age (median 7 days). Semi-serial cross sections of the coronary arteries were screened for maximal intimal thickening at 0.2 mm intervals. The length of the internal elastic lamina, the areas of arterial media and intima were measured from cross-sections. Irregular linings of the arteries were mathematically transformed to circles. The percentage of intimal and musculoelastic layer area to luminal area encircled by arterial media was calculated. RESULTS: intimal thickening increased with age but was also associated with the presence of infectious disease at death. Already in the newborn children, who died shortly after the birth, the percentage of intimal and musculoelastic layer area to luminal area encircled by arterial media was big, maximally 55%. In the left coronary artery the mean percentages were 32 and 21% in the groups with viral and bacterial infections, respectively as compared to 16% in the group with no evidence of infection. CONCLUSION: infections in general and viral infections in particular, seem to be associated with intimal thickening, which may predispose coronary arteries to atherosclerosis. Atherogenesis might have a rapid dynamic component. PMID- 10030396 TI - Comparison of variance components and sibpair-based approaches to quantitative trait linkage analysis in unselected samples. AB - We compared the statistical performance of sibpair-based and variance components approaches to multipoint linkage analysis of a quantitative trait in unselected samples. As a benchmark dataset, we used the simulated family data from Genetic Analysis Workshop 10 [Goldin et al., 1997], and each method was used to screen all 200 replications of the GAW10 genome for evidence of linkage to quantitative trait Q1. The sibpair and variance components methods were each applied to datasets comprising single-sibpairs and complete sibships, and for further comparison we also applied the variance components method to the nuclear family and extended pedigree datasets. For each analysis, the unbiasedness and efficiency of parameter estimation, the power to detect linkage, and the Type I error rate were estimated empirically. Sibpair and variance components methods exhibited comparable performance in terms of the unbiasedness of the estimate of QTL location and the Type I error rate. Within the single-sibpair and sibship sampling units, the variance components approach gave consistently superior power and efficiency of parameter estimation. Within each method, the statistical performance was improved by the use of the larger and more informative sampling units. PMID- 10030397 TI - Computing probabilities of homozygosity by descent. AB - A person is autozygous at a locus if the person inherits the same allele twice identical by descent along two distinct paths from the same ancestor. Autozygosity is a common cause of recessive diseases in inbred populations. Homozygosity mapping uses this fact to locate the genes that cause recessive diseases. The probability of autozygosity can be used to estimate the probability of a true positive and of a false positive in homozygosity mapping. Thompson [1994] and Guo [1997] therefore studied the problem of computing the prior, unconditional (multilocus) probability of autozygosity (MPA). I consider a different quantity: the interval probability of autozygosity (IPA). The two measures are identical in the single-locus case. IPA has two notable advantages over MPA: 1. IPA does not include the possibility of heterozygous regions between the homozygous markers. 2. IPA can be computed in time that is polynomial in the pedigree size. My polynomial-time algorithm for the single-locus case solves a problem mentioned by Guo. I implemented a program to compute the IPA. The contribution of this work is the application of basic, abstract methods from computer science to address a problem in genetics. PMID- 10030398 TI - Inclusion of risk factor covariates in a segregation analysis of a population based sample of 426 breast cancer families. AB - Although many segregation analyses of breast cancer have been published, few have included risk factor covariates. Maximum likelihood segregation analyses examining age-at-onset (model 1) and susceptibility (model 2) models of breast cancer were performed on 426 four-generation families originally ascertained between 1944 and 1952 through a breast cancer proband. Cancer status and risk factor data were collected through interviews of participants or surrogates. When segregation analyses were performed on 10,791 women, without estimation of any covariates, all hypotheses under both models were rejected. Model 1, which required estimation of fewer parameters than model 2, provided a better fit to the data according to Akaike's Information Criterion. Further segregation analyses were performed under model 1 on a subset of women with complete data on education, age at first birth (nulliparous women included), and alcohol use, covariates that were found to significantly (P<0.05) improve the fit over the addition of exam age alone in logistic regression models. All three covariates improved the fit of the models, as did year of birth, but at all stages of model building, all of the hypotheses were still rejected. After the allele frequency was fixed at 0.0033, a subset of families appeared to fit a dominant model. Using this model, risk estimates were calculated based on inferred genotype, age, and covariate values. The penetrance was estimated to be 0.15, much lower than previous estimates based on families ascertained through breast cancer probands with early onset. Moreover, the estimates of penetrance were not greatly influenced by incorporation of the measured risk factors. PMID- 10030400 TI - Trends in prenatal diagnosis of Down syndrome and other autosomal trisomies in Scotland 1990 to 1994, with associated cytogenetic and epidemiological findings. AB - The present report summarizes findings on 670 cases of autosomal trisomy diagnosed in Scotland, with actual or expected dates of delivery in 1990 to 1994 inclusive. Cases were notified by cytogenetic service laboratories. There were 277 prenatal and 369 postnatal diagnoses and 24 spontaneous losses. Excluding the latter, numbers diagnosed with trisomy 21, trisomy 18, trisomy 13, and other trisomies were, respectively, 470 (72.8%), 108 (16.7%), 36 (5.6%), and 32 (5.0%). Estimated maternal age-specific birth rates for trisomy 21 were close to published values from other jurisdictions. However, comparisons with a clinically based national register of congenital anomalies suggested that 3-4% of Down syndrome births were never karyotyped, most being early neonatal deaths. There was a striking increase over the period in the proportion of cases detected prenatally, associated with increased maternal serum screening in mothers <35 years old. Over the 3 final years (1992-1994), prenatal screening followed by elective termination was estimated to reduce the birth rate in trisomy 21 by 24% in mothers aged <35 years, by 57% in older mothers, and by 35% in all mothers. The crude incidence per 1,000 births fell from 1.08 in 1990-1991 to 0.77 in 1992 1994, in spite of an upward shift in the overall maternal age distribution. For trisomies 18 and 13, the estimated overall reductions in the birth rate over the whole 5-year period were respectively, 26 and 17%. In free trisomy 18, there was a significant reduction in the sex ratio (male/female) to 0.65, in line with earlier studies. PMID- 10030399 TI - Family history of coronary heart disease and pre-clinical carotid artery atherosclerosis in African-Americans and whites: the ARIC study: Atherosclerosis Risk in Communities. AB - The association between family history of coronary heart disease (CHD) and morbidity and mortality due to atherosclerotic sequelae, although well documented in population-based samples of whites, has been little studied in African Americans. Less is known about the relationship between a family history of CHD and pre-clinical atherosclerosis. We report the relation between family history of CHD, summarized in a family risk score (FRS), and asymptomatic atherosclerosis at the extracranial carotid arteries, measured by B-mode ultrasound. The FRS was assessed in relatives of 3,034 African Americans and 9,048 white probands aged 45 to 64 years, in the four community-based cohorts of the ARIC Study. The analyses were restricted to individuals free of clinically manifest CHD. The distribution of CHD FRS by ethnic-gender groups was right skewed, with slightly higher mean values for white than African-American males, and for African-American than white females. In a series of multivariate linear regression models with mean carotid artery intima-media wall thickness (IMT) as the dependent variable, FRS was associated positively with IMT in white and African-American women and white men. In a multiple regression model, approximately one-half of the quantitative statistical relationship of the CHD FRS with IMT in whites was statistically explained by the major risk factors considered as intervening, explanatory variables in this analysis. This association in African-American women was fully explained by the major risk factors. The FRS was not, however, associated with atherosclerosis or major risk factors in African-American males, in the ARIC Study. PMID- 10030401 TI - Genetic determinants of variation in gallbladder disease in the Mexican-American population. AB - Since there have not been any studies that quantify the influence of genetic factors on gallbladder disease (GBD) in humans using information from families, we utilized pedigree data to explore the genetic control of variation in liability to GBD. Using an extension of a variance components approach, we performed genetic analyses of GBD using information from 32 low-income Mexican American families with two slightly different general models incorporating several sex-specific GBD risk factors. After evaluating the relative magnitudes of the covariate effects from these two models, we identified a parsimonious model including only significant predictors of GBD. According to this model, heritability for GBD was high (h2 = 0.44+/-0.18), after accounting for the significant effects of age, leptin in both sexes, total cholesterol, and HDL cholesterol in males only. We have shown quantitatively that variation in GBD is under strong genetic control. However, there are two major limitations to our findings: (1) since GBD was defined by a self-reported clinical history rather than an ultrasound examination, the prevalence of GBD could have been underestimated; and (2) since our design did not allow for shared environmental effects, our estimate of heritability may have been inflated. PMID- 10030402 TI - Genetic association of five apolipoprotein polymorphisms with serum lipoprotein lipid levels in African blacks. AB - Genetic studies carried out mainly in European and European-derived populations have shown that common polymorphisms in genes coding for apolipoproteins are significant determinants of serum lipoprotein-lipid levels variation. However, except for a few sporadic studies, the distribution of apolipoprotein polymorphisms and their association with serum lipoprotein-lipid levels have not been evaluated systematically in African or African-derived populations. In this investigation we have studied five apolipoprotein polymorphisms, including APOA1/MspI-75 bp, APOA1/MspI+83 bp, APOC3/PvuII, APOE, and APOH in 786 Africans (493 men, 293 women) from Nigeria. The sample is comprised of Nigerian civil servants consisting of 462 junior staff (less affluent) and 324 senior staff (more affluent) where staff status is a correlate of their socioeconomic status. We first examined genetic associations in the total sample stratified by gender to determine the role of apolipoprotein polymorphisms in affecting serum lipid profile in the general population, and then by staff status to evaluate possible gene-environment interactions. In the total sample, the APOC3/PvuII polymorphism showed significant effect on HDL-cholesterol (P = 0.029) and HDL3-cholesterol (P = 0.009) in women, and the APOE polymorphism was significantly associated with total cholesterol (P = 0.031) and LDL-cholesterol (P = 0.0006) in women. Multiple regression analyses showed that the APOC3/PvuII polymorphism accounts for about 2 and 3% of the variation in HDL-cholesterol and HDL3-cholesterol, respectively, in women; while the APOE polymorphism accounted for about 5 and 6% of the variation in total- and LDL-cholesterol, respectively, in women. Whereas the association of the APOE polymorphism was independent of the staff status, the significant affect of the APOC3/PvuII polymorphism on HDL- and HDL3-cholesterol was confined to senior staff women where it explained about 7% of their variation. We also observed an interaction between staff and the APOH polymorphism in affecting cholesterol levels. The APOH polymorphism showed significant association with total cholesterol (P = 0.010) and LDL-cholesterol (P = 0.016) in senior staff women and explained about 7 and 5% of their phenotypic variations, respectively. These data indicate that gene-environment interaction may play an important role in affecting serum lipid profile in African populations. PMID- 10030403 TI - Predictors of recurrence after local excision. PMID- 10030404 TI - Myocutaneous pedicle flaps after abdomino-perineal resection for recurrent rectal cancer. PMID- 10030405 TI - Chemoradiation for localized pancreatic cancer: another perspective. PMID- 10030406 TI - Staging of soft tissue sarcomas. PMID- 10030407 TI - Radiation safety considerations for sentinel node techniques. PMID- 10030408 TI - Will the true sentinel node please stand? PMID- 10030409 TI - Microstaging of sentinel lymph nodes. PMID- 10030410 TI - A survival benefit from axillary dissection: was Halsted correct? PMID- 10030411 TI - Absence of the cell cycle inhibitor p27Kip1 protein predicts poor outcome in patients with stage I-III colorectal cancer. AB - BACKGROUND: The p27Kip1 protein regulates the G1 to S phase transition of cell cycle by binding to and inhibiting the cyclin E/Cdk2 complex. This study explores the prognostic significance of the absence of the p27Kip1 protein in patients with colorectal cancer (CRC). METHODS: Formalin-fixed tumor sections from 124 patients who underwent curative resection for stage I-III CRC were analyzed by immunohistochemistry using MoAb anti-p27KiP1. RESULTS: Detectable levels of p27Kip1 protein were found in 86% of tumors. Median follow-up was 55 months. Actuarial 5-year disease-free survival (DFS) and overall survival (OS) were 76% and 85%, respectively, in patients with tumors with p27Kip1 protein expression and 34% and 40%, respectively, in those whose tumors lacked p27Kip1 protein expression (P < .001). At multivariate analysis, tumor stage (III vs. I-II) and p27Kip1 protein status (absence vs. presence) were found to be independent prognostic factors for DFS and OS. CONCLUSIONS: Lack of p27KiP1 protein expression in CRC is a negative prognostic marker and may therefore be useful in selecting early-stage patients more likely to benefit from adjuvant treatment. PMID- 10030412 TI - Predictors of recurrence after local excision and postoperative chemoradiation therapy of adenocarcinoma of the rectum. AB - BACKGROUND: Local excision of rectal cancer preserves anal continence, bladder function, and normal sexual function. However, local recurrence after excision remains a significant problem. To further define the indications for local excision, we analyzed possible factors predictive of recurrence after local excision of rectal cancer. METHODS: The charts of all patients undergoing local excision of adenocarcinoma of the rectum between 1985 and 1995 at a single institution were reviewed. Patients with metastatic disease at the time of excision and patients treated preoperatively with chemoradiation therapy were excluded. All available slides were reviewed by a single pathologist, who assessed the depth of invasion; the presence or absence of vascular invasion, lymphatic invasion, perineural invasion, and lymphocytic infiltrate; the mucinous status; and the degree of differentiation. Using the log-rank test and Cox proportional hazards model, univariate and multivariate analyses were performed to identify predictors of recurrence. RESULTS: Ninety patients underwent local excision, 46 transanally and 44 using a Kraske approach. The breakdown of patients by tumor stage was as follows: Tis, 13%; T1, 41%; T2, 30%; T3, 15%; and Tx, 1%. Sixty-eight percent of patients with T1 tumors were treated with postoperative radiotherapy; all patients with T2 or T3 tumors were treated postoperatively with or without 5-fluorouracil. The median duration of follow-up was 51 months. The median tumor diameter was 2.5 cm (range, 0.4 to 7 cm), and the median distance of the tumor from the anal verge was 4.5 cm (range, 1 to 10 cm). The 4-year actuarial local disease-free survival rate broken down by tumor stage was as follows: Tis, 100%; T1, 95%; T2, 80%; and T3, 73%. The median time to local recurrence was 23 months (range, 7 to 61 months). Multivariate analysis showed that only tumor stage and margin status were predictors of local recurrence. CONCLUSIONS: Local excision and postoperative radiotherapy result in adequate local control of early stage (Tis and T1) adenocarcinoma of the rectum. Higher rates of recurrence were seen in patients with T2 and T3 tumors, especially in those with positive margins. PMID- 10030413 TI - Immediate reconstruction of the perineal wound with gracilis muscle flaps following abdominoperineal resection and intraoperative radiation therapy for recurrent carcinoma of the rectum. AB - BACKGROUND: Morbidity associated with a nonhealing perineal wound is the most common complication following proctectomy, particularly in the setting of recurrent carcinoma of the rectum and radiation therapy. Immediate reconstruction using the gracilis myocutaneous and muscle flaps significantly reduces the incidence of major infection associated with perineal wound closure. The purpose of this study was to assess the value of immediate reconstruction of the perineal wound using a gracilis flap in patients undergoing abdominoperineal resection and intraoperative radiation therapy. METHODS: This study retrospectively reviewed our experience with immediate pelvic reconstruction using gracilis muscle flaps for patients undergoing rectal extirpation and irradiation for recurrent carcinoma of the rectum. From 1990 to 1995, 16 patients underwent abdominoperineal resection (APR) or pelvic exenteration accompanied by immediate wound closure with unilateral or bilateral gracilis muscle flaps. Morbidity and mortality outcomes were compared to those of 24 patients from our institution who, between 1988 and 1992, underwent proctectomy and irradiation for recurrent rectal carcinoma with primary closure of the perineal wound. RESULTS: Major complications (i.e., major infection requiring hospitalization and/or operation) occurred in 2 (12%) of the patients with gracilis flaps versus 11 (46%) of the patients with primary closure (P = .028 by chi2 analysis for flap vs. primary closure). Minor complications (i.e., persistent sinus and subcutaneous abscess) occurred in 4 (25%) of the patients with gracilis flaps versus 5 (21%) of those with primary closure. CONCLUSION: Immediate perineal reconstruction using the gracilis myocutaneous flap following proctectomy and irradiation for recurrent rectal carcinoma significantly reduces the incidence of major infection associated with perineal wound closure. PMID- 10030415 TI - Current advances and changes in treatment strategy may improve survival and quality of life in patients with potentially curable gastric cancer. AB - BACKGROUND: The treatment strategy for gastric cancer is determined by the stage of disease. Advances in diagnostic techniques such as endoscopic ultrasound (EUS) and in staging have increased the accuracy of pretreatment staging. Correct staging is a prerequisite for the optimal treatment of gastric cancer patients. Long-term expected survival and quality of life (QOL) are the major criteria determining the therapeutic strategy. RESULTS: Surgical resection offers excellent survival rates for early gastric cancer (EGC) patients. D1 resection is sufficient for mucosal cancers (T1m) and for most submucosal cancers (Tlsm); however, for the rest (about 5%) of these patients with N2 disease a D2 resection is required for complete tumor resection (R0). Considering QOL, endoscopic mucosal resection (EMR) or laparoscopic wedge resection is the best front-line therapy for several mucosal cancers. Prediction and selection of node-negative patients with the help of certain macroscopic and histologic criteria can eliminate the possibility for residual disease in perigastric lymph nodes. However, long-term survival data are needed before these new techniques become more generally accepted. In contrast, an aggressive approach is necessary for the treatment of advanced gastric cancer. Total gastrectomy, with the exception of distal tumors that can be treated by subtotal gastrectomy, is the procedure of choice. Splenectomy is indicated for proximal advanced tumors. Distal pancreatectomy should be avoided, however, because its adverse effect has been documented in all randomized trials. Although the survival benefit of extended (D2) lymphadenectomy is unproven in randomized trials, D2 resection increases the R0 resection rate and may improve survival in some selected node-positive patients. D2 resection has little effect on preventing peritoneal tumor spread and liver metastasis, and the traditional late administration of chemotherapeutic drugs has been proven ineffective. Current data suggest a possible beneficial effect of combined treatment for patients with local advanced gastric cancer (LAGC). Ongoing phase-III randomized trials will prove whether patients with LAGC treated by neoadjuvant chemotherapy plus D2 resection versus surgery alone or surgery plus intraoperative intraperitoneal chemotherapy derive any benefit from these combined treatment modalities. CONCLUSION: Evaluation of all information concerning tumor stage, location, histologic type, expected survival, and QOL after resection is of paramount importance for the surgeon planning the extent of surgery. The therapeutic approach should be stratified according to the stage of disease. PMID- 10030414 TI - Preoperative chemoradiation for patients with locally advanced adenocarcinoma of the pancreas. AB - BACKGROUND: Improved resectability is a major theoretical benefit of preoperative chemoradiation for pancreatic cancer. Since 1994, patients at Duke University Medical Center with locally advanced pancreatic cancer have been treated with multimodality preoperative therapy. The purpose of this study was to review our experience with preoperative therapy for locally advanced pancreatic cancer and determine if an aggressive neoadjuvant regimen would not only downstage these tumors pathologically but also improve the odds of complete surgical resection. METHODS: The charts of 25 patients treated with neoadjuvant chemoradiation at Duke University Medical Center with biopsy-proven, locally advanced adenocarcinoma of the pancreas were reviewed. Tumors were defined as locally advanced based on radiographic or intraoperative evidence of disease that abuts the superior mesenteric artery or vein (n = 22) or involves lymph nodes that are within the proposed radiation field (n = 3). All 25 patients received external beam radiotherapy (median dose 4500 cGy) in daily fractions of 180 cGy over 5 weeks. All patients concurrently received 5-fluorouracil (FU), and many also received mitomycin C or cisplatin, or both. Patients were given a 3- to 4-week break before a restaging computed tomographic (CT) scan was performed. Three patients were not restaged: one died from metastatic disease; one was reclassified as having a neuroendocrine tumor; and one was lost to follow-up. RESULTS: On restaging after neoadjuvant therapy, 64% of patients had stable or decreased primary tumor size. Radiographically, two patients appeared potentially resectable, and seven others developed evidence of metastatic disease. Eight patients underwent exploration, but only five could be resected. Of the five patients resected, only one had negative margins and negative lymph nodes. This patient had significant pancreatitis on initial exploration. After neoadjuvant therapy, he had a complete response radiographically, and there was no residual cancer in his resection specimen. Pathologic examination of the other resection specimens suggested that despite significant tumor fibrosis, malignant cells persist even at the periphery of the lesions. CONCLUSION: Although neoadjuvant chemoradiation has many theoretical advantages in managing pancreatic malignancy, true pathologic downstaging of locally advanced lesions into tumors that can be removed with negative nodes and margins appears to be a rare event with currently used therapeutic regimens. PMID- 10030416 TI - Modified staging system for extremity soft tissue sarcomas. AB - BACKGROUND: The establishment of a universally acceptable staging system for soft tissue sarcomas has been hampered by the low incidence, various grading systems, and lack of consensus regarding the value of different prognostic factors. We aimed to evaluate prognostic factors in patients with extremity soft tissue sarcomas and to test the validity of the AJCC/UICC staging system. METHODS: Prospectively collected data from 316 previously untreated patients with primary extremity soft tissue sarcomas treated at a single institution between 1989 and 1995 were studied. The influence of clinical and pathological factors on local recurrence, distant metastasis, and disease-specific survival was analyzed by univariate and multivariate techniques. RESULTS: Large tumor size and high histological grade were independent adverse prognostic factors for distant metastasis. Large size, high grade, and positive microscopic surgical margins were independent adverse prognostic factors, and liposarcoma histology was an independent favorable prognostic factor for disease-specific survival. Within each histological grade, there was a progressive decline in survival with increasing tumor size, as reflected by an almost linear increase in hazard ratios. Similarly, there was a progressive fall in survival with increasing grade within each size group (<5 cm, 5 to 10 cm, 10 to 15 cm, and > 15 cm). AJCC staging did not correlate well with prognosis. Survival for intermediate-grade tumors smaller than 5 cm (stage IIA) was better than that for low-grade tumors larger than 5 cm (stage IB) (86% vs. 73%). Survival for high-grade tumors smaller than 5 cm (stage IIIA) was better than that for intermediate-grade tumors larger than 5 cm (stage IIB) (72% vs. 57%). A modified staging system was formulated based on the additive influence of size and grade on the estimated hazard ratios for disease-specific survival, as follows: stage IA, G1T1; stage IB, G1T2 or G2T1; stage IIA, G1T3 or G2T2 or G3T1; stage IIB, G1T4 or G2T3 or G3T2; stage IIIA, G2T4 or G3T3; stage IIIB, G3T4; and stage IV, M1 (G1, G2, G3 = low, intermediate, and high grade; T1, T2, T3, T4 = tumor size < 5 cm, 5-10 cm, 10-15 cm, and > 15 cm, respectively). The 5-year disease-specific survivals of stages IA, IB, IIA, IIB, IIIA, and IIIB were 100%, 83%, 74%, 61%, 39%, and 18%, respectively. The 5-year disease-specific survival for stages I, II, III, and IV were 90%, 67%, 31%, and 6% respectively. The survival difference between each stage was statistically significant (P < .001). CONCLUSION: Histological grade and tumor size are equally important determinants of distant metastases and survival. The AJCC/UICC staging system is based primarily on the grade of the tumor, with size used to subgroup each stage. A staging system for extremity soft tissue sarcomas with equal emphasis on grade and size is proposed that correlates extremely well with prognosis. PMID- 10030417 TI - Angiogenesis correlates with metastasis in melanoma. AB - BACKGROUND: Angiogenesis has been correlated with melanoma progression, but its role in melanoma metastasis is unclear. METHODS: To determine whether angiogenesis correlates with the presence of melanoma metastases, we compared the number of microvessels in the primary melanomas of 12 patients presenting with metastases to those of 13 patients without metastases. Patient groups were matched for gender, age, tumor depth, and histological type and anatomical location of the primary melanoma. Microvessels were stained with factor VIII antibody and counted. RESULTS: Microvessel counts were significantly greater for the metastatic than the nonmetastatic melanomas (51.63+/-14.95 vs. 24.86+/-8.415; P < .0001). One hundred percent of the metastatic melanomas had a mean microvessel count of > or = 37, whereas only 8% of the nonmetastatic melanomas had a mean microvessel count of > or = 37 (sensitivity = 1.00, specificity = .92). Interestingly, patients with lymph node metastases had significantly lower microvessel counts than did patients with distant metastases (42.00+/-3.482 vs. 58.50+/-16.40; P < .05), and significantly higher microvessel counts than did patients without metastases (42.00+/-3.482 vs. 24.86+/-8.415; P < .001). CONCLUSIONS: An increased number of microvessels in the primary tumors of patients with melanoma correlates with the simultaneous presence of metastases. This suggests that angiogenesis may be important in the process of melanoma metastasis. PMID- 10030418 TI - Guidelines for the safe use of radioactive materials during localization and resection of the sentinel lymph node. AB - BACKGROUND: Several reports have demonstrated accurate prediction of nodal metastasis with radiolocalization and selective resection of the radiolocalized sentinel lymph node (SLN) in patients with breast cancer and melanoma. As reliance on this technique grows, its use by those without experience in radiation safety will increase. METHODS: Tissue obtained during radioguided SLN biopsies was examined for residual radioactivity. Specimens with a specific activity greater than the radiologic control level (RCL) of 0.002 microCi/g were considered radioactive. Radiation exposure to the surgical team was measured. RESULTS: A total of 24 primary tissue specimens and 318 lymph nodes were obtained during 57 operations (37 for breast cancer, 20 for melanoma). All 24 (100%) of the specimens injected with radiopharmaceutical and 89 of 98 (91%) of the localized nodes were radioactive after surgery. Activity fell below the RCL 71+/ 3.6 hours in primary tissue specimens, 46+/-1.7 hours in nodes from melanoma patients, and 33+/-3.5 hours in nodes from breast cancer patients (P = .037). The hands of the surgical team (n = 22 cases) were exposed to 9.4+/-3.6 mrem/case. CONCLUSION: Although low levels of radiation exposure are associated with radiolocalization and resection of the SLN, the presented guidelines ensure conformity to existing regulations and allow timely pathologic analysis. PMID- 10030419 TI - Filtered versus unfiltered technetium sulfur colloid in lymphatic mapping: a significant variable in a pig model. AB - BACKGROUND: Lymphatic mapping with sentinel node biopsy is becoming a standard diagnostic test for melanoma and is being extensively investigated for use with other soft tissue tumors. Both filtered and unfiltered technetium sulfur colloid (Tc 99) have been used for preoperative lymphoscintigraphy, as well as intraoperative lymphatic mapping, and it is not clear if one is preferable over the other. The purpose of this study was to compare these two preparations to determine whether the form of Tc 99 used affects the results of lymphatic mapping. METHODS: Mock skin sites were placed on each extremity of 12 domestic pigs totaling 48 skin sites. Twenty-four of the lesions were injected with unfiltered Tc 99; the remaining 24 were injected with Tc 99 passed over a 0.2 microm filter. Both preparations of Tc 99 were mixed with 1 mL of isosulfan blue before injection. Sentinel node dissection was performed using a gamma probe, with counts recorded over a 10-second period and timed to begin 5 minutes after injection. RESULTS: Sentinel nodes were identified in all 48 lymph node basins draining the mock sites and characterized as hot (10x background), blue, or both. Significantly more sentinel nodes were found in the filtered (105 total, X = 4.4/basin), than in the unfiltered group (total 53, X = 2.2/basin, P <.0001). The filtered group had both a higher number of nodes that were hot (35 vs. 6) and more nodes that were hot and blue (69 vs. 43). In addition, hot secondary level lymph nodes (iliac and deep cervical) were found in 11 of 24 of the basins (46%) in the filtered group compared to 1 of 24 (4%) in the unfiltered group (P <.003). There was no significant difference in injection site or residual basin counts between the two groups, but in vivo counts over the sentinel node sites were significantly lower in the unfiltered group (X = 2670+/-1829 vs. X = 6027+/-4333; P = .003). CONCLUSION: Use of filtered Tc 99 results in more sentinel nodes (both hot/blue and hot non-blue) and a higher proportion of secondary lymph nodes. These findings indicate that the Tc 99 preparation used is a significant variable in the results of lymphatic mapping. It is critical that future clinical studies document which preparation of Tc 99 was used. Only large clinical trials will be able to determine whether the additional nodes found with filtered Tc 99 increase the sensitivity of the technique or merely increase the number of nodes that must be removed unnecessarily. PMID- 10030420 TI - Cellular immunity delimits adenoviral gene therapy strategies for the treatment of neoplastic diseases. AB - BACKGROUND: Adenoviral gene therapy is a promising new approach for the treatment of neoplastic diseases. To design rational clinical trials and distinguish the effects of therapeutic transgene expression from those caused by viral infection alone, the immune response to the vector must be understood. In these experiments, we further define cellular immunity to recombinant adenovirus. METHODS: The immune response to hepatic adenoviral gene transfer was studied in infected mice by depleting T cells with an anti-CD3 antibody, measuring splenocyte cytokine production, determining the impact of transgene expression on inflammation, and assessing liver MHC protein expression. RESULTS: The cellular immune response to recombinant adenovirus is (1) averted by T lymphocyte depletion, (2) marked by a TH1 response with increased IL-2 production, (3) directed against both the transgene product and viral proteins, and (4) associated with increased hepatocyte MHC Class I expression. CONCLUSIONS: It is necessary to take into consideration the constraints imposed by the immunogenicity of recombinant adenovirus and its transient transgene expression in the clinical application of adenoviral gene transfer for the treatment of cancer. PMID- 10030421 TI - Microstaging of breast cancer patients using cytokeratin staining of the sentinel lymph node. AB - BACKGROUND: Sentinel lymph node (SLN) mapping is an effective and accurate method of axillary nodal evaluation for metastatic disease. Cytokeratin (CK) immunohistochemical (IHC) staining of the SLN has found micrometastatic disease previously undetected by routine hematoxylin and eosin (H&E) stains. The purpose of this study is to determine the number of patients who were upstaged or microstaged, i.e., detected to have micrometastatic disease only by combined lymphatic mapping with CK IHC. METHODS: Two hundred and ten patients with newly diagnosed breast cancer underwent intraoperative lymphatic mapping using a combination of vital blue dye and technetium-labeled sulfur colloid. The excised sentinel lymph nodes were examined grossly, by imprint cytology, by standard H&E histology, and by IHC stains for CK. SLNs that were only CK positive were confirmed to be malignant by histologic examination. RESULTS: CK IHC staining was performed on 381 SLNs in 210 breast cancer patients. Forty-seven of 210 patients (22.4%) had positive nodes. Thirty of these 47 patients (63.8%) had both H&E- and CK-positive SLNs, and an additional 17 of the 47 positive patients (36.2%) had only CK-positive SLNs. Seventeen of the 180 patients (9.4%) who were negative on H&E staining were upstaged by CK IHC staining of malignant cells in the SLN. Comparison of tumor size with the total number of node-positive patients demonstrated that 16 of 30 node-positive T0 and T1 patients (53.5%) and 22 of 39 nodes (56.4%) were upstaged by CK IHC staining. T2 and T3 patients were less frequently upstaged by cytokeratin analysis of lymph nodes. Only one of 17 node positive patients (5.9%) and seven of 34 nodes (20.6%) in patients with T2 and T3 tumors were upstaged. CONCLUSION: CK IHC staining of SLNs shifted 9.4% of patients from stage I to stage II. There was a significant upstaging influence noted in patients with tumor sizes under 2 cm. This microstaging shift or upstaging may account for the significant proportion of stage I breast cancer treatment failures. Microstaging of the SLNs using more sensitive assays may help identify a subgroup of patients with invasive breast cancer who would benefit from systemic adjuvant treatment, while sparing a disease-free subset of patients the additional risks of toxic adjuvant chemotherapy. PMID- 10030422 TI - Feasibility of breast conservation therapy in metachronous or synchronous bilateral breast cancer. AB - BACKGROUND: The optimal management of contralateral breast cancer (CC) in patients previously treated with breast-conserving therapy (BCT) is unclear, as is whether these patients continue to choose BCT as the preferred treatment of their second breast cancer. METHODS: Of 1328 patients treated with BCT at The University of Texas M. D. Anderson Cancer Center between 1958 and 1994, 63 developed a contralateral breast cancer. We reviewed the charts of these patients retrospectively, and standard demographic and treatment variables were evaluated. Survival was analyzed by the Kaplan-Meier method and subgroups by chi2 analysis. RESULTS: Twenty-nine percent of the patients had a family history of breast cancer. First breast cancers were detected by patient or physician in 67% of cases and by mammogram in 17% of cases, compared to 59% and 36%, respectively, of CC (P = .04). Median time to development of CC was 61 months. Sixty percent of the initial tumors were AJCC stage 0 or I with a median size of 2 cm, whereas 74% of the CC were stage 0 or I (P = .02), with a median size of 1.5 cm. Eighty-seven percent of patients chose BCT for treatment of CC. There were few treatment related complications. Recurrence rates were not significantly different from those of patients undergoing BCT for the initial cancer (P = .47), and 5- and 10 year actuarial survival rates after the first cancer were 93% and 76%, respectively. Median follow-up was 134 and 56 months from the time of diagnosis of the initial cancer and CC, respectively. CONCLUSIONS: Because contralateral breast cancer often is detected at an early stage, there are few treatment related complications, and the risk of recurrence is no different from that for the initial cancer, BCT is an acceptable and desirable option for appropriately selected patients with metachronous or synchronous bilateral breast cancers. PMID- 10030423 TI - The impact of prophylactic axillary node dissection on breast cancer survival--a Bayesian meta-analysis. AB - BACKGROUND: Because of the general acceptance of the NSABP B-04 study, prophylactic axillary node dissection for women with clinically negative axillae is considered diagnostic, but not therapeutic, by many oncologists. Nevertheless, several authors have shown that B-04 did not include enough patients to exclude a small survival advantage. METHODS: A Bayesian meta-analysis of the available literature was performed comparing standard treatment to standard treatment without axillary node dissection. Six randomized controlled trials were identified, consisting of nearly 3000 patients and spanning four decades. RESULTS: All six trials showed that prophylactic axillary node dissection improved survival, ranging from 4% to 16%, corresponding to a risk reduction of 7%-46%. Combining the six trials showed an average survival benefit of 5.4% (95% CI = 2.7-8.0%, probability of survival benefit > 99.5%). Adjusting for biases in the individual studies did not alter the conclusions, nor did subset analysis of Stage I patients. CONCLUSIONS: Axillary node dissection improves survival in women with operable breast cancer. Nevertheless, two important limitations of this analysis are noteworthy. Few of the patients in the six trials had T1a tumors, so extrapolation of these results to this subset (and those with nonpalpable tumors) may be inappropriate. Essentially no patients in the six trials were treated with adjuvant therapy, as contrasted to current clinical practice. It is possible that the risk reduction seen in this meta-analysis may be diminished in patients receiving adjuvant chemotherapy. Despite these limitations, this study suggests that axillary dissection should be performed in most women with palpable tumors for diagnostic, as well as therapeutic, purposes. PMID- 10030424 TI - Chemoradiotherapy in the management of localized tumors of the pancreas. AB - In western countries, carcinoma of the pancreas remains the most lethal of the common malignancies. Even the favorable "organ-confined" tumors present a considerable challenge. The lack of anatomic barriers to local infiltration and the biological propensity for early lymphatic, perineural, and vascular invasion are nearly insurmountable obstacles to complete surgical eradication of this malignancy. Various combinations of chemotherapy and radiotherapy (RT) have been used with marginal but measurable success. Earlier trials conducted by the Gastrointestinal Tumor Study Group established roles for 5-fluorouracil chemotherapy and RT in the treatment of patients with resectable or locally advanced pancreatic cancer. More recently, computed tomography-guided conformal RT and a variety of intraoperative RT techniques have enabled more reliable sterilization of the local surgical field and escalation of doses to potentially curative levels (7000 cGy) for unresectable lesions. Chemotherapy dose intensification through the use of portable programmable pumps for protracted venous infusions and the development of active systemic agents in addition to 5 fluorouracil suggest that an effective combination chemotherapeutic regimen might soon be developed. This report reviews the current standards of practice and integrates recent developments to construct a modern algorithm for the use of chemoradiotherapy in the management of localized (nonmetastatic) pancreatic cancer. The likely directions of future investigations are also discussed. PMID- 10030425 TI - Drug treatment of epilepsy in people with intellectual disability. PMID- 10030426 TI - Use of antiepileptic drugs in the treatment of epilepsy in people with intellectual disability. AB - The main principles of antiepileptic drug treatment of epilepsy in patients with intellectual disability are basically the same as for other patients with epilepsy. However, some specific issues need to be taken into account These are primarily associated with the diagnostic difficulties of epilepsy in this population. In addition, a number of other relevant issues, including the degree and location of brain lesion, the nature of the underlying disease, the higher frequency of difficult-to-treat epilepsies, the additional intellectual impairment caused by inappropriate antiepileptic medication, or by frequent and prolonged seizures, the appropriate use of monotherapy versus rational polytherapy, and the use of broad-spectrum antiepileptic drugs will be discussed in the present paper. Although the goals of treatment are to keep the patient seizure-free and alert while preventing possible mental deterioration, we have to accept compromises between these primary goals in many cases. Some people with epilepsy and intellectual disability are very vulnerable to insidious neurotoxic effects; for example, sedative effects caused by phenobarbital, or cognitive and/or cerebellar dysfunction caused by long-term phenytoin, especially together with other drugs. Because of the adverse effects of phenobarbital and phenytoin, these drugs are no longer recommended as a first-choice drugs when long-term antiepileptic medication is required. In primary generalized tonic-clonic seizures, valproate, oxcarbazepine/carbamazepine and lamotrigine are recommended in this order of preference. The corresponding recommendations are: in typical absences, valproate, ethosuximide and lamotrigine; in atypical absences, valproate and lamotrigine; in juvenile myoclonic epilepsy, valproate, lamotrigine and clobazam; in infantile spasms vigabatrin, ACTH and valproate; in Lennox Gastaut syndrome, valproate, lamotrigine and vigabatrin; in atonic seizures, valproate and lamotrigine; in simple and complex partial seizures with or without secondary generalization, oxcarbazepine/carbamazepine, valproate/ vigabatrin and lamotrigine; and in status epilepticus lorazepam, diazepam and clonazepam together with phenytoin or fosphenytoin. In cases of poor response to the monotherapy recommended above, the following combinations may be indicated: in primary generalized tonic-clonic epilepsy, valproate and oxcarbazepine/ carbamazepine, or valproate and lamotrigine; in typical absences, valproate and lamotrigine, or valproate and ethosuximide; in juvenile myolonic epilepsy, valproate and lamotrigine, or valproate and clonazepam; and in partial epilepsies, add to the monotherapy one of the following drugs, vigabatrin, lamotrigine, gabapentin, tiagabine, topiramate, zonisamide or clobazam. So far, the order of preference of these new drugs remains undetermined. More data are needed on the efficacy and adverse effects of the new drugs based on controlled studies on patients with intellectual disability and epilepsy. PMID- 10030427 TI - Barbiturates in the treatment of epilepsy in people with intellectual disability. AB - Barbiturates are effective drugs in the treatment of epileptic disorder. The systemic side-effects are minimal. The main limiting factor is the presence of cognitive and behavioural problems. Relevant research is presented in this paper; however, it is somewhat difficult to extrapolate some of these experiences to a population of children and adults with intellectual disability and epilepsy. Recent reviews of this subject have suggested that, although the cognitive deficiencies seem to be a serious problem when phenobarbital is given in high doses, the problem is much less severe when the doses are on the low side. The most consistent findings with regard to behaviour are the exacerbation of behaviour disorders (mostly hyperactivity), as well as sleep disorders and depression in individuals who already have a predisposition to these disorders. However, the clinical experience of many professionals involved with the care of people with intellectual disability strongly suggests that barbiturates, and especially phenobarbital, produces intolerable side-effects at the point that the use of phenobarbital has been reduced to a minimum, and it is no longer considered a drug of choice. It is probably that the simultaneous presence of brain damage, epilepsy, intellectual disability and psychiatric disorders in people with intellectual disability is responsible for the high incidence of behaviour problems observed by clinicians. PMID- 10030428 TI - Phenytoin: effective but insidious therapy for epilepsy in people with intellectual disability. AB - Phenytoin (5,5-diphenylhydantoin), which has been in use for 60 years, is still an important antiepileptic drug. Its primary mechanism of action is modulation of the sustained repetitive firing of neurones by direct inhibition and blockage of voltage-gated sodium channels in the neuronal cell membrane, and by delay of cellular reactivation. The plasma protein binding of phenytoin is normally between 90% and 95%. The drug is rapidly distributed from the blood to the tissues and is almost completely metabolized in the liver. The plasma phenytoin concentration normally reaches the steady-state level within 1-2 weeks. The half life of phenytoin is less than 20 h in low doses, but is prolonged in high doses, newborn infants and elderly people. The half-life is shortened when phenytoin is given concomitantly with an enzyme-inducing drug, such as phenobarbital or carbamazepine. Phenytoin is effective for treating generalized tonic-clonic seizures, partial seizures with or without generalization, and convulsive status epilepticus. Over the years, many new, and even serious, adverse effects of phenytoin have been recognized. Phenytoin encephalopathy, manifesting as cognitive impairment and a cerebellar syndrome, is an important adverse neurological effect, the development of which depends on the saturation kinetics of phenytoin, individual differences in phenytoin metabolism, an inhibitory effect of certain drugs on phenytoin metabolism, or the ability of certain drugs to displace phenytoin from plasma proteins, leading to an increase in the plasma level of unbound phenytoin. Because of its potentially adverse effects, phenytoin is not recommended as the first choice for treating epileptic seizures, except as a co-drug for managing convulsive status epilepticus. In patients with epilepsy who also have intellectual disability, and are susceptible to balance disturbances and cognitive dysfunction, it is wise to replace phenytoin with another drug, such as carbamazepine or oxcarbazepine. The long-term use of phenytoin is not recommended for patients with loss of locomotion, marked cognitive impairment, or symptoms and signs of cerebellar disease. The prevention of phenytoin intoxication, with the subsequent development of phenytoin-induced encephalopathy, depends on careful observation of the patients and frequent monitoring of plasma levels of phenytoin and other concomitantly administered antiepileptic drugs. PMID- 10030429 TI - Valproate in the treatment of epilepsy in people with intellectual disability. AB - Valproate is a major broad-spectrum antiepileptic drug effective against many different types of epileptic seizures. Valproate is a first-line drug in the treatment of primary generalized seizures and syndromes, but it is also effective in other seizure and epilepsy types. The possible mechanisms of action and the pharmacokinetics of valproate are outlined. A limited number of studies on the efficacy and safety of valproate treatment in patients with West syndrome and Lennox-Gastaut syndrome have shown that even therapy-resistant people with intellectual disability can benefit from add-on valproate medication. In status epilepticus, valproate can be effective either intravenously, by gastric drip or following rectal administration. Patient tolerance towards valproate is generally good. The most serious adverse effect of valproate include hepatotoxicity and teratogenicity. PMID- 10030430 TI - Carbamazepine in the treatment of epilepsy in people with intellectual disability. AB - Carbamazepine is a major antiepileptic drug which is primarily used to treat epileptic patients suffering from partial seizures with or without secondary generalization, but which also has applications in those suffering from primary generalized tonic-clonic seizures. Besides its antiepileptic effect, carbamazepine is also indicated in the treatment of trigeminal and occipital neuralgia, and in manic depressive disorders. Because of its minimal unwanted effects on cognition and behaviour, carbamazepine is an excellent drug for the treatment of people with intellectual disability and epilepsy. Carbamazepine is still one of the most commonly prescribed medications in the treatment of epileptic disorders. PMID- 10030431 TI - Oxcarbazepine in the treatment of epilepsy in children and adolescents with intellectual disability. AB - Oxcarbazepine is similar to carbamazepine in its mechanisms of action and antiepileptic efficacy, but has better tolerability and fewer interactions with other drugs. Very few data are available on the usefulness of oxcarbazepine in patients with intellectual disability and epilepsy. From January 1991 until October 1994, the present authors treated 40 patients with intellectual disability and epilepsy under the age of 18 years with oxcarbazepine. The mean age at onset of epilepsy was 12 months (range = 0-132 months). All patients had previously been intractable to antiepileptic drugs (including carbamazepine in 29 patients). The age at onset of oxcarbazepine therapy ranged from 0.8 to 17.1 years (mean = 6.2 years). Thirty-one patients (78%) received other antiepileptic drugs simultaneously with oxcarbazepine. The mean follow-up with oxcarbazepine treatment was 18.8 months. The mean maximum oxcarbazepine dose was 49 mg kg(-1) day(-1) (range = 21-86 mg kg(-1) day(-1). A reduction in seizures of at least 50% during oxcarbazepine treatment was observed in 14 out of 28 (50%) patients with localization-related epilepsy and in 5 out of 12 (42%) patients with generalized epilepsy. Efficacy was transient in three patients. An increase of atypical absences was observed in one child and an emergence of drop attacks in another. Side-effects were observed in 16 (40%) patients; in eight (20%), these lead to dose reduction or discontinuation. Oxcarbazepine appears to be an effective and well-tolerated drug for children and adolescents with intellectual disability and epilepsy. PMID- 10030432 TI - Antiepileptic efficacy of vigabatrin in people with severe epilepsy and intellectual disability. AB - The short- and long-term clinical efficacy of add-on vigabatrin treatment was evaluated in a group of 36 patients with intellectual disability and drug refractory epilepsy. The results were compared to the efficacy of vigabatrin in 75 non-retarded patients with drug-resistant complex partial and secondarily generalized seizures. After 3 months, 42% of the patients with intellectual disability had experienced a reduction in seizure frequency of more than 50% (responders). The percentage of responders was still 22% after 6 years. No impairment in psychological function was observed during vigabatrin treatment compared with baseline values. However, one patient was excluded from long-term treatment because of psychotic depression and two patients because of psychomotor slowing after 1-2 years of treatment The need for extra supervision appeared to diminish and three patients were able to be discharged from institutional care during the follow-up. In the group of non-retarded patients, the percentages of the responders were 55% and 27% after 3 months and 6 years of treatment, respectively. The results from these studies suggest that vigabatrin is effective and relatively well tolerated, and that the successful treatment of epilepsy also has socio-economic consequences in patients with intellectual disability and severe epilepsy. PMID- 10030433 TI - Lamotrigine in the treatment of epilepsy in people with intellectual disability. AB - Information about the mechanism of action and pharmacology of lamotrigine is summarized. A brief review of the literature on the use of this drug in people with intellectual disability is followed by a suggested framework for evaluating antiepileptic drugs in this population. The role of lamotrigine is systematically examined against the suggested framework. This leads to the conclusion that lamotrigine is a very favourable drug for treating epilepsy in people with intellectual disability because it has a broad spectrum of action, is effective in treating subtle seizures, shows no loss of effect with time, is not usually sedative, does not produce difficult-to-manage adverse effects, appears to have no direct adverse behavioural effects and is available in a range of 'patient friendly' preparations. However, it is important to use the drug wisely. This implies starting with low doses of lamotrigine and escalating the dose slowly to avoid adverse effects, especially rash, and being aware of drug interactions which could cause difficulty, including the prolongation of half-life with valproate, the pharmacodynamic interaction when it is added to carbamazepine and the pharmacokinetic interactions of lamotrigine with a number of antiepileptic drugs. PMID- 10030434 TI - Gabapentin in the treatment of refractory partial epilepsy in children with intellectual disability. AB - Twenty-six children with intellectual disability and six normal children, all suffering from refractory partial seizures, received open-label gabapentin (range = 10-50 mg kg(-1) day(-1); mean = 26.7 mg kg(-1) day(-1) as an add-on medication to their antiepileptic drug regimen. Mean seizure frequency during baseline was 9.5 seizures per week. Both groups had a significant reduction in seizure frequency. Response scores and response ratios did not differ between the intellectually disabled and normal groups (1.67+/-0.67 and 1.25+/-0.69, P = 0.697, and -0.400+/-0.089 and -0.283+/-0.159, P = 0.961, respectively). Behavioural side-effects were more likely to occur in patients with intellectual disability in comparison with the mentally normal group (P = 0.0107). In the present patient population, patients younger than 10 years of age, all of whom had intellectual disability, were more likely to have side-effects than those older than 10 years of age. Observed adverse effects, which were generally mild, occurred in patients with baseline intellectual disability, attention deficit disorder and behavioural problems. Behavioural adverse effects warranted discontinuation of the medication in only three patients. The severity of intellectual disability (mild versus moderate or severe) did not affect the extent of the response or the occurrence of side-effects. It is concluded that gabapentin is equally effective as an add-on medication against partial seizures in patients with or without intellectual disability. However, children with intellectual disability who also are less than 10 years of age with baseline attention deficit appear to be at a higher risk of behavioural side-effects. PMID- 10030435 TI - Tiagabine: a new therapeutic option for people with intellectual disability and partial epilepsy. AB - Tiagabine exerts its antiepileptic drug (AED) activity by selectively inhibiting the uptake of gamma-aminobutyric acid (GABA) onto the transporter molecules, and thus, increasing extracellular concentrations of GABA in the brain. The absorption and elimination of tiagabine follow linear pharmacokinetics. Tiagabine is metabolized by hepatic cytochrome P450 enzymes and enzyme-inducing AEDs increase tiagabine clearance by 50-65%. Tiagabine has shown no clinically important interactions with other drugs, including oral contraceptives. In the perforant pathway stimulation model of status epilepticus, tiagabine reduced the seizure number and severity, and also prevented the loss of pyramidal cells in the hippocampus as well as alleviated impairment of the spatial memory impairment associated with hippocampal damage. Tiagabine has both antiepileptogenic and anticonvulsant effects in the kindling model of epilepsy. Based on the data from the short- and long-term add-on studies, tiagabine is effective adjunctive therapy for all partial seizure types in adolescents and adults. Conversion to tiagabine monotherapy has been also possible in substantial amount of patients with partial seizures in three trials. Tiagabine is generally well-tolerated. The most common adverse events in controlled studies involve the central nervous system; for example, dizziness, asthenia, nervousness, tremor, depressed mood and emotional lability. Special safety analyses with formal neuropsychological testing suggest that tiagabine does not adversely affect cognition or mood. Tiagabine represents an important new therapeutic option for patients with treatment-refractory partial seizures. The role of tiagabine in the management of partial epilepsy of patients with intellectual disability is especially emphasized since tiagabine has a low side-effect profile in the cognitive area. PMID- 10030436 TI - Long-term effects of zonisamide in the treatment of epilepsy in children with intellectual disability. AB - Zonisamide is a new drug with broad-spectrum antiepileptic activity against partial as well as generalized seizures. The purpose of the present study was to compare the long-term efficacy of zonisamide in the treatment of epilepsy in children with intellectual disability (ID) with those with normal intelligence (NI). One hundred and thirty children (74 ID, 56 NI) were included in the study. Fifteen of the subjects were eliminated from the study because of adverse effects or aggravation of seizures. The remaining 115 children (66 ID, 49 NI) were followed up for more than one year. Twenty-eight children (6 ID, 22 NI) were in zonisamide monotherapy. The mean numbers of different antiepileptic drugs were 4.5 and 3 for the ID and NI groups, respectively. The overall improvement rates, defined as a >50% reduction in the number of seizures, were 41% (ID) and 67% (NI) (P<0.01). Side-effects were observed in 27% and 30% of subjects in the ID and NI groups, respectively. However, in the monotherapy group, side-effects were observed in 50% (ID) and in 27% (NI). In conclusion, the effectiveness of zonisamide was weaker in children with ID than those with NI. This is in agreement with the known phenomenon that epileptic children with ID are likely have more intractable seizures than those with NI. PMID- 10030437 TI - Topiramate: uses in people with an intellectual disability who have epilepsy. AB - The novel anticonvulsant topiramate has been shown to have efficacy across a range of seizure types including both generalized and partial seizures in several well-designed randomized controlled trials. It has also been shown to be effective in atonic seizures associated with Lennox-Gastaut syndrome. Tolerability data show a tendency to neuropsychiatric side-effects, such as confusion and word finding difficulties, when topiramate is used in polytherapy; these side-effects are reduced in monotherapy usage. The efficacy and spectrum of seizures treated by topiramate suggests that it has an important role in managing epilepsy in people with intellectual disability. The predictable side-effects can be monitored in clinical practice and possibly reduced by slow dose increments. The data set of patients with intellectual disability is still too small to rule out idiosyncratic drug reaction. PMID- 10030438 TI - Benzodiazepines in the treatment of epilepsy in people with intellectual disability. AB - All the benzodiazepines (BZDs) in clinical use have the capacity to promote the binding of the major inhibitory neurotransmitter, gamma-amino-butyric acid (GABA), to sub-types of GABA receptors which exist as multi-subunit ligand-gated chloride channels. Thus, the BZDs facilitate the actions of GABA in the brain. The BZDs in use as antiepileptic drugs are diazepam, clonazepam, clobazam, nitrazepam, and lately, also lorazepam and midazolam as emergency therapy. The BZDs have a wide-spectrum of proven clinical efficacy in the prevention of different kind of seizures. Clonazepam and clobazam, as well as nitrazepam in some cases, can be useful as an adjunct treatment in refractory epilepsies. However, the clinical use of BZDs for the prophylactic treatment of epilepsy is associated with two major problems which have limited the long-term use of these drugs: the potential for side-effects, especially sedative effects, and the high risk of development of tolerance. Despite the limitations of BZDs in the prophylactic treatment of epilepsies, these drugs play a prominent role in clinical practice in the emergency management of acute seizures and status epilepticus. Diazepam, clonazepam and lorazepam are all considered first-line agents in the emergency management of acute seizures and status epilepticus. Furthermore, the value of midazolam as an emergency therapy in epilepsy has been increasingly recognized in recent years. PMID- 10030439 TI - Prader-Willi syndrome and psychotic symptoms: 1. Case descriptions and genetic studies. AB - Six people with Prader-Willi syndrome (PWS) who developed psychoses are described. Along with other literature reviewed in the present paper, the results imply an association between PWS and psychotic symptoms. Genetic studies were possible in five cases and SNRPN expression was examined in three cases. Maternal uniparental disomy and 15q11q13 deletions were found, demonstrating that psychotic symptoms are not associated with a single type of genetic abnormality. PMID- 10030440 TI - Prader-Willi syndrome and psychotic symptoms: 2. A preliminary study of prevalence using the Psychopathology Assessment Schedule for Adults with Developmental Disability checklist. AB - The Psychopathology Assessment Schedule for Adults with Developmental Disability (PAS-ADD) checklist was used to screen for psychotic symptoms among people with Prader-Willi syndrome (PWS) aged 16 years and over. The scoring instructions for the PAS-ADD checklist were modified to take account of knowledge about the behavioural phenotype of PWS. Using modified scoring, 6.3% of the 95 people for whom checklists were completed had a possible psychotic disorder in the month before the assessment was made. The results should be treated as a crude estimate of the prevalence of psychotic symptoms associated with PWS in adult life in view of potential biases in the sample reported. These findings lend some support to the hypothesis that PWS has a non-chance association with psychotic symptoms and that the association is not entirely accounted for by the increased prevalence of psychosis associated with intellectual disability. PMID- 10030441 TI - Prader-Willi syndrome and cycloid psychoses. AB - The psychiatric symptomatology of people with Prader-Willi syndrome (PWS) has mainly been described in case reports and some large-scale descriptive studies. Unfortunately, there is still no systematic description of all the psychiatric symptoms which accompany this chromosomal error. Symptoms of mood disorder and anxiety dominate the picture of PWS, although some reports also mention psychotic symptoms with variations in prevalence of between 15% and 60%. The present paper presents six case reports of adult male subjects with a diagnosis of PWS and psychiatric symptoms who fulfill the criteria for cycloid psychosis (ICD-10 F.23.0). This psychotic disorder requires a specific psychopharmacological approach with mood stabilizing agents, particularly Lithium. It is concluded that subjects with PWS may be especially vulnerable to the development of cycloid psychosis, which suggests the existence of a specific 'psychopathological phenotype'. PMID- 10030442 TI - Affective psychosis and Prader-Willi syndrome. AB - Previous studies have demonstrated that maladaptive behaviours are common amongst adults with Prader-Willi syndrome (PWS). Case reports have also previously demonstrated that psychosis can occur amongst adults with PWS. The present study was undertaken in order to gain a better understanding of the psychopathology of the psychosis of PWS. Twenty-three out of 25 adults identified with PWS living in Northamptonshire, UK, agreed to participate. Comprehensive psychiatric assessments (using the PPS-LD), and measures of adaptive and maladaptive behaviours (using the AAMR-ABS) were completed. Comparisons were made for the prevalence of psychiatric disorders against those from a previous epidemiological study of adults with intellectual disability of other aetiologies from a neighbouring county. The PWS group was found to have higher rates of affective disorders (a point prevalence of 17.4%), in which psychotic symptoms were common, but similar rates of schizophrenia/delusional disorders (4.3%) compared with the comparison group. Behaviour disorders were also common. Surprisingly, none of the PWS group was found to have generalized anxiety or phobic disorders. The diagnostic criteria for the episodes including psychotic symptoms are explored. The high rates of affective disorders is of clinical (i.e. treatment) importance as well as being of academic interest with regard to the genetics of psychiatric disorders. PMID- 10030443 TI - The latent variable structure of the Compulsive Behaviour Checklist in people with Prader-Willi syndrome. AB - The presence and severity of compulsive behaviours may be evaluated via the Compulsive Behaviour Checklist (CBC) and this instrument has been successfully employed in people with intellectual disability. However, the applicability of the overall CBC scoring system, which entails tallying the number of behavioural categories represented (i.e. five) as well as the number of individual behaviours endorsed (i.e. 25), is not known in the population with Prader-Willi syndrome (PWS). The present investigation examined the latent variable structure of the CBC in people with PWS in order to identify possible population-specific scoring and interpretation considerations. The 25 behaviour-specific items of the CBC were analysed for 75 people with PWS (44 females and 31 males) aged between 4 and 41 years (mean +/- SD = 11.4+/-9.4) via factor analysis with principal component extraction and equamax rotation. The most suitable solution was determined on the basis of multiple empirical criteria: (1) the scree test; (2) eigenvalues >1.00; (3) salient loadings >0.30; (4) the clarity of item assignment to a single latent dimension; (5) the internal consistency of the latent dimension(s) (coefficient alpha > or = 0.70); and (6) item-total correlations between 0.20 and 0.79. In addition, solutions were examined with respect to psychological theory and previous research. A 'general factor' (i.e. single latent dimension) solution which adhered to all a priori criteria was indicated. Twenty-four out of 25 items achieved salient loadings ranging from 0.46 to 0.80 on the general factor. The single item which failed to achieve salience, 'deviant grooming-skin picking', exhibited both substantial unique variance (0.997) and moderate reliability (r = 0.59, P<0.001). The internal consistency of the general factor was strong (alpha = 0.93) and all salient items were suitably correlated with the unit-weighted total score (r(item-total) = 0.41-0.77). The traditional CBC scoring system, which includes tallying the number of categories represented, would not be relevant in this PWS sample. In addition, the recommended tallying of the number of individual behaviours endorsed does not reflect the empirically indicated notion of compulsive behaviour in this special population. These findings indicate that the 24 salient items should be scored as a unit-weighted composite and that the score on the substantially unique item (skin picking) should be considered a separate measure when evaluating compulsive behaviours via the CBC in people with PWS. PMID- 10030444 TI - Distinctiveness and correlates of maladaptive behaviour in children and adolescents with Smith-Magenis syndrome. AB - This two-part study examines the distinctiveness and correlates of maladaptive behaviour in 35 children and adolescents with Smith-Magenis syndrome, a developmental disorder caused by an interstitial deletion of chromosome 17 (p11.2). Study I compares Child Behavior Checklist scores in 35 children with Smith-Magenis syndrome to age- and gender-matched subjects with Prader-Willi syndrome and mixed intellectual disability. Subjects with Smith-Magenis syndrome had significantly higher levels of maladaptive behaviour than the other groups. Although some problems were shared across groups, 12 behaviours differentiated the three groups with 100% accuracy. Study 2 assessed the frequency and correlates of self-injurious and stereotypical behaviours, including unusual features such as nail-yanking, inserting objects into bodily orifices, self hugging and a 'lick-and flip' behaviour. Nail-yanking and bodily insertions were less common than other types of self-injury, and self-hugs and the 'lick-and flip' stereotypies were seen in about half the sample. Although age and degree of delay were correlated with problem behaviours, sleep disturbance emerged as the strongest predictor of maladaptive behaviour. The implications are discussed for clinical diagnostic ambiguities between the Smith-Magenis and Prader-Willi syndromes, and for intervention. PMID- 10030445 TI - Face recognition and emotion perception in boys with fragile-X syndrome. AB - Two independent and complementary studies were conducted to assess the ability of boys with fragile-X syndrome to recognize facial and emotional expressions. Both studies failed to find any specific deficits associated with fragile-X syndrome. The performance of the test group was comparable to the level of subjects with intellectual disability and subjects of average cognitive development matched for intellectual ability. This suggests that chronological age and intellectual level are unlikely to explain the findings. The results are discussed in the context of the controversy surrounding the relationship between autism and fragile-X syndrome. The findings are consistent with fragile-X individuals having a profile of social, communicatory and ritualistic disturbances, which in some ways may differ from those found in individuals who have more typical autistic spectrum disorders. PMID- 10030446 TI - 'As required' neuroleptics: have these drugs a place in the management of challenging behaviour in intellectual disability? AB - The present study examined the prescription pattern and usage of 'as required' neuroleptics (PRNs) in the management of challenging behaviours in people with intellectual disability in a hospital setting. The prescription cards and drug administration records of residents were scrutinized to see how many of them were prescribed PRNs and how many had actually received these drugs during the previous 3 months. The results were compared in the following groups: (1) males and females; (2) the behavioural and nonbehavioural sectors; (3) intensive treatment wards (ITWs) for severe challenging behaviour which had a better staff:resident ratio than the rest of the behavioural wards; and (4) those prescribed PRNs together with the daily administration of neuroleptics and those without. It was found that more females used PRNs and that the prescription rate was higher in the behavioural sector. A better staff:resident ratio did not bring about any reduction in the usage of PRNs. The use of these drugs was not influenced by whether PRNs were prescribed along with regular neuroleptics or not. Further research is required to delineate the precise role of PRNs for challenging behaviours in this population, and to determine if PRNs can be used along with other modes of therapeutic interventions, instead of administering neuroleptics on a regular basis for this indication. PMID- 10030447 TI - Mental health and intellectual disability: an international perspective. AB - The present paper reports on the inaugural meeting of the Mental Health Special Interest Research Group (SIRG) of the International Association for the Scientific Study of Intellectual disability which was held at Fitzwilliam College, Cambridge, UK, in March 1998. The meeting was organized in conjunction with the Ninth Annual SIRG on ageing and intellectual disability. Representatives from North America, several European and Scandinavian countries, Australia, and Israel attended. Two broad themes had been determined prior to the meeting: 'Improving the detection of mental health problems' and 'Research strategies for identifying risk factors for mental health problems'. In the presentations and subsequent discussions, it was apparent that there were extremely diverse perspectives both across and within the different countries represented. Not only were individuals' experiences very different, but most strikingly, the theoretical frameworks were very diverse. This was partly a function of there being understandable differences in perspectives across disciplines, but at its most marked, there were fundamental differences in the way both intellectual disability and mental health were conceptualized. PMID- 10030448 TI - The 1996 Veylien Henderson Award of the Society of Toxicology of Canada. Current concepts: neutrophils and the activation of carcinogens in the breast and other organs. AB - Many chemical carcinogens target epithelial tissues, but the biological and biochemical bases of carcinogen specificity remain largely unknown. Focusing on the mammary gland, we discuss the concept that neutrophils metabolize carcinogens to reactive species that damage adjacent epithelial cells. This mechanism may help to explain why epithelial cells are sensitive targets for chemical carcinogenesis, despite their limited bioactivation capacity. PMID- 10030449 TI - Amantadine acetylation may be effected by acetyltransferases other than NAT1 or NAT2. AB - Amantadine is a drug with a primary amino group, and consequently a likely candidate for metabolism by acetylation. This study assessed the possibility that a person's polymorphic (NAT2) acetylator phenotype could be used to predict the extent of amantadine acetylation. Thirty-eight normal, healthy volunteers were NAT2 acetylator phenotyped with sulfapyridine. Of the six fastest (75-86%) and six slowest (34-40%) sulfapyridine acetylators, two and three, respectively, had acetylamantadine present (18-338 microg) in the 8-h urine collection. There was no correlation between NAT2 acetylator phenotype and amantadine acetylation (p<0.5), and no difference in the total urine amantadine excreted over 8 h between acetylators and nonacetylators (28.3+/-9.7 vs. 30.4+/-9.6 mg, respectively, mean +/- SD). Acetylamantadine represented 0.1-1.5% (median 0.5%) of urinary drug content over 8 h. Our data confirm that amantadine is acetylated in humans and demonstrate for the first time that the extent is not correlated with NAT2 acetylator phenotype. Parallel in vitro enzyme studies indicate the possibility that neither NATI nor NAT2 is responsible for acetylation of amantadine. PMID- 10030450 TI - Respiratory effects of pressor and depressor agents in conscious rats. AB - We hypothesized that the respiratory baroreflex in conscious rats is either more transient, or has a higher pressure threshold than in other species. To characterize the effect of arterial pressure changes on respiration in conscious rats, ventilation (V) was measured by the plethysmographic technique during injections, or infusions, of pressor and depressor agents. Bolus injections of angiotensin II (Ang II) or arginine vasopressin (AVP), transiently increased mean arterial pressure (MAP; mean +/- SE) 43+/-6 and 28+/-5 mm Hg (1 mm Hg = 133.3 Pa), respectively, and immediately reduced tidal volume (Vt) and, in the case of AVP, V. In contrast, by 10 min of a sustained elevation of MAP (40+/-3 mm Hg) with infusion of Ang II, Vt, f, and V were not different from control levels. Bolus injection of sodium nitroprusside (SNP) to lower MAP (-28+/-3 mm Hg) immediately increased breathing frequency (f) and V, whereas sustained infusion of SNP to lower MAP (-21+/-3 mm Hg) did not change for V at 10 and 20 min. In conscious rats, both injection and infusion of the pressor agent PE (+40 to 50 mm Hg) stimulated f and V; this contrasted with anesthetized rats where PE inhibited f and V, as reported by others. In conscious rats, respiratory responses associated with baroreflexes adapt rapidly and, in the case of PE, can be overridden by some other mechanism. PMID- 10030451 TI - Inhibition of airway hyperreactivity, edema, and lung cell infiltration by compound U-83836E in sensitized guinea pigs. AB - Sensitized guinea pigs were used to assess the effect of treatment with the compound U-83836E ((-)-2-[[4-(2,6-di-1-pyrrolidinyl-4-pyrimidinyl)-1 piperazinyl]methyl]-3 ,4-dihydro-2,5,7,8-tetramethyl-2H--benzopyran-6-ol, dihydrochloride) on the antigen-induced late-phase (16 h) airway hyperreactivity, increase in inflammatory cell number, edema, and release of inflammatory mediators in the bronchoalveolar lavage (BAL) fluid. After antigen challenge, an increase of the in vitro reactivity of the trachea and upper bronchi to acetylcholine and histamine and an increase in the number of leukocytes in the BAL fluid, mainly eosinophils and mononuclear cells, were observed. The concentrations of proteins, histamine, and PGE2 in the BAL fluid were also significantly increased by 53, 57, and 216%, respectively, after antigen challenge. Treatment with U-83836E (10 mg/kg) given i.p. 17 and 3 h before and 6 h after antigen challenge inhibited by approximately 80% the total cell number in the airways and the BAL fluid protein content. Moreover, this treatment totally inhibited airway hyperreactivity. Histamine and PGE2 levels in the BAL fluid were not significantly affected by U-83836E treatment. These results indicate that U 83836E is effective against some of the characteristic features of asthma in ovalbumin-sensitized guinea pigs. PMID- 10030452 TI - Differential susceptibilities of isolated hamster lung cell types to amiodarone toxicity. AB - Treatment of cardiac dysrhythmias with the iodinated benzofuran derivative amiodarone (AM) is limited by pulmonary toxicity. The susceptibilities of different lung cell types of male Golden Syrian hamsters to AM-induced cytotoxicity were investigated in vitro. Bronchoalveolar lavage and protease digestion to release cells, followed by centrifugal elutriation and density gradient centrifugation, resulted in preparations enriched with alveolar macrophages (98%), alveolar type II cells (75-85%), and nonciliated bronchiolar epithelial (Clara) cells (35-50%). Alveolar type II cell and Clara cell preparations demonstrated decreased viability (by 0.5% trypan blue dye exclusion) when incubated with 50 microM AM for 36 h, and all AM-treated cell preparations demonstrated decreased viability when incubated with 100 or 200 microM AM. Based on a viability index ((viability of AM-treated cells/viability of controls) x 100%), the Clara cell fraction was significantly (p<0.05) more susceptible than all of the other cell types to 50 microM AM. However, AM cytotoxicity was greatest (p<0.05) in alveolar macrophages following incubation with 100 or 200 microM AM. There was no difference between any of the enriched cell preparations in the amount of drug accumulated following 24 h of incubation with 50 microM AM, whereas alveolar macrophages accumulated the most drug during incubation with 100 microM AM. Thus, the most susceptible cell type was dependent on AM concentration. AM-induced cytotoxicity in specific cell types may initiate processes leading to inflammation and pulmonary fibrosis. PMID- 10030453 TI - Individual effects of dietary EPA and DHA on the functioning of the isolated working rat heart. AB - The aim of this study was to evaluate the effects of dietary pure eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) on the physiology of the heart in normoxic conditions and during postischemic reperfusion. These effects were compared with those of dietary n-6 polyunsaturated fatty acids (PUFA). Rats were fed a diet containing either sunflower seed oil (75 g x kg(-1), SSO group), or a mixture of EPA (20:5 n-3) ethyl ester and SSO (10:90, EPA group), or a mixture of DHA (22:6 n-3) ethyl ester and SSO (10:90, DHA group), or a mixture of EPA + DHA ethyl esters and SSO (4.2:5.8:90, e+D group) for 6 weeks. The hearts were then perfused according to the working mode. The perfusion was maintained either in normoxic conditions or stopped for 17 min (global zero-flow ischemia) and restored for 33 min (reperfusion). The aortic and coronary flows, aortic developed pressure, and electrocardiogram were continuously monitored. When rats were fed a diet containing either EPA and (or) DHA, the n-6/n-3 PUFA ratio of cardiac phospholipids decreased. The proportion of arachidonic acid was reduced more with DHA than dietary EPA. In the EPA group, the percentage of DHA was lower than in the DHA group, but the percentage of EPA and docosapentaenoic acid (22:5 n-3) was higher. These changes in membrane fatty acid composition altered the cardiac function. In normoxic conditions, the coronary flow was higher in the SSO group than in the DHA and EPA groups. The heart rate was lower in the DHA and e+D groups than in the EPA and SSO groups. The aortic flow, cardiac output, and aortic developed pressure were not affected. During postischemic reperfusion, the recovery of aortic flow, coronary flow, and aortic developed pressure was similar in the four groups. A slightly improved recovery of cardiac function was noticed in the EPA group, but the difference was not significant. Feeding rats 5% fish oil + 5% SSO instead of 10% SSO for 8 weeks increased the incorporation of EPA in cardiac phospholipids and favored the recovery (+120%) of aortic flow during postischemic reperfusion. In conclusion, the beneficial effect of dietary fish oil on the recovery of cardiac pump activity during reperfusion was not observed with DHA or EPA alone. It appears to be positively related to the accumulation of EPA in membrane phospholipids. The dietary conditions favouring EPA accumulation remain to be determined. PMID- 10030454 TI - Neurotransmission in the medulla mediating insular cortical and lateral hypothalamic sympathetic responses. AB - Previous evidence has shown sympathetic nerve responses to insular cortical (IC) stimulation are mediated by synapses within the lateral hypothalamic area (LHA) and ventrolateral medulla (VLM). The present study was aimed at determining the neurotransmitter(s) and receptor(s) involved at the synapse in the VLM. Twenty male Wistar rats were instrumented for renal nerve, arterial pressure, and heart rate recording. The IC or the LHA was stimulated with a bipolar electrode (200 1000 microA; 2 ms; 0.8 Hz) to elicit sympathetic nerve responses. Antagonists were then pressure-injected into the VLM (300 nL). Bilateral and unilateral kynurenate (25 mM) resulted in 100% block of IC-and LHA-stimulated sympathetic nerve responses. Bilateral injection of the non-NMDA (N-methyl-D-aspartate) receptor antagonist 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX; 200 microM) also resulted in up to 100% block of IC and LHA sympathetic responses. In addition, unilateral injections of CNQX were made in two animals, resulting in 100 and 83% block of LHA sympathetic responses. Bilateral injection of the NMDA receptor antagonist DL-2-amino-5-phosphonopentanoic acid (AP5; 200 microM) did not affect the response to IC or LHA stimulation. Kynurenate, CNQX, and AP5 all resulted in an elevation of baseline sympathetic nerve activity and a pressor response. Kynurenate resulted in a 263+/-79% increase in baseline activity, while CNQX and AP5 resulted in 83+/-19% and 91+/-21% increases. respectively. Bilateral injections of antagonists for GABA(A) (bicuculline; 0.1 microM), acetylcholine (atropine; 0.1 microM) and catecholaminergic alpha and beta receptors (phentolamine and propranolol: 0.1 microM) had no effect on LHA sympathetic responses. Thus, sympathetic responses originating in the IC and LHA are mediated by a non-NMDA receptors in the VLM, which are likely AMPA receptors. PMID- 10030455 TI - Respiratory, cardiovascular, and metabolic adjustments to hypoxemia during sleep in piglets. AB - The influence of sleep on ventilation, metabolic rate, cardiovascular function, and regional distribution of blood flow during hypoxemia (PaO2 of 45-50 mm Hg (1 mm Hg = 133.3 Pa)) was studied in piglets at 6+/-1 and 34+/-5 days (mean+/-SD). Measurement of ventilation and metabolic rate was done in a metabolic chamber, and blood flow was measured using the microsphere technique. A subgroup of animals was instrumented for cardiac output measurement (dye-dilution technique) and continuous monitoring of the hemoglobin saturation in oxygen (SaO2). We found that although sleep did not influence the metabolic and cardiac output response to hypoxemia, it affected the ventilatory response as well as the brain and the respiratory muscle blood flows. During active sleep in the older animals, the ventilatory response to hypoxemia was smaller than in the other two states; marked drops in SaO2 occurred with changes in the breathing pattern; and that state was associated with the highest rate of brain blood flow. As well, age affected the ventilatory and metabolic response, but not the cardiovascular response to hypoxemia. The age-dependent ventilatory changes with hypoxemia (smaller ventilatory response in the young than in the older animals) were related to the different levels of oxygen consumption. In summary, active sleep was responsible for all the sleep-dependent changes in the response to a moderate degree of hypoxemia. PMID- 10030456 TI - Characterization of cytochrome P450 2E1 activity by the [14C]nitrosodimethylamine breath test. AB - The objective of this study was to measure the rate of demethylation of nitrosodimethylamine in vivo in the rat and determine its value to assess CYP2E1 activity in intact animals. Nitrosodimethylamine labeled with 14C on both methyl groups was administered to rats and exhaled 14CO2 was collected during 2-3 h. The nitrosodimethylamine breath test was increased by inducers of CYP2E1, such as ethanol (+139%) and 4-methylpyrazole (+115%), and decreased by the inhibitor diallyl sulfide (-53%). In addition, the nitrosodimethylamine breath test was not changed significantly by inducers specific for other cytochrome P450 such as beta naphthoflavone, dexamethasone, and phenobarbital. The specificity of the induction by 4-methylpyrazole and of the inhibition by diallyl sulfide for CYP2E1 was determined using the [14C]caffeine (CYP1A2), [14C]aminopyrine (CYP2C11), and [14C]erythromycin (CYP3A2) breath tests. 4-Methylpyrazole treatment caused a small increase of the caffeine (+33%) and aminopyrine (+9%) breath tests and no change of the erythromycin breath test. Diallyl sulfide treatment led to a small decrease of the caffeine breath test (-33%) and of the aminopyrine breath test ( 13%) but a 23% increase of the erythromycin breath test. It is concluded that the [14C]nitrosodimethylamine breath test is useful to assess CYP2E1 activity in vivo in the rat. PMID- 10030458 TI - Influence of gender on post-tetanic potentiation in human dorsiflexors. AB - Twitch contractions of the ankle dorsiflexors were evoked before and after 7 s of tetanic stimulation at 100 Hz in young women and men. Torque decreased more in men (18%) than in women (12%) during the tetanus. There was no gender difference in twitch peak torque potentiation over the 5-min post-tetanus. Potentiation was 42% (women) and 45% (men) at 5 s post-tetanus, and still present at 5 min (women 24%, men 25%). The immediate (5 s) shortening of twitch rise time was similar in women (14%) and men (13%), but during the 5-min men's rise time came to exceed whereas women's only approached pretetanus values (e.g., +9% vs. -1% at 5 min). The immediate decrease in half-relaxation time was also similar in women (24%) and men (22%); however, women's but not men's values remained less than pretetanus values for most of the 5-min period. Twitch rate of torque development increased similarly (75%) in women and men at 5 s, with no gender difference over 5 min. In contrast, rate of torque relaxation increased significantly only in men. Rate of torque development normalized to peak torque was similar in women and men pretetanus and increased similarly 5 s post-tetanus, but women had greater values through most of the 5-min post-tetanus. Normalized rate of torque relaxation was similar in women and men and not affected by tetanus. In the dorsiflexor muscles, young women and men show a similar amount and pattern of twitch force potentiation, but there are gender differences in time-related twitch contractile properties in the first 5 min after tetanus. PMID- 10030457 TI - Developmental changes in synthesis of and responsiveness to prostaglandins I2 and E2 in hypoxic lamb lungs. AB - Previous studies have shown that the attenuated hypoxic pulmonary vasoconstriction (HPV) of young newborn lamb lungs was enhanced by cyclooxygenase inhibition. We sought to determine whether this reflected greater synthesis of and (or) responsiveness to dilator prostaglandins (PG). Protocol 1 measured responses to graded hypoxia and perfusate concentrations of 6-keto-PGF1alpha (the stable metabolite of PGI2) and PGE2 in isolated lungs from 1-day- and 1-month-old lambs. Protocol 2 compared dose responses and segmental vascular resistances during infusion of PGI2 and PGE2 in hypoxic, cyclooxygenase-inhibited, lungs from 1- to 2-day-old and 1- to 3-month-old lambs. Lungs of 1-day-old lambs with attenuated responses to 4% O2 had significantly higher perfusate concentrations of 6-keto-PGF1alpha and PGE2, but responses to both PGE2 and the more potent vasodilator, PGI2 did not differ with age. These data support the hypothesis that attenuated HPV in young newborn lamb lungs is due to increased synthesis of dilator PG, particularly PGI2. PMID- 10030459 TI - Gender effects of tall oil versus soybean phytosterols as cholesterol-lowering agents in hamsters. AB - To examine the effect of gender on the mechanisms of action of phytosterols extracted from tall oil (TO) and soybean (SB) on cholesterol and phytosterol metabolism, male and female hamsters were fed cholesterol-enriched diets containing 0.5 or 1% (w/w) TO or SB phytosterols for 90 days. Plasma lipoprotein cholesterol profile and tissue phytosterol and cholesterol biosynthesis levels were determined. Mean plasma total-cholesterol level in females fed 1% (w/w) SB was reduced (p<0.05) by 44%, while in males it was lowered (p<0.05) by 25% compared with their respective controls. Moreover, mean plasma total-cholesterol level was reduced (p<0.05) in male hamsters by -31% and female hamsters by -32% when fed 1% (w/w) TO. Cholesterol biosynthesis was higher (p<0.05) by twofold in groups fed TO at 0.5 and 1% (w/w) concentrations, compared with SB. Hamsters fed TO at 0.5 and 1% (w/w) levels also had higher (p<0.05) hepatic and enterocytic campesterol contents than SB-fed animals. These findings demonstrate gender differences in cholesterol metabolism in TO- and SB-fed hamsters. The results suggest that TO, conversely to SB phytosterol, is a more effective cholesterol lowering agent in male, but not as much in female, hamsters, over a feeding period of 90 days. PMID- 10030460 TI - PACAP enhances stimulation-induced norepinephrine release in canine pancreas in vivo. AB - The present study was to investigate whether pituitary adenylate cyclase activating polypeptide (PACAP) can modify norepinephrine (NE) release in response to pancreatic nerve stimulation in anesthetized dogs. Plasma catecholamine concentrations in aortic and superior pancreaticoduodenal (SPD) venous blood were determined by a high performance liquid chromatography method. SPD venous blood flow was measured with an electromagnetic flowmeter. Pancreatic nerves were directly stimulated for 1 min (2 ms, 12 V) at various frequencies at the level of the SPD artery. Various doses of PACAP1-27 (PACAP27) were locally infused into the pancreas through the SPD artery. Nerve stimulation significantly increased both SPD venous NE concentration and its output from the pancreas in a frequency dependent manner. With PACAP27 alone, neither SPD venous NE concentration nor its output changed significantly following the local administration of PACAP27 at any dose tested. In the presence of PACAP27, however, the net increases in NE concentration and its output in response to nerve stimulation at 2 Hz were significantly enhanced in a dose-dependent manner. The enhanced NE responses to nerve stimulation by PACAP27 were thus significantly greater than those obtained from the group receiving either PACAP27 or stimulation alone. Increases in NE concentration and its output induced by local administration of tyramine were virtually abolished by desipramine, a neural amine uptake inhibitor. However, the NE response to tyramine was not diminished by PACAP27. The results indicate that PACAP27 enhances the stimulation-induced NE release in the pancreas, and that this facilitatory effect of PACAP27 does not result from an inhibition of the neural amine uptake mechanism. The study suggests that PACAP receptor-mediated mechanisms may be involved either directly or indirectly in the local modulation of neural NE release in the canine pancreas in vivo. PMID- 10030461 TI - GABA(B) receptor antagonism by 7-MBFG, a benzo[b]furan analogue of baclofen, in central and peripheral tissues. AB - (R,S)-4-Amino-3-(7-methylbenzo[b]furan-2-yl)-butanoic acid (7-MBFG), a new benzofuran analogue of the GABA(B) receptor agonist baclofen, has been evaluated for pharmacological activity on GABA(B) receptors in the guinea-pig isolated ileum and rat neocortical slices. 7-MBFG (300 and 500 microM) reversibly antagonized the (R,S)-baclofen induced depression of cholinergic twitch contractions in the guinea-pig ileum and shifted the concentration-response curve for baclofen to the right, in a parallel manner, giving an apparent pA2 value of 3.7+/-0.3. Likewise, 7-MBFG (300 and 500 microM) reversibly blocked the baclofen induced suppression of spontaneous discharges, in rat neocortical slices maintained in Mg2+ -free Krebs medium, and caused a rightward, parallel shift of the baclofen concentration-response curve, giving an apparent pA2 value of 4.1+/ 0.1. The compound 7-MBFG belongs to a novel, new class of antagonist at central and peripheral GABA(B) receptors, in which the antagonist properties reside in the pseudo-aromatic character of their 3-benzo[b]furan-2-yl substituents, and might provide useful leads for further development of GABA(B) receptor ligands. PMID- 10030462 TI - Changes in resting membrane potential induced by active sensitization in the guinea-pig vas deferens. AB - Smooth muscles hyperresponsiveness is a common feature in anaphylaxis and allergic diseases. The aim of the present work was to investigate whether the enhanced reactivity of sensitized guinea-pig vas deferens was associated with changes in the resting membrane potential (Er) of the smooth muscle cells. Active sensitization was performed by subcutaneous injection of egg albumen. Er was measured in vitro in isolated vas deferens with conventional KCl-filled microelectrodes. Quantification of [3H]ouabain binding sites, measurements of 86Rb efflux, and measurements of Na and K contents were also performed. In normal physiological solution, at 35 degrees C, Er was a mean of -54.1+/-0.3 mV (mean +/ SEM) in control vas deferens. Sensitization resulted in depolarizing Er by about 7 mV. In control and sensitized preparations, the 3H-ouabain binding site concentration, the efflux of 86Rb, and the K content were similar. In guinea-pig vas deferens, active sensitization induced a partial depolarization of the resting membrane potential of the smooth muscle cells, which did not result from a downregulation of Na+ -K+ pump sites. PMID- 10030464 TI - Regulation of in vivo whole blood aggregation in rats by calcitonin gene related peptide. AB - The purpose of these experiments was to determine whether calcitonin gene related peptide (CGRP) mediates physiological control of platelet function in vivo. Rat blood pressure was continuously monitored via a femoral arterial cannula, and whole blood aggregation was assessed periodically ex vivo with an impedance aggregometer before and following a 1.4 nmol/kg bolus dose of CGRP8-37, a specific receptor antagonist of CGRP. Mean arterial blood pressure was not significantly affected by CGRP8-37 over a 30-min period (p>0.05). However, whole blood aggregation increased by 38.4+/-18.0% (p<0.01) and 32.0+/-11.2% (p<0.05), at 5 and 15 min post CGRP8-37, respectively, when compared with control. Whole blood aggregation was not significantly different from control at 30 min (p>0.05), suggesting a relatively short duration of action for in vivo CGRP8-37. These data suggest that CGRP contributes to the maintenance of hemostasis, and that this function may be more important than the better known vasodilatatory effects of this neuropeptide. PMID- 10030463 TI - The effect of sinus node depression on heart rate variability in humans using zatebradine, a selective bradycardic agent. AB - Zatebradine is a bradycardic agent with a selective effect on the pacemaker current in the sinus node. The effect of such drugs on heart rate variability is not known. Thirty-six patients without structural heart disease were randomly assigned to receive 10 mg of zatebradine i.v. (n = 24) or isotonic saline (n = 12). Heart rate variability (HRV) was recorded as power in the very low frequency (VLF, 0.003-0.040 Hz), low frequency (LF, 0.040-0.150 Hz), and high frequency (HF, 0.150-0.400 Hz) spectral bands as well as total power (TP, 0.003-0.400 Hz) during 5-min ECG acquisitions at baseline, 30, and 60 min following the start of the infusion. No change in heart rate variability was detected in the control group. Zatebradine significantly reduced heart rate variability at 60 min in all frequency bands: VLF (-12+/-4%, p<0.001), LF (-19+/-4%, p<0.001), and HF (-26+/ 5%, p<0.001). The reduction in HRV following zatebradine is due to depression of sinus node response to all external stimuli and underscores the need for documentation of normal sinus node function in HRV research. PMID- 10030465 TI - Introduction to the special issue: variable-length representation and noncoding segments for evolutionary algorithms. PMID- 10030466 TI - Effects of code growth and parsimony pressure on populations in genetic programming. AB - Parsimony pressure, the explicit penalization of larger programs, has been increasingly used as a means of controlling code growth in genetic programming. However, in many cases parsimony pressure degrades the performance of the genetic program. In this paper we show that poor average results with parsimony pressure are a result of "failed" populations that overshadow the results of populations that incorporate parsimony pressure successfully. Additionally, we show that the effect of parsimony pressure can be measured by calculating the relationship between program size and performance within the population. This measure can be used as a partial indicator of success or failure for individual populations. PMID- 10030467 TI - Collective adaptation: the exchange of coding segments. AB - Coding segments are those subsegments of the chromosome that contribute positively to the fitness evaluation of the chromosome. Clique detection is a NP complete problem in which we can detect such coding segments. We extract coding segments from chromosomes, and we investigate the duplication of coding segments inside the chromosome and the collection of coding segments outside of the chromosome. We find that duplication of coding segments inside the chromosomes provides a back-up mechanism for the search heuristics. We further find local search in a collective memory of coding segments outside of the chromosome, collective adaptation, enables the search heuristic to represent partial solutions that are larger than realistic chromosomes lengths and to express the solution outside of the chromosome. PMID- 10030468 TI - Code growth, explicitly defined introns, and alternative selection schemes. AB - Previous work on introns and code growth in genetic programming is expanded on and tested experimentally. Explicitly defined introns are introduced to tree based representations as an aid to measuring and evaluating intron behavior. Although it is shown that introns do create code growth, they are not its only cause. Removing introns merely decreases the growth rate; it does not eliminate it. By systematically negating various forms of intron behavior, a deeper understanding of the causes of code growth is obtained, leading to the development of a system that keeps unnecessary bloat to a minimum. Alternative selection schemes and recombination operators are examined and improvements demonstrated over the standard selection methods in terms of both performance and parsimony. PMID- 10030469 TI - ptGAs--genetic algorithms evolving noncoding segments by means of promoter/terminator sequences. AB - In this article we present work on chromosome structures for genetic algorithms (GAs) based on biological principles. Mainly, the influence of noncoding segments on GA behavior and performance is investigated. We compare representations with noncoding sequences at predefined, fixed locations with "junk" code induced by the use of promoter/terminator sequences (ptGAs) that define start and end of a coding sequence, respectively. As one of the advantages of noncoding segments a few researchers have identified the reduction of the disruptive effects of crossover, and we solidify this argument by a formal analysis of crossover disruption probabilities for noncoding segments at fixed locations. The additional use of promoter/terminator sequences not only enables evolution of parameter values, but also allows for adaptation of number, size, and location of genes (problem parameters) on an artificial chromosome. Randomly generated chromosomes of fixed length carry different numbers of promoter/terminator sequences resulting in genes of varying size and location. Evolution of these ptGA chromosomes drives the number of parameters and their values to (sub)optimal solutions. Moreover, the formation of tightly linked building blocks is enhanced by self-organization of gene locations. We also introduce a new, nondisruptive crossover operator emerging from the ptGA gene structure with adaptive crossover rate, location, and number of crossover sites. For experimental comparisons of this genetic operator to conventional crossover in GAs, as well as properties of different ptGA chromosome structures, an artificial problem from the literature is utilized. Finally, the potential of ptGA is demonstrated on an NP-complete combinatorial optimization problem. PMID- 10030471 TI - Parity with what? PMID- 10030470 TI - Putting more genetics into genetic algorithms. AB - The majority of current genetic algorithms (GAs), while inspired by natural evolutionary systems, are seldom viewed as biologically plausible models. This is not a criticism of GAs, but rather a reflection of choices made regarding the level of abstraction at which biological mechanisms are modeled, and a reflection of the more engineering-oriented goals of the evolutionary computation community. Understanding better and reducing this gap between GAs and genetics has been a central issue in an interdisciplinary project whose goal is to build GA-based computational models of viral evolution. The result is a system called Virtual Virus (VIV). VIV incorporates a number of more biologically plausible mechanisms, including a more flexible genotype-to-phenotype mapping. In VIV the genes are independent of position, and genomes can vary in length and may contain noncoding regions, as well as duplicative or competing genes. Initial computational studies with VIV have already revealed several emergent phenomena of both biological and computational interest. In the absence of any penalty based on genome length, VIV develops individuals with long genomes and also performs more poorly (from a problem-solving viewpoint) than when a length penalty is used. With a fixed linear length penalty, genome length tends to increase dramatically in the early phases of evolution and then decrease to a level based on the mutation rate. The plateau genome length (i.e., the average length of individuals in the final population) generally increases in response to an increase in the base mutation rate. When VIV converges, there tend to be many copies of good alternative genes within the individuals. We observed many instances of switching between active and inactive genes during the entire evolutionary process. These observations support the conclusion that noncoding regions serve as scratch space in which VIV can explore alternative gene values. These results represent a positive step in understanding how GAs might exploit more of the power and flexibility of biological evolution while simultaneously providing better tools for understanding evolving biological systems. PMID- 10030472 TI - Use of risperidone and olanzapine in outpatient clinics at six Veterans Affairs hospitals. PMID- 10030473 TI - Gambling behavior in youths: why we should be concerned. PMID- 10030474 TI - Novel antipsychotic medications in the treatment of children and adolescents. PMID- 10030475 TI - Web sites worth watching. PMID- 10030476 TI - Mental health capitation for children and adolescents under Medicaid. PMID- 10030477 TI - Missing out on motherhood. PMID- 10030478 TI - A review of bipolar disorder among adults. AB - OBJECTIVE: This paper reviews the epidemiology, etiology, assessment, and management of bipolar disorder. Special attention is paid to factors that complicate treatment, including noncompliance, comorbid disorders, mixed mania, and rapid cycling. Advances in biopsychosocial treatments are briefly reviewed, including new health service models for providing care. METHODS: A MEDLINE search was done for the period from January 1988 through October 1997 using the key terms of bipolar disorder, diagnosis, and treatment. Papers selected for further review included those published in English in peer-reviewed journals. Preference was given to articles reporting randomized, controlled trials. RESULTS: Bipolar disorder is a major public health problem. The etiology of the disorder appears multifactorial. Diagnosis often occurs years after onset of the disorder. Comorbid conditions are common. Management includes a lifetime course of medication and attention to psychosocial issues for patients and their families. Standardized treatment guidelines for the management of acute mania have been developed. New potential treatments are being investigated. CONCLUSIONS: Assessment of bipolar disorder must include careful attention to comorbid disorders and predictors of compliance. Randomized trials are needed to further evaluate the efficacy of medication, psychosocial interventions, and other health service interventions, particularly as they relate to the management of acute bipolar depression, bipolar disorder co-occurring with other disorders, and maintenance prophylactic treatment. PMID- 10030479 TI - Patterns of health care costs associated with depression and substance abuse in a national sample. AB - OBJECTIVE: The associations between self-reported depressive and substance use disorders and estimated health care costs were examined in a representative national sample. METHODS: Data were from the 1994 National Health Interview Survey (N=77,183). Respondents who reported depressive symptoms or major depression (depressive syndromes) or a substance abuse disorder in the past year were compared with respondents who did not report these conditions. The mean number of inpatient days and outpatient visits in both the general medical and the specialty mental health settings were determined, and costs per individual were calculated based on mean costs of such care in each respondent's geographic region. Multivariate models were constructed to calculate mean costs, controlling for demographic variables, insurance coverage, and physical health status. RESULTS: Individuals with self-reported depressive syndromes or substance abuse had mean health care costs that were $1,766 higher than costs for individuals without these conditions. Depressive syndromes were associated with increases in both inpatient and outpatient costs. However, substance abuse was almost exclusively associated with increased inpatient expenditures rather than outpatient costs. The magnitude of increased costs associated with mental disorders was substantially larger for patients in fee-for-service plans than for those in health maintenance organizations. Only 14.3 percent of visits made by individuals reporting depressive syndromes or substance abuse were made to specialty health providers (psychiatrists, psychologists, and social workers). CONCLUSIONS: Health care costs of people with self-reported mental illness varied significantly across diagnoses and systems of care. It is crucial that researchers estimating increased costs associated with mental illness account for both diagnostic and system factors that can influence the estimates. PMID- 10030480 TI - Therapeutic alliance and psychiatric severity as predictors of completion of treatment for opioid dependence. AB - OBJECTIVE: The role of patient characteristics and the strength of the therapeutic alliance in predicting completion of treatment by opioid-dependent patients was examined. METHODS: Information about patient characteristics and scores on subscales of the Addiction Severity Index (ASI) were obtained for 114 patients at intake to a buprenorphine treatment program lasting three to four months. The strength of the therapeutic alliance was assessed by the Helping Alliance Questionnaire (HAQ). Patients were classified as treatment completers or noncompleters, and logistical regression examined predictors of treatment completion. RESULTS: Only two variables significantly predicted treatment completion: severity of psychiatric symptoms and interaction between HAQ scores and psychiatric severity. Patients with fewer psychiatric symptoms were more likely to complete treatment. The strength of the therapeutic alliance was not related to treatment completion among patients with few psychiatric symptoms, and 62 percent of these patients completed treatment. In contrast, among patients with moderate to severe psychiatric problems, less than 25 percent with weak therapeutic alliances completed treatment, while more than 75 percent with strong therapeutic alliances completed treatment. CONCLUSIONS: The results underscore the importance of early identification of opioid-dependent patients with moderate to severe levels of psychopathology. In this patient subgroup, a strong therapeutic alliance may be an essential condition for successful treatment. PMID- 10030481 TI - Treatment costs and patient outcomes with use of risperidone in a public mental health setting. AB - OBJECTIVE: Risperidone's effectiveness in reducing symptoms and its cost were compared with the effectiveness and cost of standard antipsychotic medication among matched groups of outpatients with schizophrenia. METHODS: Data on 56 subjects started on risperidone were compared with data for a matched group of 56 subjects over the 12 months before and after initiation of risperidone. Global Assessment of Functioning (GAF) scores were used to assess effectiveness. Service utilization data were used to calculate the cost of treatment. RESULTS: Total treatment costs for the two groups were not significantly different, although there was a trend toward higher costs in the risperidone group. Monthly GAF scores revealed no group differences in the effectiveness of the medications. CONCLUSIONS: No significant differences in treatment effectiveness or costs were found between the risperidone and comparison groups, despite a trend to higher treatment costs for the risperidone group. PMID- 10030482 TI - Services to families of adults with schizophrenia: from treatment recommendations to dissemination. AB - OBJECTIVE: Data from the Schizophrenia Patient Outcomes Research Team project were examined to determine the extent to which families of adults with schizophrenia receive services and whether training staff in the provision of family services increases service availability. METHODS: For patients with a diagnosis of schizophrenia, paid claims for family therapy were identified in 1991 in a nationally representative sample of Medicare data and one state's Medicaid data. In a field study in two states, 530 patients were asked about services received by their families. A quasiexperimental dissemination of a family intervention was done at nine agencies; staff at four agencies received a standard didactic presentation, and staff at five received that standard presentation paired with intensive training. RESULTS: In the representative national Medicare sample of 15,425 persons with schizophrenia, .7 percent (N=108) had an outpatient claim for family therapy. This figure was 7.1 percent in the Medicaid sample of 5,393 persons with schizophrenia in one state. Of the 530 patients in the field study who reported having contact with their families, 159 (30 percent) reported that their families had received information, advice, or support about their illness, and 40 (8 percent) responded that their families had attended an educational or support program. At the four agencies where staff received only didactic training, no changes in family services were found after one year. Three of the five agencies where staff participated in intensive training enhanced their family services. CONCLUSIONS: A minority of families of persons with schizophrenia receive information about the illness from providers. Implementation of model family interventions is possible with considerable technical assistance. A gap exists between best practices and standard practices for families of persons with schizophrenia. PMID- 10030483 TI - Parenting and adjustment in schizophrenia. AB - OBJECTIVE: Patients with schizophrenia who became parents and those who remained childless were compared on premorbid characteristics and current clinical and social adjustment. METHODS: Subjects were 400 men and women with a DSM-III-R diagnosis of chronic schizophrenia based on the Structured Clinical Interview for DSM-III-R (SCID). Assessments measured concurrent substance abuse and antisocial behavior, positive and negative symptoms using the Positive and Negative Syndrome Scale, functional status using the Global Assessment of Functioning scale, family support, and treatment compliance. A total of 158 patients were parents (47 men and 111 women), and 242 were childless (153 men and 89 women). RESULTS: Compared with childless subjects, parents were more likely to have had better premorbid social adjustment, to have ever been married or involved in a conjugal relationship, and to have become ill at a later age. More than two-thirds of parents entered parenthood before the onset of schizophrenia. More women than men were parents, and parents were more likely to be members of ethnic minority groups. No differences were found in current clinical and social adjustment of parents and childless subjects. CONCLUSIONS: Parenthood was associated with better premorbid social adjustment, but it conferred no advantage in the long term course of schizophrenia. Patients who experience a later onset of schizophrenia or have better premorbid social skills may be more likely to undertake marriage and parenthood, but they will then also be more likely to need special support for the parenting role once the illness begins and takes its typical course. PMID- 10030484 TI - Subgroups of frequent users of an inpatient mental health program at a community hospital in Canada. AB - OBJECTIVE: The study examined demographic and clinical characteristics of frequent users of mental health services at a large community hospital in an urban-suburban area in Canada to identify subgroups within this patient population. METHODS: Patients who had had three or more inpatient admissions over any 12-month period between January 1, 1993, and December 31, 1995, were included in the study. Medical records were reviewed to collect summary data on 23 variables encompassing demographic characteristics and admission and discharge information. Quick cluster analysis was performed to identify subgroups within the frequent-user population. Chi square tests and analysis of variance were used to analyze group differences between clusters. RESULTS: Three patient subgroups accounted for 67 of the 83 patients (80.7 percent) identified as frequent users. Admission patterns were the strongest predictors of subgroup differences. CONCLUSIONS: Identifying subgroups within the frequent-user population may help in developing appropriate treatment and discharge plans with the aim of reducing the need for frequent utilization of inpatient mental health services. PMID- 10030485 TI - Intensity and continuity of services and functional outcomes in the rehabilitation of persons with schizophrenia. AB - OBJECTIVE: The intensity and continuity of services delivered to individual clients in a community-based psychosocial rehabilitation program were examined in relationship to functional changes in the clients that occurred during the first 12 months of the program. METHODS: Subjects were 41 clients with schizophrenia or schizoaffective disorder who were admitted to an intensive psychosocial rehabilitation program. Measures of clinical and psychosocial functioning were derived from client interviews administered at baseline and six and 12 months later. Measures of service intensity and continuity came from data gathered daily by staff over 12 months. RESULTS: The results supported the hypotheses that greater intensity and longitudinal continuity of services are related to more client improvement as indicated by reduced rates of hospitalization and improved psychosocial functioning after both six and 12 months. Although clients' symptom levels increased over time, a significant relationship was noted between service intensity and continuity and better symptom outcomes after 12 months. Multiple regression analyses indicated that an average of 22 percent, and as much as 28 percent, of the change in clinical and functional outcomes after 12 months of rehabilitation was explained by the intensity and longitudinal continuity of services. CONCLUSIONS: Clients who received more contact hours with staff and who had fewer gaps in service delivery achieved greater rehabilitative improvement in social, work, and independent-living domains and had fewer days of hospitalization. Based on these findings, clinicians, administrators, and researchers can assume that the intensity and longitudinal continuity of services are important to achieving rehabilitative outcomes in some community-based psychosocial rehabilitation models. PMID- 10030486 TI - Demographic differences in medication use among individuals with self-reported major depression. AB - In a nationally representative household-based sample, more than one-third of those who identified themselves as having major depression reported not taking any medications in the last year. Male gender, minority status, excellent health, and being at either end of the age continuum were associated with nonuse of medication. Lower-income, widowed, and never-married individuals showed a trend toward being less likely to use medication. The results suggest the need to further assess the role of potential factors in the limited use of medication among various demographic subgroups of individuals who identify themselves as being depressed. PMID- 10030487 TI - Experience with a rural telepsychiatry clinic for children and adolescents. AB - Access to child and adolescent psychiatric services in many rural areas is limited by lack of physicians and long travel times. A child and adolescent telepsychiatry clinic that is part of the University of Kansas Medical Center's telemedicine program addresses this problem by linking the medical center with a county mental health center in rural Pittsburg, Kansas. The clinic receives ten to 18 visits a week and has been able to serve severely disturbed children and children in crisis. The quality of clinical interactions in the telepsychiatry clinic appears comparable to that in face-to-face meetings. PMID- 10030488 TI - The prevalence of low literacy in an indigent psychiatric population. AB - Research has shown that individuals with low or limited literacy experience significant obstacles in gaining access to and using health care services. In a study of the prevalence of low literacy in an indigent psychiatric population, 45 patients seeking mental health services at a shelter-based clinic for the homeless were given the Rapid Estimate of Adult Literacy in Medicine screening test. Thirty-four participants (76 percent) read at or below the seventh- to eighth-grade level. Ten patients in this low-literacy group (29 percent) reported that they read "very well," 16 (47 percent) that they read "well," and eight (24 percent) that they read "not well." The results suggest the need for providers to consider formal screening for low literacy in clinical settings. PMID- 10030489 TI - A survey of psychiatrists' attitudes toward electroconvulsive therapy. AB - Sixty-seven psychiatrists who were employed in state hospitals in Texas were surveyed about their attitudes toward use of electroconvulsive therapy (ECT) and the laws and regulations associated with its use. The majority of respondents agreed with accepted professional guidelines on ECT usage and had a positive attitude toward ECT treatment. However, the number of referrals for ECT by these psychiatrists was low, perhaps due to the view that Texas laws and policies about ECT are restrictive and limiting to patient care. The majority of respondents indicated that more professional education about laws and policies related to ECT is needed. PMID- 10030490 TI - Defending telepsychiatry. PMID- 10030491 TI - Defending telepsychiatry. PMID- 10030492 TI - Defending telepsychiatry. PMID- 10030493 TI - Treating the least well off. PMID- 10030494 TI - Treating the least well off. PMID- 10030495 TI - A jail diversion program. PMID- 10030496 TI - Study finds widespread implementation of managed behavioral health care programs in the public sector. PMID- 10030497 TI - Attention-deficit hyperactivity disorder subject of new consensus statement from National Institutes of Health. PMID- 10030498 TI - Federal task force says lack of health care coverage is major barrier to employment of persons with disabilities. PMID- 10030499 TI - FDA to require pediatric studies for drugs commonly used in children. PMID- 10030500 TI - Rules set for dissemination of off-label-use information. PMID- 10030501 TI - Lyme disease vaccine cleared for marketing. PMID- 10030502 TI - Pharmacy technician helps cancer patients look good. PMID- 10030503 TI - Guiding patients through the maze of drug information on the Internet. PMID- 10030504 TI - Responsibility for medication errors. PMID- 10030505 TI - Ropinirole: a dopamine agonist for the treatment of Parkinson's disease. AB - The pharmacology, pharmacokinetics, clinical efficacy, adverse effects, dosage and administration, and formulary considerations of ropinirole are reviewed. Ropinirole is a nonergoline dopamine agonist that binds to dopamine D2-receptors; the drug is indicated for use in the symptomatic treatment of early and late Parkinson's disease (PD). Ropinirole is rapidly absorbed after oral administration and undergoes extensive hepatic metabolism to active metabolites. The elimination half-life averages about six hours. Ropinirole has a low potential to interact with other drugs likely to be administered to PD patients. In patients with early PD, initial monotherapy with ropinirole was more effective than placebo or bromocriptine in the absence of selegiline and was as effective as bromocriptine in the presence of selegiline. Ropinirole was as effective as levodopa in patients with earlier stages of PD. In one subset of patients with advanced PD not adequately controlled by levodopa, adjunctive ropinirole was more effective than placebo and bromocriptine. Ropinirole was more effective than bromocriptine in patients previously given high-dose levodopa and was as effective in patients previously given low-dose levodopa or adjunctive dopamine agonist therapy. The most frequent adverse effects are nausea, somnolence, and dizziness; the dosage should be increased gradually to minimize adverse effects. Ropinirole is less expensive than bromocriptine and pergolide and similar in cost to pramipexole. Ropinirole appears to be a useful addition to existing therapeutic approaches to PD and is approved for both early and later stages of the disease. PMID- 10030506 TI - Work patterns of ambulatory care pharmacists with access to electronic guideline based treatment suggestions. AB - The effects of the electronic display of guideline-based, patient-specific treatment suggestions on pharmacist work patterns were studied. A total of 28 pharmacists at a hospital-based ambulatory care pharmacy were randomly assigned to intervention and control groups. The intervention group had access to electronic treatment suggestions for heart failure, ischemic heart disease, reactive airways disease, and uncomplicated hypertension, while the control group did not. Starting 9 and 19 months after the initial display of treatment suggestions, all pharmacists recorded the time they spent on a variety of activities, the purpose of each activity, and persons contacted during the activity; these observations were recorded in response to a pager-like device that randomly buzzed four times an hour. A total of 11,102 observations were recorded. Pharmacists in the intervention group spent significantly more of their time discussing information, advising and informing, and solving problems than pharmacists in the control group but significantly less of their time checking and filling prescriptions. Pharmacists in both groups completed a majority of their work alone, but pharmacists in the intervention group worked significantly less by themselves and significantly more with other pharmacy personnel, patients, and physicians and nurses than control-group pharmacists. The delivery of patient-specific information to pharmacists at the time of dispensing had a significant positive impact on pharmacist work patterns. PMID- 10030507 TI - Health care costs associated with chronic hepatitis B. AB - The long-term health care costs of patients with chronic hepatitis B (CHB) were compared with those of patients without CHB. Patients with laboratory markers for CHB were identified from an HMO database and matched with up to four control patients (either not tested for hepatitis B infection or with negative test results). Cost data were collected retrospectively for both groups of patients for the period up to 30 days before identification of the first marker for hepatitis B (prediagnosis), 30 days before identification of the first marker through 180 days after the identification (peridiagnosis), and 181 days after identification through the end of the six-year study period. Costs were categorized as emergency room, inpatient, short-stay inpatient, laboratory, radiology, office visit, pharmacy, outside claim, or other and were analyzed as ratios of the costs of each patient with CHB to the median of the corresponding control patients. Eighty-eight patients were identified as having CHB; there were 342 control patients. In the seven months surrounding the appearance of their first diagnostic marker, the patients with CHB had costs 3.3 times those of the corresponding control patients and, after the first seven months, 2.9 times those of the control patients per month. Peridiagnosis costs in the categories of laboratory, radiology, office visits, and pharmacy were significantly higher for patients with CHB than for control patients. Except for emergency room costs, postdiagnosis costs per month of the patients with CHB were significantly higher than those of the corresponding control patients. Examination of an HMO database showed that, compared with patients without CHB, patients with CHB had significantly higher health care costs around and after the CHB diagnosis. PMID- 10030508 TI - Therapeutic selection during an emergency response. AB - Therapeutic selection in a postdisaster setting is described. Therapeutic selection is the process of assessing a patient's pharmaceutical requirements and selecting the appropriate therapy. Although the primary criteria for drug selection during a disaster response are the same as in usual pharmacy practice, there is a shift in emphasis created by communication and transportation limitations and by changes in the patient's general living environment. The cost of agents is no longer viewed in terms of dollars but in the context of limited inventories. A disaster may exacerbate health problems or make adverse drug effects more common and problematic. Drug administration and patient compliance will be hampered. Pre-established guidelines for appropriate patient care should be reviewed and approved by a group of representative health care providers. General policies for pharmaceutical care should include guidelines for a formulary, prescription refills, dispensing limitations, and prescriber approval. Therapeutic selection should involve obtaining a medical history, selecting a drug regimen, educating and counseling the patient, and documenting the process. Pharmacists should use familiar procedures that they are comfortable with to minimize stress and optimize outcomes. Procedures should be flexible to adjust to circumstances and individual patient needs. Therapeutic selection during a disaster response, although based on the same principles as traditional therapeutic selection, is more complex. Pharmacists will need to tailor their approach to the circumstances and to individual patient needs. PMID- 10030509 TI - Stability of lamotrigine in two extemporaneously prepared oral suspensions at 4 and 25 degrees C. AB - The stability of lamotrigine 1 mg/mL in two extemporaneously prepared oral suspensions at 4 and 25 degrees C was studied. Lamotrigine tablets were ground to powder, and the powder was combined with a 1:1 mixture of Ora-Sweet and Ora-Plus or a 1:1 mixture of Ora-Sweet SF and Ora-Plus (Paddock Laboratories) to produce two 1-mg/mL suspensions. One 100-mg lamotrigine tablet was used to prepare one 100-mL batch of each suspension. The suspensions were stored in amber polyethylene terephthalate prescription bottles at 4 or 25 degrees C. Samples were collected on days 0, 7, 14, 28, 42, 56, 70, and 91 for analysis of lamotrigine content by high-performance liquid chromatography; pH was measured, and the samples were visually observed against a black and white background. The mean concentration of lamotrigine was >99% of the initial concentration in all samples throughout the 91-day study period; there was no change in apparent pH, odor, or physical appearance. Lamotrigine 1 mg/mL in two extemporaneously compounded oral suspensions was stable for 91 days in polyethylene terephthalate prescription bottles at 4 and 25 degrees C. PMID- 10030510 TI - Stability of terbinafine hydrochloride in an extemporaneously prepared oral suspension at 25 and 4 degrees C. AB - The stability of terbinafine 25 mg/mL (as the hydrochloride salt) in an extemporaneously prepared oral suspension at 25 and 4 degrees C was studied. Twenty 250-mg terbinafine tablets were crushed to a fine powder and diluted to a concentration of 25 mg/mL with sweetened vehicle. The suspension was stored in amber polyethylene prescription bottles at 25 or 4 degrees C. Samples were taken on days 0, 7, 14, 28, 42, 56, 70, and 91 for duplicate analysis of terbinafine content by high-performance liquid chromatography and to observe any changes in color and odor; pH was measured as well. Through the initial 42 days, the mean concentration of terbinafine in the samples stored at both temperatures was >93% of the initial concentration; by day 56, the mean concentration was <88%. No appreciable changes in color or odor were observed during the study period. The apparent pH of the suspension decreased slightly over the 91 days, from an initial 5.6 to 5.5. Terbinafine 25 mg/mL (as the hydrochloride salt) in an extemporaneously prepared oral suspension was stable for up to 42 days in polyethylene prescription bottles at 25 and 4 degrees C. PMID- 10030511 TI - Stability of high-dose vancomycin and ceftazidime in peritoneal dialysis solutions. PMID- 10030512 TI - Clinical research: business opportunities for pharmacy-based investigational drug services. AB - The application by an academic health center of business principles to the conduct of clinical research is described. Re-engineering of the infrastructure for clinical research at the University of Wisconsin and University of Wisconsin Hospital and Clinics began in 1990 with the creation of the Center for Clinical Trials (CCT) and the restructuring of the investigational drug services (IDS). Strategies to further improve the institution's clinical research activities have been continually assessed and most recently have centered on the adaptation of a business philosophy within the institution's multidisciplinary research infrastructure. Toward that end, the CCT and IDS have introduced basic business principles into operational activities. Four basic business concepts have been implemented: viewing the research protocol as a commodity, seeking payment for services rendered, tracking investments, and assessing performance. It is proposed that incorporation of these basic business concepts is not only compatible with the infrastructure for clinical research but beneficial to that infrastructure. The adaptation of a business mindset is likely to enable an academic health center to reach its clinical research goals. PMID- 10030513 TI - Clinical research: regulatory issues. AB - The regulatory issues faced by institutions performing clinical research are described. Many institutions do not have on staff an expert who understands the regulatory issues involved in managing investigational new drug research and who knows the institution's obligations under the federal rules. Because pharmacists understand the FDA regulations that apply to the management of drugs in clinical research, institutions are asking pharmacists to expand their role and manage clinical research offices. Many authorities govern various aspects of investigational drug research. FDA has published regulations for good clinical practice (GCP), and the International Conference on Harmonisation is developing an international standard for the proper management of clinical trials. The guidelines published by the Joint Commission on Accreditation of Healthcare Organizations aim to protect patients who are in the institution to receive health care and also participate in clinical trials. The Social Security Administration Acts specifically state that only items and services that are reasonable and necessary for the diagnosis and treatment of injury or disease can be billed to the government; research-related billings are excluded from coverage. Proper management of drug research is crucial to the success of a research program that is integrated with patient care. PMID- 10030514 TI - Reimbursement for unlabeled medication use. PMID- 10030515 TI - The pharmacist and assisted suicide. PMID- 10030516 TI - Glucosamine sulfate use in osteoarthritis. PMID- 10030517 TI - Preparing for parenteral nutrition therapy at home. PMID- 10030518 TI - Simultaneous use of two protease inhibitors in HIV infection. PMID- 10030519 TI - Expensive lesson in administration of goserelin implant. PMID- 10030521 TI - Current literature. PMID- 10030520 TI - Response rates from poster presenters at ASHP meetings. American Society of Health-System Pharmacists. PMID- 10030523 TI - Requirements for FDA-approved patient information spelled out in final rule. PMID- 10030522 TI - Decisions loom on selective COX-2 inhibitors. PMID- 10030524 TI - Panel finds inconsistencies in ADHD care. PMID- 10030526 TI - New sexual harassment rules under Title VII of the Civil Rights Act of 1964. PMID- 10030525 TI - Growing popularity of alternative medicine documented in new survey. PMID- 10030527 TI - Echinacea. PMID- 10030528 TI - Mirror to health-system pharmacy. PMID- 10030529 TI - Unsafe and potentially safe herbal therapies. AB - Unsafe and potentially safe herbal therapies are discussed. The use of herbal therapies is on the rise in the United States, but most pharmacists are not adequately prepared educationally to meet patients' requests for information on herbal products. Pharmacists must also cope with an environment in which there is relatively little regulation of herbal therapies by FDA. Many herbs have been identified as unsafe, including borage, calamus, coltsfoot, comfrey, life root, sassafras, chaparral, germander, licorice, and ma huang. Potentially safe herbs include feverfew, garlic, ginkgo, Asian ginseng, saw palmetto, St. John's wort, and valerian. Clinical trials have been used to evaluate feverfew for migraine prevention and rheumatoid arthritis; garlic for hypertension, hyperlipidemia, and infections; ginkgo for circulatory disturbances and dementia; ginseng for fatigue and cancer prevention; and saw palmetto for benign prostatic hyperplasia. Also studied in formal trials have been St. John's wort for depression and valerian for insomnia. The clinical trial results are suggestive of efficacy of some herbal therapies for some conditions. German Commission E, a regulatory body that evaluates the safety and efficacy of herbs on the basis of clinical trials, cases, and other scientific literature, has established indications and dosage recommendations for many herbal therapies. Pharmacists have a responsibility to educate themselves about herbal therapies in order to help patients discern the facts from the fiction, avoid harm, and gain what benefits may be available. PMID- 10030530 TI - ASHP national survey of pharmacy practice in acute care settings: prescribing and transcribing--1998. American Society of Health-System Pharmacists. AB - Results of the 1998 ASHP national survey of pharmacy practice in acute care settings that pertain to prescribing and transcribing practices are presented. Pharmacy directors at 1058 general and children's medical-surgical hospitals in the United States were surveyed by mail. Data on hospital characteristics were supplied by SMG Marketing Group, Inc.; the survey sample was drawn from SMG's hospital database. The response rate was 51.8%. Respondents reported that at least 90% of hospital and health-system pharmacy and therapeutics (P&T) committees are responsible for formulary development and management, drug policy development, medication-use evaluation, adverse-drug-reaction reporting, and medication error monitoring. More than 90% of the facilities use pharmacoeconomic, clinical and therapeutic, and cost information in formulary development; 83% have a medication-use-evaluation program designed to improve prescribing; more than 95% have P&T committees, infection control committees, and quality control committees; and more than 80% provide pharmacist consultations on drug information, dosage adjustments for patients with renal impairment, antimicrobials, and pharmacokinetics. A majority of respondents reported that accurate transcription of medication orders is ensured by use of standardized physician order forms, clarification of illegible orders, reconciliation of medication administration records (MARs) and pharmacy profiles at least daily, and use of computer-generated MARs. The 1998 ASHP survey results suggest that pharmacists in acute care settings have positioned themselves well to improve the prescribing and transcription components of the medication-use process. PMID- 10030531 TI - Management of adolescent and adult inpatients with cystic fibrosis. AB - A program in which pharmacists help care for cystic fibrosis patients is described. The Egleston Cystic Fibrosis Center at Emory University houses outpatient clinic facilities and a 10-bed inpatient unit and is affiliated with Egleston Children's Hospital. The center provides full-service care for nearly 500 patients. Patients with mild to moderate exacerbations of pulmonary problems can receive their entire course of therapy at the center, and those with severe illness may complete their hospital stay there. A care team consisting of pharmacists, physicians, nurses, and others provides preventive and acute care. Patients can choose a "care partner" who will assist them with their care during any hospitalizations and at home. Both patient and care partner are taught drug administration, nutrition, and physical therapy and meet regularly with the care team. Patients must receive their medication education from a pharmacist before they can administer their own drugs. Pharmacists at the center also evaluate serum drug concentrations, stock the automated dispensing device, monitor for drug interactions, answer drug information questions, and attend multidisciplinary rounds. Pharmacy residents can work with the care team through rotations and clinic experience. Pharmacists at a cystic fibrosis center provide clinical services to patients and promote self-care. PMID- 10030532 TI - Relationships between aminoglycoside and vancomycin pharmacokinetics in patients with hematopoietic stem-cell transplants. PMID- 10030533 TI - Stability of tacrolimus with morphine sulfate, hydromorphone hydrochloride, and ceftazidime during simulated intravenous coadministration. PMID- 10030534 TI - Clinical research: managing the issues. PMID- 10030535 TI - Clinical research: trends affecting the pharmaceutical industry and the pharmacy profession. PMID- 10030536 TI - Phenobarbital for alcohol withdrawal syndrome. PMID- 10030537 TI - Pharmacist positions in Saudi Arabia. PMID- 10030538 TI - Other sources of stability research. PMID- 10030539 TI - Other sources of stability research. PMID- 10030540 TI - Correlates of protection: the crosstalk between immunology and medical microbiology. PMID- 10030541 TI - Iscom is an efficient mucosal delivery system for Mycoplasma mycoides subsp. mycoides (MmmSC) antigens inducing high mucosal and systemic antibody responses. AB - The purpose of this study was to explore the iscom as a mucosal delivery system for Mycoplasma mycoides subsp. mycoides small colony (MmmSC) antigens. BALB/c female mice were immunised intranasally (i.n.) twice, 8 weeks apart with three different doses (3, 10 and 20 microg) or subcutaneously (s.c.) with 3 microg of M. mycoides antigens incorporated into iscoms. Mycoplasma cells were administered s.c. twice, 8 weeks apart at a dose of 3 microg or i.n. at 10 microg as for iscoms. Both i.n. and s.c. modes of immunisation with iscoms induced prominent primary serum antibody responses in a dose-dependent manner, which were efficiently boosted. Compared to whole mycoplasma cells, iscoms enhanced the total Ig and IgG subclass (IgG1, IgG2a and IgG2b) responses in serum and in lungs greatly, and this enhancement was more prominent after i.n. than after s.c. immunisation. By the i.n. mode of immunisation iscoms containing mycoplasma antigens induced a 60-fold higher IgA response in lungs than the whole cell antigen. Iscoms also induced substantially higher total Ig and IgG subclass responses in the lungs. By Western blot a reduced number of bands (7) were detected in lung secretion after both i.n. and s.c. immunisations with iscoms compared to a high number of bands (more than 30) detected by serum antibodies. Interestingly i.n. immunisation with iscoms induced antibodies in lungs as well as in serum to mycoplasma cell antigens which differed from those induced by s.c. immunisation as revealed by the Western blot patterns. PMID- 10030542 TI - Carriage of Neisseria meningitidis and Neisseria lactamica among ethnic Greek school children from Russian immigrant families in Athens. AB - During February and March 1995, a survey of meningococcal carriage in 625 school children was carried out in a suburb of Athens in which there was a large number of ethnic Greeks who had immigrated from Russia beginning in the early 1990s. The objectives of the study were: (1) to determine if factors associated with carriage of meningococci observed in a previous study of Greek school children were similar for the immigrant population; (2) to compare phenotypic characteristics of meningococci from the immigrant population with those isolated from children in Athens. Overall isolation rate for meningococci was 82/625 (13.1%), significantly higher than that found for school children in Athens (5.8%) during the winter of 1990 1991 (5.8%) (chi=25.98, P=0.0000003). By univariate analysis, carriage was not associated with sex, number of individuals per household, blood group, secretor status, socioeconomic level or maternal smoking; however, it was associated with fathers' smoking. The high proportion of men who smoked compared with the low proportion of women smokers might contribute to this finding. The main serogroup of meningococci isolated from this population was A (28%). While serogroup A appears to be more prevalent among Russian and Kurdish immigrants (14%) than among Greek school children or military recruits (4%), there has not been an increase in group A meningococcal disease in Greece. The isolation rate for N. lactamica was high 105/625 (17.3%). A few of these strains bound some of the monoclonal antibodies used for meningococcal serotyping and subtyping, and they are being examined in greater detail. PMID- 10030543 TI - Low molecular mass protein patterns in mycobacterial culture filtrates and purified protein derivatives. AB - Mycobacterial polypeptides from 2 kDa to 14 kDa may be involved in host response to infection and be useful for new diagnostics and vaccines. Tris-tricine SDS polyacrylamide gel electrophoresis separation of proteins in tuberculin purified protein derivative (PPD) and in 6-8-week culture filtrates of Mycobacterium tuberculosis, Mycobacterium bovis BCG, and other Mycobacterium species demonstrated as many as 10 low molecular mass bands. Common and distinct bands were observed among different species and PPD. These low molecular mass culture filtrate proteins may represent potential diagnostic reagents and vaccines for Mycobacterium tuberculosis. PMID- 10030545 TI - Postantibiotic effects of rifampin, amikacin, clarithromycin and ethambutol used alone or in various two-, three- and four-drug combinations against Mycobacterium avium. AB - The postantibiotic effects (PAEs) of rifampin, amikacin, clarithromycin, and ethambutol were determined radiometrically against five AIDS-associated isolates of Mycobacterium avium. and were found to be 20.8+/-3.4. 18.4+/-2.5, 11.8+/-1.7. and 2.4+/-0.9 h, respectively. Various two-, three- or four-drug combinations were also screened: the PAEs for a two-drug combination were generally longer than individual drugs (mean PAE of 13.8+/-1.5 to 29.2+/-7.4 h instead of 2.4+/ 0.9 to 18.4+/-2.5 h for single drugs). The addition of a third drug further increased the mean PAE to a range of 21.0+/-2.6 to 32.4+/-6.1 h. Both rifampin+clarithromycin and rifampin+amikacin were the most potent two-drug combinations resulting in longer PAEs than individual drugs, whereas rifampin+amikacin+clarithromycin was the most potent three-drug combination. Parallel viable count determinations showed a good correlation between the PAE results obtained by the radiometric method or by bacterial viability assessment. These results are useful in planning future clinical investigations to clarify the possible implication of PAE in drug schedule and dosage, a line of information that is urgently needed to guide the drug administration in M. avium infected AIDS patients, who are presently over-burdened with the administration of too many drugs for HIV-treatment and opportunistic infections. PMID- 10030544 TI - The effect of cigarette smoke on adherence of respiratory pathogens to buccal epithelial cells. AB - Smoking is associated with an increased risk of respiratory tract infection in adults. In children, exposure to cigarette smoke is a risk factor for respiratory tract infection and bacterial meningitis: Active smoking and passive exposure to cigarette smoke is also associated with carriage of some potentially pathogenic species of bacteria in both adults and children. The aims of the study were to determine the effect of active smoking on: (1) bacterial binding to epithelial cells; (2) expression of host cell antigens that act as receptors for some species; and (3) the effects of passive exposure to water-soluble components of cigarette smoke on bacterial binding. Flow cytometry was used to assess binding to buccal epithelial cells of the following species labelled with fluorescein isothiocyanate: Neisseria meningitidis, Neisseria lactamica, Streptococcus pneumoniae, Bordetella pertussis, Haemophilus influenzae, Moraxella catarrhalis, Staphylococcus aureus. Flow cytometry was also used to assess expression of host cell antigens which have been identified as bacterial receptors. For each species, binding to cells of smokers was significantly higher than to cells of non-smokers; however, expression of host cell antigens was similar on epithelial cells of both groups. Non-dilute cigarette smoke extract reduced binding of bacteria to epithelial cells, but dilutions between 1 in 10 and 1 in 320 enhanced binding. We conclude that smokers might be more densely colonised by a variety of potentially pathogenic bacteria. The enhanced bacterial binding to epithelial cells of smokers is not related to enhanced expression of host cell antigens that can act as receptors for some species, but possibly to components in the smoke that alter charge or other properties of the epithelial cell surface. Passive coating of mucosal surfaces with components of cigarette smoke might enhance binding of potentially pathogenic bacteria. PMID- 10030546 TI - Direct detection of Clostridium perfringens enterotoxin in patients' stools during an outbreak of food poisoning. AB - An outbreak of diarrhoea in a hotel affected 25 time keepers attending the 1997 Mediterranean Games. Epidemiological investigation implicated a 'pasta al ragu' consumed at the hotel's restaurant and Clostridium perfringens food poisoning was identified by direct detection of C. perfringens enterotoxin in patients' stools. This report confirms that a careful evaluation of epidemiological features, together with the availability of direct and rapid laboratory methods, may lead to a prompt identification of C. perfringens food poisoning. PMID- 10030547 TI - Recent emergence of serogroup C meningococcal disease in Greece. AB - The number of cases of meningococcal disease reported to the Meningitis Reference Laboratory in Athens rose dramatically in 1996-1997. The aims were (1) to determine if the increase was due to introduction of new strains, (2) to assess the geographic and age distribution of the cases, (3) to compare antibiotic sensitivity patterns of the current isolates with strains from the early 1990s. In 1993-1994, 15/19 (74%) of the cases for which information on age was available were in children < or = 5 years; in 1995-1997, 80/179 (45%) of cases were in children < or = 5 years and 99 (55%) in the older age range (P < 0.02). From 593 cases in 1993 1997, 214 (36%) isolates were available for characterisation. Serogroup B was predominant in the early 1990s, but by 1997, serogroup C accounted for 46/72 (64%) of isolates and serogroup B for 25/72 (35%). Serogroup B was predominant in children < or = 5 years (44/78, 56%) but only 19/99 (18%) of older children and adults (P=0.0000005). Sulfonamide resistance decreased from 10/22 (45%) in 1993-1994 to 27/192 (14%) in 1995-1997 (P<0.01). Multilocus enzyme electrophoresis of 70 strains obtained during this period identified the epidemic ET-15 clone in 24 (34.3)%. The profiles of the Greek ET-15 isolates were identical to C:2a:P1.2(P1.5) strains responsible for the epidemic in the Czech Republic which began in 1993. This genotype was not found in Greek strains isolated prior to 1993. We conclude that the increase in meningococcal disease is due to introduction of the epidemic serogroup C:2a:P1.2(P1.5) strain responsible for disease in the Czech Republic and Canada. PMID- 10030548 TI - Transmission electron microscopy studies of Moraxella (Branhamella) catarrhalis. AB - A trypsin-sensitive 200-kDa protein has been reported to be exclusively associated with haemagglutinating isolates of Moraxella (Branhamella) catarrhalis. Transmission electron microscopy studies revealed that haemagglutination by M. catarrhalis to both human and rabbit erythrocytes was mediated by a trypsin-sensitive outer fibrillar coat. This fibrillar layer was absent on non-haemagglutinating isolates examined. Immuno-electron microscopy, using a polyclonal antiserum containing antibodies to the 200-kDa protein as a probe, showed that the 200-kDa protein is present on the outer fibrillar layer of the bacterium. These findings suggest that the haemagglutinin of M. catarrhalis is a 200-kDa protein present on the outer fibrillar coat. PMID- 10030549 TI - A typical bacterial ornithine-containing lipid Nalpha-(D)-[3 (hexadecanoyloxy)hexadecanoyl]-ornithine is a strong stimulant for macrophages and a useful adjuvant. AB - Nalpha-[3-(Hexadecanoyloxy)hexadecanoyl]-ornithine is a typical bacterial ornithine-containing lipid (OL). The configuration of the 3-hydroxy fatty acids in the OL was proved to be D by using HPLC with chiral column. For this analysis, Nalpha-(D or L)-[3-(hexadecanoyloxy)hexadecanoyl]-L-ornithine were synthesized and used as standards. The typical bacterial OL, as well as the synthesized one, exhibited strong interleukin-1- and prostaglandin E2-inducing activities, and further, it induced the production of high IgG anti-tetanus toxoid antibodies in mice. The typical OL is expected to be utilized as a nontoxic, potent adjuvant. PMID- 10030550 TI - Invasive infections due to Clavispora lusitaniae. AB - Three cases of Clavispora lusitaniae invasive fungal infections are reported. All three infections appeared in cancer patients presented with fungaemia, one additionally with meningitis. Two of them were breakthrough -- they developed during therapy with conventional amphotericin B with a dose of 0.5 mg kg(-1) day( 1) . All three were cured: two with intravenous fluconazol and one with an increasing dose (1 mg kg(-1) day(-1)) of amphotericin B. In one of two breakthrough cases the sensitivity of the strain to antifungals was tested against antifungal agents and showed in vitro resistance to amphotericin B (MIC 2 eta g ml(-1)). PMID- 10030551 TI - Peripapillary atrophy in primary angle-closure glaucoma: a comparative study with primary open-angle glaucoma. AB - PURPOSE: To investigate the characteristics of peripapillary atrophy in primary angle-closure glaucoma and to compare peripapillary atrophy in primary angle closure glaucoma with that in primary open-angle glaucoma. METHODS: Twenty-one eyes (of 21 patients) with chronic primary angle-closure glaucoma that had no evidence of an acute attack or combined-mechanism glaucoma and 31 eyes (31 patients) with primary open-angle glaucoma were enrolled in this study. The cup to-disk area ratio and the visual field mean deviation were matched in both groups. The prevalence of peripapillary atrophy and peripapillary atrophy-to-disk area ratio of eyes with primary angle-closure glaucoma and eyes with primary open angle glaucoma were compared. The correlation between the peripapillary atrophy area and the cup-to-disk area ratio or the mean deviation was also evaluated. RESULTS: Eight (38%) of 21 eyes with primary angle-closure glaucoma and 21 (68%) of 31 eyes with primary open-angle glaucoma had peripapillary atrophy. The peripapillary atrophy-to-disk area ratio averaged 0.16 in primary angle-closure glaucoma and 0.41 in primary open-angle glaucoma. There were statistically significant differences regarding the prevalence of peripapillary atrophy (P = .048) and peripapillary atrophy-to-disk area ratio (P = .005) between the two groups. There was no significant correlation between the peripapillary atrophy area and the cup-to-disk area ratio or the mean deviation in primary angle closure glaucoma. In contrast, the peripapillary atrophy-to-disk area ratio significantly correlated with the cup-to-disk area ratio (P = .003) and the mean deviation (P = .0001) in primary open-angle glaucoma. CONCLUSIONS: The peripapillary atrophy in primary angle-closure glaucoma has a different relationship to the structural and functional optic disk changes than that in primary open-angle glaucoma. Different mechanisms seem to be involved in the development of the optic disk damage in the two types of glaucoma. PMID- 10030552 TI - Flap complications associated with lamellar refractive surgery. AB - PURPOSE: Corneal lamellar refractive surgery for myopia reduces the risk of corneal haze but adds to the risk of flap complications. We retrospectively determined the incidence of flap complications in the initial series of eyes undergoing lamellar refractive surgery by one surgeon. We assessed the incidence of flap complications overall, the trend in these complications during the surgeon's learning curve, and the impact of the complications on best spectacle corrected visual acuity. METHODS: Charts of the first 1,019 eyes that underwent myopic keratomileusis in situ or laser in situ keratomileusis were reviewed for flap complications and visual outcome. RESULTS: Of the 1,019 eyes, 490 eyes underwent myopic keratomileusis in situ, and 529 eyes underwent laser in situ keratomileusis. Eighty-eight (8.6%) of 1,019 eyes had flap-related complications. Six eyes had two complications. Intraoperative complications included irregular keratectomy in nine eyes (0.9%), incomplete keratectomy in three eyes (0.3%), and a free cap in 10 eyes (1.0%). The incidence of intraoperative complications was six (6.0%) in the first 100 consecutive eyes, 14 (2.3%) in the next 600 consecutive eyes (P = .04, chi-square test), and one (0.3%) in the last 300 eyes (P = .03, chi-square test). Postoperative complications included displaced flaps that required repositioning in 20 eyes (2.0%), folds in the flap that required repositioning in 11 eyes (1.1%), diffuse lamellar keratitis in 18 eyes (1.8%), infectious keratitis in one eye (0.1%), and epithelial ingrowth that required removal in 22 eyes (2.2%). The incidence of flap displacement and folds in 200 eyes in which we irrigated under the flap and allowed it to settle without further manipulation averaged 8.5%, whereas the incidence in other groups of 100 consecutive eyes averaged 0.8% (P < .00001, chi-square test). The incidence of diffuse lamellar keratitis was 0.2% in eyes that had undergone myopic keratomileusis in situ and 3.2% in eyes treated by laser in situ keratomileusis (P = .0003, chi-square test). No eye lost 2 or more lines of best spectacle corrected visual acuity because of flap complications. CONCLUSION: Flap complications after lamellar refractive surgery are relatively common but rarely lead to a permanent decrease in visual acuity. Physician experience with the microkeratome and with the handling of the corneal flap decreases the incidence of flap complications. PMID- 10030553 TI - Causes of severe visual loss in the early treatment diabetic retinopathy study: ETDRS report no. 24. Early Treatment Diabetic Retinopathy Study Research Group. AB - PURPOSE: To describe the causes of and risk factors for persistent severe visual loss occurring in the Early Treatment Diabetic Retinopathy Study (ETDRS). METHODS: The ETDRS was a randomized clinical trial investigating photocoagulation and aspirin in 3,711 persons with mild to severe nonproliferative or early proliferative diabetic retinopathy. Severe visual loss, defined as best-corrected visual acuity of less than 5/200 on at least two consecutive 4-month follow-up visits, developed in 257 eyes (219 persons). Of these 257 eyes, 149 (127 persons) did not recover to 5/200 or better at any visit (persistent severe visual loss). Ocular characteristics of these eyes were compared with those of eyes with severe visual loss that improved to 5/200 or better at any subsequent visit. Characteristics of patients with severe visual loss that did and did not improve and those without severe visual loss were also compared. RESULTS: Severe visual loss that persisted developed in 149 eyes of 127 persons. In order of decreasing frequency, reasons recorded for persistent visual loss included vitreous or preretinal hemorrhage, macular edema or macular pigmentary changes related to macular edema, macular or retinal detachment, and neovascular glaucoma. Compared with all patients without persistent severe visual loss, patients with persistent severe visual loss had higher mean levels of hemoglobin A1c (10.4% vs 9.7%; P = .001) and higher levels of cholesterol (244.1 vs 228.5 mg/dl; P = .0081) at baseline. Otherwise, patients with persistent severe visual loss were similar to patients with severe visual loss that improved and to those without severe visual loss. CONCLUSIONS: Persistent severe visual loss was an infrequent occurrence in the ETDRS. Its leading cause was vitreous or preretinal hemorrhage, followed by macular edema or macular pigmentary changes related to macular edema and retinal detachment. The low frequency of persistent severe visual loss in the ETDRS is most likely related to the nearly universal intervention with scatter photocoagulation (either before or soon after high-risk proliferative diabetic retinopathy developed) and the intervention with vitreous surgery when clinically indicated. PMID- 10030555 TI - Topical indomethacin solution versus dexamethasone solution for treatment of inflamed pterygium and pinguecula: a prospective randomized clinical study. AB - PURPOSE: To compare the effect of topical indomethacin 0.1% solution with the effect of topical dexamethasone 0.1% phosphate solution on signs and symptoms of inflamed pterygium and pinguecula. METHODS: Of 50 consecutive patients who had inflamed pterygia (n = 17) or pingueculae (n = 33), met the study criteria, and signed an informed consent, one eye of each patient was evaluated in a comparative, prospective, randomized, double-masked, controlled study. Objective signs (conjunctival congestion, redness and edema, and staining of cornea) and subjective complaints (photophobia, pain, foreign-body sensation, discomfort, and tearing) were evaluated and scored. We also evaluated "total signs," "total symptoms," and "total score." Group 1 (n = 25) received topical indomethacin 0.1% solution, and group 2 (n = 25) received a topical dexamethasone phosphate 0.1% solution six times daily for 3 days, then four times daily over the following 11 days. Patients were examined before treatment, on days 3, 7, and 14 after the treatment was initiated, and 2 and 4 weeks after the treatment was discontinued. RESULTS: In both groups, the scores for "total signs," "total symptoms," and "total score" were significantly lower (P = .001) by day 14. There were no differences between groups 1 and 2 for "total signs," "total symptoms," and "total score" at days 3, 7, and 14 (P = .07 to P = .88). After treatment was discontinued, the dexamethasone-treated group experienced a significantly greater recurrence of "total signs" (P = .023 at day 30, P = .02 at day 45), but there was no statistically significant difference in "total symptoms" and "total score." Patients in group 2 reported more stinging after drops were administered than patients in group 1 (P = .002). CONCLUSIONS: This study indicates that topical indomethacin 0.1% solution is as effective as topical dexamethasone phosphate 0.1% solution for the treatment of inflamed pterygium and pinguecula and, therefore, is suggested as an effective treatment for these conditions. PMID- 10030554 TI - Effects of carteolol and timolol on plasma lipid profiles in older women with ocular hypertension or primary open-angle glaucoma. AB - PURPOSE: To determine the effect on serum lipid levels of carteolol hydrochloride 1.0% or timolol maleate 0.5% given twice a day to women age 60 years and older with primary open-angle glaucoma or ocular hypertension. METHOD: We included 112 patients in this double-masked, randomized, multicenter trial. Fasting clinical laboratory studies were evaluated at baseline and at 12 weeks. Patients were instructed not to change their dietary, alcohol consumption, or exercise habits during the study. RESULTS: For the carteolol group, the high-density lipoprotein (HDL) and total cholesterol/high-density lipoprotein (TC/HDL) ratio at baseline of 50.1 +/- 1.5 mg/dl and 4.7 +/- 0.2 changed by the 12-week visit to 51.3 +/- 1.9 mg/dl (P = .25) and 4.6 +/- .02 (P = .47), respectively. For the timolol maleate group, the baseline HDL and TC/HDL ratio of 53.6 +/- 2.2 mg/dl and 4.4 +/ 0.2 changed to 50.2 +/- 1.9 mg/dl (P < .001) and 4.7 +/- 0.2 (P = .001), respectively, at the 12-week visit. Carteolol patients showed no significant change from baseline, whereas the HDL (P < .001) and TC/HDL ratio decreased (P = .001) significantly in the timolol maleate group. There also was a significant difference in the change from baseline at 12 weeks between carteolol and timolol maleate groups for the HDL and TC/HDL ratio (P = .01 and .012, respectively). No differences in TC, low-density lipoprotein (LDL), or triglycerides (TG) or in changes from baseline were observed between groups at 12 weeks (P > .05). At 12 weeks, no differences were observed between carteolol and timolol maleate groups in intraocular pressure or safety (P > .05), except that patients given carteolol demonstrated fewer solicited ocular symptoms (P = .007). CONCLUSIONS: Carteolol appears to be neutral in its effect on serum lipid levels, whereas timolol maleate adversely affects the HDL and TC/HDL ratio in women age 60 years and older with ocular hypertension or primary open-angle glaucoma. PMID- 10030556 TI - Effects of hypoxia on corneal epithelial permeability. AB - PURPOSE: Epithelial permeability to fluorescein (Pdc) increases with closed-eye soft contact lens wear. Possible mechanisms responsible for this change include corneal hypoxia (and acidosis) during overnight wear and interference of the lens with normal tear exchange. In this study we used a local environmental chamber to examine the effects of hypoxia on Pdc. METHODS: After baseline slit-lamp examination, autofluorescence, and central corneal thickness measurements, 35 subjects were fitted with a pair of airtight swimming goggles. One eye was exposed to a humidified gas mixture containing 95% nitrogen (N2) and 5% carbon dioxide (CO2), and the fellow (control) eye was exposed to air. The experimental eye and the eye measured first were assigned using a randomized block design. After the subjects wore the goggles for 1 hour, corneal thickness measurements were repeated and Pdc was assessed as previously described. A final slit-lamp examination was performed by a masked examiner to assess epithelial integrity. RESULTS: There was no significant difference in the mean ln(Pdc) (95% confidence interval) for eyes exposed to N2/CO2 when compared with paired eyes exposed to air (-2.70 [-2.99, -2.41] vs -2.51 [-2.72, -2.30] ln[nm/sec], P = .272). Although there was also no substantial difference in the slit-lamp appearance of the experimental and control eyes, the mean (95% confidence interval) change in corneal thickness for the hypoxic eyes was 19.78 (15.72, 23.84) microm compared with 3.40 (-0.67, 7.47) microm (P < .0001) in the control eyes. CONCLUSION: One hour of hypoxia caused a significant increase in corneal thickness with no apparent change in Pdc. This suggests that other factors, either alone or in combination with hypoxia, may be responsible for increased Pdc during closed-eye contact lens wear. PMID- 10030557 TI - Comparative corneal topography and refractive variables in monozygotic and dizygotic twins. AB - PURPOSE: To investigate the role of heredity in determining corneal shape, axial length, and overall refractive error. METHODS: Twenty monozygotic and 19 dizygotic twin pairs, age 12 to 73 years, were enrolled in the study. Zygosity was determined by physical similarity and by responses to questions adapted from surveys. Two twin pairs were excluded because of undetermined zygosity and one pair because of keratoconus (both siblings). Refractive error was determined by an automated refractor. Manifest refraction was also recorded, as well as cycloplegic refraction in subjects under age 18 years. Corneal topography data and manual keratometer readings were also obtained. Axial lengths were determined by A-scan ultrasound. Data were analyzed by Student t tests only in the right eye. Left-eye data were comparable for all variables. RESULTS: Mean intrapair difference in refractive error (spherical equivalent) was less for monozygotic than for dizygotic twins (RE: 0.41 vs 1.53; P = .001). Mean intrapair difference in axial length was less for monozygotic twins (RE: 0.39 vs 0.76 mm; P = .031). Corneal topography data (power and meridian) in all zones (3, 5, and 7 mm) also showed smaller mean differences among monozygotic pairs than dizygotic, but the difference was statistically significant only for the 5-mm zone. In addition, most Holladay Diagnostic Summary variables that were studied did not show any statistically significant differences. CONCLUSIONS: Axial length and overall refractive error have a significant genetic basis. Corneal topography data appear to have other overriding determining factors for several of the variables studied. PMID- 10030558 TI - Corneal endothelial deposits in children positive for human immunodeficiency virus receiving rifabutin prophylaxis for Mycobacterium avium complex bacteremia. AB - PURPOSE: To assess the potential ocular effects of prophylactic administration of rifabutin in children with symptomatic human immunodeficiency virus (HIV) infection and CD4 counts less than 50 cells per mm3. METHODS: Twenty-five children with HIV infection were enrolled in a phase I-II study of prophylactic administration of systemic rifabutin for prevention of disseminated Mycobacterium avium complex infection and monitored prospectively for the development of ocular complications secondary to HIV infection or drug toxicity. RESULTS: The dose of rifabutin ranged from 5.0 mg to 15.0 mg per kg, and the median ophthalmic follow up was 24 months. During the study period, six of the children receiving rifabutin prophylaxis for M. avium complex developed unusual bilateral, initially peripheral, stellate, corneal endothelial deposits without associated uveitis. Review of serial corneal drawings and photographs showed an increase in the number of corneal deposits with continued administration of rifabutin. The duration of rifabutin treatment (P = .017) and follow-up (P = .0011) was significantly longer in patients who developed these corneal endothelial changes. CONCLUSION: Corneal endothelial deposits should be considered a potential side effect of rifabutin therapy. To date, these findings have not been sight threatening. PMID- 10030559 TI - Ophthalmic plaque radiotherapy for age-related macular degeneration associated with subretinal neovascularization. AB - PURPOSE: To evaluate ophthalmic plaque radiotherapy for the treatment of subretinal neovascularization associated with age-related macular degeneration. METHODS: In a prospective phase I clinical trial, we treated 23 patients (23 eyes) with ophthalmic plaque radiotherapy for subfoveal exudative macular degeneration. Palladium 103 ophthalmic plaque brachytherapy was delivered to a retinal apex dose of 1,250 to 2,362 cGy (rad). Early Treatment Diabetic Retinopathy Study type visual acuity determinations, ophthalmic examinations, and angiography were performed before and after treatment. Clinical evaluations were performed in a nonrandomized and unmasked fashion. RESULTS: Patients were followed up for a mean (+/-SD) of 19 +/- 10.7 months (range, 3 to 37 months). Six months after radiation therapy, three (16%) of 19 eyes had lost 3 or more lines of best-corrected visual acuity; 12 months after radiation therapy, four eyes (31% of 13 eyes), and 24 months after radiation therapy, only two (22% of nine eyes) lost 3 or more lines of visual acuity. No eye suffered sudden irreversible loss of central vision. No radiation retinopathy, optic neuropathy, or cataract could be attributed to radiotherapy within this follow-up period. CONCLUSION: Ophthalmic plaque radiotherapy can be used to treat neovascular age-related macular degeneration. In contrast to external beam radiotherapy, ophthalmic plaque radiotherapy is a unilateral treatment, which allows a larger dose to be delivered to the macula with less irradiation of normal ocular structures. We have found no sight-limiting complications at the doses, dose rates, and follow up evaluated in this study. PMID- 10030560 TI - Idiopathic intracranial hypertension in prepubertal pediatric patients: characteristics, treatment, and outcome. AB - PURPOSE: To report the features of idiopathic intracranial hypertension in prepubertal children, with emphasis on presentation, treatment, and outcome. METHODS: We retrospectively reviewed the charts of all patients 11 years and younger diagnosed with idiopathic intracranial hypertension at two university affiliated medical centers. Inclusion critera included papilledema, normal brain computed tomography or magnetic resonance imaging, cerebrospinal fluid pressure greater than 200 mm H2O, normal cerebrospinal fluid content, and a nonfocal neurologic examination except for sixth nerve palsy. Patients with concomitant systemic illness were excluded. RESULTS: Of the 10 patients, four were girls and six were boys. Only one patient was obese. The most common presenting symptoms were stiff neck (four patients) and diplopia (four patients), and the most common presenting sign was strabismus (eight patients). Six of eight patients with strabismus had abducens nerve palsy (four bilateral), one patient had a sensory exotropia, and one had a comitant esotropia. Visual field abnormalities were present in 11 of 13 eyes (85%), and severe visual loss resulting in no light perception vision occurred in one eye of one patient. Nine patients were treated medically, four with a combination of prednisone or dexamethasone and acetazolamide and five with acetazolamide alone. One patient in this group also required a lumboperitoneal shunt. One patient was treated with lumbar puncture only. Resolution of papilledema occurred rapidly in all patients, with a mean of 4.7 +/- 2.6 months. Resolution of sixth nerve palsy also occurred rapidly in four of six patients in a mean of 1.6 +/- 1.2 months. One patient required strabismus surgery for persistent esotropia and one was lost to follow-up. CONCLUSIONS: Idiopathic intracranial hypertension in prepubertal children is rare and is different than the disease in adults. In our series, there appeared to be no sex predilection, and obesity was uncommon. Children are likely to present with strabismus and stiff neck rather than headache or pulsatile tinnitus. Both papilledema and sixth nerve palsy resolved rapidly with treatment. However, children can sustain loss of visual field and visual acuity despite treatment. PMID- 10030561 TI - Schwannoma in patients with isolated unilateral trochlear nerve palsy. AB - PURPOSE: To describe the clinical features of patients with isolated unilateral trochlear nerve palsy secondary to imaging-defined schwannoma of the trochlear nerve. METHODS: A chart review of all patients seen at the Neuro-Ophthalmology Unit at Emory University since 1989. Of 221 patients with trochlear nerve palsy, six had a lesion consistent with a trochlear nerve schwannoma. RESULTS: The six patients had isolated unilateral trochlear nerve palsy. Duration of diplopia before diagnosis averaged 6 months. Magnetic resonance imaging demonstrated circumscribed, enhancing lesions along the cisternal course of the trochlear nerve, all measuring less than 5 mm in greatest dimension. Five of the patients were seen in follow-up, over periods ranging from 11 to 26 months from initial presentation (mean, 15.6 months; standard deviation, 6.0 months). All of these patients remained stable except one, who was slightly worse at 15 months by clinical measurements and magnetic resonance imaging. None of these patients have developed additional symptoms or signs of cranial nerve or central nervous system involvement. CONCLUSIONS: The differential diagnosis of an isolated unilateral fourth cranial nerve palsy should include an intrinsic neoplasm of the trochlear nerve. Magnetic resonance imaging is useful, both for diagnosis and follow-up. These patients can remain stable and may not require neurosurgical intervention. PMID- 10030562 TI - Ophthalmic manifestations of allergic fungal sinusitis. AB - PURPOSE: To highlight allergic fungal sinusitis as a cause of ophthalmic and sinus problems by identifying the profile of the patient with allergic fungal sinusitis and presenting a successful treatment approach. METHODS: Six consecutive cases of patients with ophthalmic manifestations of allergic fungal sinusitis were reviewed. Ophthalmic findings, sinus involvement, mycology, immune response, imaging studies, and treatment were examined. The characteristics of this patient group with ophthalmic manifestations of allergic fungal sinusitis were compared with those of the general group of patients with allergic fungal sinusitis. RESULTS: All six patients had proptosis. One had symptomatic diplopia and one had visual loss. Imaging studies, fungal characterization, and immune profiles were similar to the reported allergic fungal sinusitis population. After treatment there was no recurrence of ophthalmic or sinus symptoms at a mean follow-up of 34 months (range, 8 to 48 months). There were no complications of treatment. CONCLUSIONS: Initial diagnosis of allergic fungal sinusitis requires suspicion on the part of the ophthalmologist. Proptosis is the most common ophthalmic sign. Differentiation from invasive forms of fungal sinus disease is crucial, because systemic antifungal medication and extensive surgical tissue debridement are not required in allergic fungal sinusitis. Treatment consists of extirpation of the allergic mucin and fungus, sinus aeration, and systemic and topical corticosteroids. PMID- 10030563 TI - Factitious disease of periocular and facial skin. AB - PURPOSE: To describe the clinical appearance of factitious (or self-inflicted) lesions on periocular skin and face. METHODS: All patients with factitious cutaneous disease who were examined at Mayo Clinic, Rochester, Minnesota, between 1985 and 1997 were identified. For patients with lesions on the face and periocular skin, the demographic features, clinical descriptive characteristics of their lesions, associated psychopathology, and treatments were ascertained. RESULTS: Of 38 patients with factitious dermatitis, 18 (47%) had facial lesions. Of these 18 patients, 15 (83%) were female. The mean age (+/- SD) of the patients with facial lesions was 35.2 +/- 15.7 years (range, 9 to 66 years). Eight patients (44%) had neurotic excoriations, nine (50%) had dermatitis artefacta, and one (6%) had trichotillomania. The working diagnoses of five patients cared for initially in the Department of Ophthalmology were corneal epithelial and facial desquamation associated with severe pain of unknown cause, medial cicatricial ectropion of probable vasculitic cause, basal cell carcinoma of the nasojugal fold, recurrent preseptal cellulitis resistant to medical treatment, and madarosis of the upper eyelids of unknown cause. CONCLUSION: Cutaneous factitious disease may masquerade as numerous clinical entities and should be included in the differential diagnosis of lesions of the periocular skin. PMID- 10030564 TI - Flap complications of lamellar refractive surgery. PMID- 10030565 TI - Corneal topography in asymptomatic family members of a patient with pellucid marginal degeneration. AB - PURPOSE: To report corneal topographic patterns in asymptomatic family members of a patient with pellucid marginal degeneration. METHODS: Computer-assisted corneal topography was used to study the corneas of five family members of a patient with pellucid marginal degeneration. RESULTS: In all five asymptomatic family members, corneal biomicroscopy was normal. Corneal topography, however, showed various abnormalities in different members of this family, particularly a topographic pattern suggesting keratoconus in one family member and a topographic pattern suggesting pellucid marginal degeneration in another family member. CONCLUSION: This study reinforces the hypothesis that corneal ectatic disorders may represent different manifestations of a clinical spectrum. PMID- 10030566 TI - New technique for the cytologic identification of presumed Acanthamoeba from corneal epithelial scrapings. AB - PURPOSE: To describe a cytologic technique for the rapid identification of presumed Acanthamoeba organisms from corneal epithelial scrapings. METHODS: After administering topical anesthesia, we removed the affected corneal epithelium with a scalpel blade. The tip of the blade, containing the scrapings, was washed off into a cuvette with a solution of an alcohol-based fixative for cytology specimens. The blade was immersed in the cuvette and agitated to ensure that the sample was collected. The specimen was fixed for at least 10 minutes and processed by cytospin centrifugation. RESULT: Seventy-five patient samples have been studied with this technique, with excellent preservation of the organism. CONCLUSIONS: The organism preservation with this technique is superior to that of conventional smears and permits confirmatory organism identification by immunohistochemistry. PMID- 10030567 TI - Infectious crystalline keratopathy and endophthalmitis secondary to Mycobacterium abscessus in a monocular patient with Stevens-Johnson syndrome. AB - PURPOSE: To describe the clinical and laboratory features of infectious crystalline keratopathy and endophthalmitis secondary to Mycobacterium abscessus in a patient with Stevens-Johnson syndrome. METHOD: Case report. A 19-year-old man with a history of Stevens-Johnson syndrome and multiple corneal transplants developed white crystalline corneal infiltrates. RESULTS: Anterior chamber aspirate disclosed acid-fast bacilli. A repeat corneal transplant was performed and antibiotic therapy begun. Histopathology showed focal acute inflammation surrounding collections of acid-fast bacilli, which were speciated as M. abscessus. CONCLUSIONS: M. abscessus is a cause of infectious crystalline keratopathy and endophthalmitis. Risk factors include ocular surface disease, corneal transplantation, and immunosuppressive therapy. PMID- 10030569 TI - Mini-trabeculectomy without radial incisions. AB - PURPOSE: To describe a new modification of Cairns trabeculectomy. METHODS: Surgical adjustment includes a small, 3-mm, fornix-based conjunctival flap, a circumferential scleral incision at a distance of only 1 mm from the corneoscleral limbus, and a sclerocorneal tunnel without scleral radial incisions. RESULT: Among the various clinical and technical advantages of the procedure is the possibility of performing more operations through the superior limbus rather than reverting to an inferior trabeculectomy or implantation of an aqueous shunt. CONCLUSION: The reduced surgical area and manipulations of the current procedure appear to offer advantages over the standard approach. PMID- 10030568 TI - Resolution of microsporidial sinusitis and keratoconjunctivitis by itraconazole treatment. AB - PURPOSE: To report successful treatment of ocular infection caused by the microsporidium Encephalitozoon cuniculi in a person with acquired immunodeficiency syndrome (AIDS) and nasal and paranasal sinus infection. METHOD: Case report. RESULTS: Microsporidial infection in a person with AIDS and with chronic sinusitis and keratoconjunctivitis was diagnosed by Weber modified trichrome stain and transmission electron microscopy. Symptoms completely resolved with itraconazole treatment (200 mg/day for 8 weeks) after albendazole therapy (400 mg/day for 6 weeks) was unsuccessful. CONCLUSION: Itraconazole can be recommended in ocular, nasal, and paranasal sinus infection caused by E. cuniculi parasites when treatment with albendazole fails. PMID- 10030570 TI - Foldable posterior chamber intraocular lens implantation in the absence of capsular and zonular support. AB - PURPOSE: To implant foldable posterior chamber intraocular lenses in the absence of capsular and zonular support. METHODS: Case reports. In two patients, two eyes with aphakia, lack of capsular or zonular support, and contact lens intolerance underwent the implantation of a silicone and an acrylic foldable posterior chamber intraocular lens, respectively. RESULTS: In the two eyes, final visual acuity was 20/25 and 20/50, respectively. No intraoperative vitreal, retinal, or choroidal complications were noted. The postoperative recovery was rapid, and there was minimal induced astigmatism. CONCLUSIONS: The implantation of foldable posterior chamber intraocular lenses in aphakic eyes without capsular and zonular support may result in fewer intraoperative complications. It also allows for faster postoperative recovery and less postoperative astigmatism. PMID- 10030571 TI - Cataracts, bilateral macular holes, and rhegmatogenous retinal detachment induced by lightning. AB - PURPOSE: To report ocular injuries, including a unilateral rhegmatogenous retinal detachment, induced by lightning. METHOD: Case report. A 30-year-old man was injured by lightning. RESULTS: The patient developed a severe decrease in visual acuity in both eyes, an afferent pupillary defect in his left eye, bilateral cataracts, posterior vitreous detachments, macular holes, and an inferotemporal retinal detachment with an associated flap retinal tear in his left eye. CONCLUSIONS: This is a case of bilateral cataracts, posterior vitreous detachments, macular holes, and a unilateral retinal detachment associated with lightning. We postulate that the heating of the retinal surface, the concussive forces on the eye, and a sudden lateral contraction of the attached vitreous resulted in bilateral posterior vitreous detachments and a unilateral peripheral retinal break. PMID- 10030572 TI - Siderosis bulbi resulting from an intralenticular foreign body. AB - PURPOSE: To report a case of siderosis bulbi that resulted from a small intralenticular foreign body. METHOD: Case report. RESULTS: A 36-year-old man with normal visual acuity and a peripheral intralenticular iron foreign body in the left eye was treated conservatively. Nine weeks after the injury, he had ocular signs of siderosis bulbi, with changes in the electroretinogram. A clear lens aspiration with removal of the foreign body was performed. After removal of the iron foreign body, no progression or regression of the ocular signs of siderosis bulbi has occurred, and the electroretinogram has not changed over a 2 year period. CONCLUSIONS: Even in the presence of good vision, a patient with an intralenticular ferrous foreign body should be followed closely, and the foreign body should be removed before irreversible siderosis bulbi occurs. PMID- 10030573 TI - Age-related macular degeneration and optic disk morphology. AB - PURPOSE: To assess the relationship between age-related macular degeneration and appearance of the optic disk. METHOD: By morphometric evaluation of wide-angle color fundus photographs, 143 patients with age-related macular degeneration were compared with 33 normal subjects and with 83 diabetic patients. RESULTS: Size and shape of the optic disk and size of parapapillary atrophy did not vary significantly (P > .12) between the study groups. CONCLUSIONS: Age-related macular degeneration is not associated with special features in the appearance of the optic disk. Parapapillary atrophy, large or small optic disk, and abnormal disk shape are neither risk factors nor protective factors of age-related macular degeneration. PMID- 10030574 TI - Comparison of intraocular to plasma HIV-1 viral burden in patients with cytomegalovirus retinitis. AB - PURPOSE: To determine the relationship between plasma and intraocular human immunodeficiency virus-1 (HIV-1) viral loads in 12 consecutive patients undergoing ganciclovir implant surgery for cytomegalovirus (CMV) retinitis. METHODS: Aqueous and vitreous specimens were assayed for HIV-1 viral load by polymerase chain reaction analysis (Roche Amplicor HIV Monitor; Roche Diagnostics Systems, Inc, Branchburg, New Jersey). RESULTS: It was possible to quantitatively assay HIV-1 burden in intraocular fluids using polymerase chain reaction analysis. In general, patients with plasma viral loads less than 250,000 copies/ml had undetectable (<200 copies/ml) HIV-1 in their aqueous and vitreous. CONCLUSIONS: It is likely that intraocular viral levels have several determinants in addition to plasma viral loads, with which they only partially correlate. PMID- 10030575 TI - Bartonella henselae infection associated with peripapillary angioma, branch retinal artery occlusion, and severe vision loss. AB - PURPOSE: To report atypical clinical features of Bartonella henselae neuroretinitis treated with combination antibiotics. METHOD: Case report. RESULTS: A 20-year-old man with a positive B. henselae titer developed a unilateral neuroretinitis, a large peripapillary angiomatous lesion, branch artery occlusion with ischemic maculopathy, and vision loss that failed to improve with clindamycin. Treatment with doxycycline and rifampin led to rapid clinical improvement. The severe vision loss in this case is atypical. CONCLUSIONS: Ocular findings associated with B. henselae infection may include retinal angiomatous lesion and branch retinal artery occlusion. Doxycycline and rifampin were successful in treating the infection. PMID- 10030576 TI - A technique for suturing peripapillary radioactive plaques. AB - PURPOSE: To describe a technique for suturing radioactive plaques positioned posteriorly and adjacent to the optic nerve. METHODS: Posterior and juxtapapillary notched radioactive iodine-125 plaques were sutured using four 5/0 nylon sutures. Two sutures were placed in the sclera at the anterior border of the plaque position and passed through the eyelets at the anterior edge of the plaque. Two sutures were attached to the posterior eyelets and brought to either side of the optic nerve, under the rectus muscles, to be sutured to sclera anterior to the insertion of the recti muscles. The position of the plaques was documented intraoperatively using sterile B-scan ultrasonography. RESULTS: Plaques positioned and sutured using this technique were found by ultrasonography to be tight up against the sclera and optic nerve. PMID- 10030577 TI - Translocation of chromosomes 11 and 22 in choroidal metastatic Ewing sarcoma detected by fluorescent in situ hybridization. AB - PURPOSE: To describe a patient with metastasis of Ewing sarcoma to the choroid and the molecular genetics of the tumor. METHODS: A 26-year-old woman with metastatic Ewing sarcoma developed large choroidal masses in the left eye and died 2 months later. Autopsy of the eyes was performed. Dual-color fluorescent in situ hybridization was used to detect genetic alteration in the ocular tumor with EWS and FLI-1 probes. RESULTS: Histopathology confirmed choroidal metastatic Ewing sarcoma. Molecular analysis showed chromosomal translocation t(11;22)(q24;q12) or EWS/FLI-1 rearrangement in the malignant cells of the eye. CONCLUSIONS: Ewing sarcoma can rarely metastasize to the uvea. Molecular detection of the t(11;22)(q24;q12) translocation in Ewing sarcoma is valuable in the differential diagnosis of small round cell tumors. PMID- 10030578 TI - Metastatic esophageal carcinoma to the orbit. AB - PURPOSE: To report a case of esophageal adenocarcinoma and areas of gastric differentiation in the esophagus (Barrett esophagus) metastatic to the orbit. METHODS: A 47-year-old man with a history of esophageal carcinoma developed turgescence around his left eye. He underwent a biopsy and histologic examination of a left orbital mass. RESULTS: Histopathology of the orbital tumor was consistent with metastatic adenocarcinoma from the esophagus. CONCLUSIONS: This metastatic adenocarcinoma to the orbit likely arose in Barrett esophagus. PMID- 10030579 TI - Bilateral optic disk edema caused by sarcoidosis mimicking pseudotumor cerebri. AB - PURPOSE: To present a case of retrobulbar optic nerve and chiasm sarcoidosis that mimicked pseudotumor cerebri. METHODS: A 34-year-old, thin, black woman presented with transient visual obscurations, normal visual acuity, bilateral optic disk edema, and enlarged blind spots. Clinical, medical, and radiologic evaluations were consistent with pseudotumor cerebri. The patient improved while taking acetazolamide, but 6 months later her symptoms worsened. Neuroimaging disclosed enhancement of the optic nerve and chiasm. RESULTS: Despite administration of intravenous corticosteroids, the patient's vision worsened. Bilateral optic nerve sheath fenestrations were performed, and pathology disclosed sarcoidosis. CONCLUSION: Sarcoidosis of the optic nerves and chiasm may mimic pseudotumor cerebri. PMID- 10030580 TI - Severe ocular and orbital toxicity after intracarotid etoposide phosphate and carboplatin therapy. AB - PURPOSE: To report severe ocular and orbital toxicity after administration of intracarotid etoposide phosphate and carboplatin. METHOD: Case report. RESULTS: A 52-year-old man with glioblastoma multiforme underwent left intracarotid administration of eto poside phosphate and carboplatin inferior to the ophthalmic artery. Within 7 hours, a nonpupillary block angle-closure glaucoma developed secondary to uveal effusion in the ipsilateral eye, which was relieved by cycloplegia. Four days later, severe orbital inflammation resulted in a visual acuity of counting fingers, proptosis, optic neuropathy, and total external ophthalmoplegia in the eye. The patient's condition improved after a lateral cantholysis and administration of high-dose intravenous corticosteroids. Two weeks later, an anterior uveitis occurred in the left eye, which responded to topical corticosteroids. During a 2-month period, the patient recovered to a visual acuity of 20/70, near normal motility, and normal intraocular pressure, and the ocular and orbital inflammation resolved. Preexisting ipsilateral chemotherapy-induced maculopathy became more pronounced. CONCLUSION: Ocular and orbital toxicity after intracarotid etoposide phosphate and carboplatin therapy is infrequently reported. PMID- 10030581 TI - Magnetic resonance imaging of acquired Brown syndrome in a patient with psoriasis. AB - PURPOSE: To report the occurrence of acquired Brown syndrome and associated magnetic resonance imaging findings in a patient with psoriasis. METHODS: A 42 year-old woman with a history of psoriasis developed pain, double vision, and limited elevation of her left eye in adduction. An orbital magnetic resonance image with gadolinium enhancement was obtained. RESULTS: Orbital magnetic resonance image disclosed abnormal enhancement of the left trochlea/tendon complex. The patient's symptoms resolved with corticosteroid therapy. CONCLUSIONS: Acquired Brown syndrome may be associated with psoriasis. The inflammation of the trochlea/tendon complex that can cause acquired Brown syndrome can be demonstrated on magnetic resonance image. PMID- 10030582 TI - Pituitary macroadenoma manifesting as an isolated fourth nerve palsy. AB - PURPOSE: To describe an unusual ophthalmic manifestation of a pituitary adenoma. METHODS: Case report. RESULTS: A 32-year-old man had left supraorbital and frontal headaches and new-onset vertical diplopia. Examination showed a left fourth nerve palsy and increased vertical fusional amplitudes. Magnetic resonance imaging disclosed a sellar mass consistent with a pituitary macroadenoma. CONCLUSION: A pituitary adenoma may rarely manifest with an isolated fourth nerve palsy. PMID- 10030583 TI - Fourth cranial nerve palsy in pediatric patients with pseudotumor cerebri. AB - PURPOSE: To describe three children with acute fourth cranial nerve palsy secondary to pseudotumor cerebri. METHODS: We reviewed the medical records of children younger than 18 years who were diagnosed with pseudotumor cerebri between 1977 and 1997. Pseudotumor cerebri was defined by normal neuro-imaging, elevated intracranial pressure measured by lumbar puncture, and normal cerebrospinal fluid composition. RESULTS: Three children with pseudotumor cerebri presented with vertical diplopia and clinical signs of fourth cranial nerve palsy including a hypertropia of the affected eye, which increased with adduction and ipsilateral head tilt. The fourth cranial nerve palsy resolved after reduction of the intracranial pressure in all three children. CONCLUSIONS: Fourth cranial nerve palsy may occur in children with pseudotumor cerebri and may be a nonspecific sign of elevated intracranial pressure. PMID- 10030584 TI - Optic nerve hypoplasia with posterior pituitary ectopia: male predominance and nonassociation with breech delivery. AB - PURPOSE: To determine whether posterior pituitary ectopia in children with optic nerve hypoplasia has a male predominance or an increased incidence of breech delivery. METHOD: Retrospective analysis of 12 children with optic nerve hypoplasia and posterior pituitary ectopia. RESULTS: Eleven of 12 patients with posterior pituitary ectopia were boys. No child had a history of breech delivery. Two children had a history of breech positioning but were delivered by cesarean section. CONCLUSION: Posterior pituitary ectopia with optic nerve hypoplasia shows a strong male predominance but no association with breech delivery. PMID- 10030585 TI - Fingertip dermatitis in an ophthalmologist caused by proparacaine. AB - PURPOSE: To report the late diagnosis of allergic response to proparacaine hydrochloride in an ophthalmologist. METHOD: Case report. In a 49-year-old practicing ophthalmologist, the history, clinical findings of fingertip dermatitis, skin pathology, and skin patch testing are described. RESULTS: Proparacaine, as the initiating agent, took almost 3 years to identify because of the unusual pattern of allergy. We explored numerous treatment options before identifying and removing the offending agent. CONCLUSIONS: Ophthalmologists may be exposed to proparacaine on a daily basis. This unique report heightens the awareness of this rare work-related complication. PMID- 10030586 TI - Threshold perimetry of each eye with both eyes open in patients with monocular functional (nonorganic) and organic vision loss. PMID- 10030587 TI - Bilateral zonular cataract associated with the mitochondrial cytopathy of Pearson syndrome. PMID- 10030588 TI - Capsular bag distention syndrome noted 5 years after intraocular lens implantation. PMID- 10030589 TI - Randomized trial of intraoperative mitomycin C in surgery for pterygium. PMID- 10030590 TI - Expression of the paired-box genes Pax-1 and Pax-9 in limb skeleton development. AB - Vertebrate Pax genes encode a family of transcription factors that play important roles in embryonic patterning and morphogenesis. Two closely related Pax genes, Pax-1 and Pax-9, are associated with early axial and limb skeleton development. To investigate the role of these genes in cartilage formation we have examined the expression profiles of Pax-1 and Pax-9 in developing chick limb mesenchyme in vivo and in vitro. Both transcripts are detected by reverse transcription polymerase chain reaction and Northern blotting throughout chick limb development, from the early bud stages (Hamburger-Hamilton 20-23) to fully patterned appendages (stage 30). Whole-mount in situ hybridization reveals complex, nonoverlapping expression domains of these two genes. Pax-1 transcripts first appear at the anterior proximal margin of the limb buds, while Pax-9 is expressed more distally at what will be the junction of the autopod and the zeugopod. In situ hybridization to serial sections of the girdles reveals that in the pectoral region Pax-1 is expressed proximally in condensed mesenchyme surrounding the junction of the developing scapula, humerus, and coracoid. In the pelvis, Pax-1 is expressed between the femur and the developing acetabulum and along the ventral edge of the ischium; this transcript was also found in the distal hindlimb along the posterior edge of the fibula. Pax-9 transcripts were not detected in the pectoral girdle at any stage, and only weakly in the pelvis along the ventral ischial margin. In the distal parts of both wings and legs, however, Pax-9 is strongly expressed between the anterior embryonic cartilages (e.g., distal radius or tibia) and the anterior ectodermal ridge. The expression of both genes was strongest in undifferentiated cells of precartilage condensations or at the margins of differentiated cartilages, and was absent from cartilage itself. In micromass cultures of chondrifying limb bud mesenchyme expression of Pax-1 and Pax-9 is maintained for up to 3 days in vitro, most strongly at the end of the culture period during chondrogenic differentiation. As seen in vivo, transcripts are found in loose mesenchyme cells at the outer margins of developing cartilage nodules, and are absent from differentiated chondrocytes at the nodule center. Taken together, these investigations extend previous studies of Pax-1 and Pax-9 expression in embryonic limb development while validating limb bud mesenchyme culture as an accessible experimental system for the study of Pax gene function and regulation. Our in vivo and in vitro observations are discussed with reference to 1) the relationship between somitic and limb expression of these two Pax genes, 2) what regulates this expression in different regions of the embryo, and 3) the putative cellular functions of Pax-1 and Pax-9 in embryonic skeletogenesis. PMID- 10030591 TI - Characterization of beta cells developed in vitro from rat embryonic pancreatic epithelium. AB - The present study evaluates the development and functional properties of beta cells differentiated in vitro. The authors have previously demonstrated that when E12.5 rat pancreatic rudiments are cultured in vitro in the absence of mesenchyme, the majority of the epithelial cells differentiate into endocrine beta cells. Thus, depletion of the mesenchyme provokes the expansion of endocrine tissue at the expense of exocrine tissue. The potential use of this procedure for the production of beta cells led the authors to characterize the beta cells differentiated in this model and to compare their properties with those of the endocrine cells of the embryonic and adult pancreas. This study shows that the beta cells that differentiate in vitro in the absence of mesenchyme express the homeodomain protein Nkx6.1, a transcription factor that is characteristic of adult mature beta cells. Further, electron microscopy analysis shows that these beta cells are highly granulated, and the ultrastructural analysis of the granules shows that they are characteristic of mature beta cells. The maturity of these granules was confirmed by a double-immunofluorescence study that demonstrated that Rab3A and SNAP-25, two proteins associated with the secretory pathway of insulin, are strongly expressed. Finally, the maturity of the differentiated beta cells in this model was confirmed when the cells responded to stimulation with 16 mM glucose by a 5-fold increase in insulin release. The authors conclude that the beta cells differentiated in vitro from rat embryonic pancreatic rudiments devoid of mesenchyme are mature beta cells. PMID- 10030592 TI - Multiple cis-acting regulatory regions are required for restricted spatio temporal Hoxa5 gene expression. AB - Genetic analyses have revealed the essential role of the murine Hoxa5 gene for the correct specification of the cervical and upper thoracic region of the skeleton, and for the normal organogenesis and function of the respiratory tract, both structures expressing Hoxa5 during embryogenesis. To understand how the expression domains of the Hoxa5 gene are established during development, we have analyzed the cis-acting control regions mediating Hoxa5 gene expression using a transgenic approach. Four transcripts are derived from the Hoxa5 locus. The shortest and most abundant one displays a specific spatio-temporal profile of expression at earlier stages and in more anterior structures along the embryonic axis than the larger forms. We established that an 11.1 kilobase pair (kb) genomic fragment, extending from position -3.8 kb to +7.3 kb relative to Hoxa5 transcription initiation site, was sufficient to reproduce the temporal expression and substantially reconstitute the spatial pattern of the major Hoxa5 transcript. By deletion analyses, we identified a 2.1 kb fragment located downstream of the Hoxa5 gene that possesses mesodermal enhancer activity. Overall, the findings demonstrate that cis-acting regulatory elements essential for the correct expression of the major Hoxa5 transcript are located both upstream and downstream of the Hoxa5 coding sequences. PMID- 10030593 TI - Ectopic expression of the transforming growth factor beta type II receptor disrupts mesoderm organisation during mouse gastrulation. AB - Transforming growth factor beta (TGFbeta) regulates the cell cycle and extracellular matrix (ECM) deposition of many cells in vitro. We have analysed chimaeric mouse embryos generated from embryonic stem cells with abnormal receptor expression to study the effect of TGFbeta on these processes in vivo and the consequences for normal development. The binding receptor for TGFbeta, TbetaRII, is first detected in the embryo proper around day 8.5 in the heart. Ectopic expression of TbetaRII from the blastocyst stage onward resulted in an embryonic lethal around 9.5 dpc. Analysis of earlier stages revealed that the primitive streak of TbetaRII chimaeras failed to elongate. Furthermore, although cells passed through the streak and initially formed mesoderm, they tended to accumulate within the streak. These defects temporally and spatially paralleled the expression of the TGFbeta type I receptor, which is first expressed in the node and primitive streak. We present evidence that classical TGFbeta-induced growth inhibition was probably the cause of insufficient mesoderm being available for paraxial and axial structures. The results demonstrate that (1) TGFbeta mRNA and protein detected previously in early postimplantation embryos is present as a biologically active ligand; and (2) assuming that ectopic expression of TbetaRII results in no other changes in ES cells, the absence of TbetaRII is the principle reason why the embryo proper is unresponsive to TGFbeta ligand until after gastrulation. PMID- 10030594 TI - Selective expression of purinoceptor cP2Y1 suggests a role for nucleotide signalling in development of the chick embryo. AB - Responses to extracellular nucleotides (e.g., ATP, ADP, etc.) have been demonstrated in a number of embryonic cell types suggesting they may be important signalling molecules during embryonic development. Here the authors describe for the first time the expression of a G-protein-coupled receptor for extracellular ATP, chick P2Y1 (cP2Y1), during embryonic development of the chick. During the first 10 days of embryonic development, cP2Y1 is expressed in a developmentally regulated manner in the limb buds, mesonephros, brain, somites, and facial primordia, suggesting that this receptor may have a role in the development of each of these systems. PMID- 10030595 TI - Heat shock protein 70 (Hsp70) protects postimplantation murine embryos from the embryolethal effects of hyperthermia. AB - Previous work has shown that there is a positive correlation between the induction of Hsp70 and its transient nuclear localization and the acquisition and loss of induced thermotolerance in postimplantation rat embryos. To determine whether Hsp70 is sufficient to induce thermotolerance in postimplantation mammalian embryos, we used a transgenic mouse in which the normally strictly inducible Hsp70 is constitutively expressed in the embryo under the control of a beta-actin promoter. Day 8.0 mouse embryos heterozygous for the Hsp70 transgene were not protected from the embryotoxic effects of hyperthermia (43 degrees C); however, homozygous embryos, expressing approximately twice as much Hsp70 as heterozygous embryos, were partially protected (increased embryo viability) from the embryolethal effects of hyperthermia. Although the viability of transgenic embryos was significantly increased compared with that of nontransgenic embryos, this protection did not extend to embryo growth and development. To determine whether the failure to achieve a more robust protection was related to the expression of insufficient Hsp70 in transgenic embryos, we undertook experiments to determine whether the level of Hsp70 correlated with the level of thermotolerance induced by various lengths of a 41 degrees C heat shock. A 41 degrees C, 5-minute heat shock failed to induce Hsp70 or thermotolerance, a 41 degrees C, 15-minute heat shock induced Hsp70 and a significant level of thermotolerance, while a 41 degrees C, 60-minute heat shock induced an even higher level of Hsp70 as well as a higher level of thermotolerance. Quantitation of Hsp70 levels indicated that thermotolerance was associated with levels of Hsp70 of 820 pg/microg embryo protein or greater. Subsequent quantitation of the amount of Hsp70 expressed in homozygous transgenic embryos indicated a level of 577 pg/microg embryo protein, that is, a level below that associated with induced thermotolerance. Overall, results presented indicate that Hsp70 does play a direct role in the induction of thermotolerance in postimplantation mouse embryos; however, the level of thermotolerance is dependent on the level of Hsp70 expressed. PMID- 10030596 TI - Stabilization of fibronectin mats with micromolar concentrations of copper. AB - Fibronectin, a large extracellular matrix cell adhesion glycoprotein has diverse functions in wound repair including organization of matrix deposition and promotion of angiogenesis. We have previously shown that purified plasma fibronectin can be made into three-dimensional, fibrous materials, termed fibronectin mats (Fn-mat). The aim of this study was to examine means of increasing the stability of Fn-mats using a novel treatment with micromolar concentrations of copper ions which may be used to improve wound healing/nerve repair. Cytotoxicity of incorporated copper was determined using rat Schwann cells, rat tendon fibroblasts and human dermal fibroblasts. Dissolution of protein from the Fn-mat showed that treatment with the lowest concentration of copper used (1 microM) increased the stability of mats by 3-4 times at room temperature relative to control mats and twofold at 37 degrees C. Copper mediated increase in stability was dose dependent. Orientation of the Fn-fibres (within mats), monitored by scanning electron microscopy was retained with 1 microM copper but disappeared with higher concentrations. Schwann cells grew in culture with mats stabilized by 1 microM copper treatment without reduction in cell number but growth was inhibited at 10-200 microM Cu. All types of fibroblasts were unaffected by copper treatment upto 200 microM. Fn-mats can be successfully stabilized by this technique producing longer survival in vitro. The differential effects of copper on these cell types suggests that CuFn-mats may be used to select the type of cells which colonize these materials. PMID- 10030597 TI - An in vitro model for mineralization of human osteoblast-like cells on implant materials. AB - An in vitro mineralizing cell-implant system was developed to study osteoblast attachment, secretion of extracellular (ECM) matrix proteins and mineralization. Saos-2 cells were plated on Tivanium (Tiv, Ti-6A1-4V), Zimaloy (Zim, Co-Cr-Mo) and glass disks. The cells were cultured in alpha-MEM medium with 10% fetal bovine serum and 50 microg ml(-1) ascorbic acid. The cultures were analyzed for calcification and for mRNA expression for ECM proteins after 1, 2, 4 and 6 weeks. Calcium content was significantly higher in cells on Tiv, less on Zim and least on glass disks. With the addition of 3 mm beta-glycerophosphate (beta-GP), the cell layer was more calcified on Zim than on Tiv and all substrates had three times more calcium than cultures without beta-GP. All subsequent experiments were performed without beta-GP. Phalloidin immunofluorescence microscopy of the actin based cytoskeleton at 2 weeks demonstrated nodules composed of multilayered, cobblestone-appearing osteoblasts overlying calcified matrix which was stained with calcein. On Tiv, calcified nodules were connected in a trabecular-like pattern while on Zim, calcification was dispersed throughout the cell layer. Northern blots for alkaline phosphatase, bone sialoprotein, osteocalcin and alpha1(I) procollagen mRNAs were performed at different time points. The amount and pattern of calcification as well as the expression of ECM-mRNAs differed on each implant material. The results indicate that Tiv stimulates the production of more ECM proteins and mineralized matrix than Zim or glass in this osteoblast like cell/implant culture. PMID- 10030598 TI - Osteoblast population migration characteristics on substrates modified with immobilized adhesive peptides. AB - The process of cell migration is inextricably linked with the process of cell adhesion and, therefore, with cell/substrate adhesiveness. The present study adapted an under-agarose cell migration assay to quantitatively examine population migration characteristics of osteoblasts, on substrates modified with adhesive peptides, in the absence and presence of growth factors. Short-term, that is, 48 h osteoblast migration distances on substrates modified with adhesive Arg-Gly-Asp-Ser peptides were significantly (P < 0.05) less than migration distances on substrates modified with non-adhesive Arg-Asp-Gly-Ser peptides, demonstrating that osteoblast population haptokinesis was significantly decreased on substrates modified with adhesive peptides. Random motility coefficients calculated in the present study for osteoblast populations were an order of magnitude lower than a published random motility coefficient for leukocytes, proving quantitatively that, compared to leukocytes, osteoblasts migrate via haptokinesis more slowly. The 48 and 72 h osteoblast population migration differentials in the presence of an initial mass of 60 ng of basic Fibroblast Growth Factor, on substrates modified with Arg-Gly-Asp-Ser or with Arg-Asp-Gly Ser, were larger than all other chemotactic differentials on these substrates. Quantitative investigations (such as the present study) of cell population migration characteristics on model biomaterial surfaces will become increasingly necessary as the discipline of cell/tissue engineering matures. PMID- 10030599 TI - Resistance of antibiotic-bonded gelatin-coated polymer meshes to Staphylococcus aureus in a rabbit subcutaneous pouch model. AB - This study examines the efficacy of the bonding of rifampicin, vancomycin or gentamicin to gelatin-coated knitted polymer meshes to prevent perioperative infection. Antibiotic bonding was obtained by soaking the meshes for 15 min in a solution containing 20 mg ml(-1) of rifampicin or 10 mg ml(-1) of vancomycin or gentamicin. A polymer mesh was implanted in a subcutaneous pouch in 16 rabbits: four received a rifampicin-soaked mesh, four received a vancomycin-soaked mesh, four received a gentamicin-soaked mesh, and four received an untreated mesh (control group). At the time of implantation, all the meshes were contaminated locally with 10(8) colony forming units of Staphylococcus aureus. Meshes were harvested one week later and submitted to bacterial counts. At the time of explantation, none of the antibiotic-soaked meshes were infected, whereas all the untreated meshes were infected. These results show that antibiotic soaking evidently prevents perioperative infection of gelatin-coated knitted polymer meshes in this model. PMID- 10030600 TI - The role of trabecular demineralized bone in combination with perichondrium in the generation of cartilage grafts. AB - The use of a composite graft of bovine trabecular demineralized bone matrix (DBM) and perichondrium has been found a reliable method for in vivo generation of cartilage. In the present study, the mechanism whereby this commercially available matrix increases cartilage formation was investigated. First, the time course of cartilage formation in vivo, in the combined implant of perichondrium and DBM in the rabbit ear was studied, with special focus on tissue reactions to DBM. DBM was colonized by macrophages from day 3 post-operatively, reaching a maximum after 2 weeks. Only a minimal number of neutrophils was found. After 3 weeks the DBM appeared to be resorbed. In the first week the DBM was invaded with chondroblasts, and chondrogenesis occurred between the first and second week of implantation. After 3 weeks, the initially formed islets of cartilage had fused. Next, the chondrogenic capacity of DBM itself was investigated by implantation of DBM without perichondrium. This never resulted in cartilage formation. Immunohistochemistry showed only a faint staining of the DBM for growth factors. This indicates a minimal chondrogenic effect of DBM alone and the requirement of perichondrium as cell provider. In order to define the conditions which cause chondrogenesis in composites of perichondrium and DBM, a series of in vitro culture experiments was performed in which the in vivo situation was mimicked step by step. The basic condition was perichondrium cultured in medium with 10% FCS. In this condition, cartilage formation was variable. Because in the in vivo situation both DBM and macrophages can release growth factors, the effect of IGF1, TGFbeta2 or OP1 added to the culture medium was tested. Neither the incidence nor the amount of cartilage formation was stimulated by addition of growth factors. Perichondrium wrapped around DBM in vitro gave cartilage formation in the perichondrium but the incidence and amount were not significantly stimulated compared to cultures of perichondrium without DBM. However, cartilage-like cells were found in the DBM suggesting an effect of DBM on perichondrium-derived cells. Finally, macrophages and/or blood were added to the composite DBM-perichondrium to mimic the in vivo situation as close as possible. However, no effect of this treatment was found. In conclusion, this study indicates that DBM itself has few chondrogenic qualities but functions merely as a spacer for cell ingrowth. The fast resorption of DBM by macrophages in vivo seems of importance for the cartilage forming process, but in vitro the presence of macrophages (in combination with blood) could not enhance chondrogenesis. PMID- 10030601 TI - In vitro and in situ intercellular adhesion molecule-1 (ICAM-1) expression by endothelial cells lining a polyester fabric. AB - In order to improve long-term patency of vascular grafts, the promising concept of endothelial cell seeding is actually under investigation. Our laboratory tested a polyester coated with albumin and chitosan which permits a rapid colonization by human umbilical vein endothelial cells (HUVEC) and it seems relevant to test in vitro the expression of adhesive molecules expressed by cells with regard to the inflammatory process. We studied intercellular adhesion molecule-1 (ICAM-1) expression and focused our work on the determination of ICAM 1 sites expressed per adherent cell lining the biomaterial, thus in situ, in comparison to control HUVEC on plastic wells: the results obtained by binding experiments were correlated to flow cytometry analyses and showed that the polyester does not induce a proinflammatory state and that HUVEC covering the structure are able to respond to a stimulus. PMID- 10030602 TI - Tyrosine-PEG-derived poly(ether carbonate)s as new biomaterials. Part I: synthesis and evaluation. AB - Tyrosine PEG-derived poly(ether carbonate)s were prepared by condensation copolymerization with phosgene. The resulting polymers were random copolymers with weight average molecular weights from 40 000 to 200 000 dalton. Chemical structure and purity were confirmed by NMR and FTIR spectral analysis. General structure property correlations were established. The glass transition temperature decreased with increasing PEG content and increasing pendent chain length. When higher molecular weight PEG blocks were used, the glass transition temperature increased relative to identical polymers having shorter PEG blocks. The tensile modulus increased with decreasing PEG content, decreasing pendent chain length, and when longer PEG blocks were used. Water uptake and the rate of backbone degradation increased with increasing PEG content. Microspheres could be prepared by solvent evaporation techniques from copolymers with low PEG content. Release rate of pNA and FITC-dextran from the microspheres increased with increasing PEG content. While tyrosine-derived polycarbonates were excellent substrates for cell attachment and growth, the presence of only 5 mol% of PEG1000 led to low or no cell attachment in short-term cell culture with both rat lung fibroblasts and osteoblasts. The polymers were non-cytotoxic. PMID- 10030603 TI - Tyrosine-PEG-derived poly(ether carbonate)s as new biomaterials. Part II: study of inverse temperature transitions. AB - Tyrosine-poly(alkylene oxide)-derived poly(ether carbonate)s represent a new group of degradable biomaterials that exhibit inverse temperature transitions. Poly(DTE co 70%PEG,1000 carbonate) was chosen as an example to study this special phase transition behavior of the polymers. The observed transition temperature varied slightly depending on the technique used, e.g. CD always gave a lower temperature than UV/Vis. CD and UV/Vis studies indicated that the transition temperature was both heating rate and concentration dependent. Thermodynamic parameters of the transition (enthalpy, entropy, and free energy) were determined by DSC. The molecularity of the transition was 2.6, as calculated from UV and DSC data. The transition temperature could be varied from 18 to 58 degrees C by changing the polymer structure. The new poly(ether carbonate)s may be used in medical applications such as injectable drug delivery formulations and bioresorbable barriers for the prevention of surgical adhesions. PMID- 10030604 TI - Leukocyte spreading behavior on vascular biomaterial surfaces: consequences of chemoattractant stimulation. AB - Chemoattractant-induced phenomena of polarity and migration of polymorphonuclear leukocytes (PMN) are believed to play a key physiological role in controlling bacterial infections on implantable vascular biomaterials. Our study targeted the spreading behavior of human PMN adherent to expanded polytetrafluoroethylene (ePTFE), pretreated with various plasma proteins, in response to the chemoattractant, N-formyl-methionyl-leucyl-phenylalanine (fMLP). To this end, a novel imaging configuration was developed to allow in situ reconstructive analysis of PMN 3-D morphology on opaque ePTFE surfaces, using optical sectioning confocal microscopy. Following fMLP stimulation, PMN morphological polarity was enhanced on all substrates studied except fibrinogen treated ePTFE. 3-D PMN morphometry revealed that in the absence of fMLP, overall cell spreading was minimized on albumin-treated ePTFE and maximized on fibrinogen and immunoglobulin G-treated ePTFE. Following fMLP stimulation, overall PMN spreading increased markedly on untreated and albumin-coated ePTFE, while it stayed invariant on IgG and plasma treated ePTFE, and decreased on fibrinogen-treated ePTFE. Spatial analysis of PMN spreading following fMLP stimulation revealed enhanced PMN attachment on untreated and albumin treated ePTFE and diminished attachment on fibrinogen and plasma treated ePTFE. Thus, chemoattractant stimulation altered a wide range of PMN spreading attributes on ePTFE, including morphological polarity, substrate attachment, and 3-D membrane spreading, in a substrate dependent manner. These chemoattractant-induced spreading responses may also have important consequences for PMN phagocytosis. We report that fMLP stimulation led to enhanced unopsonized particulate phagocytosis on untreated and albumin treated ePTFE, but caused no discernible change in phagocytosis on other protein substrates. Thus, chemoattractant modulation of PMN spreading on ePTFE is highly substrate-regulated, and manifests in concerted effects on PMN phagocytosis. PMID- 10030605 TI - Investigation into the biological stability of collagen/chondroitin-6-sulphate gels and their contraction by fibroblasts and keratinocytes: the effect of crosslinking agents and diamines. AB - Artificial skin substitutes based on autologous keratinocytes cultured on collagen-based substrata are being developed for grafting onto patients with severe burns. The properties of the substratum can be manipulated by crosslinking the collagen with the glysocaminoglycan, chondroitin-6-sulphate (Ch6SO4), carbodiimides and polyamines. Biological stability, assessed by resistance to collagenase, was increased by incorporation of Ch6SO4, but crosslinking with the carbodiimides, 1-ethyl-3-(dimethylaminopropyl)carbodiimide and 1,1 carbonyldiimidazole or the polyamines, putrescine or diaminohexane, had little further benefit. Contraction of the collagen gels occurred to a greater extent when seeded with fibroblasts than with keratinocytes. The extent of contraction by either cell type was not influenced by the presence of Ch6SO4 in the gel, but the carbodiimides, and to a lesser extent the polyamines, limited cell-mediated contraction, particularly that mediated by fibroblasts. Optimum substratum composition for artificial skin substitutes will involve a compromise between the desired attributes of biological stability, rate of contraction, mechanical strength, biocompatibility and promotion of cell growth. PMID- 10030606 TI - Evaluation of the in vitro biocompatibility of various elastomers. AB - A previous study highlighted the superior shock absorption of silicone rubbers compared to other elastomers. We evaluated and compared the in vitro biocompatibility of silicone-based rubbers and propose them as an alternative to conventional products. We used the MTT colorimetric test to assess cell viability and flow cytometry to evaluate cell proliferation. Tests were conducted at 24 and 72 h. Changes in cell morphology were evaluated by scanning electron microscopy. Positive (polyurethane) and negative (polystyrene) toxicity controls were included. The number of viable cells was significantly higher on polystyrene than on polyurethane. A decrease in the total number of cells from 24 to 72 h compared to the negative control was correlated with a lower percentage of S-phase cells. The differences in cell viability noted between the samples and the polystyrene control mainly resulted from an initial lack of adhesion, which was confirmed by scanning electron microscopy. The biocompatibility of the three silicone rubbers was comparable to the best of the three products currently being used. These results, combined with those of the previous study, indicate that silicone rubber could be considered for the manufacture of mouth guards. PMID- 10030607 TI - Contact lenses and the shaping of 21st century optometry. PMID- 10030608 TI - WWW review. PMID- 10030609 TI - Assessing the predictive ability of the test-positive findings of an elementary school vision screening. PMID- 10030610 TI - On-eye power characteristics of soft contact lenses. PMID- 10030611 TI - Myocardial infarction and coronary artery involvement in giant cell arteritis. AB - PURPOSE: To describe the pathologic findings in an unusual case of giant cell arteritis that presented initially with visual loss and rapidly culminated in myocardial infarction. CASE REPORT: After the death of the patient, a complete autopsy was performed, including bilateral enucleation. All specimens, including a temporal artery biopsy completed before the patients death, were processed for routine paraffin histology and initially stained with hematoxylin and eosin. Elastic stains were subsequently used on specimens of temporal and coronary artery. The patient presented with loss of vision in the right eye. The clinical diagnosis was anterior ischemic optic neuropathy, secondary to temporal arteritis. The temporal artery biopsy was positive. Despite high-dose corticosteroid administration, the patient progressed to neurologic impairment, and subsequently to a fatal myocardial infarction. DISCUSSION: Previous reports of temporal arteritis with coronary involvement are summarized. Myocardial infarction may be a more common early complication of temporal arteritis than appreciated previously. This important complication can occur despite administration of high-dose corticosteroid therapy. PMID- 10030612 TI - Three interferometric methods for measuring the thickness of layers of the tear film. AB - The thickness of different layers of the tear film has been measured by three types of interference method, namely, wavelength-dependent fringes (WDFs), thickness-dependent fringes (TDFs), and angle-dependent fringes (ADFs). This review begins with a discussion of characteristics which are common to all these methods--high-, intermediate-, and low-index layers, phase, optical path difference, and contrast. For each of the three methods, we present a figure showing constructive and destructive interference, derive equations for calculating tear layer thickness, describe a typical optical system, and show representative results. The particular advantages and limitations of each method are discussed. Given the clinical importance of the tear film in dry eye syndrome and contact lens wear, it is unfortunate that there are considerable discrepancies among the results of interferometric and other methods for measuring tear film thickness; further development of these noninvasive, interferometric methods should help to provide a clearer picture of the thickness of different layers of the tear film, in normal and dry eyes, and in contact lens wear. PMID- 10030613 TI - Change in refractive anisometropia in presbyopic adults wearing monovision contact lens correction. AB - BACKGROUND: Researchers studying the refractive development of infant monkeys suggest that monocular refractive error changes in response to induced ametropia; specifically, slightly blurring one eye may cause a difference to develop between each eye's correction (anisometropia) when none existed before wearing the correction. The important question of whether similar changes occur in humans has not been addressed. METHODS: We compared premonovision correction and the correction after at least 12 months of monovision soft contact lens wear (artificially induced anisometropia prescribed to focus one eye for near and the other for distance so that bifocal glasses are not needed) for 62 healthy predominantly female soft contact lens wearers and (a) 62 age- and sex-matched spectacle wearers and (b) 62 age- and generally sex-matched contact lens wearers. Control patients wore corrections of like power and had similar follow-up periods. RESULTS: Development of anisometropia occurred significantly more frequently among monovision wearers than among spectacle (p = 0.043) or contact lens wearing controls (p = 0.025). Changes in anisometropia greater than or equal to 0.50 D, with amounts up to 1.25 D, occurred in 29% of monovision wearers. CONCLUSIONS: Changes in refractive correction occur for adults who have monocular blur intentionally induced with monovision contact lenses. Similar changes may also occur after refractive surgery if one eye is corrected for a different distance than the other. Care should be taken when counseling presbyopic patients so that they are aware of the possibility of inducing refractive changes after monovision correction. PMID- 10030614 TI - Corneal shape evaluation by using laser keratopography. AB - Corneal topography assessment plays a fundamental role in the detection of keratoconus and the evaluation of the refractive surgery patient. The main drawbacks of the methods based on the use of Placido's disk (the most commonly used technique) have been pointed out recently, and new techniques are being sought that allow clinicians to be more confident about the measurement. Some years ago, we proposed a new technique based on a scan of the corneal surface with a low power HeNe laser beam; by measuring the deflection of the reflected beam, it is possible to compute the shape of the scanned cornea. In this paper, we explain the basic theory behind the method and present numerical simulations which show that errors in the surface heights of less than 1 microm may be obtained. In this work, we do not consider the effect of experimental errors. We discuss some possible extensions and improvements to the theory. PMID- 10030615 TI - Study of luminance effects on pinhole test results for visually impaired patients. AB - PURPOSE: The visual acuity of visually impaired patients has been reported to improve after a refraction, despite pinhole test results that show a decline or no change in acuity. Our aim was to investigate whether the pinhole-induced reduction in retinal illuminance accounted for these unreliable predictions of best-corrected acuity. METHODS: Participants were 64 adult patients referred for low-vision rehabilitation. Neutral density filters reproduced the pinhole-induced luminance loss, allowing pinhole test and postrefraction acuities to be measured at essentially equivalent levels of retinal illuminance. The following data were collected in random order from each subject's better eye: (1) habitual visual acuity, (2) habitual visual acuity with filter, (3) habitual visual acuity with pinhole, (4) best-corrected/postrefraction visual acuity, (5) postrefraction visual acuity with filter. RESULTS: On average, the pinhole test under-estimated postrefraction visual acuity by six letters (95% confidence limits = +/- 20). The pinhole test underestimated postrefraction visual acuity with the filter by two letters (95% confidence limits = +/- 16). Among subjects whose acuity improved with the pinhole test (N = 24), 83% experienced better postrefraction visual acuity. Among subjects whose acuity declined or remained unchanged with the pinhole test (N = 40), 50% achieved better postrefraction visual acuity. CONCLUSIONS: The pinhole-induced luminance loss contributed to inadequate predictions of postrefraction visual acuity. Pinhole test results were enormously variable, underestimating and overestimating postrefraction visual acuity. The pinhole test was less reliable when improvements in postrefraction visual acuity were small. Visually impaired patients deserve periodic refractions, and the pinhole test result should not be used as a dichotomizer for clinical decisions regarding the need for a refraction. PMID- 10030616 TI - Effect of yellow filters on pupil size. AB - The purpose of this study was to investigate the size of the pupil while viewing through yellow and neutral density (ND) filters. Previous studies have shown that the pupil of the human eye is relatively more sensitive to short wavelengths than indicated by the photopic luminosity curve. We first measured the consensual horizontal pupil diameter of 11 observers as a function of luminance (0.144 to 18,150 cd/m2) to establish the luminance-response function for each observer. We then measured the pupil diameter while the observer viewed through a Corning Photochromic Filter (CPF) 550 lens and two ND filters (ND 0.5 and 1.0). The pupil diameters obtained with each filter were compared to the diameters at an equivalent luminance based upon each observer's luminance-response function. Our results show that the pupil diameter is larger with the yellow lens than when viewing a broad spectrum white field at an equivalent luminance. We speculate that our results may explain some, but not all, of the well-known subjective brightness enhancement that occurs when viewing through yellow filters. PMID- 10030617 TI - Lack of covariation of the effects of luminance and eccentricity on contrast sensitivity. AB - BACKGROUND AND PURPOSE: Qualitative individual differences in visual processing along various stimulus dimensions have been previously documented. For instance, as compared to the foveal contrast sensitivity function (CSF), the peripheral CSF of some subjects shifts toward lower frequencies, but it scales down for others; also, sensitivity to low spatial frequencies increases monotonically with luminance in some subjects, but it displays a decline at high luminances in others. Although these qualitatively distinct eccentricity- and luminance-related patterns have been thoroughly described separately, their joint occurrence has never been studied. This study aimed at determining whether there is covariation between the effects of luminance and eccentricity on contrast sensitivity, i.e., whether each eccentricity-related pattern occurs with one and only one of the luminance-related patterns. METHODS: We have measured contrast sensitivity to sine-wave grating patches as a function of luminance and eccentricity in a sample of 18 subjects. RESULTS: We found positive evidence of lack of covariation between the effects of eccentricity and luminance: we found subjects who show the same eccentricity-related pattern but differ as to their luminance-related patterns, and we have also found a subject who, unlike the rest, shows qualitatively distinct luminance-related patterns at different eccentricities. CONCLUSION: The dependence of contrast sensitivity on eccentricity and luminance is subject to qualitative variations both across and within individuals, suggesting that meaningful conclusions on the effects of luminance and eccentricity on contrast sensitivity cannot be drawn when the data from all available subjects are aggregated. PMID- 10030618 TI - Molecular and anatomic considerations in the pathogenesis of breast cancer. AB - In spite of the recent recognition of specific genes associated with an elevated lifetime incidence risk of breast cancer, the molecular mechanisms of breast tumor formation remain largely unknown. Tumorigenesis is thought to be highly complex, likely involving the accumulation of 5-10 genetic and epigenetic events. Recent investigations have begun to identify some of these events, and in vitro model systems for breast tumorigenesis, including radiation-induced breast cancer, are expected to provide further insight. Normal human breast epithelial cells exhibit a finite life span, both in vivo and in vitro. A critical event in oncogenic transformation is the ability of cells to multiply indefinitely, a phenomenon referred to as "immortalization." Using human papillomavirus (HPV) oncogenes, multiple normal breast epithelial subtypes have been shown to have distinct susceptibilities to immortalization by the HPV E6 and E7 oncogenes. Because HPV E6 and E7 inactivate two well-known tumor suppressor proteins, p53 and Rb, respectively, this suggests that a cell-type-specific predominance exists with respect to these tumor suppressor pathways. Additional evidence for variability to oncogenic stimuli among normal breast epithelial cells is provided by findings of locally confined loss of heterozygosity. An in vitro model of radiation-induced breast cancer is associated with early abrogation of p53 function. The resultant pair of normal and radiation-transformed breast epithelial cells serves as a useful system to identify other genes critically relevant to breast tumorigenesis. These and other models should help further define the molecular mechanisms underlying the early steps of breast cancer formation. PMID- 10030619 TI - Telomeric length in individuals and cell lines with altered p53 status. AB - Telomeres play an important role in maintaining chromosomal stability and are often shortened in transformed cells. p53 is the most commonly mutated gene in cancers and its status is thought to reflect the level of genomic stability. We measured telomeric length by Southern blot analysis in cells from cancer-prone syndromes and in selected cancer cells with altered p53 status. Mean telomeric lengths in the cancer-prone syndromes Li-Fraumeni syndrome, Fanconi's anemia, and ataxia telangiectasia, were shorter in the affected individuals than in their unaffected parents. We also found that altered p53 expression in selected cancer cell model systems may be associated with shortened telomeric length, but did not appear to be associated with significant alterations in telomerase activity. PMID- 10030620 TI - Effect of combined adoptive immunotherapy and radiotherapy on tumor growth. AB - Advanced squamous cell carcinomas of the head and neck are difficult to control despite optimal surgery, radiotherapy and/or chemotherapy, and the tumors are usually not immunogenic. Because of the anatomic accessibility of the tumors, local adoptive immunotherapy of these tumors is feasible and may interact with radiotherapy to retard tumor growth. It is hypothesized that antigens released from tumor cells injured by radiation may stimulate, in the presence of interleukin-2, an enhanced immunocytodestruction of live tumor cells by adoptively transferred lymphokine activated killer cells and recruited tumor cytotoxic cells. DBA/2 mice were injected subcutaneously with 5 x 10(5) syngeneic squamous cell carcinoma cells in the thigh and the resulting tumors were treated for two weeks with daily peritumoral injections of interleukin-2 (1,000 International Units) or saline, four radiation treatments of 625 cGy each, and four peritumoral injections of 10(7) lymphokine activated killer cells. The results suggested that radiotherapy combined with peritumoral injection of lymphokine activated killer cells and interleukin-2 resulted in a significant reduction (P < 0.01) of tumor size whereas radiation alone, at the same dose, failed to produce a significant effect. Such results may have direct clinical application in enhancing the response of tumors to radiotherapy and in reducing the incidence of tumor recurrence. PMID- 10030621 TI - PSA kinetics following I-125 radioactive seed implantation in the treatment of T1 T2 prostate cancer. AB - Although there is renewed interest in prostate brachytherapy, little information is available on the effect of the procedure on prostate-specific antigen (PSA) changes over time. This study describes PSA kinetics after iodine-125 (I-125) transrectal ultrasound-guided transperineal implantation of the prostate. From February 1991-September 1997, 207 patients were treated with an I-125 prostate implant alone for T1-T2 prostate cancer. PSA values were obtained prior to treatment and at 1-73 months (median, 24 months). The change in PSA after implantation of the prostate was measured as a fraction of the pretreatment PSA (PSA at follow-up/pretreatment PSA). PSA failure was defined as two elevations in PSA or PSA > 1 ng/ml. One hundred fifty-five patients had PSA values recorded at the 1-month time period. A PSA value greater than the pretreatment PSA at 1 month was found in 27% (42/155). This had no significant effect on future PSA failure. The median percentage change in PSA after implantation for all patients were as follows: 1 month, 0.73; 3 months, 0.30; 6 months, 0.18; 12 months, 0.12; 18 months, 0.12; 24 months, 0.08; 30 months, 0.07; 36 months, 0.08; 42 months, 0.08; and 48 months, 0.05. The most significant decline occurred in the first 12 months. This was followed by a more gradual decline between 12-24 months. There was little change in PSA values after 24 months. The 1-year PSA value had a significant effect on PSA failure. Patients with a 1-year PSA <1 ng/ml (66) had an actuarial 4-year freedom-from-failure rate of 90%, compared to a rate of 62% for those with values >1 ng/ml (69) (P = 0.002). Twenty-seven patients developed PSA failure. The time to PSA failure ranged from 12-48 months (median, 24 months), but most (20/27) failures occurred after 18 months. We conclude that the greatest decline in PSA after I-125 implantation of the prostate occurs during the first year, and little change occurs after 2 years. A 1-year PSA value > 1 ng/ml is highly predictive of eventual PSA failure, which occurs in most patients after 18 months posttreatment. PMID- 10030622 TI - Hyperfractionated and accelerated-hyperfractionated radiotherapy for glioblastoma multiforme. AB - Because of promising radiobiological advantages allowing dose escalation and/or reduction of treatment time, hyperfractionated and accelerated-hyperfractionated radiotherapy (hf-rt, ahf-rt) were introduced as part of treatment of glioblastoma multiforme (gbm). In December 1988 we started a prospective study of hf-rt (total dose 78 Gy, two daily fractions of 1.3 Gy, interval between daily fractions 6 hr, treatment time 6 weeks, n = 34 patients). The results were compared with our previous regimen of conventionally fractionated radiotherapy (cf-rt: total dose 60 Gy, single dose 2 Gy, treatment time 6 weeks, n = 32 patients). In June 1990, the protocol was modified in order to reduce treatment time (ahf-rt: total dose 60 Gy, two daily fractions of 1.5 Gy, interval 6 hr, treatment time 4 weeks, n = 92 patients until December 1996). No chemotherapy was given. Entry criteria were: age > or = 17 years, pathological diagnosis of supratentorial gbm, and no previous treatment other than surgery. The ahf-rt group included significantly more patients with previous surgical resection instead of biopsy only. Compared with the cf-rt group, both the hf-rt and the ahf-rt group included significantly more patients with frontal tumor location. We found no significant survival difference between the groups (median survival 7-10 months, 1-year survival rate 19%-29%). Progression-free survival, clinical course, and toxicity were also not significantly different. Karnofsky performance status, age, and corticosteroid dose during radiotherapy were the most important prognostic factors. The results of this trial are in large agreement with most previous publications. It demonstrated no improved survival. However, it showed that treatment time can be reduced by ahf-rt without loss of survival benefit or intolerable toxicity. A short radiotherapy course might be appropriate for many patients with gbm who are not suitable for rather aggressive investigational therapies. PMID- 10030623 TI - Significance of pretreatment hemoglobin level in patients with T1 glottic cancer. AB - Recent reports have suggested that pretreatment hemoglobin level (Hgb) is significantly associated with local control (LC) and overall survival (OS) in patients with T1 and T2 squamous cell carcinoma of the glottic larynx. To further evaluate the association of pretreatment Hgb level and other factors with outcome, we performed a retrospective review limited to patients with T1 squamous cell carcinoma of the glottic larynx treated with external beam radiation therapy. One-hundred thirty-nine patients with T1 squamous cell carcinoma of the glottic larynx were analyzed. Median follow-up was 5 years (range 2-22). Median pretreatment Hgb was 14.4 gm/dl (range 8.2-17.2). The following parameters were analyzed for their impact on LC, OS, and disease specific survival (DSS): age; gender; pretreatment Hgb; tumor grade; anterior commissure involvement; field size; total dose; dose per fraction; and overall treatment time. Five-year actuarial LC was 84%. Pretreatment Hgb was not a significant predictor for LC when assessed as a continuous variable (P = 0.38), nor as a dichotomous variable with a cutoff at 13 gm/dl. Local control was 82% for patients with Hgb >13 vs. 92% for Hgb < or = 13 (P= 0.13). No other factor was significant for LC. Five year actuarial OS was 74%. Univariate analysis revealed that, pretreatment Hgb, total dose, and patient age were significant factors for OS. Overall survival was 78% for patients with pretreatment Hgb > 13 gm/dl vs. 68% for patients with Hgb < or = 13 gm/dl (P = 0.004). Overall survival was 77% for patients treated with > 66 Gy vs. 67% for those treated with < or =66 Gy (P = 0.0013), and 80% for patients < or =61 years as opposed to 69% for patients older than 61 years (P = 0.017). Multivariate analysis revealed that only age (P = 0.014) and Hgb concentration (P = 0.001) retained significance. Five-year actuarial DSS was 92%. Pretreatment Hgb was not a prognostic factor for DSS, nor were any other analyzed factors. Pretreatment Hgb is not a significant prognostic factor for LC in patients with T1 squamous cell carcinoma of the glottic larynx, but it does predict for a poorer OS without affecting DSS. This suggests that patients with lower pretreatment Hgb may have confounding medical problems that detract from their overall survival. PMID- 10030624 TI - Results of a phase II concurrent chemoradiotherapy study using three-dimensional conformal radiotherapy with cisplatin and oral etoposide in stage III nonsmall cell lung cancer. AB - This phase II study was designed to utilize conformal radiation therapy with cisplatin and oral etoposide in patients with stage III or locally recurrent non small-cell lung cancer to determine tolerance and toxicity of therapy. From April 1992-February 1996, 18 patients with pathologically confirmed stage IIIA, IIIB, or locally recurrent non-small-cell lung cancer (NSCLC) were entered on study. Metastatic workup included a CT scan of the thorax and upper abdomen as well as a bone scan. Chemotherapy consisted of IV cisplatin (100 mg/m2) with IV etoposide (25 mg/m2) on day 1; oral etoposide was given (50 mg/m2) days 2-14. Using three dimensional planning, 40-45 Gy were delivered to the clinical target volume, followed by a boost to the gross tumor volume for a total of 70 Gy. Patients with recurrent disease received 40-50 Gy in total. Eighteen patients were enrolled: 16 patients were treated with curative intent and were evaluable for outcome. Two patients were treated for locally recurrent NSCLC and were not included in the outcome analysis. Stages included IIIA (44%) and stage IIIB (54%). Forty-four percent had T3/4 tumors, and 69% had N2/3 disease. Overall survival at 1 year was 64%, while 2-year overall survival was 50%. Distant metastasis-free survival at 1 year was 67%, and at 2 years 60%. The 1-year chest progression-free survival was 57%, and at 2 years 50%. Sixty-three percent required hospitalization for dehydration or neutropenia. Fifty-six percent developed leukopenia (<1,000 cells/microl) sometime during the therapy. We conclude that concurrent cisplatin and oral etoposide with conformal radiation therapy provide encouraging results in stage III lung cancer. The major toxicities of this therapy included leukopenia, thrombocytopenia, and mucosal esophagitis. Local progression of disease continues to be a problem with the current doses given. Future studies should evaluate dose escalation of radiation therapy with limited volumes, utilizing conformal radiation and chemotherapy to improve local control and potentially impact upon distant metastases. PMID- 10030625 TI - "Bacterial profile of ground beef made from carcass tissue experimentally contaminated with pathogenic and spoilage bacteria before being washed with hot water, alkaline solution, or organic acid and then stored at 4 or 12 degrees C," a comment on: J. Food Prot. 61(9):1109-1118 (1998) PMID- 10030626 TI - Response surface models for effects of temperature, pH, and previous growth pH on growth kinetics of Salmonella Typhimurium in brain heart infusion broth. AB - Response surface models were developed for effects of temperature (15 to 40 degrees C), pH (5.2 to 7.4), and previous growth pH (5.7 to 8.6) on lag time (lambda) and specific growth rate (mu) of Salmonella Typhimurium in brain heart infusion broth (BHIB). Seventy-five growth curves for model development and 30 growth curves for model validation were fit to a two-phase linear growth model to obtain direct estimates of lambda and mu of Salmonella Typhimurium in BHIB. Response surface models for natural logarithm transformations of lambda and mu as a function of temperature, pH, and previous growth pH were obtained by regression analysis. Previous growth pH did not alter (P > 0.05) or interact with temperature or pH to alter subsequent growth kinetics of Salmonella Typhimurium. However, lambda and mu of Salmonella Typhimurium in BHIB were affected (P < 0.05) by linear and quadratic effects of temperature and pH. The models were validated against data not used in their development. Mean absolute relative error of predictions (model accuracy) was 7.8% for lambda and 6.6% for mu. Median relative error of predictions (model bias) was -1.8% for lambda and -2.8% for mu. Results of the current study indicated that the models developed accurately predicted growth kinetics of Salmonella Typhimurium in BHIB within the matrix of factors modeled and that the range of previous growth pH (5.7 to 8.6) investigated did not alter the subsequent growth kinetics of Salmonella Typhimurium in BHIB. PMID- 10030627 TI - Use of capillary tubes and plate heat exchanger to validate U.S. Department of Agriculture pasteurization protocols for elimination of Salmonella enteritidis from liquid egg products. AB - D values for a five-strain cocktail of Salmonella Enteritidis in five different liquid egg products (whole egg, egg yolk, egg white, egg yolk + 5% sucrose + 5% NaCl, and egg yolk + 10% NaCl) were determined using 100-microl capillary tubes. The egg products were inoculated with approximately 1 X 10(10) organisms/ml and heated in capillary tubes to temperatures ranging from 51 to 68 degrees C for various time intervals. Using a pilot scale plate heat exchanger, the U.S. Department of Agriculture (USDA) protocols for pasteurization were also evaluated using egg products inoculated with approximately 1 x 10(7) Salmonella Enteritidis/ml. Results of experiments with capillary tubes suggested that almost all processes would result in less than the 9D process recommended by the USDA. However, when the egg products were pasteurized using the plate heat exchanger, a greater than 9D process was achieved for Salmonella Enteritidis in all products except egg yolk containing 5% sucrose + 5% NaCl, which received approximately a 4D process. PMID- 10030628 TI - Salmonella Thompson associated with improper handling of roast beef at a restaurant in Sioux Falls, South Dakota. AB - In October 1996, we investigated an outbreak of Salmonella serotype Thompson infections associated with Restaurant A in Sioux Falls, South Dakota, and conducted two cohort studies among persons who ate at luncheons catered by Restaurant A. Fifty-two Salmonella Thompson infections were identified between 29 September and 14 October 1996. Infections occurred among employees and patrons at Restaurant A and among attendees at three luncheons catered by the restaurant on 7 October. Roast beef cooked at Restaurant A was the only food item significantly associated with illness. Cooking times and storage temperatures for roast beef were inadequate to prevent multiplication of Salmonella, and the chefs were unaware of proper cooking and storage temperatures. We conclude that improper handling of roast beef probably caused this outbreak of Salmonella Thompson infections. Better knowledge of food safety practices by the cooking staff at Restaurant A, through required food safety education, might have prevented the outbreak. PMID- 10030629 TI - High prevalence of yadA-positive Yersinia enterocolitica in pig tongues and minced meat at the retail level in Finland. AB - Polymerase chain reaction (PCR) was used to determine the prevalence of yadA positive Yersinia enterocolitica in pig tongues and minced meat at the retail level in Finland and to confirm the yadA-positive Y. enterocolitica isolates recovered from the same samples using the conventional culture method. A total of 51 pig tongues purchased at 12 retail outlets and 255 minced meat samples purchased at 40 retail outlets in the Helsinki area were studied. The prevalence of Y. enterocolitica carrying the yadA gene was 92% in pig tongues and 25% in minced meat using PCR and 78% in tongues and 2% in minced meat with the culture method. The prevalence of yadA-positive tongues was higher (98%) when both PCR- and culture-positive results were included because Y. enterocolitica carrying the yadA gene could also be isolated in three PCR-negative tongue samples. In the minced meat samples, all PCR-negative samples were also culture-negative. With the culture method, 66 of 80 yadA-positive isolates in 38 tongues and all yadA positive isolates (4) in four minced meat samples were recovered after selective enrichment. A total of 92 isolates of Y. enterocolitica bioserotype 4/O:3 in tongues and 5 isolates in minced meat were found, of which 13% in tongues and 20% in minced meat did not carry the yadA gene. PMID- 10030630 TI - Inhibition of growth of Escherichia coli O157:H7 in fresh radish (Raphanus sativus L.) sprout production by calcinated calcium. AB - The inhibitory effect of calcinated calcium on the growth of Escherichia coli O157:H7 during fresh radish (Raphanus sativus L.) sprout production was studied. It was revealed that the addition of 0.4% (wt/vol) calcinated calcium into radish sprouting medium which was artificially contaminated with E. coli O157:H7 (3.0 to 3.2 log CFU/ml) completely inhibited the growth or inactivated the microorganism. When radish seed extract was used instead of radish sprout production, the same extent of growth inhibition or inactivation was observed with much lower amounts (0.07%) of calcinated calcium under similar experimental conditions. The findings suggested that calcinated calcium may be useful to control E. coli O157:H7 contamination during the production of radish sprouts. PMID- 10030631 TI - Escherichia coli O157:H7 in retail ground beef in Seattle: results of a one-year prospective study. AB - Escherichia coli O157:H7 was sought systematically in 1,400 samples of retail ground beef in Seattle in a 1-year prospective study. Sorbitol-nonfermenting, lactose-fermenting, indole-positive colonies isolated after enrichment culture were probed for the presence of Shiga toxin genes. Totals of 67,040 sorbitol nonfermenting and 66,705 sorbitol-fermenting colonies were characterized, but E. coli O157:H7 was not identified. The sensitivity of this technique was usually sufficient to detect E. coli O157:H7 at a concentration below 1 CFU/g of meat. These data demonstrate that retail ground beef in Seattle is neither frequently nor heavily contaminated with E. coli O157:H7. PMID- 10030633 TI - Decontamination of beef carcass surface tissue by steam vacuuming alone and combined with hot water and lactic acid sprays. AB - Hot beef carcass surface regions (outside round, brisket, and clod) contaminated with feces spread over a 5-cm2 (1-in2) area were cleaned using a steam-vacuum spot-cleaning system alone or combined with subsequent sanitizing treatments of hot water (95 degrees C at the nozzle), or warm (55 degrees C) 2% lactic acid spray, or combinations of these two sanitizing methods. These treatments were compared for effectiveness in reducing aerobic plate counts (APC) and counts of Enterobacteriaceae, total coliforms, thermotolerant coliforms, and Escherichia coli. All treatments significantly reduced the numbers of each group of bacteria on beef carcass surfaces. However, reductions obtained by steam vacuuming were significantly smaller than those obtained by a combination of steam vacuuming with any sanitizing treatment. No differences in bacterial reductions were observed between different carcass surface regions. Steam vacuuming reduced the number of different indicator organisms tested by ca. 3.0 log cycles but also spread the bacterial contamination to areas of the carcass surface adjacent to the contaminated sites. This relocated contamination after steam vacuuming was most effectively reduced by spraying with hot water and then lactic acid. This combined treatment consistently reduced the numbers of Enterobacteriaceae, total and thermotolerant coliforms, and E. coli to undetectable levels (<1.0 log10 CFU/cm2) on areas outside the initial 5-cm2 inoculated areas. PMID- 10030632 TI - Sources and extent of microbiological contamination of beef carcasses in seven United States slaughtering plants. AB - This study determined microbiological loads of beef carcasses at different stages during the slaughtering to chilling process in seven (four steer/heifer and three cow/bull) plants. Potential sources of contamination (feces, air, lymph nodes) were also tested. Each facility was visited twice, once in November through January (wet season) and again in May through June (dry season). Carcasses were sampled by aseptic excision of surface tissue (100 cm2) from the brisket, flank, and rump (30 samples each) after hide removal (pre-evisceration), after final carcass washing, and after 24-h carcass chilling. The samples were analyzed individually by standard procedures for aerobic plate counts (APC), total coliform counts (TCC), Escherichia coli biotype I counts (ECC), and presence of Salmonella. Incidence of Salmonella was higher on dry feces of older compared to younger animals, fresh feces of younger compared to older animals, and on cow/bull carcasses compared to steer/heifer carcasses. Most factors and their interactions had significant (P < or = 0.05) effects on the bacterial counts obtained. Depending on plant and season, APC, TCC, and ECC were < or =10(4), < or =10(2), and < or =10(1) CFU/cm2 in 46.7 to 93.3, 50.0 to 100.0, and 74.7 to 100.0% of the samples, respectively. TCC exceeded 10(3) CFU/cm2 in 2.5% (wet season) and 1.5% (dry season) of the samples. ECC exceeded 10(2) CFU/cm2 in 8.7%, 0.3%, and 1.5% of the pre-evisceration, final carcass-washing, and 24-h carcass chilling samples, respectively, during the wet season; the corresponding numbers during the dry season were 3.5%, 2.2%, and 3.0%, respectively. These data should serve as a baseline for future comparisons in measuring the microbiological status of beef carcasses, as the new inspection requirements are implemented. PMID- 10030634 TI - Microbiological contamination of reindeer carcasses in different reindeer slaughterhouses. AB - The microbiological contamination of reindeer carcasses was studied in 10 Finnish reindeer slaughterhouses. Six of the slaughterhouses were field slaughterhouses and four were plant slaughterhouses. In each slaughterhouse 11 to 30 carcasses were sampled, with abdomen, brisket, and foreleg as sampling sites. Sampling was performed immediately after slaughter, using a nondestructive swabbing method. The overall mean bacterial count of carcasses was 3.12+/-0.61 log CFU/cm2. The mean bacterial value of the carcasses and the bacterial counts of abdomen and brisket were significantly lower in field slaughterhouses than in plant slaughterhouses, suggesting that the controlled conditions of plant slaughterhouses do not necessarily improve the microbiological quality of reindeer carcasses. However, the highest bacterial contamination was found in a field slaughterhouse where the slaughter was performed after rain when the ground was without snow. Carcass contamination seemed to be increased by the use of an evisceration apron, the unnecessary washing of forelegs, and the unnecessary handling of carcasses with hands and arms. PMID- 10030635 TI - Residual triose phosphate isomerase activity and color measurements to determine adequate cooking of ground beef patties. AB - The objectives were to (i) compare the use of triose phosphate isomerase (TPI) activity and internal color scores for determination of cooking adequacy of beef patties and (ii) determine the effect of frozen storage and fat content on residual TPI activity in ground beef. Ground beef patties (24.4% fat) were cooked to five temperatures ranging from 60.0 to 82.2 degrees C. TPI activity decreased as beef patty cooking temperature was increased from 60.0 to 71.1 degrees C; however, no difference (P > 0.05) in activity (6.3 U/kg meat) was observed in patties cooked to 71.1 degrees C and above. Degree of doneness color scores, a* values and b* values, of ground beef patties decreased as internal temperature was increased from 60.0 to 71.1 degrees C; however, temperature had no effect on L* values. TPI activity in raw ground beef after five freeze-thaw cycles did not differ from the control. Three freeze-thaw cycles of raw ground beef resulted in a 57.2% decrease in TPI activity after cooking. TPI activity of cooked beef increased during 2 months of frozen storage, but TPI activity in ground beef stored for 3 months or longer did not differ from the unfrozen control. While past research has shown color to be a poor indicator of adequate thermal processing, our results suggest that undercooked ground beef patties could be distinguished from those that had been adequately cooked following U.S. Department of Agriculture guidelines using residual TPI activity as a marker. PMID- 10030636 TI - Ex vivo effects of lactobacilli, streptococci, and bifidobacteria ingestion on cytokine and nitric oxide production in a murine model. AB - Increasing numbers of functional foods and pharmaceutical preparations are being promoted with health claims based on the potential probiotic characteristics of lactic acid bacteria and on their capacity for stimulating the host immune system. However, the specific immune effects of oral administration of these microbes still remains undefined. In this study, we tested the hypothesis that production of immunologic mediators by leukocytes in mice is affected by orally administered lactic acid bacteria. The specific objectives of this study were to evaluate the effects of exposure to eight different lactic acid bacteria in mice on ex vivo cytokine and nitric oxide production in leukocyte cultures. Mice were gavaged with 1 X 10(9) viable bacteria and peritoneal, Peyer's patch and splenic leukocytes were isolated 8 h later. These were cultured for 2 or 5 days in the presence or absence of mitogens and then interleukin (IL)-6, IL-12, interferon (IFN)-gamma, tumor necrosis factor (TNF)-alpha, and nitric oxide production was measured. The results revealed that Lactobacillus acidophilus and L. casei potentiated IL-6 and IL-12 production by peritoneal cells whereas L. acidophilus upregulated IFN-gamma and nitric oxide. In contrast, L. helveticus, L. gasseri, L. reuteri, and Bifidobacterium attenuated the production of IL-6, IFN-gamma, and nitric oxide by peritoneal cells. TNF-alpha was not detectable in peritoneal cultures. None of the bacteria altered ex vivo production of cytokines or nitric oxide by Peyer's patch or spleen cell cultures. Taken together, the results suggest that prior oral exposure to lactic acid bacteria could differentially potentiate or attenuate subsequent cytokine and nitric oxide production by peritoneal cells. PMID- 10030637 TI - Development and validation of a dynamic growth model for Listeria monocytogenes in fluid whole milk. AB - Listeria monocytogenes, a psychrotrophic microorganism, has been the cause of several food-borne illness outbreaks, including those traced back to pasteurized fluid milk and milk products. This microorganism is especially important because it can grow at storage temperatures recommended for milk (< or =7 degrees C). Growth of L. monocytogenes in fluid milk depends to a large extent on the varying temperatures it is exposed to in the postpasteurization phase, i.e., during in plant storage, transportation, and storage at retail stores. Growth data for L. monocytogenes in sterilized whole milk were collected at 4, 6, 8, 10, 15, 20, 25, 30, and 35 degrees C. Specific growth rate and maximum population density were calculated at each temperature using these data. The data for growth rates versus temperature were fitted to the Zwietering square root model. This equation was used to develop a dynamic growth model (i.e., the Baranyi dynamic growth model or BDGM) for L. monocytogenes based on a system of equations which had an intrinsic parameter for simulating the lag phase. Results from validation of the BDGM for a rapidly fluctuating temperature profile showed that although the exponential growth phase of the culture under dynamic temperature conditions was modeled accurately, the lag phase duration was overestimated. For an alpha0 (initial physiological state parameter) value of 0.137, which corresponded to the mean temperature of 15 degrees C, the population densities were underpredicted, although the experimental data fell within the narrow band calculated for extreme values of alpha0. The maximum relative error between the experimental data and the curve based on an average alpha0 value was 10.42%, and the root mean square error was 0.28 log CFU/ml. PMID- 10030638 TI - A preliminary survey of antibiotic residues and viable bacteria in milk from three Caribbean Basin countries. AB - There is widespread concern about the presence of antimicrobial drugs in milk. The presence of drug residues in milk may have public health implications. Milk samples (n = 25 to 65/country) were collected from bulk tanks and commercial vendors in Barbados, Costa Rica, and Jamaica between February 1996 and August 1997. Bulk tank samples were collected from high milk-producing regions of Jamaica and Costa Rica and from 26 dairy farms in Barbados. Milk pH, bacterial growth (total CFU/ml and the presence of Streptococcus agalactiae and Staphylococcus aureus), and the presence of antimicrobials were determined. Milk samples were tested by a microbial inhibition test (Delvotest-P, Gist-Brocades Food Ingredients, Inc.) to screen for antimicrobial drugs. All positives were retested for the presence of beta-lactam antibiotics after incubating with penicillinase and some positives were identified by high-pressure liquid chromatography-UV. Mean pH values ranged from 6.5 to 6.7. S. aureus was identified in bulk tank samples from Costa Rica (52%), Barbados (44%), and Jamaica (46%). S. agalactiae was identified in bulk tank samples from Costa Rica (28%), Barbados (8 and 16%), and Jamaica (18%). Antimicrobial residues were detected in some bulk tank samples from Barbados (8%) and Jamaica (10%) but not in samples from Costa Rica. All positives in milk from Jamaica and Barbados were determined to be beta-lactams. No residues were detected in pasteurized milk samples from Barbados or ultrahigh-temperature milk from Jamaica. The presence of beta-lactam residues in some of these samples suggests the appropriateness of testing milk prior to processing for consumption. PMID- 10030639 TI - Effects of yogurt ingestion on mucosal and systemic cytokine gene expression in the mouse. AB - To assess the potential for ingestion of yogurt to modulate immunity, its effects on basal gene expression of cytokines in systemic and mucosal sites were determined in mice. Yogurts were manufactured from pasteurized nonfat dry milk using five commercial starter cultures with or without Bifidobacterium sp. and Lactobacillus acidophilus. Treatment mice were fed the AIN-93G diet mixed 1:1 with unheated yogurt or heat-treated yogurt (wt/wt) for 2 and 4 weeks, and control mice were fed the AIN-93G diet mixed 1:1 (wt/wt) with nonfat dry milk. The viability of the various bacterial groups in unheated yogurts was maintained above 10(6) CFU/g throughout the feeding period. The yogurt-feeding regimens did not significantly affect weight gain. Relative mRNA levels in spleen, mesenteric lymph nodes, or Peyer's patches for the cytokines interferon-gamma, tumor necrosis factor-alpha, interleukin-2, -4, and -6, and the "housekeeping gene" beta2-microglobulin were determined by reverse transcriptase-polymerase chain reaction in conjunction with hybridization analysis. Prolonged feeding of some yogurts decreased expression of several cytokine mRNAs, the depression of tumor necrosis factor-alpha mRNA in the spleen being the most prominent effect. Heat treated yogurts were more effective in altering cytokine mRNA expression than were unheated yogurts containing viable organisms. Generally, yogurts either had no effect or decreased specific cytokine mRNA in the test organs, regardless of whether they contained Bifidobacterium sp. and L. acidophilus. These results suggest that, in contrast with previous studies in vitro, some yogurt formulations may reduce rather than stimulate basal cytokine expression and that these effects are most prominent in the systemic compartment. PMID- 10030640 TI - A differential medium for the isolation of Kluyveromyces marxianus and Kluyveromyces lactis from dairy products. AB - A selective and differential solid medium, called Kluyveromyces Differential Medium (KDM), is described for the isolation of Kluyveromyces marxianus and K. lactis from dairy products. Its discriminative potential is based on the detection of the enzyme beta-galactosidase, in the absence of lactose. Of the more than 95 strains tested, including yeasts, bacteria, and filamentous fungus, only the strains of K. marxianus and K. lactis produced blue colonies on the medium due to the presence of X-Gal/ IPTG. The bacterial strains were not able to grow in KDM. On this basis, the medium was very satisfactory when testing naturally or experimentally contaminated dairy food products. When quality assessment tests were performed, optimal values of productivity (growth and color) and selectivity were obtained for K. marxianus and K. lactis. PMID- 10030641 TI - Fate of gram-positive bacteria in reconditioned, pork-processing plant water. AB - This study investigated the responses of Enterococcus faecium (ATCC 19433), Staphylococcus aureus (196E), and Listeria monocytogenes Scott A in water from a local meat-processing plant. Each bacterium was added to a starting count of 3 log10 CFU/ml and held from 5 to 28 degrees C. At intervals (0, 2, 7, 14, and 21 days), aliquots were plated on appropriate selective agars. In contrast to the gram-negative bacteria studied previously and which grew, the three gram-positive bacteria survived with some slight increase in number in only nonchlorinated, reconditioned water, either filtered (0.22 microm pore size) or nonfiltered. The presence of chlorine in either potable or reconditioned water contributed to the rapid decline in viable counts for all three bacteria. These results further emphasize the importance of residual chlorine in preventing the growth of these gram-positive bacteria in potable and reconditioned waters. PMID- 10030642 TI - Evaluation of immunomagnetic separation and plating media for recovery of Salmonella from meat. AB - Immunomagnetic separation (IMS) was compared with selective enrichment in selenite cystine (SC) broth for isolation of Salmonella from 86 artificially contaminated ground beef samples. Both Rambach agar (RA) and Hektoen enteric (HE) agar were used as selective plating media. The highest count of Salmonella colonies per plate was obtained after enrichment in SC broth and plating on RA (mean value: 111.1+/-58.1 CFU per plate); the lowest count was obtained after IMS and plating on HE agar (mean value: 65.4+/-36.6 CFU per plate). Salmonella in preenrichment was concentrated 1.7-fold by IMS and represented 31% of the microbial population captured by the beads, but nonspecific binding was high. As a result of the large numbers of competing bacteria, isolations on both RA and HE agar following IMS were quite difficult (mean value for Salmonella colonies: 79.9+/-42.7 CFU per plate; mean value for non-Salmonella colonies: 144.1+/-75.7 CFU per plate; ratio of Salmonella to non-Salmonella colonies: 0.8). This study indicates that SC broth is superior to IMS in the isolation of Salmonella from raw ground meat. PMID- 10030643 TI - Analysis of underivatizated patulin by a GC-MS technique. AB - An alternative approach based on the use of gas chromatography-mass spectrometry (GC-MS) is used to confirm the presence of patulin in apple juice. In the gas chromatography (GC) methods previously described, derivatization of patulin was always necessary in order to achieve good chromatographic detection. The use of electronic pressure control (EPC) and on-column injection avoids the need for patulin derivatization and allows a sensitive analysis of patulin. A detection limit of 4 microg/liter in apple juice can be attributed to the method. PMID- 10030644 TI - Assessment of borderzone ischemia with a combined MR imaging-MR angiography-MR spectroscopy protocol. AB - We attempted to assess whether magnetic resonance imaging (MRI)-MR angiography (MRA)-MR spectroscopy (MRS) measurements can be used in the differentiation of patients in whom severe carotid lesions result in chronically hypoperfused regions and in whom the collateral capacity is sufficient to maintain a normal cerebral blood flow. Sixty-six patients with severe stenosis of the internal carotid artery (ICA) and 19 control subjects underwent MRI, 1H MRS, and MRA. Anaerobic metabolic changes in the middle cerebral artery (MCA) territory were studied by assessing N-acetyl-L-aspartate (NAA)/choline and lactate/ NAA ratios. Quantitative flow was measured in the ICA, in the basilar artery, and in the MCA. Thirty-four patients had borderzone infarcts, 16 patients had territory infarcts, and 16 patients had no infarcts on MRI. Patients with border-zone infarcts had significantly reduced flow in the ICA (P < 0.001) and in the MCA (P < 0.05) and decreased NAA/ choline ratios (P < 0.001) in non-infarcted regions compared with control subjects (P < 0.001) but also compared with patients with territory infarcts (P < 0.05) and patients without infarcts (P < 0.05). Flow measurements in the ICA and MCA and metabolic measurements in the MCA territory can be applied to select patients in whom cerebral perfusion pressure is insufficient to maintain normal cellular integrity. PMID- 10030645 TI - Metabolic characterization of AIDS dementia complex by spectroscopic imaging. AB - Prospective proton chemical shift imaging (CSI) of the brain was performed in 30 HIV- 1-seropositive patients and 11 healthy controls. Significant (P < 0.05) reductions in the N-acetyl-L-aspartate (NAA)/total creatine (Cr), and NAA/total choline (Cho) ratios and significant increases in Cho/Cr occurred in patients with 1) AIDS-defining diagnoses; 2) <200 CD4 lymphocyte counts/microl; 3) neurological evidence for an AIDS dementia complex (ADC); 4) magnetic resonance imaging (MRI) signs of cerebral atrophy. The basal ganglia and the insula were affected to approximately the same extent and without indications of spatial variations within these areas. Reduced NAA seems to indicate progressive neuronal injury or loss due to productive HIV infection in the brain and its clinical picture ADC. Spectroscopic abnormalities were, however, also observed in neurologically normal HIV patients or those with normal MRI results. Proton CSI may therefore serve as an early quantitative marker of central nervous system involvement in AIDS. PMID- 10030646 TI - Influence of acoustic masking noise in fMRI of the auditory cortex during phonetic discrimination. AB - The application of functional magnetic resonance imaging (fMRI) to study activation of auditory cortex suffers from one significant confounding factor, namely, that of the acoustic noise generated by the gradient system, which is an integral part of the imaging process. Earlier work has shown that it is indeed possible to distinguish cortical activation resulting from presentation of auditory stimuli despite the presence of background noise from the gradient system. The influence of acoustic noise from the gradient system of the MRI scanner on the blood oxygen level-dependent (BOLD) response during functional activation of the auditory cortex has been investigated in six healthy subjects with no hearing difficulties. Experiments were performed using gradient-echo echoplanar imaging (EPI) and a verbal, auditory discrimination paradigm, presented in a block-wise manner, in which carefully aligned consonant-vowel syllables were presented at a rate of 1 Hz. For each volunteer the experiment was repeated three times with all parameters fixed, except slice number, which was 4, 16, or 64. The positioning of the central four slices in each experiment was common. Thus, the fraction of TR during which the stimulus is on but no imaging is being performed, varies from almost zero, in the case of 64 slices, to over 8 seconds, in the case of four slices. Only the central four slices were of interest; additional slices simply generated acoustic noise and were discarded. During the four-slice experiment, all subjects showed a robust BOLD response in the superior temporal gyrus covering the primary and secondary auditory cortex. The spatial extent and the z-scores of the activated regions decreased with longer duration of gradient noise from the scanner. For a phonetic discrimination task, the results indicate that presentation of the stimulus during periods free from scanner noise leads to a more pronounced BOLD response. PMID- 10030647 TI - Magnetic resonance imaging and cochlear implants: compatibility and safety aspects. AB - With cochlear implants, magnetic resonance imaging (MRI) has until recently been contraindicated due to excessive magnetic and electromagnetic interference. The aim of this study was to determine the MRI compatibility of the Med-E1 Combi 40/40+ cochlear implant, within a wide range of clinical MRI applications. In vitro experiments on a 1.5 T MR scanner were performed. Torque, force, demagnetization, artifacts, induced voltages, and temperature increase were measured in worst case scenarios for the implant. In addition, stabilization experiments were performed. It was shown that most of the electromagnetic interferences between the cochlear implant and the 1.5 T scanner remained within acceptable limits. One exception is the torque on the internal magnet, which represents a hazard for patients with these cochlear implants. Therefore, MRI examination should only be performed if there is a strong medical indication, and certainly some assessment of the relative risks involved versus the risk of not providing the diagnostic capabilities of MRI, will have to be made. Appropriate safety measures should be taken. PMID- 10030648 TI - Automated T2 quantitation in neuropsychiatric lupus erythematosus: a marker of active disease. AB - Active neuropsychiatric systemic lupus erythematosus (NPSLE) is characterized by brain edema as measured by manual quantitative magnetic resonance (MR) relaxometry. An automated image processing method was developed to segment gray matter (GM), while minimizing the effects of confounding factors, specifically cerebral atrophy and volume averaging artifacts. Twenty patients with SLE (10 major, 10 minor), matched for atrophy, were studied. We compared T2 calculated for GM segmented by manual and automated methods. Both methods demonstrated a marked increase in GM T2 in patients with major NPSLE (P < 0.001), confirming the presence of cerebral edema. The results from each method were highly correlated, (r = 0.64, P = 0.002). The automated method effectively identifies GM, minimizes volume averaging artifacts, and produces results similar to the manual method. This method markedly decreases analysis time and will make quantitative relaxometry a valuable contribution to the clinical management of NPSLE. PMID- 10030649 TI - Regional cerebral blood volume: a comparison of the dynamic imaging and the steady state methods. AB - Accurate assessment of regional cerebral blood volume (rCBV) is of critical importance in the study of cerebrovascular disease and other disorders of the central nervous system. Currently, magnetic resonance imaging (MRI) is able to measure rCBV non-invasively with two commonly used methods: the dynamic imaging (DI) and steady state (SS) approaches. In this study, two questions were investigated. First, how do partial volume effects between gray matter (GM) and white matter (WM) and between epicortical vessels and brain parenchyma affect the estimation of rCBV when using the SS approach? Second, how comparable are the ratios of rCBV in GM to rCBV in WM (rCBV GM/WM) obtained with the two methods? We used a paramagnetic contrast agent, OPTIMARK (Mallinckrodt, St. Louis, MO), at a dose of 0.2 mmol/kg in anesthetized pigs (n = 6) to obtain rCBV maps using both methods. When a 10% rCBV threshold was used to minimize effects from large epicortical vessels, and tissue segmentation was used to separate GM from WM, rCBV values of 4.8 +/- 0.3% and 3.3 +/- 0.5% were obtained for GM and WM, respectively, with the SS approach. Significantly higher rCBV values for both GM (P < 0.001) and WM (P < 0.01) were observed when the contribution from large epicortical vessels was not removed. When tissue segmentation and rCBV thresholding were used on SS data, an rCBV GM/WM ratio of 1.5 +/- 0.2 was obtained. This value did not differ significantly from the rCBV GM/WM ratio of 1.8 +/- 0.6 obtained using the DI approach. PMID- 10030650 TI - Usefulness of diffusion-weighted MRI with echo-planar technique in the evaluation of cellularity in gliomas. AB - The purpose of this study was to evaluate the utility of diffusion-weighted magnetic resonance imaging (MRI) with echo-planar imaging (EPI) technique in depicting the tumor cellularity and grading of gliomas. Twenty consecutive patients (13 men and 7 women, ranging in age from 13 to 69 years) with histologically proven gliomas were examined using a 1.5 T superconducting imager. Tumor cellularity, analyzed with National Institutes of Health Image 1.60 software on a Macintosh computer, was compared with the minimum apparent diffusion coefficient (ADC) and the signal intensity on the T2-weighted images. The relationship of the minimum ADC to the tumor grade was also evaluated. Tumor cellularity correlated well with the minimum ADC value of the gliomas (P = 0.007), but not with the signal intensity on the T2-weighted images. The minimum ADC of the high-grade gliomas was significantly higher than that of the low-grade gliomas. Diffusion-weighted MRI with EPI is a useful technique for assessing the tumor cellularity and grading of gliomas. This information is not obtained with conventional MRI and is useful for the diagnosis and characterization of gliomas. PMID- 10030652 TI - Magnetic resonance navigator echo diaphragm monitoring in patients with suspected diaphragm paralysis. AB - Real-time magnetic resonance (MR) navigator echo (NE) monitoring of the diaphragm is now possible. Using this technique, temporal changes in diaphragm position can be analyzed in a non-invasive fashion, without x-ray exposure. In this preliminary study, we have optimized three NE parameters (the NE column area, the NE repeat time, and the location of the NE on the diaphragm surface), and demonstrated the clinical application of MR NE diaphragm monitoring in patients with suspected diaphragm paralysis. The NE parameters were defined in 10 healthy volunteers, and diaphragm traces were scored for variance in NE diaphragm position registration. Using the optimal NE column parameters, we investigated four patients with diaphragm paralysis, one of whom required positive pressure ventilation while in the MR scanner, to show the utility of this technique. The NE diaphragm position registration was significantly affected by the area of the NE column, with poor position registration for the smallest column area (2.25 cm2 vs. 4 cm2 vs. 6.25 cm2, variance 6.3 vs. 0.6 vs. 0.3, P = 0.006). Diaphragm position registration was also significantly affected by the NE repeat time, with misregistration for the shortest repeat time (250 msec vs. 500 msec vs. 1000 msec, variance 11.9 vs. 0.6 vs. 1.0, P = 0.02), and data clipping, with loss of end-expiratory and end-inspiratory position registration, for the longest repeat time. Finally, if the NE was positioned too anteriorly, the diaphragm traces were of poor quality (anterior vs. dome vs. posterior, variance 11.8vs. 0.6vs. 3.2, P < 0.001). Application of the technique confirmed diaphragm paralysis in all four patients. The technique can be applied during positive pressure ventilation if necessary. The optimal NE parameters for diaphragm monitoring at 0.5 T were: column area, 400 mm2; NE repeat time; 500 msec; NE column positioned on the diaphragm dome. MR NE diaphragm monitoring provides a safe, non-invasive method of assessing diaphragm motion in patients with suspected diaphragm paralysis and may prove useful for long-term follow-up and monitoring of therapeutic interventions in these subjects. PMID- 10030651 TI - Prospective comparison of MR lung perfusion and lung scintigraphy. AB - This study attempted to assess the accuracy and potential of lung magnetic resonance (MR) perfusion imaging compared with perfusion scintigraphy in the evaluation of patients with suspected lung perfusion defects. The technique, which uses an inversion recovery turbo-FLASH sequence with ultra-short TE (1.4 msec), was tested in 24 patients suspected clinically of having acute pulmonary embolism (n = 19) and in patients with severe pulmonary emphysema (n = 5). Perfusion lung scintigraphy was performed within 48 hours prior to the MRI examination in both groups of patients. The dynamic study was acquired in the coronal plane and consisted of 10 images of 6 slices (a total of 60 images per series). Gadopentetate dimeglumine (0.1 mmol/kg) was manually injected as a compact bolus during the acquisition of the first image. Three senior radiologists reviewed all unprocessed two-dimensional coronal sections. They were blinded to clinical data and other imaging modalities. For the three observers, the average sensitivity and specificity of MR were 69% and 91%, respectively. The overall agreement between MR and scintigraphy appears to be good, with a good correlation between the two modalities (kappa = 0.63). However, the data showed variability depending on the location of the perfusion defect, with higher accuracy in the upper lobes. The agreement between MR perfusion and scintigraphy appears to be moderate in the left inferior lobe (kappa = 0.48). The data showed an overall good interobserver agreement (kappa = 0.66). MR perfusion of the lung is a promising technique in detecting lung perfusion defects. PMID- 10030653 TI - Assessment of gastric motor function during the emptying of solid and liquid meals in humans by MRI. AB - Gastric emptying and motility have previously been assessed by magnetic resonance imaging (MRI) using liquid test meals. The aim of this study was to extend the applicability of our MRI method to the assessment of gastric emptying and motility of solid meals. Gastric emptying and motility of a liquid and a solid meal, of similar chemical properties, were studied in eight volunteers. The MRI protocol combined a multislice turbo spin-echo (TSE) sequence (volume scan, resolution: 1.5 mm) and a dynamic FFE sequence (motility scan, 1 sec/image, resolution: 3.1 mm). Gastric emptying of the liquid meal was faster than emptying of the solid meal when considering half-times of emptying. However, during the first 15 minutes after ingestion, the liquid meal emptied more slowly. This was related to reduced motility with the liquid meal. In conclusion, with our MRI method it is feasible to assess gastric emptying and motility of liquid and solid meals. PMID- 10030654 TI - Differentiation of hepatic malignancies from hemangiomas and cysts by T2 relaxation times: early experience with multiply refocused four-echo imaging at 1.5 T. AB - The purpose of this study was to examine hepatic lesions with a sequence designed to yield improved T2 measurements and evaluate the clinical utility of these measurements in distinguishing malignant from benign disease. Using a modified Carr-Purcell sequence incorporating features designed to compensate for imperfections in the imaging system, including a train of refocusing pulses emitted in an MLEV pattern oriented in composite fashion along all three coordinate axes, and a single spatially selective pulse placed immediately before a spiral readout, 14 benign lesions and 13 malignant lesions were evaluated prospectively with a conventional 1.5 T imager. The maximum, minimum, and mean T2 values of malignant lesions, hemangiomas, and cysts exceeded corresponding published values from spin-echo and echoplanar studies. The mean T2 value of the malignant lesions differed significantly (P < 0.0001) from those of hemangiomas and cysts. All malignant lesions and all benign lesions were distinguishable by their T2 values, which had ranges of no greater than 118.6 msec and no less than 134.3 msec, respectively. This early experience suggests that improved T2 measurements can facilitate the differentiation of hepatic malignancies from hemangiomas and cysts. PMID- 10030655 TI - Echo-train STIR MRI of the liver: comparison of breath-hold and non-breath-hold imaging strategies. AB - The purpose of this study was to evaluate echo-train short inversion-time inversion recovery (STIR) sequences and compare the results obtained with breath hold and non-breath-hold imaging strategies. Forty-one patients referred for hepatic magnetic resonance were imaged with both a breath-hold STIR (BH-STIR; acquisition time [TA] 16-20 seconds x 2) and a non-breath-hold STIR (NBH-STIR; TA 210-256 seconds). Quantitative analysis of the liver, spleen, and up to five hepatic lesions per patient was performed. Three blinded readers recorded the number of focal lesions depicted by each study and qualitatively evaluated overall image quality, lesion conspicuity, and image artifacts. The BH-STIR had greater sensitivity (98.8% vs. 91.6%) for detection of hepatic lesions than the NBH-STIR. The BH-STIR was statistically superior in four measures of image quality and had fewer image artifacts. The NBH-STIR images had statistically higher signal-to-noise (S/N, P < 0.001) and liver-lesion contrast-to-noise (C/N, P = 0.005) ratios. For the evaluation of focal hepatic lesions, a breath-hold echo-train STIR sequence provided superior overall image quality and allowed for detection of more lesions in a shorter amount of time than a non-breath-hold echo train STIR sequence. PMID- 10030656 TI - MRI of primary lymphoma of bone: cortical disorder as a criterion for differential diagnosis. AB - To investigate the pattern and dimension of cortical bone abnormality on magnetic resonance imaging (MRI) as a feature to distinguish primary lymphoma of bone from osteosarcoma and Ewing sarcoma, 46 patients with primary malignant bone lesions with a soft tissue mass (16 osteosarcomas, 15 Ewing sarcomas, 15 lymphomas) were examined with MRI (T1-weighted pre-/postcontrast spin-echo sequences and T2 weighted spin-echo and fast spin-echo sequences; 1.5 T system). Qualitative image analysis revealed no differences for signal characteristics and enhancement. Lymphomas appeared significantly more often homogeneous (47%; Ewing sarcoma 20%; osteosarcoma 6%/o), and patients were significantly older (cutoff point 30 years). Lymphomas showed significantly less frequent cortical abnormality (60%; Ewing sarcoma 87%; osteosarcoma 100%), complete penetration (13%; Ewing sarcoma 67%; osteosarcoma 87%), focal destruction (13%; Ewing sarcoma 40%; osteosarcoma 81%), and complete destruction (0%; Ewing sarcoma 13%; osteosarcoma 19%). In conclusion, primary lymphoma of bone is characterized by minimal cortical changes despite an accompanying soft tissue mass in a patient over 30 years of age. PMID- 10030657 TI - Assessment of myocardial function and perfusion in a canine model of non occlusive coronary artery stenosis using fast magnetic resonance imaging. AB - Magnetic resonance (MR) functional and perfusion imaging were employed in a canine model of coronary artery stenosis (n = 6) for the quantification of functional and perfusion deficits before and after dipyridamole administration. Left anterior descending and circumflex (LCX) coronary blood flow were measured continuously after placing Doppler flowmeters. Inversion recovery gradient echo images during the transit of MR contrast medium gadolinium benzyloxypropionictetraacetate dimeglumine (Gd-BOPTA/Dimeg) and fast breath-hold cine MR images were acquired at baseline, during LCX stenosis in basal state, and during LCX stenosis with vasodilation (dipyridamole 0.5 mg/kg). The extent of the functional defect and perfusion defect was expressed as percent of left ventricle (LV) circumference. During stenosis (LCX flow: 62.6 +/- 5.6% of baseline) the extent of the functional defect was slightly larger than the perfusion defect (11.0 +/- 1.8% versus 6.3 +/- 1.70% of LV circumference, respectively; P < 0.01). During vasodilation the extent of the functional defect was considerably smaller than the perfusion defect (25.3 +/- 2.5% versus 35.3 +/- 3.5%; P < 0.01). Thus, the sizes of ischemic regions displayed by MR perfusion defect and functional defect differ from each other. PMID- 10030658 TI - Three-dimensional motion tracking with volumetric phase contrast MR velocity imaging. AB - Motion tracking based on single-slice cine-phase contrast magnetic resonance imaging data has limitations. In the presence of nontrivial three-dimensional motion and deformation, volumetric data are necessary for accurate reconstruction of material point trajectories. A three-dimensional Fourier tracking method that uses volumetric data for motion tracking is presented. The method reconstructs a material point trajectory by computing its various harmonics. For any given temporal sampling rate, a frequency domain perspective of the tracking problem indicates that the method is accurate in estimating all reconstructible harmonics of a trajectory. The algorithm incorporates an intra-voxel linear spatial model into the integration to address potential tracking performance degradation due to possibly reduced spatial resolution, which may be most relevant in the slice direction (z) if the volumetric data are obtained as multiple two-dimensional slices. The tracking method was evaluated on computer-generated data sets that simulated various motion patterns. The method was also tested with two sets of in vitro data obtained using a phantom, one acquired as multiple two-dimensional slices and the other using a three-dimensional sequence capable of higher spatial resolution in the z direction. These studies demonstrated that the algorithm can achieve high sub-voxel tracking accuracy. PMID- 10030659 TI - Construction of a protocol for measuring blood flow by two-dimensional phase contrast MRA. AB - Our aim is to describe and demonstrate the steps we have found to be useful in the construction and evaluation of protocols for triggered and nontriggered measurement of blood flow by two-dimensional phase-contrast magnetic resonance angiography (MRA). To achieve this goal, we start with a survey of factors governing the accuracy (validity) and precision (repeatability) of MR flow measurements. This knowledge, combined with prior information regarding the diameter of the target vessel and the prevailing flow conditions, is then employed to define a protocol for measuring flow with negligible systematic error. In the absence of a gold standard for in vivo flow measurements, the protocol is subsequently validated for a range of flow conditions by representative phantom experiments. Precision is then calculated from the signal to-noise ratio (SNR) of blood in the accompanying magnitude images or, less conveniently, estimated from the standard deviation of repeated measurements. The desired precision is finally achieved by adjusting the appropriate SNR parameters. All steps involved in protocol development are demonstrated for both flow-independent and flow-dependent acquisitions. PMID- 10030660 TI - Investigation of longitudinal vascular changes in control and chemotherapy treated tumors to serve as therapeutic efficacy predictors. AB - The impact of chemotherapy on longitudinal vascular changes taking place during the growth of an animal tumor, R3230 AC adenocarcinoma, was investigated. Two contrast agents of different molecular weights, gadolinium-diethylene-triamine pentaacetic acid (Gd-DTPA; < 1 kD) and gadomer-17 (35 kD), were used in the dynamic imaging studies. Enhancement kinetics were analyzed by a pharmacokinetic model to derive parameters related to vascular volume and permeability on a pixel by-pixel basis. Responders and non-responders were separated according to tumor size 10 days after the therapy. Changes in the vascular volume measured by gadomer-17 at 4 days after therapy revealed a clear distinction between the controls and the responders/non-responders. Mean vascular volume decreased by 42% in responders but was not significantly changed in the controls. The one non responder had increased vascular volume after chemotherapy. Enhancement kinetics of gadomer-17 detected the changes earlier and with greater sensitivity than Gd DTPA. In the control group, vascular permeability determined by gadomer-17 correlated with the longitudinal growth rates of tumors, suggesting that vascular permeability assessed by gadomer-17 could potentially serve as an indicator of aggressive tumor growth. PMID- 10030661 TI - Temperature measurement using echo-shifted FLASH at low field for interventional MRI. AB - We investigated the feasibility of using echo-shifted fast low-angle shot (FLASH) for temperature-monitored thermo-therapeutic procedures in a 0.2 T interventional magnetic resonance (MR) scanner. Based on the proton resonance frequency shift technique, modified echo-shifted FLASH has sufficiently high signal-to-noise ratio to provide accurate temperature maps with short scan times, i.e., 5 seconds in phantoms (TR = 20.5 msec; effective TE = 30 msec; one echo shift; NSA = 2) and ex vivo experiments (TR = 19.4 msec; effective TE = 28.9 msec; one echo shift; NSA = 2) and 3 seconds (TR = 19.4 msec; effective TE = 28.9 msec, one echo shift; NSA 1) for an in vivo case. The proton resonance frequency shifts with temperature observed in a 0.2 T MR scanner using this sequence were -0.0072 ppm/degrees C (temperature uncertainty = +/-2.5 degrees C) for polyacrylamide phantoins and -0.0086 ppm/degrees C (temperature uncertainty = +/- 1 degrees C) for ex vivo bovine liver. These experiments demonstrated that echo-shifted FLASH is a viable method for low-field temperature monitoring despite the decreased signal and decreased phase sensitivity compared with its counterpart in a 1.5 T MR imaging system. The improved temporal resolution of temperature images, now possible in low-field interventional MR systems using echo-shifted FLASH, will allow clinicians more accurate monitoring of interstitial ablation in MR-guided interventional procedures. PMID- 10030662 TI - Extraslice spin tagging (EST) magnetic resonance imaging for the determination of perfusion. AB - A new magnetic resonance technique to measure perfusion is described in detail. The means by which this is done is to invert all the spins in the radiofrequency RF coil with a non-spatially selective pulse and immediately re-invert the spins in the imaging plane. The net effect is that the spins in the imaging plane experience minimal perturbation of their magnetization while the spins outside the plane (extraslice) are inverted, or tagged. Tagged spins that flow into the imaging plane before image data are acquired decrease the signal intensity in the imaging plane when compared with an image in which the inflowing spins are not tagged. This decrease in signal can be used to calculate the number of spins that have flowed into the imaging plane, i.e., can be used to calculate the perfusion in mL x 100 g(tissue)(- 1)x min(-1). The extraslice spin tagging (EST) magnetization preparation period was coupled with a fast imaging sequence to obtain perfusion maps for normal volunteers. PMID- 10030663 TI - MRI in patients with intraspinal bullets. AB - The purpose of this study was to determine whether neurologic sequelae occur in patients with intraspinal bullets or bullet fragments who undergo magnetic resonance imaging (MRI). Nineteen patients with bullets or bullet fragments adjacent to the cord or nerve roots underwent clinical MRI studies at 1.5 T. Sequences included conventional spin echo, fast spin echo, gradient-recalled echo, and inversion recovery. Patients were queried during scanning for symptoms of discomfort, pain, or change in neurologic status. Detailed neurologic examinations were performed prior to MRI (baseline), post MRI, and at the patients' discharge. Sixteen patients were completely paralyzed (ASIA-A), and three were not paralyzed. The length of time from injury was 2-24 months. No patients experienced pain or discomfort during the procedure. No change in neurologic status occurred. Follow-up radiographic studies showed no bullet movement following the scanning. We conclude that in patients with complete spinal cord injury, MRI in patients with intraspinal bullets may be performed. PMID- 10030664 TI - Role of hypoxia-induced Bax translocation and cytochrome c release in reoxygenation injury. AB - We investigated mechanisms of cell death during hypoxia/reoxygenation of cultured kidney cells. During glucose-free hypoxia, cell ATP levels declined steeply resulting in the translocation of Bax from cytosol to mitochondria. Concurrently, there was cytochrome c release and caspase activation. Cells that leaked cytochrome c underwent apoptosis after reoxygenation. ATP depletion induced by a mitochondrial uncoupler resulted in similar alterations even in the presence of oxygen. Moreover, inclusion of glucose during hypoxia prevented protein translocations and reoxygenation injury by maintaining intracellular ATP. Thus, ATP depletion, rather than hypoxia per se, was the cause of protein translocations. Overexpression of Bcl-2 prevented cytochrome c release and reoxygenation injury without ameliorating ATP depletion or Bax translocation. On the other hand, caspase inhibitors did not prevent protein translocations, but inhibited apoptosis during reoxygenation. Nevertheless, they could not confer long-term viability, since mitochondria had been damaged. Omission of glucose during reoxygenation resulted in continued failure of ATP production, and cell death with necrotic morphology. In contrast, cells expressing Bcl-2 had functional mitochondria and remained viable during reoxygenation even without glucose. Therefore, Bax translocation during hypoxia is a molecular trigger for cell death during reoxygenation. If ATP is available during reoxygenation, apoptosis develops; otherwise, death occurs by necrosis. By preserving mitochondrial integrity, BCL-2 prevents both forms of cell death and ensures cell viability. PMID- 10030665 TI - A telomere-independent senescence mechanism is the sole barrier to Syrian hamster cell immortalization. AB - Reactivation of telomerase and stabilization of telomeres occur simultaneously during human cell immortalization in vitro and the vast majority of human cancers possess high levels of telomerase activity. Telomerase repression in human somatic cells may therefore have evolved as a powerful resistance mechanism against immortalization, clonal evolution and malignant progression. The comparative ease with which rodent cells immortalize in vitro suggests that they have less stringent controls over replicative senescence than human cells. Here, we report that Syrian hamster dermal fibroblasts possess substantial levels of telomerase activity throughout their culture life-span, even after growth arrest in senescence. In our studies, telomerase was also detected in uncultured newborn hamster skin, in several adult tissues, and in cultured fibroblasts induced to enter the post-mitotic state irreversibly by serum withdrawal. Transfection of near-senescent dermal fibroblasts with a selectable plasmid vector expressing the SV40 T-antigen gene resulted in high-frequency single-step immortalization without the crisis typically observed during the immortalization of human cells. Collectively, these data provide an explanation for the increased susceptibility of rodent cells to immortalization (and malignant transformation) compared with their human equivalents, and provide evidence for a novel, growth factor sensitive, mammalian senescence mechanism unrelated to telomere maintenance. PMID- 10030666 TI - Rac1 is required for the formation of three germ layers during gastrulation. AB - The Rac1, a member of the Rho family proteins, regulates actin organization of cytoskeleton and cell adhesion. We used genetic analysis to elucidate the role of Rac1 in mouse embryonic development. The rac1 deficient embryos showed numerous cell deaths in the space between the embryonic ectoderm and endoderm at the primitive streak stage. Investigation of the primary epiblast culture isolated from rac1 deficient embryos indicated that Rac1 is involved in lamellipodia formation, cell adhesion and cell migration in vivo. These results suggest that Rac1-mediated cell adhesion is essential for the formation of three germ layers during gastrulation. PMID- 10030667 TI - Ryk is expressed in a differentiation-specific manner in epithelial tissues and is strongly induced in decidualizing uterine stroma. AB - Ryk is a ubiquitously expressed tyrosine kinase-like receptor of unknown activity and associations. We examined ryk expression in adult mouse epithelial tissues and during embryonic development at the histological level. Ryk RNA is present at greatly increased levels in cells at particular stages of epithelial differentiation: the basal layer of skin and tongue epithelia, the intervillous layer and some crypt bases of the intestine and the lower matrix region of the hair follicle. Although ryk RNA is expressed at similar levels in a variety of tissues from embryonic day 10.5 to 18.5, specific induction of ryk RNA can be seen by in situ hybridization in the basal layer of skin and hair follicle at day 15.5-16.5, and protein staining localizes to the hair follicle by immunohistochemistry. At day 4.5 and 6.5, little if any ryk is present in the blastocyst, but it is transiently induced at a high level in mature decidual cells of the uterine stroma. We review a number of independent isolations of ryk, including fruit fly and nematode members of the ryk family. Because ryk is induced in epithelial cells seeking a final place in a differentiated tissue, or during remodeling of the endometrium, and a homologous gene, derailed, is known to regulate muscle and nerve target seeking in Drosophila, ryk may also be involved in cellular recognition of appropriate context. PMID- 10030668 TI - Re-expression of endogenous p16ink4a in oral squamous cell carcinoma lines by 5 aza-2'-deoxycytidine treatment induces a senescence-like state. AB - We have previously reported that a set of oral squamous cell carcinoma lines express specifically elevated cdk6 activity. One of the cell lines, SCC4, contains a cdk6 amplification and expresses functional p16ink4a, the other cell lines express undetectable levels of p16ink4a, despite a lack of coding-region mutations. Two of the cell lines, SCC15 and SCC40 have a hypermethylated p16ink4A promoter and a third cell line, SCC9, has a mutation in the p16ink4a promoter. Using the demethylation agent 5-aza-2'-deoxycytidine, we showed that the p16ink4a protein was re-expressed after a 5-day treatment with this chemical. One cell line, SCC15 expressed high levels of p16ink4a. In this line, cdk6 activity was decreased after 5-aza-2'deoxycytidine treatment, and the hypophosphorylated, growth suppressive form of the retinoblastoma tumor suppressor protein pRB was detected. Expression of p16ink4a persisted, even after the drug was removed and the cells expressed senescence-associated beta-galactosidase activity. Ectopic expression of p16ink4a with a recombinant retrovirus in this cell line also induced a similar senescence-like phenotype. Hence, it was possible to restore a functional pRB pathway in an oral squamous cell carcinoma line by inducing re expression of endogenous p16ink4a in response to treatment with a demethylating agent. PMID- 10030669 TI - Telomeric repeats on small polydisperse circular DNA (spcDNA) and genomic instability. AB - Small polydisperse circular DNA (spcDNA) is a heterogeneous population of extrachromosomal circular molecules present in a large variety of eukaryotic cells. Elevated amounts of total spcDNA are related to endogenous and induced genomic instability in rodent and human cells. We suggested spcDNA as a novel marker for genomic instability, and speculated that spcDNA might serve as a mutator. In this study, we examine the presence of telomeric sequences on spcDNA. We report for the first time the appearance of telomeric repeats in spcDNA molecules (tel-spcDNA) in rodent and human cells. Restriction enzyme analysis indicates that tel-spcDNA molecules harbor mostly, if not exclusively, telomeric repeats. In rodent cells, tel-spcDNA levels are higher in transformed than in normal cells and are enhanced by treatment with carcinogen. Tel-spcDNA is also detected in some human tumors and cell lines, but not in others. We suggest, that its levels in human cells may be primarily related to the amount of the chromosomal telomeric sequences. Tel-spcDNA may serve as a unique mutator, through specific mechanisms related to the telomeric repeats, which distinguish it from the total heterogeneous spcDNA population. It may affect telomere dynamics and genomic instability by clastogenic events, alterations of telomere size and sequestration of telomeric proteins. PMID- 10030670 TI - Activation and repression of p21(WAF1/CIP1) transcription by RB binding proteins. AB - The Cdk inhibitor p21(WAF1/CIP1) is a negative regulator of the cell cycle, although its expression is induced by a number of mitogens that promote cell proliferation. We have found that E2F1 and E2F3, transcription factors that activate genes required for cell cycle progression, are strong activators of the p21 promoter. In contrast, HBP1 (HMG-box protein-1), a novel retinoblastoma protein-binding protein, can repress the p21 promoter and inhibit induction of p21 expression by E2F. Both E2Fs and HBP1 regulate p21 transcription through cis acting elements located between nucleotides -119 to +16 of the p21 promoter and the DNA binding domains of each of these proteins are required for activity. Sequences between -119 and -60 basepairs containing four Sp1 consensus elements and two noncanonical E2F binding sites are of major importance for E2F activation, although E2F1 and E2F3 differ in the extent of their ability to activate expression when this segment is deleted. The opposing effects of E2Fs and HBP1 on p21 promoter activity suggest that interplay between these factors may determine the level of p21 transcription in vivo. PMID- 10030671 TI - EB1, a protein which interacts with the APC tumour suppressor, is associated with the microtubule cytoskeleton throughout the cell cycle. AB - The characteristics of the adenomatous polyposis coli (APC) associated protein EB1 were examined in mammalian cells. By immunocytochemistry EB1 was shown to be closely associated with the microtubule cytoskeleton throughout the cell cycle. In interphase cells EB1 was associated with microtubules along their full length but was often particularly concentrated at their tips. During early mitosis, EB1 was localized to separating centrosomes and associated microtubules, while at metaphase it was associated with the spindle poles and associated microtubules. During cytokinesis EB1 was strongly associated with the midbody microtubules. Treatment with nocodazole caused a diffuse redistribution of EB1 immunoreactivity, whereas treatment with cytochalasin D had no effect. Interestingly, treatment with taxol abolished the EB1 association with microtubules. In nocodazole washout experiments EB1 rapidly became associated with the centrosome and repolymerizing microtubules. In taxol wash-out experiments EB1 rapidly re-associated with the microtubule cytoskeleton, resembling untreated control cells within 10 min. Immunostaining of SW480 cells, which contain truncated APC incapable of interaction with EB1, showed that the association of EB1 with microtubules throughout the cell cycle was not dependent upon an interaction with APC. These results suggest a role for EB1 in the control of microtubule dynamics in mammalian cells. PMID- 10030672 TI - Identification of a human HECT family protein with homology to the Drosophila tumor suppressor gene hyperplastic discs. AB - Use of the differential display technique to isolate progestin-regulated genes in T-47D human breast cancer cells led to identification of a novel gene, EDD. The cDNA sequence contains a 2799 amino acid open reading frame sharing 40% identity with the predicted 2894 amino acid product of the Drosophila melanogaster tumor suppressor gene hyperplastic discs, while the carboxy-terminal 889 amino acids show 96% identity to a rat 100 kDa HECT domain protein. EDD mRNA was progestin induced in T-47D cells and was highly abundant in testes and expressed at moderately high levels in other tissues, suggesting a broad role for EDD. Anti EDD antibodies immunoprecipitated an approximately 300 kDa protein from T-47D cell lysates. HECT family proteins function as E3 ubiquitin-protein ligases, targeting specific proteins for ubiquitin-mediated proteolysis. EDD is likely to function as an E3 as in vitro translated protein bound ubiquitin reversibly through a conserved HECT domain cysteine residue. EDD was localized by FISH to chromosome 8q22, a locus disrupted in a variety of cancers. Given the homology between EDD and the hyperplastic discs protein, which is required for control of imaginal disc growth in Drosophila, EDD potentially has a role in regulation of cell proliferation or differentiation. PMID- 10030673 TI - Expression of dominant negative Erk2 inhibits AP-1 transactivation and neoplastic transformation. AB - The mitogen activated protein (MAP) kinases or extracellular signal-regulated kinases (Erks) are activated in response to Ras expression or exposure to tumor promoters or to growth factors, and have been implicated in AP-1 transactivation in some models. We have shown that tumor promoter induced activation of the transcription factor AP-1 is required for induced neoplastic transformation in the Balb/C JB6 cell model. Jun and Fos family protein levels have been found not to be limiting for AP-1 response. The present study asks whether activation of Erks1 and 2 is required for AP-1 transactivation and transformation of JB6 cells and whether Erks might be targeted for cancer prevention. Expression of either of two different dominant negative kinase inactive Erk2 mutants in transformation sensitive (P+) JB6 cells substantially inhibited the tumor promoter induced activation of Erks1 and 2 and of AP-1 measured by a collagenase-luciferase reporter. Multiple mutant Erk2 expressing clonal lines were also rendered non responsive to induced neoplastic transformation. These observations, together with our recent finding attributing AP-1 non-responsiveness to Erk deficiency in a clonal line of transformation resistant (P-) cells, argue for a requirement for Erks1 and/or 2 activation in AP-1 transactivation in the mouse JB6 neoplastic progression model, and suggest the utility of Erks as a prevention target. PMID- 10030674 TI - Novel regions of allelic deletion on chromosome 18p in tumors of the lung, brain and breast. AB - Lung cancer is now the number one cause of cancer death for both men and women. An age-adjusted analysis over the past 25 years shows that in women specifically, lung cancer incidence is on the rise. It is estimated that 10-20 genetic events including the alteration of oncogenes and tumor suppressor genes will have occurred by the time a lung tumor becomes clinically evident. In an effort to identify regions containing novel cancer genes, chromosome 18p11, a band not previously implicated in disease, was examined for loss of heterozygosity (LOH). In this study, 50 matched normal and NSCLC tumor samples were examined using six 18p11 and one 18q12.3 PCR-based polymorphic markers. In addition, LOH was examined in 29 glioblastoma pairs and 14 paired breast carcinomas. This analysis has revealed potentially two regions of LOH in 18p11 in up to 38% of the tumor samples examined. The regions of LOH identified included a 2 cm area between markers D18S59 and D18S476, and a more proximal, 25 cm region of intermediate frequency between D18S452 and D18S453. These results provide evidence for the presence of one or more potential tumor suppressor genes on the short arm of chromosome 18 which may be involved in NSCLC, brain tumors and possibly breast carcinomas as well. PMID- 10030675 TI - Mutant p53 can provoke apoptosis in p53-deficient Hep3B cells with delayed kinetics relative to wild-type p53. AB - Wild-type (wt) p53 frequently induces apoptosis when expressed in tumor cells whereas mutant p53 acts as an oncoprotein and consequently, stimulates cell proliferation. We report here exceptions to that rule. p53 conformational mutant 175H and DNA contact mutant 273H provoke apoptosis in human p53-deficient Hep3B hepatoma cells with delayed kinetics relative to wt p53. Similarly, c-Myc strongly stimulates apoptosis in these cells. In contrast, viral oncoproteins E1A and E7, and the cellular oncoprotein MDM-2, fail to elicit cytocidal responses. Efficient apoptotic cell death by mutant p53 requires oligomerization as 175H and 273H with deletions between amino acid residues 326 and 347 of the oligomerization domain are nontoxic. Apoptosis by mutant or wt p53 was significantly inhibited by the serine protease inhibitor AEBSF but not by the inactive analog AEBSA. Together, these results suggest that a wt p53-independent control mechanism is operational in Hep3B cells that eliminates cells upon sensing illegitimate proliferation signals originating from certain oncoproteins, including mutant p53 and Myc. We suggest that some tumor cell types lack p53 altogether because they tolerate neither wild-type nor mutant forms of the protein. PMID- 10030677 TI - Galvanic stimulation evokes short-latency EMG responses in sternocleidomastoid which are abolished by selective vestibular nerve section. AB - OBJECTIVE: To describe vestibulocollic responses in sternocleidomastoid (SCM) evoked by transmastoid galvanic (DC) stimulation. METHODS: We studied the averaged responses in the unrectified EMG of SCM to transmastoid galvanic stimulation (5 mA/2 ms) and also to 100 dB clicks. Two patients with Meniere's disease were studied both before and after unilateral selective vestibular nerve section. RESULTS: Transmastoid galvanic stimulation produced a positive-negative biphasic EMG response at short latency in the SCM ipsilateral to the side of cathode placement, which resembled that which followed vestibular activation by loud clicks (p13/n23). Selective unilateral vestibular nerve section abolished this galvanic-evoked response. CONCLUSIONS: Galvanic-evoked vestibulocollic responses can be recorded in SCM. This is a new method of studying vestibular reflex function which may have application in the clinical assessment of vestibular disorders. PMID- 10030676 TI - Isolation and characterization of a human homologue of the latrophilin gene from a region of 1p31.1 implicated in breast cancer. AB - We have identified a region of chromosome 1p31.1 that shows high frequency loss of heterozygosity (LOH) in human breast cancer. This region forms part of a 7 Mb YAC/BAC contig. In order to identify candidate sequences, mutation of which might contribute to the development of disease, we have carried out mapping studies of ESTs localized to 1p31.1. This analysis, coupled with library screening and a modified 5' RACE-PCR strategy, resulted in the identification and characterization of a novel gene (LPHH1) which is located adjacent to the smallest region of overlapping loss (SRO) seen in tumours. The 4209 bp open reading frame of the 7 kb LPHH1 transcript encodes a peptide which shows approximately 65% identity to rat latrophilin, a G-coupled, seven span transmembrane protein, which binds alpha-latrotoxin. In the human sequence, whilst conservation of the transmembrane domain is high, the intra- and extracellular domains show two regions of variable structure, which are presumably generated by alternative splicing. Surprisingly, while expression of the rat gene is tightly restricted to neurological and perhaps some endocrine cells, the human sequence appears to be expressed very widely in all normal tissues tested. Northern and RT-PCR analysis of a panel of tumour cell lines showed that LPHH1 expression was variable, apparently elevated in some lines and absent or markedly reduced in others. Furthermore, characterization of the range of transcripts encoded in a breast tumour cell line, compared to normal breast, suggested that gene product variability was higher in the tumour. PMID- 10030678 TI - H-reflex modulations during voluntary and automatic movements following upper motor neuron damage. AB - OBJECTIVES: It is not known whether similar mechanisms account for the impairments of voluntary movement and automatic postural responses of individuals with spasticity secondary to damage to the sensorimotor cortex and its projections (i.e. upper motor neuron syndrome (UMN)). METHODS: The present study examined changes in soleus H-reflexes preceding and during voluntary tibialis anterior (TA) muscle contraction of standing subjects and during balance platform induced postural perturbations that elicited similar TA muscle contractions. Twenty-two subjects (12 non-disabled; 4 with spastic-type cerebral palsy; 6 with adult-onset cerebral vascular accident) participated in the study. Data were analyzed using ANOVAs and Tukey HSD post-hoc comparison tests to assess the timing and magnitude of soleus H-reflex amplitude changes relative to the onset of TA muscle activation. RESULTS: Results indicated that, regardless of the level of TA activation, soleus H-reflexes of subjects with UMN involvement did not demonstrate inhibition either. during voluntary movements or during automatic postural perturbations. CONCLUSIONS: These findings indicate that postural reflexes, as well as volitional movements, are impaired following UMN damage and that deficits in neural pathways subserving reciprocal inhibition contribute to the impairments. PMID- 10030679 TI - Body position can be monitored in 3D using miniature accelerometers and earth magnetic field sensors. AB - OBJECTIVES: The study and diagnosis of movement disorders can be improved by monitoring body position simultaneously with the EMG. METHODS: We developed a monitor of the 3-dimensional (3D) orientation of body parts that can be applied in long-term ambulatory recordings in the daily life of a patient. The 3D sensor combines miniature sensors for earth's gravity and magnetism. It measures 60 x 50 x 10 mm and draws less than 1 mA of current from +/-5 V battery power. The non horizontal direction of earth magnetism, as well as torque (pronation) of the body part, is corrected mathematically. RESULTS: This results in a measurement of the 3D orientation of a body part in terms of vertical inclination and horizontal azimuth. CONCLUSIONS: Calibration measurements indicate that this method is fairly accurate and practically applicable. PMID- 10030680 TI - Reduced excitability of the cortico-spinal system during the warning period of a reaction time task. AB - Seven subjects made a wrist flexion movement as rapidly as possible in response to a cutaneous shock on the opposite hand. In some trials, an auditory warning signal was given 0.5 s beforehand. In random trials, transcranial magnetic stimulation (TMS) was used to elicit EMG responses (MEPs) in forearm flexor and extensor muscles 0-500 ms before the cutaneous shock. H-reflexes were elicited in flexor muscles at the same intervals. The warning stimulus reduced reaction time from about 400 ms to 200 ms. MEPs in the flexor muscles were significantly suppressed from 125 ms after the warning stimulus until the time of the cutaneous shock whilst MEPs in the extensors, and H-reflexes in the flexor were either unaffected, or reduced by a smaller amount at a later time. Responses in relaxed contralateral muscles were unchanged. If the task was changed to a choice reaction, in which the imperative stimulus (but not the warning signal) indicated whether to flex or extend the wrist, then there was no change in the MEPs or H reflex in the warning period. A similar effect was seen if the duration of the warning period was extended from 0.5 to 2 s in a simple reaction (flexion) task. We conclude that increased excitability of the corticospinal output is not required to speed up reaction times. The time taken to discharge cortical output elements is relatively unimportant compared with the time needed to process the sensory input and link it to the motor output. PMID- 10030681 TI - Can medical audit change electromyographic practice? AB - Considerable variation in EMG practice has been described previously. Since 1992, 7 clinical neurophysiologists from 6 European countries prospectively collected electromyographic (EMG) examinations. The aim of this study was to examine whether several years of mutual influence among physicians using medical audit resulted in a more uniform EMG practice. We studied whether there was a change in the number of examinations per patient and the techniques used from the first 12 to the last 12 EMG examinations on patients with polyneuropathy. For F-wave studies and motor nerve studies, there was a clear change towards a more uniform practice. For sensory nerve conduction studies and muscle studies, there were only minor changes. With regard to examination techniques, there was a reduction in the use of more time-consuming examination techniques (near-nerve sensory studies and quantitative muscle studies). It seems possible to change the EMG practice of individual physicians by international collaboration and medical audit. However, until now most changes have been minor and large differences in European EMG practices persist. The diversity of practices suggests a need for studies on the optimal application of existing examination techniques. PMID- 10030682 TI - Age-dependent changes in physiological threshold asymmetries for the motor evoked potential and silent period following transcranial magnetic stimulation. AB - OBJECTIVE: To study the effect of age on the physiological threshold asymmetries for the motor evoked potential (MEP) and silent period (SP) following transcranial magnetic stimulation. METHODS: We studied 63 right-handed subjects and 13 young left-handed subjects (19-39 years). The right-handers were classified into three age groups; 22 young (20-38 years), 20 middle-aged (40-58 years) and 21 old (61-82 years) subjects. We measured the MEP thresholds at rest and during voluntary contraction (VC), and the SP thresholds from the right and left abductor pollicis brevis (APB) muscles. We also measured the side to side differences of the F wave persistency and the F wave/M wave amplitude ratio from the same muscles. RESULTS: Among young subjects, all of the MEP and SP thresholds for the right APB were significantly lower than those for the left APB in the right-handers, and the reverse was true in the left-handers. The results in the middle-aged right-handers were similar to those in the young right-handers, but in the old right-handers, none of the thresholds were different between the two sides. We did not find any asymmetries of the F wave in the subjects of any age group. CONCLUSION: We speculate that the age-dependent threshold asymmetries are preferentially related to functional asymmetries at the cortical level. PMID- 10030683 TI - Conditioning of the masseter inhibitory reflex by homotopically applied painful heat in humans. AB - During contraction of the jaw-closing muscles, afferent input from the intraoral and perioral region can elicit two bilateral suppression periods (SP1 and SP2, respectively) in the masseter electromyogram (EMG). Non-painful electrical stimulation 2 cm from the left labial commissure was used in the present study to evoke these trigeminal inhibitory reflexes. The subjects maintained a level of 50% of their maximum masseter EMG. The degree of suppression was quantified as the percentage suppression of the mean EMG activity in a fixed post-stimulus interval (SP2, 40-90 ms). Further, brief (200 ms) painful radiant heat conditioning stimuli were delivered to the ipsilateral cheek, in order to investigate the influence of nociceptive input on the (non-nociceptive) trigeminal masseter inhibitory reflex. Nine different conditions combining radiant heat and electrical stimuli were used. Twelve stimuli were presented for each condition. The radiant heat preceded the electrical test stimuli by fixed inter-stimulus intervals (ISI), ranging from 100 ms to 500 ms. At 250-350 ms ISIs, the bilateral SP2 suppression was significantly reduced to less than 10%, in comparison to an average suppression degree of 32.5% without conditioning stimuli. The subjects perceived the heat stimulus before the electrical stimulus for a majority of the 12 pairs of stimuli at these ISIs. No differences were found in the VAS ratings for the different conditions. For the contralateral SP1, larger suppression was seen for the 300 ms ISI compared with stimulation without conditioning heat stimuli. Onset and offset for the SP1 was, however, only detected in three subjects using a criteria of 20% suppression of the pre stimulus activity. A pre-pulse inhibitory effect onto inter-neurons in the SP2 pathways or habituation of the same inter-neurons by the heat stimuli are suggested as possible explanations for the interaction between the non nociceptive and nociceptive input in the present study. PMID- 10030684 TI - Immediate effects of therapeutic facilitation on the gait of hemiparetic patients as compared with walking with and without a cane. AB - OBJECTIVES: Although the neurodevelopmental technique (Bobath) is the most widely used approach in the gait rehabilitation of hemiparetic subjects in Europe, there is little neurophysiological evidence for its presumed effects on gait symmetry and facilitation of paretic muscles during the therapeutic intervention. The study, therefore, investigated the immediate effects of gait entrainment by a physical therapist on the gait of hemiparetic subjects. METHODS: Cycle parameters, gait symmetry, hip joint movement and the electromyographic activity of several lower limb muscles were assessed in 22 patients during a classic intervention by five Bobath therapists and while walking with and without a cane. RESULTS: Multivariate statistics revealed that, while being assisted by the therapist, patients walked faster (P = 0.022), with a longer relative stance period of the affected leg (P = 0.005), a higher symmetry (P = 0.002), larger hip extension (P = 0.001) and more activation (P = 0.026) of the Mm. triceps surae, vastus lateralis, biceps femoris and gluteus medius as compared to walking with and without a cane. Extensor spasticity of the plantar-flexor tended to increase (n.s.). In five subjects, no after-effect could be documented 1 h after a gait training of 30 min. CONCLUSIONS: The study confirmed a more balanced walking pattern in conjunction with facilitation of various weight bearing muscles during the therapeutic intervention. A prolonged single stance period of the affected leg, an unobstructed hip movement, enhanced weight acceptance and a faster gait seemed to be responsible for the observed immediate effects of the therapeutic intervention. PMID- 10030685 TI - Delayed focal involvement of upper motor neurons in the Madras pattern of motor neuron disease. AB - We report the case of a young man from the south of India, initially presenting the typical signs of benign monomelic amyotrophy (BMA) in the left upper limb. After several years, the involvement of other limbs and the appearance of bulbar signs suggested the possible diagnosis of the Madras pattern of motor neuron disease (MMND). Serial motor evoked potential (MEP) recordings allowed detection of the onset of a focal involvement of upper motor neurons (UMN) controlling innervation in the originally amyotrophic limb. Therefore, serial MEP recordings can be useful for the early detection of sub-clinical UMN damage in motor neuron disease presenting with pure lower motor neuron (LMN) signs. PMID- 10030687 TI - Relationships of liver weight, cholesterol, albumin and alpha2-macroglobulin concentrations with ovarian function in swine. AB - In two genetic swine models selected for diversity in ovulation rates (White composite controls and ovulation rate selection line, n = 131; 1/2 White composite: 1/2 Meishan crossbreds, n = 387), a positive relationship was established with liver weight and ovulation rate (P < 0.01). Serum changes of cholesterol, albumin and alpha2-macroglobulin were monitored during various stages of the luteal phase and follicular phase (days 17 and 19 of the estrous cycle; 1/2 White composite: 1/2 Meishan gilts). Serum cholesterol concentrations increased with liver weights (r = 0.19; P < 0.01) and corpora lutea numbers (r = 0.14; P < 0.01). Albumin concentrations were negatively correlated with corpora luteal numbers (r = -0.3; P < 0.01) but had no relationship with liver weight. Serum concentrations of alpha2-macroglobulin were not related to liver weight or corpora lutea numbers. Circulating concentrations of cholesterol and alpha2 macroglobulin increased with day of the estrous cycle (P < 0.01). Testosterone concentrations were inversely related to circulating cholesterol concentrations during the estrous cycle, but testosterone concentrations on day 17 or 19 of the cycle were unrelated to corpora lutea numbers. Concentrations of estrone on day 17 or 19 (as an index of follicles destined to ovulate) were also not related to numbers of corpora lutea. Many interactions between liver and ovarian function involving metabolic and endocrine systems are plausible, but defined mechanisms resulting in coordinate increases in liver weight and ovulation rates are presently unelucidated. PMID- 10030686 TI - The human glucocorticoid receptor promoter upstream sequences contain binding sites for the ubiquitous transcription factor, Yin Yang 1. AB - Studies on the human glucocorticoid receptor (GR) promoter were carried out so as to understand the regulation of GR expression. A -2738 to +19 fragment of the human GR promoter was used to identify important regulatory elements involved in the control in GR expression in NIH 3T3 cells (mouse fibroblasts) and HeLa cells (human cervical carcinoma cells). Important regulatory domains in the distal region of the human GR promoter were identified by sequential 5' end deletion analysis. A region between -2490 and -2025 contributed 50% of the measured transcriptional activity to the promoter. Using DNase I footprint analysis, four sites in this region were identified: -2362 to -2339 (mouse footprint, mFP); 2301 to -2293 (distal YY1, dYY1); -2130 to -2122 (middle YY1, mYY1); and, -2086 to -2078 (proximal YY1, pYY1). Three sites contained an identical core sequence, CCAAGATGG and were identified as Yin Yang 1 (YY1) binding sites. The site located at -2362 to -2339 was footprinted in NIH 3T3 cells only. The sequence of this site is a direct repeat with a 2-nucleotide spacer region, and it does not share homology with any known transcription factor binding sites. Computer analysis of the entire promoter sequence revealed an additional YY1 site located at -260 to 249 (initiator YY1, iYY1) with the sequence CTCCTCCATTTTG. Electrophoretic mobility supershift assays, with an anti-YY1 antibody, were used to confirm YY1 binding to these four putative YY1 binding sites. Site-directed deletion of all three upstream YY1 sites but not the iYY1 site, or the iYY1 site alone, showed a approximately 60% decrease in transcriptional activity of the hGR promoter in HeLa cells but had no effect in NIH 3T3 cells. A similar (50%) decrease in the expression of a full-length hGR/luciferase reporter gene was obtained when HeLa cells were cotransfected with a full-length antisense YY1 expression plasmid. Additionally, a region between -1841 and -1689 contributed to hGR promoter activity in both cell types tested. An Sp1 binding site was identified in this region (-1748 to -1733) by DNase I footprint and mobility supershift analyses. The presence of four YY1 binding sites in the human GR promoter suggests that these sites play a critical role in GR gene regulation. PMID- 10030688 TI - Two-dimensional gel electrophoresis analyses identify nucleophosmin as an estrogen regulated protein associated with acquired estrogen-independence in human breast cancer cells. AB - We have used two-dimensional gel electrophoresis to identify proteins associated with estrogen-induced proliferation in MCF-7 breast cancer cells and their progression to estrogen-independent proliferation. We compared the total cellular proteins from MCF-7 cells and an estrogen independent derivative of the MCF-7 cells MCF-7/LCC1 (Brunner et al. Cancer Research 1993, 53, 283-290), each grown with and without estradiol. These comparisons reveal seven estrogen-regulated proteins. Three of these proteins (HI-1: 36 kDa/pI 4.5, HI-10: 40 kDa/pI 5.5 and HI-19: 62 kDa/pI 5.0) exhibit a 'progression-like' pattern, being induced by estradiol in MCF-7 cells and constitutively present/upregulated in the MCF-7/LCC1 growing without estradiol. HI-11 (65 kDa/pI 5.5) is strongly induced by estradiol in MCF-7 cells but constitutively downregulated and unresponsive to estradiol in the MCF-7/LCC1 cells. Two proteins exhibit a suppressor pattern and are downregulated by estradiol in the estrogen-dependent MCF-7 cells (HI-3: 44 kDa/pI 4.4 and HI-4: 56 kDa/ pI 5.2) and present in MCF-7/LCC1 cells growing without estradiol at levels comparable to that seen in estrogen-treated MCF-7 cells. One protein (HI-9: 68 kDa/pI 5.5) exhibits a marked estrogen regulated pI shift, rather than changes in abundance. We purified and sequenced the HI-10 protein, which we identified as the nucleolar protein, nucleophosmin (NPM). One- and two dimensional Western blot analyses of MCF-7/LCC1 cell lysates confirmed that HI-10 is immunoreactive with an antinucleophosmin antibody. Western blotting also confirmed the estrogenic regulation of NPM seen in the initial two-dimensional gel electrophoresis studies. Thus, NPM is induced by estradiol in the MCF-7 cells and upregulated in the MCF-7/LCC1 cells growing without estrogen, clearly associating its expression with an acquired estrogen-independent phenotype. NPM has several potentially important roles in regulating cell function and signaling. It is a substrate for phosphorylation by p34cdc2 kinase, protein kinase C and nuclear kinase II, and a repressor of the transcriptional regulating activities of both the IRF-1 tumor suppressor protein and the YY1 transcription factor. Studies are currently underway to determine which of these NPM functions may be involved in the hormonal progression of breast cancer. PMID- 10030689 TI - Macrophages, estrogen and the microenvironment of breast cancer. AB - Estrogen is a major mitogenic stimulus to established breast cancer. Estrogen sources include ovarian, extraglandular sites and breast tissue. Which source primarily maintains benign and breast cancer tissue estrogen concentrations remains unclear. While macrophages may comprise up to 50% of the mass of breast carcinomas, previous studies neglected to study them as possible sources of estrogen. We present evidence that breast macrophages constitute an in situ source of estradiol and that the amount produced is sufficient to mediate cellular proliferation. We utilized immunohistochemistry and RT-PCR to study cell specific aromatase expression in (i) 29 breast biopsies, (ii) human monocytes/macrophages and (iii) a myeloid cell line (THP-1) capable of differentiating into macrophages. Use of a breast cancer cell line (MCF-7) provided biologic confirmation of the role of aromatization in cell proliferation. We demonstrated considerable amounts of immunoreactive-aromatase (irARO) in breast tissue macrophages and a positive correlation between the proportion of irARO present in macrophages and lesion severity. Using in vitro techniques, we demonstrated that monocytes and THP-1 cells require differentiation into macrophages to produce aromatase in amounts approaching placental levels. The amount of estrogen produced by THP-1 cells stimulated MCF-7 cells to proliferate, an effect blocked by aromatase inhibitors. Estrogen production by macrophages in breast tissue appears sufficient to stimulate the proliferation of adjacent epithelial cells and to autoregulate cytokine production. These findings represent a new dimension of cellular regulation in breast tissue with major biologic implications, amenable to pharmacological manipulation. PMID- 10030690 TI - Estrogenic and antiestrogenic activities of 16alpha- and 2-hydroxy metabolites of 17beta-estradiol in MCF-7 and T47D human breast cancer cells. AB - The comparative mitogenic activities of 17beta-estradiol (E2) and four metabolites, 2-hydroxyestradiol (2-OHE2), 2-hydroxyestrone (2-OHE1), 16alpha hydroxyestradiol (16alpha-OHE2) and 16alpha-hydroxyestrone (16alpha-OHE1) were determined in estrogen receptor (ER)-positive MCF-7 and T47D human breast cancer cells. E2 (1 nM) induced a 7- to 13-fold increase in cell number in both cell lines compared to untreated cells and the mitogenic potencies of 16alpha-OHE1 or 16alpha-OHE2 were comparable to or greater than E2. In contrast, 2-OHE1 and 2 OHE2 were weak mitogens in both cell lines and in cells cotreated with 1 nM E2 and 100 or 1000 nM 2-OHE1 or 2-OHE2, there was a significant inhibition of hormone-induced cell proliferation. The comparative ER agonist/antagonist activities of E2 and the metabolites on transactivation were determined in T47D cells transiently transfected with constructs containing promoter inserts from the cathepsin D (pCD) and creatine kinase B (pCKB) genes. E2, 16alpha-OHE2 and 16alpha-OHE1 induced reporter gene activity in both MCF-7 or T47D cells transfected with pCKB or pCD. In contrast, 2-OHE1 and 2-OHE2 did not exhibit ER agonist activity for these transactivation assays, but in cells cotreated with E2 plus 2-OHE1 or 2-OHE2, there was a significant decrease in the hormone-induced response. These results demonstrate that 16alpha-OHE1/16alpha-OHE2 exhibit estrogenic activities similar to that observed for E2, whereas the 2 catecholestrogens are weak ER agonists (cell proliferation) or antagonists (cell proliferation and transactivation). PMID- 10030691 TI - Regulation of human estrogen receptor by phytoestrogens in yeast and human cells. AB - Phytoestrogens are defined as plant substances that are structurally or functionally similar to estrogen. They are present in many foods and their higher consumption in certain populations has been correlated with protection against many diseases including coronary heart disease, breast cancer and endometrial and ovarian cancer. In this report, ten phytoestrogens with diverse chemical structures were studied for their binding to the human estrogen receptor and their transcription activation properties in yeast and mammalian cells. Our results showed that some of these compounds bind with relatively high affinity to the estrogen receptor and activate the receptor in the yeast and mammalian cell system. In addition, none of these compounds showed anti-estrogenic activity. We conclude that the yeast system accurately predicts the estrogenic activity of compounds with diverse chemical structures in mammalian cells. In addition, our data with phytoestrogens that do not show transcription activation properties raise the possibility that these compounds may exert their biological effects through pathways different from the classical estrogen signalling mechanism. PMID- 10030692 TI - Integration of estrogen and progesterone receptors with pathological and molecular prognostic factors in breast cancer patients. AB - In this study we have examined biopsies from women with localized primary breast cancer to investigate the prognostic performance of estrogen receptors (ER) and progesterone receptors (PR) for estimating the metastatic probability of the patients, and to explore whether discrimination gets better by combining clinicopathological and other molecular parameters into a score. This prospective study involved 205 patients with a median follow-up of 5 y. Among the evaluated clinicopathological data were: patient's age; tumor size; axillary lymph node involvement; and tumor grade. The most representative tumor samples were derived to a single laboratory for immunohistochemical evaluation of the following molecular markers: ER, PR, proliferating cell nuclear antigen (PCNA), p53 protein product, erbB-2 (HER-2/neu) oncoprotein, and P170 glycoprotein (mdrl gen product). Distant metastases (study endpoint) appeared in 19.5% (40/205) of the patients, most of these patients presented a mixture of poor, regular and good prognostic factors. Disease-free survival analysis procedures (Kaplan-Meier method) identified tumor size, axillary lymph node involvement, tumor grade, receptor status, PCNA, p53, erbB-2 and P170 as useful prognostic factors. Proportional hazard regression analysis (Cox) identified in order of importance erbB-2, tumor size, receptors status, tumor grade and PCNA as useful prognostic factors. To facilitate the evaluation of the prognostic factors, a practical and simple score system was derived. A high pathological score identified 65% of the patients that developed distant metastases, while a high molecular score was obtained in 57% of patients with metastatic disease. There was a significant improvement in the diagnosis of probability of being with distant metastases when the pathological score was combined with the molecular score, 82% of the patients with distant metastases showed an elevated combined score. Validation of this scoring system will need further larger studies (validation set as opposed to the training set used in the present study). Due to the complexity of events in cancer, the evaluation of a combination of prognostic factors should be of value to clinicians to make a more objective estimate of the prognosis of individual breast cancer patients. PMID- 10030693 TI - Immunoassay of 7-hydroxysteroids: 1. Radioimmunoassay of 7beta-hydroxy dehydroepiandrosterone. AB - High sensitivity radioimmunoassay of 3beta,7beta-dihydroxy-5-androsten-17-one (7beta-OH-DHEA) has been developed and evaluated. The method is based on polyclonal rabbit antisera raised against its 19-O-(carboxymethyl)oxime bovine serum albumin conjugate and bridge- and position homologous [125I]iodotyrosine methyl ester as a tracer. Alternatively, [3H]tracer has been prepared, which was recognized by the antiserum as well, but the assay sensitivity was lower. The identity of measured immunoreactive material was confirmed by high performance liquid chromatography which separated 7beta-OH-DHEA from its 7alpha-isomer. Using radioiodinated tracer, the sensitivity of the method was 3.48 fmol (1.06 pg) per tube, the mean recovery of standard added to steroid-free serum was 98.5%. Free (unconjugated and not-esterified) 7beta-OH-DHEA amounted in average 5.8% of the total 7beta-OH-DHEA present in human serum. It was measured in 42 normal subjects (28 females and 14 males) and in 92 randomly selected patients with various endocrinopathies. The mean values +/- SD in normals were 2.05 +/- 1.02 nmol l( 1), the broad range of values from undetectable levels to 10.3 nmol l(-1) was found in the patients. Serum levels of free 7beta-OH-DHEA in the patients significantly correlated with DHEA and its sulfate. PMID- 10030694 TI - A preliminary study of steroid reproductive hormones in human hair. AB - Nowadays research and clinical studies of human reproductive endocrinology are generally carried out using human blood reproductive hormone assays. However the acquisition of human blood samples has some shortcomings. In search of new approaches, we paid attention to the fact that progesterone can be detected in cow's hair. Consequently we investigated whether or not steroid hormones are measurable in human hair. The results showed that the levels of steroid hormones in hair are not affected by shampoo and do not significantly vary between different segments of hair (i.e. top, middle and basal segments). The menstrual estradiol and progesterone rhythm of female hair is similar to that of female serum. The ratio of hair estradiol to serum estradiol in the female is 41.2% and that of hair progesterone to serum progesterone is 59.0%; the ratio of hair testosterone to serum testosterone in male is 116%. There are significant correlations between hair and serum steroid hormones of healthy human adult: gamma (estradiol) = 0.395 (n = 20), p < 0.05; gamma (progesterone) = 0.440 (n = 22), p < 0.025 and gamma (testosterone) = 0.395 (n = 25), p < 0.05. PMID- 10030695 TI - Transformation of steroids by Bacillus strains isolated from the foregut of water beetles (Coleoptera:Dytiscidae): I. Metabolism of androst-4-en-3,17-dione (AD). AB - Two Bacillus strains were isolated from the foregut of the water beetle Agabus affinis (Payk.) and tested for their steroid transforming ability. After incubation with androst-4-en-3,17-dione (AD), 13 different transformation products were detected. AD was hydroxylated at C6, C7, C11 and C14, resulting in formation of 6beta-, 7alpha-, 11alpha- and 14alpha-hydroxy-AD. One strain also produced small amounts of 6beta,14alpha-dihydroxy-AD. Partly, the 6beta-hydroxy group was further oxidized to the corresponding 6-oxo steroids. In addition, a specific reduction of the delta4-double bond was observed, leading to the formation of 5alpha-androstane derivatives. In minor yields the carbonyl functions at C3 and C17 were reduced leading to the formation of 3zeta-OH or 17beta-OH steroids. EI mass spectra of the trimethylsilyl and O-methyloxime trimethylsilyl ether derivatives of some transformation products are presented for the first time. PMID- 10030696 TI - Sustained reduction in the carriage of Neisseria meningitidis as a result of a community meningococcal disease control programme. AB - The effect of a community intervention programme of antibiotics and meningitis vaccine on pharyngeal carriage of Neisseria meningitidis was investigated. Carriage rates were determined in pupils at both secondary schools (ages 11-18 years) included in the community intervention programme and compared with two schools outside the area matched for socio-economic status. A total of 1869 pupils were studied 6 months after the programmes, and 2457 pupils after 11 months. Six months after the programme was completed there was a 72% reduction in pharyngeal carriage of Neisseria meningitidis in pupils attending the schools in the intervention area compared with pupils in the control schools. After 11 months this difference persisted in the 11-14 age group but not in the 15-18 age group. No resistance to the antibiotics used in the programme was found. A community intervention programme of antibiotics and vaccine for the control of meningococcal disease led to a long-term reduction in Neisseria meningitidis carriage in some age groups. PMID- 10030697 TI - Acquisition and carriage of meningococci in marine commando recruits. AB - Meningococcal acquisition is a prerequisite for invasive disease. Three hundred and eleven male marine commando recruits were studied throughout 29 weeks of basic training to identify factors influencing meningococcal carriage and acquisition including troop number, season, smoking, respiratory infection, antibiotic usage and nasopharyngeal bacterial interference flora. A high carriage rate on entry to training (118/311, 37.9%) and subsequent sustained high rates of meningococcal acquisition were found. Of the potential factors examined, only active and passive smoking were found to be associated significantly with meningococcal carriage on entry. The association between active smoking and meningococcal carriage was dose-dependent, with odds ratios (OR) of 2.2 (95% CIs 1.0-4.8) and 7.2 (95% CIs 2.3-22.9) for light and heavy smokers respectively. Passive smoking predisposed independently to carriage (OR 1.8, 95% CIs 1.1-3.0). Active and passive smoking combined to give an attributable risk for meningococcal carriage of 33%. In contrast, despite a high and sustained rate of meningococcal acquisition in the study population, none of the risk factors investigated, including active smoking, was associated significantly with meningococcal acquisition. No cases of meningococcal disease occurred during the 16-month study period. Therefore smoking may increase the duration of meningococcal carriage rather than the rate of acquisition, consistent with the increased risk of meningococcal disease from passive as opposed to active smoking. Public health measures that reduce the prevalence of smoking should reduce the risk of meningococcal disease. PMID- 10030698 TI - Epidemiological characterization of methicillin-resistant Staphylococcus aureus isolated in the North West of England by protein A (spa) and coagulase (coa) gene polymorphisms. AB - In a comparative study, isolates of methicillin-resistant Staphylococcus aureus (MRSA) with known pulsed-field gel electrophoresis (PFGE) and bacteriophage type were analysed by polymerase chain reaction (PCR) and restriction fragment length polymorphisms (RFLP) for additional discriminatory subtyping information. PFGE was previously performed using standardized, commercially available kits and pre programmed software. Isolates were examined for coagulase (coa) and protein A (spa) gene polymorphisms following PCR amplification of the coa hypervariable and spa repeat regions. Coa gene RFLPs produced a total of 38 distinct combined patterns after digestion with HaeIII and AluI and identified the predominant epidemic (EMRSA) types 15 and 16. A unique HaeIII restriction site was identified by RFLP and sequence analysis in the coa gene for EMRSA 15 but not EMRSA 16. The spa gene PCR yielded a total of 14 different profiles ranging from 3-18 repeats with the 2 predominant EMRSA types falling into 2 distinct groups. PCR detection of coa and spa polymorphisms offer a rapid preliminary strain identification and discriminatory subtyping information for surveillance of MRSA. PMID- 10030699 TI - A community outbreak of invasive and non-invasive group A beta-haemolytic streptococcal disease in a town in South Wales. AB - An increase in the incidence of invasive and non-invasive infections caused by group A beta-haemolytic streptococci (GAS) was noted in and around the town of Glynneath (population approx. 4000) in West Glamorgan, South Wales between 1 January and 30 June 1995. A total of 133 cases was ascertained with 127 (96%) occurring between 1 March and 30 June 1995. Six patients had invasive disease (one died) and all presented at the peak of the outbreak. There were 127 non invasive cases of whom 7 were hospitalized. The outbreak was investigated to determine its extent and whether it was caused by a single M-serotype of GAS. Serotyping showed that 13 different M-serotypes were involved with the M1 serotype predominating. The overall incidence of GAS invasive disease in West Glamorgan (population 365,000) increased sevenfold from a crude incidence of 0.5/10(5) per year in 1994 to 3.5/10(5) per year in 1995, but fell back to 0.75/10(5) per year in 1996. Eighty-two (80%) out of 102 individuals affected by GAS replied to a health questionnaire; sore throat was the commonest symptom reported (97%). Thirty-nine of these index cases identified at least one other member of their household who had experienced similar symptoms. The interval between the onset of illness in members of a single household was 0-83 days with a mean of 22 days. The mean duration of illness was 13.5 days and 61% of patients were treated with penicillin V for a mean duration of 9.3 days. Twenty-one per cent of GAS isolates were erythromycin-resistant and the M4 and M6 serotypes were especially resistant to erythromycin (87.5 and 100% resistance, respectively). Penicillin V failed to eradicate GAS from the throats of 25% of assessable patients. In this community, an outbreak of non-invasive disease caused by GAS was linked in time and place with an outbreak of serious invasive disease. PMID- 10030700 TI - Previous respiratory tract infections and antibiotic consumption in children with long- and short-term carriage of penicillin-resistant Streptococcus pneumoniae. AB - Previous respiratory tract infections (RTI) and antibiotics consumption as possible risk factors for extended duration of PRP carriage were investigated in 24 children (cases) with previous carriage of penicillin-resistant pneumococci (PRP) for a duration exceeding 120 days (median 168 days) and a control group of 53 children with a duration of PRP carriage less than 90 days (median 21 days). The cases had experienced 0.99 episodes of acute otitis media (AOM) per life-year compared to 0.79 episodes in the controls (P = 0.32). For antibiotic-treated RTI other than AOM, the corresponding numbers were 0.49 and 0.29 episodes per life year, respectively (P = 0.01). No differences in antibiotic consumption in the 3 months preceding the carriage, nor during the carriage period were noted. Other factors than impaired host defence to respiratory tract pathogens or antibiotics consumption seem to be more important in determining the duration of PRP carriage. PMID- 10030701 TI - Increase in paediatric acute otitis media diagnosed by primary care in two Finnish municipalities--1994-5 versus 1978-9. AB - In recent decades, several epidemiological studies have been published on acute otitis media (AOM), indicating that the occurrence of AOM is increasing. However, the comparison between the surveys is complicated and biased by several factors, e.g. variable study demography and design and dissimilar diagnostic criteria. The present study was performed with an identical set-up in 1978-9 and 1994-5 to find out potential changes in the occurrence of AOM. All the attacks of AOM among children under 10 years diagnosed by a physician during the 12-month periods 1 June, 1978 to 31 May 1979 and 1 June 1994 to 31 May 1995 were registered retrospectively in two Finnish municipalities. The incidence rate (total number of AOM attacks per 100 child years) was 19 (95% CI 18-21) in 1978-9 and 32 (95% CI 30-34) in 1994-5. The increase in the occurrence of AOM was 68% (95% CI 53 79%, P < 0001). PMID- 10030702 TI - Ribotypes of clinical Vibrio cholerae non-O1 non-O139 strains in relation to O serotypes. AB - The emergence of Vibrio cholerae O139 in 1992 and reports of an increasing number of other non-O1 serogroups being associated with diarrhoea, stimulated us to characterize V. cholerae non-O1 non-O139 strains received at the National Institute of Infectious Diseases, Japan for serotyping. Ribotyping with the restriction enzyme BglI of 103 epidemiological unrelated mainly clinical strains representing 10 O-serotypes yielded 67 different typing patterns. Ribotype similarity within each serotype was compared by using the Dice coefficient (Sd) and different levels of homogeneity were observed (serotypes O5, O41 and O17, Sd between 82 and 90%: serotypes O13 and O141 Sd of 72; and O2, O6, O7, O11, O24 Sd of 62-66%). By cluster analysis, the strains were divided into several clusters of low similarity suggesting a high level of genetic diversity. A low degree of similarity between serotypes and ribotypes was found as strains within a specific serotypes often did not cluster but clustered with strains from other serotypes. However, epidemiological unrelated O5 strains showed identical or closely related ribotypes suggesting that these strains have undergone few genetic changes and may correspond to a clonal line. Surprisingly, 10 of 16 O141 strains studied contained a cholera toxin (CT) gene, including 7 strains recovered from stool and water samples in the United States. This is to our knowledge the first report of CT-positive clinical O141 strains. The closely related ribotypes shown by eight CT-positive strains is disturbing and suggest that these strains may be of a clonal origin and have the potential to cause cholera-like disease. Despite the low degree of correlation found between ribotypes and serotypes, both methods appears to be valuable techniques in studying the epidemiology of emerging serotypes of V. cholerae. PMID- 10030703 TI - Detection of campylobacter in gastroenteritis: comparison of direct PCR assay of faecal samples with selective culture. AB - The prevalence of campylobacter gastroenteritis has been estimated by bacterial isolation using selective culture. However, there is evidence that certain species and strains are not recovered on selective agars. We have therefore compared direct PCR assays of faecal samples with campylobacter culture, and explored the potential of PCR for simultaneous detection and identification to the species level. Two hundred unselected faecal samples from cases of acute gastroenteritis were cultured on modified charcoal cefoperazone deoxycholate agar and subjected to DNA extraction and PCR assay. Culture on CCDA indicated that 16 of the 200 samples contained 'Campylobacter spp.'. By contrast, PCR assays detected campylobacters in 19 of the 200 samples, including 15 of the culture positive samples, and further identified them as: C. jejuni (16), C. coli (2) and C. hyointestinalis (1). These results show that PCR offers a different perspective on the incidence and identity of campylobacters in human gastroenteritis. PMID- 10030704 TI - Emergence of multidrug-resistant Salmonella enterica serotype Typhimurium phage type DT104 among salmonellae causing enteritis in Israel. AB - The relative frequency of salmonella strains isolated from hospitalized and non hospitalized patients in Southern Israel changed during the period, 1994-6. Salmonella enterica serotype Typhimurium definitive phage-type 104 (DT104) appeared in Israel in 1994 and became the most prevalent strain in 1996. An outbreak of enteritis due to Salmonella enterica serotype Agona occurred in Israel, in October 1994 and lasted for 4 months. The relative frequency of Salmonella enterica serotype Enteritidis remained almost constant during these years, with seasonal fluctuations only. The importance of the increase in the prevalence of Typhimurium DT104 has been the epidemic spread of a multiresistant strain of R-type ACT (A, ampicillin; C, chloramphenicol; T, tetracycline) belonging to this phage-type. Since 1995 the frequency of Typhimurium DT104 isolates that possess, in addition to the above R-type, a chromosomally encoded resistance to the quinolone drug, nalidixic acid, increased tenfold. In 1996, 27% of the Typhimurium DT104 isolates were of R-type ACTN. S. Enteritidis exhibited over 95% susceptibility to at least eight of the most commonly used antibiotic drugs, and none of the isolates was resistant to quinolone or fluoroquinoline. PMID- 10030705 TI - Risk factors for the occurrence of sporadic Salmonella enterica serotype enteritidis infections in children in France: a national case-control study. AB - To determine risk factors associated with the occurrence of sporadic cases of Salmonella enteritidis infections among children in France, we conducted a matched case-control study. Cases were identified between 1 March and 30 September 1995. One hundred and five pairs of cases and controls matched for age and place of residence were interviewed. In the 1-5 years age group, illness was associated with the consumption of raw eggs or undercooked egg-containing foods (OR 2.4, 95% CI 1.2-4.8). Storing eggs more than 2 weeks after purchase was associated with Salmonella enteritidis infection (OR 3.8, 95% CI 1.4-10.2), particularly during the summer period (OR 6.0, 95% CI 1.3-26.8). Cases were more likely to report a case of diarrhoea in the household 10-3 days before the onset of symptoms, particularly in the age group < or = 1 year (P = 0.01). This study confirms the link between eggs and the occurrence of sporadic cases of Salmonella enteritidis among children, highlights the potential role of prolonged egg storage and underlines the role of person-to-person transmission in infants. PMID- 10030706 TI - Salmonella infections in Norway: descriptive epidemiology and a case-control study. AB - The epidemiological progression of human salmonellosis in Norway is parallel to trends noted elsewhere in Europe. During the past two decades, the number of reported cases has increased steadily, with a special sharp rise in the early 1980s due to the emergence of Salmonella enteritidis, followed by a levelling off in recent years. However, in contrast to the situation in most other European countries, about 90% of the cases from whom a travel history is available, have acquired their infection abroad. The incidence of indigenous salmonella infections as well as the prevalence of the microorganism in the domestic food chain, are both comparatively low. In 1993-4, a national case-control study of sporadic indigenous salmonella infections was conducted to identify preventable risk factors and guide preventive efforts. Ninety-four case patients and 226 matched population controls were enrolled. The study failed to demonstrate any statistically significant association between salmonellosis and consumption of domestically produced red meat, poultry or eggs. The only factor which remained independently associated with an increased risk in conditional logistic regression analysis, was consumption of poultry purchased abroad during holiday visits to neighbouring countries. A separate analysis of Salmonella typhimurium infections incriminated food from catering establishments and foreign travel among household members, in addition to imported poultry. PMID- 10030707 TI - Evaluation of pulsed-field gel electrophoresis of genomic restriction fragments in the discrimination of Yersinia enterocolitica O:3. AB - One hundred and six Yersinia enterocolitica serogroup O:3, biotype 4 isolated from human and porcine samples in 1984 and in the years 1993 5 were examined by pulsed-field gel electrophoresis (PFGE). The genomic profiles produced by the enzymes NotI and XbaI were studied. Sixteen (A-P) and 8 (1-8) different pulsotypes were obtained, respectively. By combining the pulsotypes produced by both NotI and XbaI 24 different types were distinguished. The two major types, designated as A1 and B1, comprised 36% of all strains tested. The proportions of pulsotypes A1 and B1 were, 35.9 and 25.6%, respectively, among strains isolated in 1984. The corresponding figures among the strains isolated in 1993-5 were 35.8 and 41.8%. Nine pulsotypes were found only in 1984 and nine only in 1993-5. The proportions of the major pulsotypes, A1 and B1, in human isolates were 42.9 and 35.7% and in porcine isolates 22.2 and 36.1% respectively. Six types were found among both human and porcine isolates, 8 only among human strains and 10 only among porcine strains. PMID- 10030708 TI - High turnover rate of Escherichia coli strains in the intestinal flora of infants in Pakistan. AB - The Escherichia coli flora of infants in developed countries is dominated by one or a few strains which persist for prolonged periods of time, but no longitudinal studies have been performed in developing countries. To this end, we studied the rectal enterobacterial flora in 22 home-delivered Pakistani infants during their first 6 months of life. Three colonies were isolated and species typed on each of 11 sampling occasions. E. coli isolates were strain typed using electromorphic typing of cytoplasmic enzymes, and their O serogroups were determined. There was a very rapid turnover of enterobacterial strains in the rectal flora of individual infants. On average, 8.5 different E. coli strains were found per infant, and several biotypes of other enterobacteria. Less than 50% of the infants were colonized with E. coli from their mothers, but strains of maternal origin were four times more likely to persists in the infants' flora than other E. coli strains. Enterobacteria other than E. coli were always of non-maternal origin, and Enterobacter cloacae and Klebsiella pneumoniae biotypes recovered from contaminated feeds were later identified in the infants' rectal flora. An early colonization with klebsiella or enterobacter was significantly associated with diarrhoea during the neonatal period, although these bacteria were not likely to be the cause of the disease. The results suggest that poor hygienic conditions result in an unstable and diverse enterobacterial flora, which may influence infant health. PMID- 10030709 TI - P fimbriae and other adhesins enhance intestinal persistence of Escherichia coli in early infancy. AB - Resident and transient Escherichia coli strains were identified in the rectal flora of 22 Pakistani infants followed from birth to 6 months of age. All strains were tested for O-antigen expression, adhesin specificity (P fimbriae, other mannose-resistant adhesins or type 1 fimbriae) and adherence to the colonic cell line HT-29. Resident strains displayed higher mannose-resistant adherence to HT 29 cells, and expressed P fimbriae (P = 0.0036) as well as other mannose resistant adhesins (P = 0.012) more often than transient strains. In strains acquired during the first month of life, P fimbriae were 12 times more frequent in resident than in transient strains (P = 0.0006). The O-antigen distribution did not differ between resident and transient strains, and none of the resident P fimbriated strains belonged to previously recognized uropathogenic clones. The results suggest that adhesins mediating adherence to intestinal epithelial cells, especially P fimbriae, enhance the persistence of E. coli in the large intestine of infants. PMID- 10030710 TI - Low rates of ehrlichiosis and Lyme borreliosis in English farmworkers. AB - To determine the occupational significance of tick-borne zoonoses we sought serological evidence of Lyme borreliosis, human monocytic ehrlichiosis (HME) and human granulocytic ehrlichiosis (HGE) in a representative sample of farmworkers. Although around 20% reported ticks on their domestic and companion animals, few (< 2% per year) reported being bitten by ticks. Seroprevalence of Lyme borreliosis (0.2%), HME (0.2%) and HGE (1.5%) was low. Those seropositive for HGE were no more likely to report tick bites nor more likely to report ticks on their animals. This study provides evidence that farmworkers in England are exposed to tick-borne zoonoses but that they are uncommon. Since the severity of these diseases is linked to delays in diagnosis and treatment, clinicians should be aware of these diagnoses in patients from rural communities, with or without a self-reported history of tick bite. PMID- 10030711 TI - An outbreak of viral gastroenteritis associated with consumption of sandwiches: implications for the control of transmission by food handlers. AB - Although food handlers are often implicated as the source of infection in outbreaks of food-borne viral gastroenteritis, little is known about the timing of infectivity in relation to illness. We investigated a gastroenteritis outbreak among employees of a manufacturing company and found an association (RR = 14.1, 95% CI = 2.0-97.3) between disease and eating sandwiches prepared by 6 food handlers, 1 of whom reported gastroenteritis which had subsided 4 days earlier. Norwalk-like viruses were detected by electron microscopy or reverse transcriptase-polymerase chain reaction (RT-PCR) in stool specimens from several company employees, the sick food handler whose specimen was obtained 10 days after resolution of illness, and an asymptomatic food handler. All RT-PCR product sequences were identical, suggesting a common source of infection. These data support observations from recent volunteer studies that current recommendations to exclude food handlers from work for 48-72 h after recovery from illness may not always prevent transmission of Norwalk-like viruses because virus can be shed up to 10 days after illness or while exhibiting no symptoms. PMID- 10030712 TI - Risk of human immunodeficiency virus infection and genital ulcer disease among persons attending a sexually transmitted disease clinic in Italy. AB - To assess the relative importance of ulcerative and non-ulcerative sexually transmitted disease in the transmission of HIV, a seroprevalence study was conducted on 2210 patients at the sexually transmitted diseases (STD) clinic of the S. Maria e S. Gallicano Hospital in Rome, between 1989 and 1994. Among male patients, by univariate analysis, strong predictors of HIV infection were homosexuality, sexual exposure to a HIV-positive partner, hepatitis B virus infection, and positive syphilis serology. An increased risk was estimated for patients with past genital herpes (odds ratio (OR) 3.86, 95% confidence intervals (CI) 0.40-18.2), and primary syphilis (OR 5.79, 95% CI 0.59-28.6). By multivariate analysis, a positive association was found with homosexuality (OR 6.9, 95% CI 2.9-16.5), and positive syphilis serology (OR 3.5, 95% CI 1.3-9.2). An adjusted OR of 2.41 was calculated for current and/or past genital herpes. These results, although not conclusive, suggest a role of ulcerative diseases as risk factors for prevalent HIV infection, and indicate that positive syphilis serology is an unbiased criterion for identifying individuals at increased risk of HIV infection. PMID- 10030713 TI - Changing epidemiology of hepatitis A in the 1990s in Sydney, Australia. AB - Surveillance of hepatitis A in residents of Eastern Sydney Health Area identified substantial epidemics in homosexual males in 1991-2 with a peak rate of 520 per 100,000 recorded in males aged 25-29 years, and again in 1995-6, with a peak rate of 405 per 100,000 per year in males aged 30-34 years. During 1994-5 an epidemic was detected among disadvantaged youth associated with injecting drug use; peak rates of 200 per 100,000 per year were reported in males aged 25-29 years and of 64 per 100,000 per year among females aged 20-24 years. The epidemiology of hepatitis A in these inner suburbs of Sydney is characterized by very few childhood cases and recurrent epidemics among homosexual men. Identified risk groups need to be targeted with appropriate messages regarding the importance of hygiene and vaccination in preventing hepatitis A. However, poor access to health services among disadvantaged youth and a constant influx of young homosexual males into these inner suburbs present major challenges to hepatitis A control. PMID- 10030714 TI - Immunosurveillance and the evaluation of national immunization programmes: a population-based approach. AB - Mass vaccination can change the epidemiological dynamics of infectious diseases. It may result in a limited persistence of natural and vaccine-induced immunity and a higher mean age of infection, which may lead to a greater risk of complications. The epidemiological situation should be monitored and immunosurveillance based on the assessment of specific antibodies against vaccine preventable diseases in human serum is one of the tools. In order to estimate the immunity of the Dutch population reliably, a large-scale, population-based, collection of serum samples was established (8359 sera in a nation-wide sampling and 1589 sera from municipalities with low vaccine coverage). In contrast to collecting residual sera from laboratories, this approach gains extensive information by means of a questionnaire regarding the determinants of the immune status and the risk factors for the transmission of infectious diseases in general. The population-based approach gives a better guarantee that the data are representative than collecting sera from laboratories does. PMID- 10030715 TI - Seroepidemiological evaluation of 1989-91 mass vaccination campaigns against measles, in Italy. AB - In 1989-91 anti-measles vaccination campaigns were conducted in several Italian regions to vaccinate all children aged between 13 months and 10-12 years without a history of measles or measles vaccination. This study was conducted to evaluate serological status after the mass vaccination campaigns. In 1994, capillary blood samples were collected from randomly selected children, aged 2-14 years, living in 13 local health units. Antibody titres were determined by ELISA. Blood spot samples were analysed for 4114 (75.6%) of 5440 selected children. Among the 835 that reported measles before 1990, 806 (96.5%) were immune and of the 2798 vaccinated, 2665 (95.2%) were immune. The Edmoston-Zagreb (E-Z) strain vaccine was associated with a lower level of immunity than the Schwarz (SW) strain. A history of measles identified almost all immune children. Vaccination with the SW strain conferred persistent immunity (at least 5 years) in 98% of vaccinees. The strategy was able to unite natural and induced immunity. PMID- 10030716 TI - A model-based evaluation of the national immunization programme against rubella infection and congenital rubella syndrome in The Netherlands. AB - In order to improve the prevention of cases of congenital rubella syndrome in The Netherlands, in 1987 the selective vaccination strategy against rubella infection in girls was replaced by mass vaccination. This decision was supported by mathematical model analyses carried out by Van Druten and De Boo. In order to compare the predicted impact of the rubella vaccination programme with the current available data in more detail, a similar model was built. Although the model predicts elimination of the rubella virus, data show that virus circulation is still present at a higher level than expected by the model. Simulation studies indicate that import of infection and a lower vaccine effectiveness, related to possible asymptomatic reinfection of vaccinated people, could be sources contributing to the present virus circulation. Even though the number of infections is much higher than the number of reported cases of disease, limited serosurveillance data and case notification data show that females of childbearing age are well protected by immunization. PMID- 10030717 TI - Detection of viruses and body fluids which may contain viruses in the domestic environment. AB - The domestic environment was investigated for the presence of viruses and body fluids that may contain viruses. A range of surfaces in 39 homes (17 visited on 2 occasions) were sampled by swabbing and analysed using cell culture, reverse transcription polymerase chain reaction for enteroviral RNA, haemoglobin as a marker for blood, amylase as an indicator of urine, saliva and sweat, and protein as an indicator of general hygiene. Haemoglobin was found on 1.9% of surfaces sampled and of the positive samples 30% were from articles frequently handled. Amylase (> 5 U/l) was found in 29.3% of samples tested. Protein was found in 97.8% of samples tested. Enteroviral RNA, indicating the presence of virus, was detected in 3 out of 448 samples tested; they were from a tap handle, telephone handpiece and a toilet bowl. No viruses were isolated in cell culture, however significant problems were encountered with bacterial and fungal contamination. This work demonstrates that only testing environmental samples for bacteria and ATP may not give a total view of the microbiological problem in the home. A range of test methods is useful to gain a broad view of the problems of hygiene in the home and to allow comparative studies of specific areas such as the kitchen and bathroom. PMID- 10030718 TI - Detection of the agent of human granulocytic ehrlichiosis (HGE) in UK ticks using polymerase chain reaction. AB - Nymphal Ixodes ricinus ticks collected from woodland areas in South Wales, UK, were tested using the polymerase chain reaction for the presence both of the causative agent of human granulocytic ehrlichiosis (HGE) and Borrelia burgdorferi. Twenty-two of 60 (37%) ticks were found positive in the PCR for B. burgdorferi and 4/60 (7%) for the HGE agent. One tick was found positive both for B. burgdorferi and HGE agent. Our findings imply the presence of the HGE agent in UK ticks and the finding of a tick apparently containing both pathogens underlines the potential for concurrent infection with HGE agent and B. burgdorferi to occur after a single tick-bite. Based on our observations, we conclude that there may be a need to consider a range of pathogens both in laboratory investigation and clinical management of suspected tick-borne disease in the UK, particularly where there is a clinical presentation atypical of Lyme borreliosis alone. PMID- 10030719 TI - Infection rate of Leptospira interrogans in the field rodent, Apodemus agrarius, in Korea. AB - Leptospirosis has significantly decreased in Korea since 1988, following the leptospiral vaccination programme initiated in 1988. Whether this wholly explains the decreased incidence is uncertain. As an initial step to answer this question, infection rates of Leptospira interrogans in field rodents, Apodemis agrarius, were examined and compared with previous data. Two hundred and twenty-two A. agrarius were captured during October-December 1996. Spirochaetes were isolated from 22 (9.9%) and leptospiral DNA was detected in an additional 6 rodents (12.6%). Subsequent microscopic agglutination tests (MAT) classified all these isolates as L. interrogans serogroup Icterohaemorrhagiae serovar lai. The above data did not significantly differ from previous surveys in 1984-7. There was no significant change of L. interrogans infection in field rodents following the introduction of the vaccination programme in Korea. Further studies are needed to determine the role of human vaccination in reducing incidence. PMID- 10030720 TI - Characterization of a new genotype of measles virus detected in China and England. AB - We report the co-circulation of a new lineage of measles virus (MV) and an Edmonston-like (Ed-like) genotype of MV in China during 1995-7. Sequence analysis of 25 strains was performed on a 282 nucleotides (nt) region of the nucleoprotein (N) gene, a 450-nt region of the haemagglutinin (H) gene and a 152-nt region of the matrix (M) gene by direct sequencing of RT-PCR amplicons obtained from clinical specimens. The entire H gene was sequenced from two strains. The results showed that 24/25 Chinese strains belonged to a new genogroup and were distinct from the vaccine strains used in China and the UK, and also from MV strains previously described in Europe, Africa and the USA. The remaining strain was Ed like. Two strains of the new genotype (IV) and one of the Ed-like genotype were also detected in the UK in 1996. PMID- 10030721 TI - Protective effect of HD-03, a herbal formulation, against various hepatotoxic agents in rats. AB - HD-03 is a polyherbal formulation containing plant drugs which are known for their hepatoprotective properties in the Ayurvedic system of medicine. In the present study, the formulation was evaluated for its protective effect against diverse hepatotoxic agents viz., paracetamol, thioacetamide and isoniazid. Treatment with HD-03 led to significant amelioration of toxin-induced changes in the biochemical parameters. Since the protective effect of HD-03 was observed in all three types of intoxication, which are different in their primary mechanism of inducing hepatotoxicity, a protective mode of action of HD-03, not specific to the hepatotoxin, is suggested. PMID- 10030723 TI - Effects of an aqueous extract of Aloe buettneri, Justicia insularis, Hibiscus macranthus, Dicliptera verticillata on some physiological and biochemical parameters of reproduction in immature female rats. AB - Different doses of aqueous extracts from the leaves of Aloe buettneri, Justicia insularis, Hibiscus macranthus and Dicliptera verticillata, locally used to regulate the menstrual cycle and to treat dysmenorrhea or infertility in women, were given daily to 22 day old rats for 5, 10, 15, 20 and 25 days by gastric intubation. At the end of each experimental period, the weights of ovaries and uteri, levels of uterine and ovarian proteins, ovarian cholesterol and serum oestradiol were evaluated. The results showed a decrease in growth rate of animals treated with 94 mg/kg per day at the end of the experimental period. The ovarian and uterine weights were high in all treated groups especially within the pubertal period (36-41 days old) when compared to the respective controls. During the same period, the parameters analysed showed significant differences in treated rats when compared to the controls. This was seen with ovarian and uterine protein levels, as well as with serum oestradiol whose level was especially high in the groups given 49 or 94 mg/kg per day of the plant extracts (52 and 42%, respectively when compared with the respective controls). A concomitant decrease in ovarian cholesterol was observed in the same treated groups. These results suggested a possible presence of oestrogenic compounds in the plant extracts. PMID- 10030722 TI - Evaluation of possible mechanism of anti-ulcerogenic activity of UL-409, a herbal preparation. AB - UL-409, a herbal preparation was investigated for its anti-ulcerogenic activity and possible mechanism of action in different experimental models. Oral administration of UL-409 at a dose of 600 mg/kg significantly reduced the volume of gastric secretion, total acidity and free acidity in aspirin + pylorus-ligated rats. The drug appeared to strengthen the gastric mucosal defense mechanism by significantly increasing the total carbohydrate:protein ratio in aspirin + pylorus-ligated rats. The major mechanism involved appears to be due to promotion of mucosal protection by augmenting gastric mucin activity. Pre-treatment with UL 409 showed inhibition of alcohol-induced contraction of isolated rat fundus preparation which was reversed by indomethacin suggesting a possible involvement of the cyclo-oxygenase system. PMID- 10030724 TI - Jamu Gendong, a kind of traditional medicine in Indonesia: the microbial contamination of its raw materials and endproduct. AB - An examination on the microbiological quality of seven kinds of Jamu Gendong (JG) and their raw materials has been conducted according to the requirements of microbial contamination in traditional medicine, issued by the Department of Health of Indonesia in 1986. Samples of JG and their raw materials were taken from producers in three districts of Surabaya. The samples were subject to the following examinations: total plate count (TPC), MPN coliform, the enumeration of molds and yeasts, the presence or absence of Staphylococcus aureus, Salmonella and Vibrio. Each time the JG samples were taken from different producers together with their raw materials. The results of this investigation showed that most of the JG samples were heavily contaminated with bacteria, yeasts and molds. For bacteria, taken from the TPC results, their numbers were ranging from 7.7 x 10(2) microorganisms/ml to too many to count (TMTC). For yeasts and molds the numbers showed variations from 0 microorganisms/ml to TMTC. Contamination with Coliform in 1 ml of JG were ranged from 0 to > 2.4 x 10(6) microorganisms. In most of the samples pathogenic Staphylococci, Salmonella sp. and Vibrio sp. were not detected, so that a conclusion can be drawn that most of the contamination in JG are saprophytic, only a few pathogenic. The results also show that it is possible to have JG which fulfill the government's requirements. Similar results were obtained with the plant material constituents of JG such as rhizomes, leaves, herbs and fruits of Piper nigrum and Piper retrofractum, with the exception of Piper betle leaves and P. retrofractum fruits, both showing low contamination of Coliform bacteria. However, the fruits of Citrus aurantifolia and Morinda citrifolia were less contaminated, just like seeds of Oryza sativa, Parkia roxburghii, bulbs of Allium sativum and the pulp of Tamarindus indica. With these plant constituents of JG, it might be of interest to screen their antibacterial and antifungal activities. PMID- 10030725 TI - Inhibitory effects of Dai-saiko-to (Da-Chai-Hu-Tang) on the progression of atherosclerotic lesions in Kurosawa and Kusanagi-hypercholesterolemic rabbits. AB - The inhibitory effects of the traditional herbal medicine Dai-saiko-to (Da-Chai Hu-Tang) on the progression of the atherosclerotic lesions were studied using the spontaneous familial hypercholesterolemia (FH) model, Kurosawa and Kusanagi hypercholesterolemic (KHC) rabbits. Changes in blood chemistry, pathology and low density lipoprotein (LDL) oxidation were measured in a control group and a Dai saiko-to-treated group. In the control group, the area of atheromatous plaques of the aorta progressed between week 12 (29.1%) and 26 (51.5%). This progression of atherosclerotic lesions did not happen in the Dai-saiko-to-treated group between week 12 (26%) and 26 (27.4%). Antioxidative effects on LDL were seen in the Dai saiko-to-treated group in weeks 16 and 18. Dai-saiko-to did not improve the hypercholesterolemia in the KHC rabbits. These results suggest that Dai-saiko-to has inhibitory effects on the development of atheromatous plaque formation in spontaneous FH model rabbits. It is possible that the antioxidative effects of Dai-saiko-to on LDL led to the beneficial effects observed in this study. PMID- 10030726 TI - Protection by Rhinax in various models of ulceration in rats. AB - The effect of Rhinax on gastric damage in different animal models including gastric ulceration induced by a necrotic agent such as 0.6 N HCl, indomethacin, and intragastric distension was studied. Treatment with Rhinax at a dose of 160 mg/kg protected gastric mucosa against the damage induced by oral administration of indomethacin and intragastric distension. The volume and acidity of gastric juice in pyloric ligated rats was reduced by Rhinax. It also significantly promoted gastric mucus secretion in normal animals. On the basis of these observations, we conclude that Rhinax possesses anti-ulcer activity and that the observed activity may be due to the modulation of defensive factors by improvement in gastric cytoprotection. PMID- 10030727 TI - Anti-hepatotoxic effects of root and root callus extracts of Cichorium intybus L. AB - The natural root and root callus extracts of Cichorium intybus were compared for their anti-hepatotoxic effects in Wistar strain of Albino rats against carbon tetrachloride induced hepatic damage. The increased levels of serum enymes (aspartate transaminase, alanine transaminase) and bilirubin observed in rats treated with carbon tetrachloride were very much reduced in the animals treated with natural root and root callus extracts and carbon tetrachloride. The decreased levels of albumin and proteins observed in rats after treatment with carbon tetrachloride were found to increase in rats treated with natural root and root callus extracts and carbon tetrachloride. These biochemical observations were supplemented by histopathological examination of liver sections. Results of this study revealed that Cichorium intybus root callus extract could afford a better protection against carbon tetrachloride induced heptocellular damage as compared to the natural root extract. PMID- 10030728 TI - Indigenous patterns of conserving biodiversity: pharmacologic implications. AB - The accelerating rate at which the world's botanical resources are being depleted today has inspired redoubled efforts on the part of global conservation programs. For the most part, this reflects the actions of outsiders who are culturally and politically detached from the threatened environments, and who identify species for conservation through western economic models. In view of this, ethnopharmacologists--and primarily those representing the social sciences--have drawn attention to the cogency of indigenous knowledge of biotic diversity and its conservation. This paper reviews how local paradigms of plant management promote conservation, and problematizes the issue specifically to the use of plants by Hausa peoples in northern Nigeria. The pharmacologic implications of indigenous patterns of plant use and conservation derive from the manifold and overlapping contexts in which plants, especially wild species, are used by local communities. These applications identify the importance of particular species and should be employed in assigning priority for the conservation of plants. PMID- 10030729 TI - Antidepressant effect of an ethanolic extract of the leaves of Cissampelos sympodialis in rats and mice. AB - An ethanolic extract of the leaves of Cissampelos sympodialis Eichl. (Menispermaceae) was found to potentiate the toxicity of pentylenetetrazol in mice. Similar to imipramine, the extract also reduced the immobility period in the forced swimming test in mice and reversed the degree of ptosis and catalepsy induced by reserpine in rats. These results suggest that the extract possesses antidepressant activity and the reported phosphodiesterase inhibitory activity of the plant may account for the observed antidepressant effect. PMID- 10030730 TI - Antimicrobial properties of Honduran medicinal plants. AB - Ninety-two plants used in the traditional pharmacopoeia of the Pech and neighboring Mestizo peoples of central Honduras are reported. The results of in vitro antimicrobial screens showed that 19 of the extracts from medicinal plants revealed signs of antifungal activity while 22 demonstrated a measurable inhibitory effect on one or more bacterial cultures. Bioassay-guided fractionation of extracts from Mikania micrantha, Neurolaena lobata and Piper aduncum produced weak to moderately active isolates. The broad spectrum of activity of the extracts helps to explain the widespread use of these plants for wound healing and other applications. PMID- 10030731 TI - Phase II trial of 5-fluorouracil and low-dose cisplatin in patients with squamous cell carcinoma of the esophagus. AB - A phase II study was conducted to determine the clinical efficacy and toxicity of 5-fluorouracil (5-FU) and low-dose cisplatin (CDDP) in patients with squamous cell carcinoma of the esophagus. Chemotherapy consisted of 5-FU at a dose of 330 mg/m2 per day, given as a 24-h infusion on days 1-7, and CDDP at a dose of 6 mg/m2 per day, given as a 2-h infusion on days 1-5. Either two or four cycles of chemotherapy were administered to 20 patients with stage III advanced esophageal carcinoma. All 20 patients were then assessed for response and toxicity. An objective response was demonstrated by 11 of the 20 patients, with one complete response (CR) and ten partial responses (PR), bringing the response rate to 55%, with a 95% confidence interval of 27% to 83%. Surgical resection of the tumor was performed in all 20 patients. One patient was found to have a grade 3 histological CR. The median survival of all the patients was 20.5 months, with a range of 4.5 to 48.0 months. Neutropenia and thrombocytopenia developed in five (25%) and two (10%) patients, respectively, and the nonhematologic toxicities were insignificant. The findings of this phase II study indicate that preoperative treatment using 5-FU and low-dose CDDP chemotherapy for patients with advanced esophageal carcinoma appears to achieve a high response rate after short-term administration without affecting the quality of sophisticated lymph node dissection. PMID- 10030732 TI - Laparoscopic resection of submucosal gastric tumors. AB - In order to elucidate the efficacy in gastric surgery, we evaluated seven resected cases of a submucosal gastric tumor in which laparoscopic techniques were used. The patients consisted of 1 man and 6 women. The tumors were located in the upper, middle, and lower third of the stomach in 4, 1, and 2 cases, respectively. Three tumors were located mainly on the anterior gastric wall, 2 were on the posterior wall, and 2 were on the lesser curvature. The resected tumor size averaged 3.2 x 2.6 cm. The tumors were classified as intraluminal type (4 cases) and the extraluminal type (3 cases) according to the classification of growth type. A histopathological examination identified 4 leiomyomas, 1 leiomyosarcoma, and 4 smooth muscle tumors of indeterminate malignant potential. After a tumor resection, no recurrence of the lesions occurred during the postoperative follow-up. An extraluminal growing tumor was easily resected by the laparoscopic method without any additional procedures, and this therefore seemed to be a good indication for the laparoscopic method. In contrast, an intraluminal tumor was found to be more difficult to resect using the laparoscopic method without a companion method, e.g., intraoperative endoscopy, because of the difficulties in the detection and resection of the tumor from the serosal side. A more efficient technique must therefore be developed for this type of tumor. PMID- 10030733 TI - Finger bougie method compared with pyloroplasty in the gastric replacement of the esophagus. AB - To elucidate the necessity of pyloroplasty for the gastric tube through the posterior mediastinum in esophageal surgery, gastric emptying and duodenogastric reflux (DGR) were evaluated in 16 cases undergoing an anterior pylorectomy (group P) and in 16 cases treated by the finger bougie method (group F). First, the obstruction and reflux symptoms were examined based on a patient questionnaire using a brief scoring system. The median value of the symptom score showed the patients in P to have more symptoms than those in F; however, the difference was not significant (8.0 vs 6.0). Secondly, the swallowed Tc O4- (85MBq) was counted using a gamma camera at three sites on the sternal bone in the upright position based on a gastric transit scintigram. Both the descending time of the RI peak and the clearance rates were similar between the two groups. Thirdly, intragastric 24-h pH monitoring was carried out. Antimony pH sensors were anchored 5 and 15cm below the esophagogastrostomy. We could not find any difference between the two groups in both the %time pH > 4 and %time pH > 7. These findings thus revealed no big difference between groups P and F. The finger bougie method to drain the vagotomized posterior mediastinal stomach was found to achieve results similar to conventional pyloroplasty, while it was also simpler and safer. PMID- 10030734 TI - Importance of positive peritoneal lavage cytology findings in the stage grouping of gastric cancer. AB - Although peritoneal lavage cytology is widely performed during surgery for gastric cancer and the results have been reported to be one of the accurate prognostic factors, the cancer stage is determined independent of the results of lavage cytology according to the First English Edition of Japanese Classification of Gastric Carcinoma. In this study we demonstrated the validity of lavage cytology for accurately staging gastric cancer. Between 1988 and 1996, peritoneal lavage cytology was performed in 347 patients with resectable gastric cancer. Among them, cytology was positive in 29 cases (8.4%). The survival rate of the cytology-positive patients in each stage was worse than that of all patients in the same stage. The prognosis of patients with positive cytology findings and serosa-exposed gastric cancer was significantly worse than that of negative cytology findings and serosa-exposed gastric cancer, and similar to that of negative cytology findings and serosa-infiltrating gastric cancer. Our data indicated that positive cytology findings thus indicated a poor prognosis, and the prognostic difference between positive and negative cytology findings was approximately a one-stage difference in the Japanese stage grouping. Based on our findings, the results of peritoneal lavage cytology should thus be included in the factors for staging gastric cancer. PMID- 10030735 TI - Expression of nm23-H1 in colorectal cancer: no association with metastases, histological stage, or survival. AB - The correlations of nm23-H1 expression in primary cancer lesions with the already confirmed 14 prognostic variables and survival were examined in 52 advanced colorectal cancer patients, because the clinical roles of nm23-H1 expression in the cancer lesions remain controversial. An immunohistochemical expression of nm23-H1 was found in 23 lesions (positive group) but not found in 29 lesions (negative group). No significant difference between the positive and negative groups was found according to 12 clinicopathological variables including vascular invasion, lymph node and liver metastases, and histological stage. The carcinoembryonic antigen levels (21.5+/-33.4 ng/ml) of the draining venous blood and argyrophilic nucleolar organizer regions score (3.35+/-1.36 per nucleus) of the cancer cells in the positive group were not significantly diffeent from those (34.1+/-102.9 ng/ml and 3.32+/-1.00 per nucleus, respectively) in the negative group. In addition, no significant difference was found in the survival curves or the 5-year survival rates of the positive and negative groups. From these results, it may be concluded that the nm23-H1 expression was not associated with the aforementioned prognostic variables and the prognosis of advanced colorectal cancer patients. PMID- 10030736 TI - Serum KL-6, a novel mucin-like glycoprotein, as an indicator of interstitial pneumonitis following lobectomy. AB - Serum KL-6 has been shown to be a useful marker of active interstitial pneumonitis in patients who have not undergone lobectomy. Considering that KL-6 is produced mainly in the distal airway epithelium, the present study was conducted to determine whether resected lung volume influenced the postoperative KL-6 levels, and also to evaluate whether it is a useful parameter in patients who have undergone lobectomy. The serum KL-6 levels decreased by 36% 1 week after lobectomy, but returned to the preoperative levels by 2 months postoperatively. Although the KL-6 levels increased by 100% 3 to 4 months after lobectomy, the levels were significantly lower than those in interstitial pneumonitis (P < 0.05). The decrease in the KL-6 levels correlated with the number of resected lung segments, but not with the changes in white blood cell count, lactate dehydrogenase level, or C-reactive protein level. In comparison with the lobectomy patients, the serum KL-6 levels decreased by half in patients who had undergone partial resection (P < 0.05). The results of this study suggest that the serum KL-6 level may be a useful indicator of interstitial pneumonitis after lobectomy. Serum KL-6 levels are influenced by the volume of the resected lung, and probably also by the upregulation of KL-6 production. PMID- 10030737 TI - Surgery for descending thoracic aortic anastomotic aneurysms with a temporary external bypass method. AB - The surgical treatment of descending thoracic aortic anastomotic aneurysms is technically challenging. The purpose of this study was to evaluate the use of a temporary external bypass method as an intraoperative measure in the surgical treatment of anastomotic aneurysms of the descending thoracic aorta. An analysis of five consecutive patients who had undergone surgery for a collective seven descending thoracic aortic anastomotic aneurysms in our university hospital over a period of 14 years was conducted. A temporary bypass technique was used as an intraoperative measure in all the operations, four of which were performed with a right axillary to left external iliac artery bypass, while other sites were used in the remaining three. Systemic heparinization was able to be avoided in six operations and was markedly reduced in the remaining one. Although the major postoperative complication was coagulated hemothorax after six procedures, all patients recovered well and are still alive after a mean follow-up period of 8.2+/-1.5 (SEM) years. The results of this analysis led us to conclude that our temporary bypass method for treating descending thoracic aortic anastomotic aneurysm prevented the risks of anticoagulant administration for circulatory support, which contributed to the success of the operation. This method can be used as adjunct treatment for anastomotic aneurysms in the descending thoracic aorta. PMID- 10030738 TI - The role of the spleen, especially regarding changes in both thromboxane A2 and the remnant liver dysfunction after extensive hepatectomy. AB - The plasma levels of thromboxane B2 (TxB2) and 6-keto-prostaglandin F1alpha (6 KF) in the peripheral and portal blood increase after an extensive hepatectomy, and even more so in cases with complications. In this cell biological study, we estimated the prostanoids in the portal system to clarify which organ produces them, while also evaluating the effect of a splenectomy in conjunction with an extensive hepatectomy. Our results showed that the level of TxB2 in the splenic vein was significantly higher than that in the mesenteric vein. Furthermore, the TxA2 produced by splenic macrophages after an extensive hepatectomy was significantly more than after a sham operation. We also observed the hepatocyte damage to be less in the group that underwent an 84% hepatectomy and splenectomy than in the group that underwent the same hepatectomy without a splenectomy. It therefore appears important both to suppress the splenic macrophages from producing TxA2 and to prevent remnant hepatic dysfunction after an extensive hepatectomy. PMID- 10030739 TI - The detection of chronic heart graft rejection by 31P NMR spectroscopy. AB - The usefulness of phosphorus-31 nuclear magnetic resonance spectroscopy (31P NMRS) for detecting heart graft rejection after transplantation has been investigated by several researchers, and it has thus been demonstrated to be a valid technique for detecting acute myocardial rejection. In this study, we investigated the value of 31P NMRS to assess chronic cardiac allograft rejection. Lewis rat hearts were transplanted into the femoral region of F-344 rat recipients which were treated with cyclosporine, 5mg/kg body weight, by a daily intramuscular injection for 30 days beginning on the day of transplantation. The control isografts employed Lewis donors and recipients not given cyclosporine. The ratios of phosphocreatine (PCr) to inorganic phosphate (Pi), beta-adenosine triphosphate (beta-ATP) to Pi, and PCr to beta-ATP were monitored using surface coil 31P NMRS. 31P NMRS was performed 3, 30, and 60 days after transplantation, and the degree of the rejection and arteriosclerosis of the coronary arteries were then assessed histologically. The PCr:Pi and beta-ATP:Pi ratios for the allografts demonstrated a significant decrease on postoperative day (POD) 60 from that on POD 30 (PCr:Pi, P < 0.001; beta-ATP:Pi, P < 0.01). Although a significant difference existed between the isografts and allografts on POD 60 (PCr: Pi, P < 0.01; beta-ATP:P, P < 0.01), no significant difference was found in the PCr:beta ATP ratio between the allografts and the isografts. On POD 60, the allografts showed significant graft rejection and arteriosclerotic changes in the coronary arteries. These findings therefore demonstrated the effectiveness of 31P NMRS for detecting chronic graft rejection in a rat model. PMID- 10030740 TI - Effects of experimental chemoendocrine therapy with a combination of a pure antiestrogen and 5-fluorouracil on human breast cancer cells implanted in nude mice. AB - The antitumor effects of an experimental chemoendocrine therapy combining a new pure antiestrogen ICI 182780 and 5-fluorouracil (5-FU) were studied on MCF-7 human breast cancer cells implanted in nude mice. ICI 182780 had a dose-dependent antitumor activity, which was potentiated by the concomitant use of 5-FU. When compared with the control group, the estrogen receptor (ER) level in the ICI 182780 group was lower and that in the combination group was markedly lower. Cell cycle analysis by flow cytometry (FCM) resulted in a lower percentage of S-phase cells (%S) in the treated mice. No significant difference was observed in the 5 FU concentrations in tumor cells, while the 5-FU content in RNA was significantly higher in the combination group. The changes in free thymidylate synthetase (TS) concentration indicated TS synthesis after the administration of 5-FU to be more greatly suppressed in the combination group than in the 5-FU group. These results suggest that ICI 182780 and 5-FU exert their combination effect mainly on ER positive cells, and that the suppression of TS synthesis in tumor cells and the potentiation of the 5-FU-induced metabolic dysfunction of RNA are thus involved in the mode of action of this combination therapy. PMID- 10030741 TI - Induction of a critical elevation of povidone-iodine absorption in the treatment of a burn patient: report of a case. AB - A critical elevation of povidone-iodine absorption which occurred in a burn patient who was topically treated with 10% povidone-iodine (PI) gel is herein reported. A 65-year-old man was admitted to our hospital for deep second- and third-degree burns covering 26% of his total body surface area. The intravenous administration with lactated Ringer's solution and topical treatment with silver sulfadiazine were applied in addition to such treatments as debridement and skin grafting. However, wound infection occurred due to Pseudomonas aeruginosa. Topical treatment with PI gel was effective for this condition. Persistent nodal bradycardia with hypotension, metabolic acidosis, and renal failure occurred 16 days after the start of PI gel treatment. Iodine toxicosis caused by PI gel was suspected with a serum iodine level of 20600 microg/dl (normal range 2-9 microg/dl). The PI gel treatment was therefore discontinued immediately, and hemodialysis was scheduled. However, the patient's family refused hemodialysis and he died 44 days after admission. To our knowledge, only eight patients with iodine toxicosis have been reported in burn patients treated with PI gel. PMID- 10030742 TI - Primary malignant fibrous histiocytoma of the ascending colon: report of a case. AB - We report herein an unusual case of primary malignant fibrous histiocytoma (MFH) of the ascending colon. A 47-year-old man was admitted to our hospital for further investigations following the discovery of a mass in the right lower quadrant of the abdomen during a medical checkup. Abdominal ultrasonography (US) and computed tomography (CT) demonstrated a mass extending to the right lateral side from the ascending colon. At laparotomy, a tumor was found originating in the ascending colon and infiltrating the right lateral peritoneum. A right hemicolectomy and partial peritoneal dissection were performed followed by an ileotransverse colostomy reconstruction. The resected specimen contained a tumor measuring 7 x 5 x 4 cm, the cut surface of which was yellowish white, and the mucosa of the colon was intact. Based on histological and immunohistochemical inspection, the tumor was diagnosed as MFH of the ascending colon. We reviewed the total 18 known cases of colorectal MFH documented in the literature including our case. After surgery, 4 of 17 patients died of local recurrence, all within 42 months, indicating that early and complete excision of tumor is essential to achieve cure. PMID- 10030743 TI - The effectiveness of chemotherapy with cisplatin and 5-fluorouracil for recurrent small cell neuroendocrine carcinoma of the rectum: report of a case. AB - We report herein the case of a 46-year-old-man with small cell neuroendocrine carcinoma (NEC) concomitant with large villous adenoma of the rectum, who underwent abdominoperineal resection with regional lymphnode dissection. The resected specimen was histologically found to contain a small lesion of NEC confined to the submucosa in the large adenoma. A computed tomography scan done 4 months postoperatively revealed recurrences in the liver, lymph nodes, and bone. Therefore, two cycles of sequential intravenous combined chemotherapy with standard doses of cisplatin and 5-fluorouracil (5-FU) were administered, after which the size of each tumor decreased remarkably. Nevertheless, the patient died 8 months after the operation. As there was a fair response of this tumor to the combined chemotherapy of cisplatin and 5-FU, this regimen against NEC of the colon and rectum should be given consideration. PMID- 10030744 TI - Primary anorectal malignant melanoma: report of a case. AB - Primary anorectal malignant melanoma is a fairly uncommon but highly malignant disease. This disease is sometimes mistaken for such benign conditions as either a hemorrhoid or rectal polyp. We herein describe a case of early primary malignant melanoma of the anal canal. In this case, magnetic resonance (MR) imaging was found to be useful for diagnosing the melanotic melanoma. We especially emphasize the usefulness of a fat-saturation MR image in distinguishing melanotic melanoma from other rectal tumors. PMID- 10030745 TI - Mesenteric cystic neoformations: report of two cases. AB - The authors present two case reports of mesenteric cystic neoformations which they themselves observed and, with the help of the literature regarding this pathology, discuss the problems of both diagnosis and treatment. PMID- 10030746 TI - Castleman disease of the pararenal retroperitoneum: report of a case. AB - We describe herein the case of a 21-year-old woman in whom Castleman disease of the pararenal retroperitoneum was successfully resected. The patient was referred to our hospital from another hospital for investigation of a retroperitoneal mass in the right middle abdomen. Ultrasonography, computed tomography, and magnetic resonance imaging demonstrated a large retroperitoneal mass with heterogeneous imaging characteristics. An aortogram showed arterial feeding to this mass from a few lumbar arteries. Although a definitive preoperative diagnosis could not be made, surgical excision was performed and histopathological examination confirmed a diagnosis of the hyaline type of Castleman disease. The patient had an uneventful postoperative course and was discharged 14 days after her operation. She now leads an active social life without any signs of sequelae or recurrence 14 months later. To the best of our knowledge, only 2% (6/315) of all reported cases of Castleman disease have been located in the pararenal and retroperitoneal area. PMID- 10030747 TI - Mild hypothermia for temporary brain ischemia during cardiopulmonary support systems: report of three cases. AB - Recovery without residual neurological damage after cardiac arrest with temporary cerebral ischemia is rare. Therefore, it is most important that every effort is made to prevent brain damage occurring immediately after successful cardiopulmonary resuscitation. We report herein the cases of three patients who suffered either cardiogenic or hypovolemic shock and were resuscitated by a cardiopulmonary support system followed by mild hypothermia. All three patients recovered completely without any neurologic damage. The outcomes of these three patients demonstrated that mild hypothermia may be important for cerebral preservation after cardiopulmonary resuscitation. PMID- 10030748 TI - Treatment for empyema with bronchopleural fistulas using endobronchial occlusion coils: report of a case. AB - We report herein the case of a woman with bronchopleural fistulas treated with the endobronchial placement of vascular embolization coils. She was referred to our hospital to undergo lavage of a postoperative empyema. She had undergone an air plombage operation for pulmonary tuberculosis 9 years previously. However, bronchopleural fistulas occurred postoperatively and she had to continue the use of a chest drainage tube since then. Lavage of her empyema space with 5kE of OK 432 (Picibanil: Chugai) plus 100 mg minocycline was performed once every 2 weeks for 3 months, and the purulent discharge from the empyema remarkably decreased. Thereafter, the bronchopleural fistulas were occluded endobronchially by the placement of vascular embolization coils. Soon after the procedure, air leakage from the fistulas was stopped and the drainage tube was removed 2 days later. The patient remains well without any additional treatment at 20 months after this treatment. As treatment for empyema with bronchopleural fistulas, it would be worth trying to lavage the empyema space with OK-432 until it is cleaned out and to plug the fistulas by the endobronchial placement of embolization coils, before such radical operations as thoracoplasty and space-filling of the empyema are considered. PMID- 10030749 TI - Iodine-131 human-mouse chimeric Fab monoclonal antibody A7 guided surgery for colorectal cancer patients: a pilot study. AB - This study was conducted to determine the clinical usefulness of radioimmunoguided surgery (RIGS) using human-mouse chimeric Fab monoclonal antibody A7 (ch-Fab-A7) for colorectal cancer patients. Ten colorectal cancer patients were given iodine-131-labeled ch-Fab-A7 intravenously (i.v.) 2 to 7 days prior to RIGS. The RIGS was carried out using a portable gamma detecting probe (GDP). Tumor localization was identified by GDP intraoperatively in 4 of the ten patients, while liver metastasis and lymph node metastasis were identified in 2 patients and 1 patient, respectively. The GDP revealed tumor/surrounding tissue radio(gamma)count ratios of 1.5 or greater in 8 of the ten resected tumors. Although RIGS using ch-Fab-A7 is a promising tool for intraoperatively identifying the tumor localization of colorectal cancer, 125I, rather than 131I, should be used as a tracer for RIGS to enhance the accuracy of ch-Fab-A7. PMID- 10030750 TI - An effective device to keep the sternum open. AB - Delayed sternal closure following cardiothoracic surgery facilitates the treatment of heart failure and arrhythmias caused by sternal closure, and also allows access to treat uncontrollable bleeding. The present study examines the use of stents made from disposable syringes for keeping the sternum open. The syringes demonstrated good strength, as well as resistance to tapping during pulmonary physical therapy and stability against body movement necessary to prevent the formation of decubitus ulcers. Thus, the proposed stent provides an inexpensive, easy, and effective method for keeping the sternum open. PMID- 10030751 TI - Toxoplasmosis and iodine deficiency in Angora goats. AB - Toxoplasmosis was diagnosed in two goat herds in the Czech Republic. The 1996 outbreak in the herd of Angora goats was associated with abortions and births of weak kids. No apparent signs of toxoplasmosis were observed in the herd of White Short-Haired (WSH) goats reared under similar conditions. Seroprevalences of 60% and 66% tested by complement fixation and indirect fluorescent antibody tests, respectively, were found in the herd of Angora goats during the outbreak of clinical toxoplasmosis. Significantly lower values were recorded in this herd in years 1994 and 1997 and in the herd of WSH goats between years 1994-1996. Iodine deficiency was also demonstrated in the herd of Angora goats in 1996. Goitre was detected by clinical examination in 39% of animals and mean urinary iodine concentration was 8.0+/-4.65 microg per 11. This concentration rose significantly to 15.7+/-5.02 microg per 11 in the subsequent year. Effects of iodine deficiency on clinical manifestation of toxoplasmosis in Angora goats were discussed. PMID- 10030752 TI - Identification of carbohydrates on Eimeria stiedai sporozoites and their role in the invasion of cultured cells in vitro. AB - The carbohydrates present on Eimeria stiedai sporozoites and their functional role in the process of invasion of host cells were examined. Lectin-binding sites on the surface of sporozoites were detected by means of peroxidase-conjugated lectins. Sporozoites showed specific binding with UEA-I and PNA lectins, which bind L-fucose and D-galactose, respectively. Exposure of sporozoites to 100 microg/ml UEA-I significantly reduced their ability to invade primary rabbit liver biliary epithelial cells, but similar treatment with PNA had no such effect. Pre-incubation of these cells in Dulbecco's minimum essential medium containing 10% fetal bovine serum and 1% L-fucose suppressed the invasion activity of the sporozoites, but pre-incubation of the sporozoites in the same medium without L-fucose had no effect on cell penetration. D-galactose added to the medium had no effect on the invasion activity of sporozoites. These results indicate that L-fucose residues on E. stiedai sporozoites and L-fucose-binding sites on host cells both are associated with the recognition and/or invasion process. PMID- 10030753 TI - Trypanosome infection rate in cattle at Nguruman, Kenya. AB - Trypanosome infection rate in cattle at Nguruman was investigated in a study conducted in 1984-1986. Shifting pastoralism significantly reduced trypanosome infections in cattle. The cattle were more heavily infected with Trypanosoma congolense (16.5%) than Trypanosoma vivax (4.95%) and Trypanosoma brucei (0.19%). Trypanosoma theileri was observed only once among the cattle examined. Mixed trypanosome infections in cattle were observed to be 2.75% and 0.014% for T. congolense/T. vivax and T. congolense/T. brucei, respectively. The duration of infection in the cattle was 55 days for T. congolense and 79 days for T. vivax. High infections in cattle were observed 2 months after the rains, which were concomitant with high tsetse densities. PMID- 10030754 TI - Bovine fasciolosis in Tabasco, Mexico. AB - To establish seasonal trends in infection and maturity of Fasciola hepatica in cattle in relation to macroclimatic factors, 2730 condemned livers were examined from March 1989 to February 1992. Livestock came from Jalapa, Tacotalpa and Teapa, all municipalities in Tabasco State. Flukes were collected monthly and separated into three different maturation stages. Mean numbers of flukes collected were determined. The analysis of the maturation stages detected in cattle showed: (a) F. hepatica matured throughout the year at all three sites; (b) the greatest mean fluke's burdens were found in Jalapa and the lowest in Teapa; large parasite populations were significantly higher from February to September than in July and/or August; (c) persistence of mature, gravid F. hepatica indicated that parasite eggs are shed throughout the year; (d) recruitment of F. hepatica occurred throughout the year with two major periods of infection, the first and main period during the dry season (from February to June), and a second minor infection period, during the rainy season (from August to October); (e) a close relationship was observed between the seasonal infection pattern in cattle and the seasonal infection pattern in snails, as well as fluctuations in the snail population according to rainfall and temperature variation. PMID- 10030755 TI - Taenia solium cysticercosis: immunity in pigs induced by primary infection. AB - The present study demonstrates that pigs experimentally infected with Taenia solium eggs develop resistance to reinfection that lasts at least five months. Thirteen 2-month-old piglets were infected with eggs of Taenia solium. After 5 months, two pigs were euthanized and five were challenged with eggs from a second tapeworm. Nine months after the first infection, six pigs were challenged with a third tapeworm. All 11 challenged pigs were euthanized 2 months after reinfection. In order to confirm the infectivity of the eggs, several piglets were inoculated with each taenia. Two of the five pigs reinfected after 5 months did not develop metacestodes, two showed few caseous non-infective forms and in the fifth pig, 14% of the metacestodes were vesicular and 86% colloidal and caseous. In the six animals challenged 9 months after the first infection, three were heavily infected with vesicular metacestodes and the other three showed only colloid and caseous forms in muscles. All parasites found in brains were vesicular. We conclude that immunity due to primary infection lasts at least 5 months. At 2 months of infection antigens of 24 and 39-42 kDa were the most frequently recognised. In those pigs with only a few caseous cysts in muscles and/or vesicular ones in brains no antibodies were detected. PMID- 10030756 TI - Physiological and parasitological responses to nematode infections of fattening cattle in the Western Pampas of Argentina. AB - The epidemiology of nematode infection was studied in fattening grazing cattle from weaning (April 1994) to market at the end of their second autumn (July 1995). Sixty Aberdeen Angus calves of seven months of age were randomly allocated by weight to two groups: GT, treated every three weeks with doramectin (200 mcg/kg); and GI, an infected group, only treated with fenbendazole (7.5 mg/kg) at weaning and on the 1st of October. The two groups were grazed together on contaminated lucerne pastures until July, on 'clean' oat pastures until October and again on contaminated lucerne until the end of the trial. Fecal egg counts (epg), herbage larvae (L3), serum pepsinogen (Pep) and blood eosinophils (Eo) were evaluated monthly. Eight steers were slaughtered for worm recovery, three in July 1994, three in December 1994 and two in July 1995. Grazing feed intake was estimated by fecal output (chromic oxide method)/l-diet digestibility and to measure non-specific response, Brucella antibodies were detected at 11 and 40 days post-vaccination in early winter. Fecal egg counts, Pep and Eo of GI increased (P<0.01) from April to July when there was a moderate-to-high level of infection. Ostertagia, Trichostrongylus and Cooperia were the predominant genera. By late winter, all parameters decreased on oat 'clean' pastures and increased again when cattle returned to moderately infected lucerne. During summer, the parameters measured reflected the negligible numbers of L3 on pastures until early autumn. At this time, increased numbers of L3 were followed by a moderate rise (P<0.01) of epg, Pep and Eo values. During winter, GT showed higher (P<0.04) Brucella antibody IgG titers while feed intake of GI was 24.9% depressed (P<0.02). There were total cumulative weight-gain (WG) differences (P<0.001) between groups (GT=263.1 kg; GI=214.3 kg). During the second autumn, the mean WG of GT steers was 16.6 kg greater (P<0.04) than that of GI. Vaccination titres against Brucella suggested non-specific depression of immunity, while higher Pep and Eo levels in second-year steers may have reflected hypersensitivity reactions. PMID- 10030757 TI - The parasites, predators, places and people I have known: a great adventure. AB - I am extremely proud to receive the WAAVP/Pfizer Animal Health award, and particularly so in Africa, the continent where I have spent a large part of my professional life. In the nearly 40 years in research I have had the privilege and excitement of being involved with many great parasites, predators, places and people. In my early days in Kenya I saw all the great wild animal predators, but soon came to appreciate that the greatest predator of all was disease, particularly parasitic disease, with the devastating effects of tsetse and ticks and the infections they transmitted, and of the all-prevailing roundworms. I learned several key lessons while working with research teams to develop better diagnostics, to improve epidemiological understanding as a basis for rational treatment and control, and to extend the understanding of disease processes with the view to developing novel methods of treatment or prevention. The Power of Pathology in diagnosing diseases, identifying new diseases and as a major tool for pathogenic diseases. The Power of Pathogenesis in identifying key mechanisms that led to new diagnostic techniques, improved methods of treatment, and possibly to future vaccines. The Power of Application of what we already know; while recognising that molecular biology will make a massive contribution to improving animal and human health, it is important to appreciate that we already have a very powerful armamentaria to diagnose, treat, control or prevent disease, and when used properly they have been successful and cost-effective. The Power of Genetic Resistance: the recognition that certain species, certain breeds, and certain individuals within breeds possess remarkable resistance to certain parasitic diseases such as trypanosomosis and helminthosis, and that this trait is genetically correlated with production, opens up a very powerful additional approach to improving animal health. The Importance of Measurement: I completely endorse the sentiments of Lord Kelvin, Professor of Natural Philosophy at Glasgow University who stated in 1846: "When you can measure what you are speaking about, and express it in numbers, you know something about it: but when you cannot measure it, your knowledge is of a meagre and unsatisfactory kind." This applies very much to Parasitology. The future is bright. The combination and integration of the new technologies of Biotechnology, Mathematical Methods and Bioinformatics coupled with advances in Computer Power will produce new standards in animal and human health in the 21st century. New methods of predicting, diagnosis, treating, controlling, prognosing and preventing disease will become available. WAAVP has a major role to play by ensuring that veterinary parasitologists are provided with the proper training, infrastructure and forum to advance new technologies and that the veterinary profession plays a leading role in the future direction they take. PMID- 10030758 TI - Parasitology crossing borders. AB - In veterinary parasitology it is important to further strengthen international collaboration and interactions. On the one hand, there is a strong and promising trend towards growth in large international programmes. However, we, as researchers, should make more serious attempts to influence the targets and structures of these programmes. On the other hand, let us not forget to fully exploit the possibilities for support to even small projects and visiting researchers' arrangements, preferably in a flexible way. The paper emphasizes the obvious need for research capacity building in the least developed countries, and advocates a partnership approach in research for development. The presentation suggests more operative initiatives in international veterinary parasitology. Finally, how language barriers can hamper international contacts and exchange of information is discussed. Ways to possibly avert this are indicated. PMID- 10030759 TI - Fasting hyperglycaemia with oral glucose tolerance in acute Trypanosoma congolense infection of rats. AB - Intraperitoneal inoculation of rats with Trypanosoma congolense (Federe strain) produced a sustained parasitaemia from days 7 to 23 post-infection (pi). The fasting tail-blood glucose (FBG) concentrations in the infected animals increased (p<0.05) from 3.8+/-0.2 mmol/l on day 0 pi to 4.6+/-0.2, 4.9+/-0.2 and 5.8+/-0.3 mmol/l on days 7, 10 and 17 pi and decreased (p<0.05) to 3.1+/-0.8 and 2.9+/-0.7 mmol/l on days 20 and 23 pi, but the values in the uninfected controls varied between 3.8+/-0.3 mmol/l on day 0 pi and 3.9+/-0.2 mmol/l on day 23 pi. After oral glucose intake (1.0 g/kg) and determination of tail-blood glucose (BG) concentrations after 2 h, the percentage increase in BG from FBG was either comparable in infected and uninfected groups (days 7, 20, 23 pi) or lower (p<0.05) in the infected group (days 10, 17), suggesting the same rate of tissue glucose delivery in both groups or a faster rate in the infected group. Therefore, oral glucose tolerance in the infected rat was not impaired, but there was initial fasting hyperglycaemia followed by fasting hypoglycaemia in the later stage. PMID- 10030760 TI - Hemorrhage into embolic brain infarcts. PMID- 10030761 TI - On recognizing and accepting the benefit management dimension of pharmacy practice. PMID- 10030762 TI - Health care professional staffing, hospital characteristics, and hospital mortality rates. AB - To evaluate associations among hospital characteristics, staffing levels of health care professionals, and mortality rates in 3763 United States hospitals, a data base was constructed from the American Hospital Association's Abridged Guide to the Health Care Field and hospital Medicare mortality rates from the Health Care Financing Administration. A multivariate regression analysis controlling for severity of illness was employed to determine the associations. Hospital characteristics associated with lower mortality were occupancy rate and private nonprofit and private for-profit ownership. Mortality rates decreased as staffing level per occupied bed increased for medical residents, registered nurses, registered pharmacists, medical technologists, and total hospital personnel. Mortality rates increased as staffing level per occupied bed increased for hospital administrators and licensed practical-vocational nurses. To our knowledge, this is the first study to show that pharmacists were associated with lower mortality rates. PMID- 10030763 TI - Hemorrhagic transformation in focal cerebral ischemia: influence of time to artery reopening and tissue plasminogen activator. AB - We used an adaptation of a well-established rat model of middle cerebral artery occlusion (MCAO) that is both minimally invasive and reproducible to determine the effects of time to reperfusion and administration of tissue plasminogen activator (t-PA) on the development of hemorrhagic transformation (HT) in a rat model of acute stroke. Animals were randomized to receive either t-PA 10 mg/kg (29 rats) or an equal volume of saline (29 rats) over 20 minutes, beginning 5 minutes before reperfusion. Time to artery reopening varied between 1 and 24 hours after MCAO in both groups. At 18-24 hours after ischemia, the animals were sacrificed and their brains were preserved for analysis of HT. Logistic regression was used to determine the influence of time on HT risk and calculate the time at which 50% of animals developed HT (HT50%). At 24 hours, HT was present in 17 of 29 animals in each group and was significantly influenced by the time of artery reopening: 3 (15%) of 20 animals reperfused less than 3 hours after onset of ischemia and 32 (84%) of 38 reperfused 3 or more hours after the onset of ischemia (p<0.001). There was no difference in HT50% between groups. Time to artery reopening is an important determinant of HT risk in this model of cerebral ischemia. This model may have utility in developing strategies to reduce HT formation after thrombolytic therapy in patients with acute stroke. PMID- 10030764 TI - Effect of helium-oxygen on delivery of albuterol in a pediatric, volume-cycled, ventilated lung model. AB - Pulmonary delivery of inhaled bronchodilators in mechanically ventilated patients is inefficient whether administered by metered-dose inhaler (MDI) or small-volume nebulizer. One of the factors that causes inefficient aerosol delivery is turbulent gas. Heliox (He:O2) is a blend of helium and oxygen that is less dense than air, making turbulent flow less likely. We assessed the effect of 70% He:O2 on albuterol delivery in a mechanically ventilated pediatric lung model. Albuterol was administered by MDI with spacer, collected on a filter proximal to a test lung, and measured by high-performance liquid chromatography. Mean amount and percentage albuterol delivered were significantly (p<0.05) greater for 70% He:O2 (395+/-29 microg, 20+/-3.2%) than for 70% nitrogen:30% oxygen (241+/-29 microg,12+/-1.7%). Thus 70% He:O2 can increase the amount of albuterol delivered at the end of the endotracheal tube, suggesting a potential role for it in the care of critically ill ventilated patients. PMID- 10030765 TI - Lack of a pharmacokinetic interaction at steady state between ropinirole and L dopa in patients with Parkinson's disease. AB - STUDY OBJECTIVE: To assess the interaction between therapeutic dosages of ropinirole and L-dopa plus a decarboxylase inhibitor administered at steady state in patients with Parkinson's disease. DESIGN. Open, 6-week, overlap trial with random allocation. PATIENTS: Thirty patients with Parkinson's disease not previously treated with dopamine agonists, of whom 28 produced evaluable pharmacokinetic data for ropinirole and 23 for L-dopa. INTERVENTION: Group A (14 patients) received L-dopa for weeks 1-5 and ropinirole in increasing increments for weeks 2-6; group B (16) received ropinirole for weeks 1-5 and L-dopa for weeks 5 and 6. MEASUREMENTS AND MAIN RESULTS: Primary end points were AUC0-8 and Cmax for ropinirole, and AUC0-8, AUC0-infinity and Cmax for L-dopa. Secondary end points were Tmax for ropinirole, and Tmax and half-life for L-dopa. Coadministration with L-dopa at steady state did not affect rate or extent of availability of ropinirole: point estimates of the geometric mean ratio for ropinirole plus L-dopa compared with ropinirole alone for both Cmax and AUC0-8 approximated to unity. The small (16%) increase in peak concentrations of L-dopa on administration with ropinirole is unlikely to be of clinical consequence, as peak concentrations of L-dopa are typically highly variable. CONCLUSION: There are no pharmacokinetic grounds for adjusting dosages of either ropinirole or L dopa when given in combination. PMID- 10030766 TI - Effects of gender and race on albuterol pharmacokinetics. AB - We evaluated the effects of race and gender on albuterol pharmacokinetics in 30 patients with moderate asthma (15 blacks, 15 whites, 16 men, 14 women). Subjects received a single dose of albuterol 8 mg oral solution and had blood samples collected at various times for 12 hours after the dose. Albuterol plasma concentrations were determined by HPLC with fluorescence detection, and pharmacokinetics were determined by compartmental analysis. The apparent volume of distribution of albuterol was significantly higher in men than in women (631+/ 171 and 510+/-109 L, respectively, p<0.05). Consequently, the maximum concentration was lower in men than women (10.3+/-2.1 and 12.0+/-1.9 ng/ml, respectively, p<0.05). Elimination rates were 0.136+/-0.008 and 0.160+0.012 hour( 1), respectively (p<0.10). When corrected for ideal body weight, apparent volume of distribution was not different by gender. No differences between blacks and whites other than lag time were noted in albuterol kinetics. The greater apparent volume of distribution in men is likely explained by differences in ideal body weight or lean body mass. PMID- 10030767 TI - Upper gastrointestinal tract bleeding in critically ill pediatric patients. AB - Similar to adults, children under physiologic stress can develop an imbalance in defensive (mucosal layer, motility) and aggressive (gastric acid, bile salts, enzymes) factors responsible for maintaining a healthy gastrointestinal tract. Hypoxia in the gastrointestinal tract likely disrupts the defensive factors, thereby permitting damage by aggressive factors to upper gastrointestinal epithelium that may progress to stress ulceration and acute upper gastrointestinal tract bleeding (UGIB). The basic pathophysiology may be similar in children and adults; however, differences in the time to developing ulceration, ulcer location, and number of ulcers have been reported. Functional development of the gastrointestinal tract is influenced by disease, gestational and postnatal age, and exposure to and type of enteral feedings, thereby confounding the development and prophylaxis of UGIB in neonates and infants. In addition, pharmacotherapy decisions are often complicated by drug administration issues and adverse effects. PMID- 10030768 TI - Newer strategies for the treatment of heparin-induced thrombocytopenia. AB - Treatment with heparin is associated with two types of thrombocytopenia. One is a mild, transient, nonimmune disorder, generally without adverse clinical consequence. The other, known as heparin-induced thrombocytopenia (HIT), is a potentially serious, immunoglobulin-mediated reaction with a paradoxic high risk of thromboembolic events. Various treatment options for HIT are discussed, with emphasis on pharmacologic approaches that control the increased thrombin generation characteristic of this disorder. PMID- 10030769 TI - Hydroxyurea to inhibit human immunodeficiency virus-1 replication. AB - Treatment of human immunodeficiency virus (HIV) infection continues to be a challenge. Drug regimens that include two nucleoside reverse transcriptase inhibitors and a protease inhibitor are now the standard of care. These regimens require strict patient adherence and have numerous adverse effects at a high cost, so clinicians must continue to explore other therapeutic options. Hydroxyurea is a ribonucleotide reductase inhibitor that may have efficacy against HIV. We conducted a critical review of the literature to examine the utility of hydroxyurea-based drug combinations. PMID- 10030770 TI - Does the addition of pindolol accelerate or enhance the response to selective serotonin reuptake inhibitor antidepressants? AB - Although in the last few years new antidepressants have become available in the United States, responses in many patients differ, from none, to partial, to delayed therapeutic response to the agents. If the antidepressant properties of these drugs could be enhanced or accelerated, it might be possible to improve patient functioning and quality of life. Pindolol, a serotonin 1A autoreceptor antagonist, accelerates and augments the therapeutic effects of antidepressants, especially selective serotonin reuptake inhibitors. PMID- 10030771 TI - Research experiences and research-related coursework in the education of doctors of pharmacy. AB - A study assessed coursework and experiential activities of students to determine the role of research in Doctor of Pharmacy education. Questionnaires were sent to all 78 (at that time) colleges and schools of pharmacy in the United States. Responses were received from 60 (76.9%), of which 57 were used, representing 139 Pharm.D. program types (entry-level, post-B.S., track-in, nontraditional). Most programs required coursework in research methodology, statistics, and drug information and literature evaluation, with research methodology required least. Although 41.0% of programs provided students the opportunity to conduct research as an elective, only 12.9% required an extensive project with data collection, analysis, and write-up. Another 6.5% required a project proposal only. Most colleges of pharmacy now offer the Pharm.D. degree, and the role of the pharmacist has also changed. Pharmacists must be able to disseminate evidence based knowledge about drug products and drug therapy and use scientific knowledge and scholarly principles to solve problems. PMID- 10030772 TI - Pregnancy outcomes after maternal exposure to fluconazole. AB - We evaluated pregnancy outcomes in 234 women exposed to fluconazole, 492 exposed to a topically administered azole preparation, 88 exposed to an oral azole preparation other than fluconazole, and 1629 not exposed to any of these agents during the first trimester of pregnancy Relative risks of having a baby with a congenital disorder for women exposed to fluconazole, oral azoles, and topical azoles in the first trimester of pregnancy compared with those who were unexposed were 1.1 (95% CI 0.4-3.3), 2.1 (95% CI 0.7-6.8), and 0.6 (95% CI 0.2-1.6), respectively These results provide reassurance that fluconazole exposure in the first trimester of pregnancy does not materially increase the risk of congenital disorders in infants. PMID- 10030773 TI - Increased risk of erythema multiforme major with combination anticonvulsant and radiation therapies. AB - Erythema multiforme major (EMM; Stevens-Johnson syndrome) is a cutaneous disorder associated with a wide variety of factors including ingestion of drugs such as phenytoin and exposure to intracranial radiation therapy. Based on observations of a 47-year-old black man with brain metastases who developed EMM after combined phenytoin and radiation therapy, we conducted a MEDLINE literature search for articles on similar cases from 1966 to the present. Twenty cases were identified that support the hypothesis that EMM is associated with combined phenytoin and radiation therapy. The reaction, or its severity, has no relationship to the phenytoin or radiation therapy dosage, or to the histologic type of brain tumor. Also, EMM has no apparent age or gender predisposition in association with phenytoin-radiation therapy. Thus this is a clinical phenomenon that occurs with unusual frequency in patients with brain tumor who undergo radiation therapy while taking phenytoin. Phenytoin and other anticonvulsants such as phenobarbital and carbamazepine induce cytochrome P450 3A and produce oxidative reactive intermediates that may be implicated in hypersensitivity reactions such as EMM. Both carbamazepine and barbiturates have shown cross-sensitivity with phenytoin; furthermore, a case of EMM in a patient receiving carbamazepine and whole brain radiation therapy has been reported. As carbamazepine, valproate, and barbiturates have been associated with EMM, gabapentin may be considered as alternative anticonvulsant therapy when appropriate. PMID- 10030774 TI - Rash in patients receiving ticlopidine after intracoronary stent placement. AB - As many as half of the approximately 400,000 patients who undergo nonsurgical coronary artery procedures every year receive an intracoronary stent. To prevent thrombus formation within the stent, antiplatelet treatment with ticlopidine and aspirin is administered. Ticlopidine is known to cause cutaneous adverse reactions in up to 5.1% of patients, with a 3.4% discontinuation rate. However, published studies of patients receiving the drug to prevent subacute thrombosis after intracoronary stent placement report a frequency of rash ranging from 0.8 1.6%. We hypothesized that the frequency of rash in this patient population is underreported, and conducted a retrospective chart review, collecting data on frequency and severity of rash, treatment required, patient demographics, and concomitant drugs that may predispose patients to rash. The frequency of rash was approximately 7% in this group of patients. PMID- 10030775 TI - Judicious evaluation of adverse drug reactions: inaccurate assessment of 3 hydroxy-3-methylglutaryl coenzyme A reductase inhibitor-induced muscle injury. AB - Adverse reactions in two patients who received HMG CoA reductase inhibitor therapy were reinvestigated because of their rarity. A case of permanent forearm myalgia was thought to be caused by atorvastatin. Closer evaluation and work-up revealed underlying lateral epicondylitis, and atorvastatin was not considered the cause of the disability. In another patient, rhabdomyolysis was suspected to be secondary to simvastatin. However, after an extensive review, the reaction was believed to be compartment syndrome of the anterior tibial area. An adverse drug reaction report requires careful and judicious assessment to assign the correct probability for the event. PMID- 10030776 TI - Use of transdermal amitriptyline gel in a patient with chronic pain and depression. AB - A man with severe inflammatory bowel disease suffered from chronic abdominal pain and depression. A transdermal amitriptyline gel preparation was compounded since he was unable to take drugs orally Serum concentrations of amitriptyline and its active metabolite nortriptyline were measured over 24 hours. Symptoms of depression were monitored before starting transdermal therapy and at the end of 6 weeks. Pain symptoms and amitriptyline adverse drug events were monitored daily Steady-state serum concentrations of drug and metabolite were within the therapeutic range over 24 hours. The patient reported that his mood was improved but his abdominal pain remained unchanged. Transdermal amitriptyline gel was well tolerated and is an alternative delivery system in patients unable to take drugs orally. PMID- 10030777 TI - Vancomycin-induced neutropenia associated with fever: similarities between two immune-mediated drug reactions. AB - A 39-year-old woman being treated for osteomyelitis with vancomycin developed severe neutropenia and drug fever. After she discontinued therapy, both disorders quickly resolved. These adverse reactions have rarely been reported with vancomycin, and share many similarities with regard to clinical features and postulated mechanisms of induction. To our knowledge this is the first case documenting drug fever as a principal component of vancomycin-induced neutropenia, and provides further evidence in support of an immune-mediated mechanism. PMID- 10030778 TI - Intravenous azithromycin-induced ototoxicity. AB - Intravenous azithromycin is increasingly administered for treatment of hospitalized patients with community-acquired pneumonia. Macrolide antibiotics cause ototoxicity, which occurs most frequently when high serum concentrations are achieved. Current dosing guidelines for intravenous azithromycin can result in much higher serum concentrations than is seen with oral administration. We describe a 47-year-old woman who developed complete deafness after receiving 8 days of intravenous azithromycin. PMID- 10030779 TI - Impact of rifampin on serum amiodarone concentrations in a patient with congenital heart disease. AB - A 33-year-old woman with congenital heart disease and atrial and ventricular arrhythmias, managed over the long term with an implantable cardioverter defibrillator, epicardial pacing system, and amiodarone, experienced an increase in palpitations and a shock from her defibrillator. Evaluation revealed decreases in amiodarone and desethylamiodarone serum concentrations from previous levels. Rifampin had been added to her therapy 5 weeks earlier. Increases in amiodarone and desethylamiodarone concentrations were observed after an increase in the amiodarone dosage and discontinuation of rifampin. The time course suggested that the addition of rifampin led to reductions in serum concentrations of both the drug and metabolite. PMID- 10030780 TI - Suspected carbamazepine-induced hepatotoxicity. AB - Carbamazepine is a potent anticonvulsant agent with proven efficacy in the treatment of partial and tonic-clonic seizures. An epileptic child treated with therapeutic dosages of carbamazepine developed severe hepatitis and hepatic insufficiency. She had a positive response to withdrawal of the drug and administration of corticosteroids. The Roussel UCLAF method for estimating causality of the adverse event was applied for an acute hepatocellular problem, with a final score of 8. This method has advantages over other tools because it involves many clinical factors that give additional guides to clinicians in patients with liver injury, but it must be adapted for adverse events in the pediatric population. PMID- 10030781 TI - Policy issues in accreditation. PMID- 10030782 TI - A comparative analysis of surveyors from six hospital accreditation programmes and a consideration of the related management issues. AB - PURPOSE: To gather data on how accreditors manage surveyors, to compare these data and to offer them to the accreditors for improvement and to the scientific community for knowledge of the accreditation process and reinforcement of the credibility of these processes. DATA SOURCE: The data were gathered with the aid of a questionnaire sent to all accreditors participating in the study. RESULTS: An important finding in this comparative study is the different contractual relationships that exist between the accreditors and their surveyors. CONCLUSION: Surveyors around the world share many common features in terms of careers, training, work history and expectations. These similarities probably arise from the objectives of the accreditors who try to provide a developmental process to their clients rather than an 'inspection'. PMID- 10030783 TI - The impact of a multidisciplinary approach on caring for ventilator-dependent patients. AB - OBJECTIVE: To determine the clinical and financial outcomes of a highly structured multidisciplinary care model for patients in an intensive care unit (ICU) who require prolonged mechanical ventilation. The structured model outcomes (protocol group) are compared with the preprotocol outcomes. DESIGN: Descriptive study with financial analysis. SETTING: A twelve-bed medical-surgical ICU in a non-teaching tertiary referral center in Ogden, Utah. STUDY PARTICIPANTS: During a 54 month period, 469 consecutive intensive care patients requiring mechanical ventilation for longer than 72 hours who did not meet exclusion criteria were studied. INTERVENTIONS: A multidisciplinary team was formed to coordinate the care of ventilator-dependent patients. Care was integrated by daily collaborative bedside rounds, monthly meetings, and implementation of numerous guidelines and protocols. Patients were followed from the time of ICU admission until the day of hospital discharge. MAIN OUTCOME MEASURES: Patients were assigned APACHE II scores on admission to the ICU, and were divided into eight diagnostic categories. ICU length of stay, hospital length of stay, costs, charges, reimbursement, and in-hospital mortality were measured. RESULTS: Mortality in the preprotocol and protocol group, after adjustment for APACHE II scores, remained statistically unchanged (21-23%). After we implemented the new care model, we demonstrated significant decreases in the mean survivor's ICU length of stay (19.8 days to 14.7 days, P= 0.001), hospital length of stay (34.6 days to 25.9 days, P=0.001), charges (US$102500 to US$78500, P=0.001), and costs (US$71900 to US$58000, P=0.001). CONCLUSIONS: Implementation of a structured multidisciplinary care model to care for a heterogeneous population of ventilator-dependent ICU patients was associated with significant reductions in ICU and hospital lengths of stay, charges, and costs. Mortality rates were unaffected. PMID- 10030784 TI - Management of asthma and COPD patients: feasibility of the application of guidelines in general practice. AB - OBJECTIVE: To examine the feasibility of the application of guidelines to the management of asthma and chronic obstructive pulmonary disease (COPD) by assessing compliance with the guidelines and listing the barriers general practitioners (GPs) encountered during implementation. Insight into the feasibility of individual items in the guidelines can guide implementation strategies in the future and, if necessary, support revision of the guidelines. DESIGN: Descriptive study of care delivered during the implementation of guidelines by means of documentation of the care provided, education, feedback on compliance and peer review. SETTING: General practice. STUDY PARTICIPANTS: Sixteen GPs in 14 general practices. MAIN OUTCOME MEASURES: Compliance was expressed as the percentage of patients per practice managed by the GPs according to the guidelines. For each patient (n=413) data were collected on the care delivered during the first year of the implementation. Barriers encountered were derived from the summaries of the discussions held during the monthly meetings. RESULTS: The GPs were most compliant on the items 'PEFR measurement at every consultation' (98%), 'allergy test' (78%) and 'advice to stop smoking' (82%), and less compliant on the items 'four or more consultations a year' (46%), 'ordering spirometry' (33%), 'adjustment of medication' (42%), 'check on inhalation technique' (38%) and referral to a chest physician (17%) or a district nurse (5%). The main barriers were the amount of time to be invested, doubts about the necessity of regular consultations and about the indications for ordering spirometry and for referral to a chest physician or a district nurse. CONCLUSION: Although the feasibility was assessed in a fairly optimal situation, compliance with the guidelines was not maximal, and differed between the individual items of care. Suggestions are given for further improvements in compliance with the guidelines and for revision of the guidelines. PMID- 10030785 TI - Quality circles in ambulatory care: state of development and future perspective in Germany. AB - OBJECTIVE: To survey the quantitative development of quality circles (peer review groups; QC) and their moderators in ambulatory care in Germany, to describe approaches to documentation and evaluation, to establish what types of facilities and support is available and to assess opinions on the future importance of QC. DESIGN: Cross-sectional survey using a standardized questionnaire and supplementary telephone interviews. SETTING: All 23 German regional Associations of Statutory Health Insurance Physicians (ASHIP) were surveyed. RESULTS: The total number of QC in ambulatory care in Germany increased rapidly from 16 in 1993 to 1633 in June 1996, with about 17% (range 1.0-52.1%) of all practicing physicians (112 158) currently involved. Throughout Germany, 2403 moderators were trained in 168 training courses by the qualifying date. Follow-up meetings were held or being planned in 20 ASHIP, with approximately 39% (23-95%) of the moderators participating. Systematic documentation of QC work was undertaken or planned in all 23 ASHIIP, and 10 ASHIP carried out comparative evaluation, with at least five others planning to start it. The ASHIP promoted the work of QC by providing organizational (22) or financial (20) support, materials (20) or mediation of resource persons (16). Eleven ASHIP received grants from drug companies. ASHIP rated the future importance of QC as increasing (18) or stable (four), but in no case as decreasing. CONCLUSIONS AND RECOMMENDATIONS: The quantitative growth of QC in Germany is encouraging, but the extent of support and evaluation appears insufficient. Increased methodological support and facilitation, follow-up meetings on a more regular basis, improved documentation and evaluation of individual QC, and problem oriented evaluation of their impact on health care are essential for further successful development. Principles, problems and solutions discussed may be relevant for similar QI activities in other countries. PMID- 10030786 TI - A comparative analysis of six audit systems for mental health nursing. AB - PURPOSE: To devise an analytical framework to help identify strengths and weaknesses in the audit process as specified by existing psychiatric nursing audit systems, in order to analyse current audit practice and identify improvements for incorporation in the Newcastle Clinical Audit Toolkit for Mental Health. DATA SOURCES: Published material relating to the following six systems: the Central Nottinghamshire Psychiatric Nursing Audit; Psychiatric Nursing Monitor; Standards of Care and Practice; Achievable Standards of Care; Quartz; and Quest. DATA EXTRACTION: Comparison of the six systems according to an analytical framework derived from detailed empirical study (structures, processes and outcomes) of one of them in use and the educational evaluation literature. Examination of the extent to which guidance is provided for operating the systems and for wider process-related aspects of audit. RESULTS OF DATA SYNTHESIS: Five of the systems failed to specify some important elements of the audit process. Conceptually, the six systems can be divided into two main types: 'instrument like' systems designed along psychometric lines and which emphasize the distance between the subjects of audit and the operators of the systems, and 'tool-like' systems which exploit opportunities for care setting staff to engage in the audit process. A third type of system is the locally-developed system which is offered to a wider audience but which does not make the same level of claim to universal applicability. CONCLUSION: The analytical framework allows different approaches to audit to be compared and contrasted not only according to the techniques used, but also according to process issues. The analysis of six systems revealed a variety of different techniques and procedures which can facilitate, in a methodologically rigorous manner, practitioner and other stakeholder involvement in audit processes. PMID- 10030787 TI - Reliability of a hospital utilization review method in Turkey. AB - OBJECTIVE: To determine whether the Appropriateness Evaluation Protocol (AEP) is reliable in Turkey. METHODS: Three reviewers, two physicians and one nurse each reviewed 196 patient-days concurrently by using the AEP at three hospitals, two of which were teaching hospitals. Inter-reviewer reliability was assessed both for all cases reviewed (overall agreement), and for only those judged inappropriate by at least one reviewer (specific agreement). In addition, overall agreement between pairs of reviewers was evaluated by the Kappa statistic. RESULTS: The overall agreement between pairs of reviewers was very high: 93.4 95.9%, and it was similar between all pairs. The level of overall agreement was highly statistically significant: k=0.725-0.833, P<0.001. The specific agreement rates ranged from a low of 61.8% to a high of 75%. CONCLUSIONS: These results show, for the first time, that the AEP method is reliable in Turkey. PMID- 10030788 TI - The role of gynaecologists in women's health care--women's views. AB - OBJECTIVE: Reproductive matters are common reasons to use health services, and both primary care providers (general practitioners and public health nurses) and specialists (gynaecologists) can be consulted. The purpose of this study was to find out how Finnish women think about and use specialist care in reproductive matters; gynaecological health checks, contraception, and prenatal care served as examples. METHODS: The data come from a questionnaire survey sent in 1994 to a representative sample (74% response rate) of 18-44-year-old Finnish women (n=2189). RESULTS: Most (87%) women considered regular health checks by a gynaecologist important, and 55% had visited a gynaecologist regularly in the past 5 years. Healthier women and women having more education were more likely to visit gynaecologists regularly. Most women (86%) preferred a gynaecologist to a general practitioner for contraceptive matters, and 54% reported visiting one for their last contraceptive visit. Maternity centres with their public health nurses and general practitioners were the main source of prenatal care. CONCLUSIONS: The results suggest the need to study the benefits of regular gynaecological health checks, and to define the best provider in common reproductive matters. Evaluation should include organizational impacts, such as those of the division of work between primary and secondary health care and small area population responsibility. PMID- 10030789 TI - Continuing education and quality improvement in primary health care. PMID- 10030790 TI - Use and interpretation of statistical quality control charts. PMID- 10030791 TI - Postinjury suppression of human neutrophil cytokine production results from the stabilization of inhibitory kappaB. AB - Postinjury neutrophil (PMN) dysfunction is a well recognized event that may be responsible for increased infections. PMN cytokine production is an important component of their bactericidal capacity. When PMNs are stimulated, inhibitory factor kappaB (IkappaB) is degraded, allowing nuclear factor kappaB (NFkappaB) to translocate to the nucleus and promotes genes for the transcription of the interleukin-8 (IL-8) and tumor necrosis factor (TNF) genes. We hypothesize that similar to their late postinjury depressed superoxide production, postinjury PMNs manifest suppressed cytokine production, which is mediated by stabilization of IkappaB levels. METHODS: Twelve severely injured patients with an injury severity score (ISS) of 24 (+/-4.6) were studied as well as 10 elective surgical patients as a control. PMNs were isolated and incubated for 24 h in RPMI. PMNs were stimulated with lipopolysaccharide (LPS; 100 ng) or PAF (200 nm) and fMLP (1 microM) and release of IL-8, TNF, and interleukin-1 receptor antagonist (IL-1ra) were measured. Postinjury PMNs were also stimulated with LPS (100 ng), and IkappaB breakdown was measured at 0, 30, and 60 min using gel electrophoresis. RESULTS: Postinjury PMNs displayed a significant suppression of both IL-8 and TNF on postinjury Days 1-3, while the release of IL-1ra was preserved throughout the entire study period. In contrast, elective surgical patients demonstrated no decrease in IL-8 or TNF. Furthermore, IkappaB levels were preserved in the postinjury PMNs as compared with normal control PMNs. CONCLUSION: Postinjury PMNs have a suppressed release of both IL-8 and TNF following injury that did not occur in elective surgical patients. Furthermore, the NFkappaB/IkappaB independent IL-1ra did not show suppression of release. In addition, stabilization of IkappaB following severe injury leads to decreased PMN IL-8 and TNF production. This genetic reprogramming may help explain PMN dysfunction and subsequent infections seen in severely injured patients. PMID- 10030792 TI - Low-dose intramuscular polymyxin B improves survival of septic rats. AB - Polymyxin B (PLB) is a cationic antibiotic that also stoichiometrically neutralizes the lipid A moiety of endotoxin. We examined effects of a small dose of PLB on the mortality of rats with cecal ligation and puncture, on LPS stimulated nitric oxide (NO) production, and on tumor necrosis factor alpha (TNF alpha) production by isolated rat Kupffer cells. MATERIALS AND METHODS: In vivo studies: Cecal ligation and puncture (CLP) was performed under anesthesia in 28 rats. One hour after CLP, either 600 U/kg of PLB or saline was administered intramuscularly every 6 h (PLB group: n = 12; control group: n = 16). Plasma endotoxin was measured at 3 and 24 h after the CLP by the Endospecy test. This was compared with survival. IN VITRO STUDIES: Kupffer cells were isolated from the normal rat liver. The cells were incubated with LPS or LPS + PLB. After 24 h, NO and TNF alpha content were measured using the Griess and ELISA methods, respectively. RESULTS: Low dose PLB significantly decreased the endotoxin levels at both 3 and 24 h (5.5 +/- 2.1 pg/mL vs. 32.8 +/- 3.6 at 3 h; 26.1 +/- 6.1 vs. 49.1 +/- 5.6 at 24 h (p < .05) after CLP. PLB significantly improved survival of CLP rats (68.8% in the control group vs. 100% in the PLB treated group on 3 days after CLP, p < .001). PLB also attenuated NO and TNF alpha production from the Kupffer cells. CONCLUSION: Intramuscular PLB administered in low doses may improve the mortality of sepsis. PMID- 10030793 TI - Bleeding induced interleukin-6 decreases blood loss via activation of coagulation. AB - Hemorrhage is known to induce the production of inflammatory cytokines such as interleukin-6 (IL-6). IL-6 plays an intermediate role as a factor in the activation of coagulation cascade and exerts a lethal effect in sepsis. To examine the effect of endogenous IL-6 on blood loss, we performed four experiments in female ddY mice. Enzyme immunoassay using an uncontrolled hemorrhage model, i.e., 75% tail resection, revealed the production of serum IL-6 (Experiment 1). We also measured cumulative blood loss and survival rate (Experiment 2); measured blood pressure and performed thrombelastogram (TEG) (Experiment 3); and measured plasma thrombin-antithrombin III (TAT) complex levels in two groups, one pretreated with 1 mg of anti-IL-6 monoclonal antibody (mAb), and one with normal rat globulin (NRG) using the same model (Experiment 4). The mAb group showed a significantly higher blood loss than the NRG group. All mice survived for 5 days in both groups. Blood pressure did not differ between either group. The TEG results suggest that administration of anti-IL-6 mAb caused mild suppression of coagulation activation, but did not affect fibrinolysis or platelets. In the mAb group, plasma TAT complex concentrations showed a significant decrease compared with the NRG group. In conclusion, hemorrhage-induced IL-6 may contribute to hemostasis through activation of coagulation, thus reducing blood loss. PMID- 10030794 TI - Role of tumor necrosis factor and interferon gamma in endotoxin-induced E selectin expression. AB - Tumor necrosis factor-alpha (TNF-alpha) and interferon-gamma (IFN-gamma), potent inflammatory cytokines, are released by macrophages during endotoxin shock. However, the contribution of these cytokines to endotoxin-induced inflammation has not been defined. The expression of E-selectin, measured using the dual radiolabeled monoclonal antibody (mAb) technique, was monitored in different tissues of endotoxin-challenged wild-type and IFN-gamma-deficient mice receiving a mAb to TNF-alpha (TN3). A significant elevation in E-selectin expression occurred in all tissues of wild-type mice challenged with endotoxin. Injection of TN3 in wild-type mice significantly attenuated the endotoxin-induced up regulation of E-selectin in all tissues (p < .05) except the pancreas. The level of reduction in endotoxin-induced E-selectin expression ranged between 30% in the stomach to 60% in the small intestine. E-selectin expression in endotoxin challenged, IFN-gamma-deficient mice was significantly reduced in the small and large intestines, when compared with endotoxin-challenged wild-type mice. Although IFN-gamma deficiency had no effect on E-selectin expression in other tissues, administration of TN3 to endotoxin-challenged, IFN-gamma-deficient mice significantly reduced E-selectin expression to levels observed in endotoxin challenged, wild-type mice that received TN3. These findings indicate that TNF alpha is essential for achievement of maximal E-selectin expression in most vascular beds during endotoxemia, whereas the contribution of IFN-gamma is largely confined to the small intestine. PMID- 10030795 TI - Beneficial effects of L-canavanine, a selective inhibitor of inducible nitric oxide synthase, on lactate metabolism and muscle high energy phosphates during endotoxic shock in rats. AB - Overproduction of NO by an inducible NO synthase (iNOS) plays a role in the pathophysiology of septic shock. In such situations, NOS inhibition might be of therapeutic value, although detrimental side effects possibly related to inhibition of constitutive NOS have been reported. The use of L-canavanine, a selective inhibitor of iNOS, might be more suitable. The aim of the study was to compare in a rodent endotoxic shock the effects of saline (2 mL/h), N(G)-methyl-L arginine(L-NMMA) (10 mg/kg/h) and L-canavanine (100 mg/kg/h) on muscle intracellular pH (pHi) and intracellular bioenergetic patterns (ATP, phosphocreatine/inorganic phosphate ratio) using in vivo 31P magnetic resonance spectroscopy (31P MRS). Three groups of anesthetized, mechanically ventilated and paralyzed rats received an intravenous infusion of 15 mg/kg of endotoxin. A fourth time-matched control group (n = 8) received 2 mL/h of saline. Mean arterial pressure, femoral blood flow, arterial blood gases, lactate, nitrate level, and 31P nuclear magnetic resonance (31P MRS) measurements were acquired at onset (T = 0), 90 min (T = 90), and 180 min (T180) after the endotoxin challenge. Femoral oxygen delivery was calculated as the product of femoral blood flow (mL/min) and arterial oxygen content. Endotoxin induced a marked decrease in arterial pressure and femoral oxygen delivery and an increase in lactate level. Intracellular pH and phosphocreatine/inorganic phosphate ratio decreased. ATP level did not change. Both L-NMMA and L-canavanine reversed the endotoxin-induced decrease in arterial pressure. L-NMMA attenuated the decrease in femoral oxygen delivery and the increase in lactate level while these were corrected by L canavanine. Considering 31P MRS derived bioenergetic indices, the endotoxin induced decrease in pHi and Pcr/Pi was attenuated by L-NMMA and corrected by L canavanine. In conclusion, in a rodent model of endotoxinic shock, the continuous infusion of L-canavanine, a selective iNOS inhibitor, improved the systemic hemodynamic parameters and the intracellular bio-energetic patterns estimated by in vivo 31P MRS. To the contrary, the continuous infusion of both constitutive and inducible NOS inhibitor L-NMMA was not followed by the same achievement. PMID- 10030796 TI - Changes in gut mucosal nitric oxide synthase (NOS) activity after thermal injury and its relation with barrier failure. AB - This study was designed to investigate changes in mucosal NOS activity after burns and its relation to barrier failure. In Experiment 1, female specific pathogen free (SPF) Sprague-Dawley rats underwent 35% total body surface area (TBSA) burn. One to six days after burn, intestinal permeability was determined from the plasma leakage of fluorescein isothiocyanate (FITC)-dextran 4400, intestinal mucosal cNOS and iNOS activity were assayed using Griess' reagent, and the cellular localization of iNOS was examined using immunostaining. In Experiment 2, S-methylisothiourea (SMT) was given (5 mg/kg, i.p. every 12 h) for 2 days to suppress inducible NOS (iNOS) activity after thermal injury. On postburn Day 2, the effect of SMT on gut mucosal NOS activity, intestinal permeability, and barrier function were evaluated. The activity of iNOS increased 24 h after the injury and up to a maximum of twofold on postburn Day 2, and decreased thereafter. The increase in iNOS activity in gut mucosa correlated well with the increase in intestinal permeability, an index for barrier failure (r = .776, p = .0002). Results from iNOS immunostaining showed that changes in mucosal iNOS activity after the burn occurred mainly in the enterocytes rather than in the macrophages. Administration of SMT decreased mucosal iNOS activity, intestinal permeability, and bacterial translocation incidence to mesenteric lymph node concurrently. In conclusion, thermal injury induces intestinal mucosal iNOS, which is principally in the enterocytes. The increased intestinal iNOS activity was closely related to barrier failure. SMT inhibited intestinal mucosal iNOS activity and prevented barrier failure as demonstrated by a decrease in BT occurrence and intestinal permeability. PMID- 10030797 TI - Endothelin-1 induces endothelial barrier failure in the cat hindlimb. AB - Our purpose was to see whether endothelin- (ET) 1 could produce a change in the endothelial membrane barrier to protein in skeletal muscle. Previous studies in other tissues have suggested that ET-1 affects this barrier, but the measurement methods used could not exclude vascular protein extravasation due to microvascular pressure changes or the effects of changes in perfused capillary surface area. We measured the protein sieving coefficient, a specific measure of the permeability of the membrane to protein, in the isolated, perfused cat hindlimb preparation. The integral-mass balance method determined this coefficient from the changes in hematocrit and plasma protein concentration induced by a period of transvascular fluid filtration. The data clearly indicate that ET-1 produces a dose (1-20 nM) dependent increase in permeability indicative of barrier dysfunction. Hence, elevated ET levels may contribute to the perivascular edema, hemoconcentration, and impaired tissue perfusion found in systemic inflammatory response syndromes and related diseases. PMID- 10030798 TI - Oral spermine administration inhibits nitric oxide-mediated intestinal damage and levels of systemic inflammatory mediators in a mouse endotoxin model. AB - Enhanced intestinal nitric oxide production observed during sepsis is thought to play a central role in lipopolysaccharide-induced intestinal damage. In contrast intestinal polyamines, both from endogenous and exogenous origin, are essential for the maintenance of mucosal integrity. Polyamines have been shown to inhibit lipopolysaccharide-induced nitric oxide release in vitro and have been claimed to exert additional antiinflammatory actions. In this study, the effect of the polyamine spermine on the release of the proinflammatory mediators nitric oxide and tumor necrosis factor-alpha by a murine macrophage cell line was investigated. Furthermore, we investigated whether oral spermine administration inhibits lipopolysaccharide-induced intestinal inducible nitric oxide synthase and nitrotyrosine expression and modulates the release of inflammatory mediators. Our results show that although spermine inhibited lipopolysaccharide-induced nitric oxide release in a murine macrophage cell line, no effect on tumor necrosis factor-alpha release was observed. In addition, oral spermine administration inhibited intestinal inducible nitric oxide synthase and nitrotyrosine expression suggesting a protective effect of spermine on lipopolysaccharide-induced intestinal damage. In parallel a decrease in serum levels of the proinflammatory mediators nitrate, nitrite, and interferon-gamma and an increase in the antiinflammatory cytokine interleukin-10 was observed, although tumor necrosis factor-alpha levels were unaffected. These results indicate that spermine inhibits lipopolysaccharide-induced nitric oxide release in vitro as well as in vivo. Further, intraluminally derived polyamines modulate the systemic immune response. It is concluded that oral spermine administration might have therapeutic perspectives for several disorders characterized by systemic inflammation and intestinal damage. PMID- 10030799 TI - Carnitine deprivation adversely affects cardiac performance in the lipopolysaccharide- and hypoxia/reoxygenation-stressed piglet heart. AB - Sepsis and hypoxia are important stressors for the neonate. Newborn infants receiving total parenteral nutrition are routinely deprived of carnitine and develop low carnitine plasma and tissue levels. Because of its high metabolic rate and dependence on fatty acids for energy, the newborn heart may be particularly vulnerable to stress in the face of an inadequate carnitine supply. To investigate whether carnitine deprivation affects cardiac performance under stress, 23 neonatal piglets received parenteral nutrition for 2-3 weeks that was either carnitine free (CARN -) or supplemented (CARN +) with L-carnitine (400 mg/L). Bacterial endotoxin (lipopolysaccharide (LPS), 250 microg/kg intravenous bolus) or saline vehicle was administered to anesthetized piglets 3 h prior to study of isolated perfused hearts. Left ventricular systolic pressure (LVSP), left ventricular end diastolic pressure, and left ventricular developed pressure (LVDP) were measured in vitro under aerobic, hypoxic, and reoxygenation conditions in all animals. Plasma and tissue carnitine values were lower in CARN than in CARN + piglets. In hearts from LPS-treated animals prior to hypoxia, there was no difference in ventricular compliance between CARN - and CARN + groups. LVSP and LVDP were lower in CARN - than CARN + hearts. During hypoxia, LVSP and LVDP fell, but left ventricular end diastolic pressure increased in hearts from both LPS- and saline- treated piglets. Reoxygenation led to poorer recovery in CARN - than CARN + hearts from LPS-treated animals, but not from saline controls. During hypoxia/reoxygenation, lactate efflux initially rose and then fell, while carnitine efflux increased continually. Acetyl- and medium-chain acylcarnitines were detected in the coronary effluent. Our findings suggest that carnitine deprivation diminishes heart carnitine concentrations and impairs cardiac recovery from combined endotoxic and hypoxic stress. Possible mechanisms include reduced acyl buffering and/or impaired transport of fatty acyl groups into mitochondria. PMID- 10030800 TI - Angiotensin II receptor antagonism increases gut oxygen delivery but fails to improve intestinal mucosal acidosis in porcine endotoxin shock. AB - The renin angiotensin system is highly activated in shock states and has been suggested to be involved in the pathophysiology of the markedly deteriorated splanchnic circulation seen in septic shock. The purpose of the present study was to elucidate the capability of losartan, a nonpeptide angiotensin II type 1 (AT1) receptor antagonist, to attenuate splanchnic blood flow disturbances and counteract intestinal mucosal acidosis in endotoxin shock. A total of 20 pigs were anesthetized and catheterized. Central and regional hemodynamics were monitored. A tonometer in the ileum was used for measurement of mucosal pH. Onset of endotoxin challenge was followed by losartan administration (n = 10) 2 h later. Ten animals receiving endotoxin only served as controls. The experiments were terminated 5 h after onset of endotoxin challenge. Endotoxin infusion induced an hypodynamic shock with a reduction in cardiac index and systemic oxygen delivery. Losartan reduced both systemic vascular resistance and pulmonary capillary wedge pressure while stroke volume was improved. Pulmonary hypertension induced by endotoxin was significantly reduced by losartan without further changes in gas exchange. The profound reduction in gut oxygen delivery in response to endotoxin was counteracted by losartan administration. However, losartan failed to improve the markedly deteriorated intestinal mucosal pH and mucosal-arterial PCO2gap (i.e., difference in intestinal mucosal PCO2 and arterial PCO2). Also the mucosal-portal venous PCO2gap, used as a monitor of the mucosa in relation to the gut as a whole (including the spleen and pancreas), was greatly increased by endotoxemia but unaffected by losartan administration. In summary, although the angiotensin II type 1 receptor antagonist losartan improved gut oxygen delivery and reduced pulmonary hypertension during established endotoxin shock, it had no effect on intestinal mucosal acidosis. These findings suggest contribution of the angiotensin II type 1 receptor to perfusion disturbances, but not to deterioration of intestinal mucosal homeostasis seen during endotoxemia. PMID- 10030801 TI - Priming of Peyer's patch lymphoid cells by hemorrhagic shock and resuscitation to produce superoxide radical. AB - Hemorrhagic shock (HS) can cause whole body ischemia including the gastrointestinal tract. We investigated whether cells from small intestine Peyer's patches (PP) were capable of producing superoxide radical when animals underwent HS or HS followed by resuscitation (HS/RS). HS was initiated by removing 60% of the blood volume of surgically prepared guinea pigs. PP lymphoid cells were purified and stimulated with phorbol 12-myristate 13-acetate in the presence of spin trap 5-diethoxyphosphoryl-5-methyl-1-pyrroline-N-oxide (DEPMPO). Electron paramagnetic resonance spectra of PP lymphoid cells from sham-treated control, HS, and HS/RS animals produced DEPMPO radical adducts characterized as the adducts of superoxide (DEPMPO/*OOH) and hydroxyl (DEPMPO/*OH) radicals. The formation of both radical adducts was totally inhibited by superoxide dismutase or a nicotinamide adenine dinucleotide phosphate (reduced form) oxidase inhibitor, diphenyleneiodonium chloride. HS/RS increased radical adduct formation, expressed as a percentage control, by 160% and 225% for DEPMPO/*OOH, and DEPMPO/*OH, respectively. When animals were allowed to recover for 24 h post HS/RS treatment, PP cells decreased the superoxide generation to the same level as controls. Thus, RS following HS may prime PP lymphoid cells for increased nicotinamide adenine dinucleotide phosphate (reduced form) oxidase-dependent superoxide generation, and this process may have cytotoxic and/or immunomodulatory effects on the host. PMID- 10030802 TI - Protective effect of N-acetylcysteine on cellular energy depletion in a non septic shock model induced by zymosan in the rat. AB - Recently, it was proposed that zymosan, a nonbacterial agent, causes cellular injury by inducing the production of peroxynitrite and consequent poly-(ADP ribose) synthetase (PARS activation). Here we investigated whether in vivo N acetylcysteine treatment inhibits cellular injury in macrophages collected from rats subjected to zymosan-induced shock. Macrophages harvested from the peritoneal cavity exhibited a significant production of peroxynitrite, as measured by the oxidation of the fluorescent dye dihydrorhodamine 123, and by nitrotyrosine. Furthermore, zymosan-induced shock caused a suppression of macrophage mitochondrial respiration, DNA strand breakage, and reduction of cellular levels of NAD+. In vivo treatment with N-acetylcysteine (40, 20, and 10 mg/kg, intraperitoneally, 1 and 6 h after zymosan) significantly reduced in a dose-dependent manner peroxynitrite formation and prevented the appearance of DNA damage, the decrease in mitochondrial respiration, and the loss of cellular levels of NAD+. Our study supports the view that the antioxidant and anti inflammatory effect of N-acetylcysteine is also correlated with the inhibition of peroxynitrite production. In conclusion, N-acetylcysteine may be a novel pharmacological approach to prevent cell injury in inflammation. PMID- 10030803 TI - The role of endothelin-1 in circulatory changes during hypodynamic sepsis in the rat. Laszlo Szalay, Jozsef Kaszaki, Sandor Nagy, and Mihaly Boros. Shock 10(2):123-128, 1998. PMID- 10030804 TI - Management issues in the multiple endocrine neoplasia syndromes. PMID- 10030805 TI - Monitoring wound infection after surgery: the quest for useful information at a reasonable cost. PMID- 10030807 TI - Merkel cell carcinoma. PMID- 10030806 TI - Food for thought: Basingstoke revisited again. PMID- 10030808 TI - Deregulation of apoptosis in colorectal carcinoma: theoretical and therapeutic implications. AB - Apoptosis, or programmed cell death, maintains the structure of the colonic crypts by providing a balance to the rate of cell proliferation. Colorectal carcinoma arises partly from a disruption in this balance in the favour of uncontrolled growth. Until recently, most research into colon cancer has focused on the molecular regulators of cell-cycle progression and proliferation, but it is now evident that apoptosis is also defective. A failure of cells to die in response to premalignant damage may allow the progression of the disease and maintain the resistance of cancer cells to cytotoxic therapy. This review outlines the importance of apoptosis in the normal colon and presents recent studies that demonstrate that induction of apoptosis is defective in colonic tumours. When the molecular regulation of apoptosis is better understood, this knowledge may lead to the earlier detection of patients at greater risk of developing colorectal carcinoma, and also to the development of more effective therapies. PMID- 10030809 TI - The genetic basis of breast cancer and its clinical implications. AB - While it has long been recognized that a proportion of breast cancer cases are the result of an inherited familial predisposition, precise knowledge of the underlying genetic processes has been lacking. Recent advances in molecular biology, however, have shown that hereditary breast cancer may eventuate as a result of mutations on several specific gene loci including BRCA1, BRCA2, ATM gene, PTEN and p53. Several other less frequently occurring predisposition genes such as the androgen receptor gene (AR), the HNPCC genes and the oestrogen receptor gene may also be involved, but to a lesser extent. Overall, approximately 5-10% of all breast cancers are thought to involve one of these inherited predisposition genes, with BRCA1 and BRCA2 being responsible for as much as 90% of this group. Because of the complex nature of genetic testing, mutation analysis is not presently routinely available outside genetic counselling clinics. In this review the current knowledge and role of each predisposition gene is outlined and the management implications of genetic testing for members of breast cancer families for both affected and non-affected members are discussed. The need to provide comprehensive counselling for women with an inherited predisposition to breast cancer has seen the evolution of the familial cancer clinic, involving a multidisciplinary specialist team approach. Familial cancer clinics will provide individuals with information about their risk of developing breast cancer and offer advice regarding further management strategies. It is important that surgeons, who have traditionally played a key role in breast cancer treatment, remain cognizant of these advances in genetic molecular biology, and in so doing continue to remain key participants in the conduct of breast cancer management. PMID- 10030810 TI - Current perspectives in the surgery of multiple endocrine neoplasias. AB - Multiple endocrine neoplasia is an uncommon but fascinating condition. In this review we examine the multifaceted presentations, the diagnostic challenges and different management strategies for various syndromes. This is an attempt to share our knowledge and experience towards achieving better outcomes in the management of the diseases. PMID- 10030811 TI - Surgical wound infection surveillance: the importance of infections that develop after hospital discharge. AB - BACKGROUND: The aim of this study was to evaluate two methods of post-discharge surgical wound surveillance and to compare the incidence and outcomes of wound infections that develop prior to patients' discharge with those that develop after hospital discharge. METHODS: One thousand, three hundred and sixty inpatients who underwent major elective surgery in an 800-bed teaching hospital in western Sydney between February 1996 and July 1997 were followed prospectively. Pre-discharge wound surveillance was performed by clinical assessment by an independent researcher on the fifth (or later) postoperative day. Post-discharge wound surveillance was performed by a mail out of questionnaires completed independently by patients and surgeons. RESULTS: Overall, 138 wound infections were diagnosed (incidence 10.1%), of which fewer than one-third (n = 44) were diagnosed before discharge (average 10.4 days postoperatively) and the remainder (n = 94) after discharge (average 20.6 days postoperatively). Seven hundred and eighty-two (57.5%) post-discharge survey forms were returned by patients and 680 (50.0%) by surgeons. When forms were returned by both surgeons and patients for the same wound (641 cases), there was substantial agreement in diagnosing infection or no infection (kappa = 0.73). CONCLUSIONS: The majority of nosocomial surgical wound infections develop after the patients' discharge from hospital. A post-discharge surveillance programme including self-reporting of infections by patients and return of questionnaires by patients and surgeons is feasible in an Australian hospital setting. However, such a programme is labour and resource intensive and strategies to increase return of questionnaires are required. PMID- 10030812 TI - Primary mucosal and glans penis melanomas: the Sydney Melanoma Unit experience. AB - BACKGROUND: Melanomas that arise on mucosal surfaces and the glans penis are rare. METHODS: A retrospective study of the Sydney Melanoma Unit experience with 69 patients treated since 1956 for these types of melanomas was undertaken to determine primary lesion site, sex, age at diagnosis, symptoms, clinical stage at first presentation. histopathology, treatment and outcome. RESULTS: Primary lesion sites were: nasal cavity (n = 9), oral cavity (n = 16), vulva/vagina (n = 25), anus/rectum (n = 13) and glans penis (n = 6). At diagnosis, 55 patients had local disease only, eight had regional lymph node metastases and six had widespread disease. Local recurrence as the first sign of relapse developed in 15 of the 55 stage I patients (three-stage system). Prognosis for the entire group was poor, only 10% being disease free 3 years after diagnosis and overall 3- and 5-year actuarial survival being 40% and 23%. respectively. The only statistically significant factor influencing survival was stage of disease at diagnosis (P = 0.002). CONCLUSIONS: Possible reasons for poor survival include: (i) non-specific symptoms resulting in late presentation; (ii) locally advanced disease not being recognized by a clinician as a rare form of melanoma, resulting in a delay in treatment; (iii) anatomical constraints precluding surgery with generous margins and consequently resulting in a high incidence of local recurrence. Also, rich vascularity and multiple lymphatic drainage pathways may mean a predisposition to early dissemination. Prompt diagnosis and referral to a specialist unit for treatment and follow up are essential. Adequate surgery remains the cornerstone of treatment for these types of melanoma until more effective systemic therapies become available. PMID- 10030813 TI - High pressures are generated at the tip of laparoscopic graspers. AB - BACKGROUND: Despite its importance the interface between tissue and instrument is poorly understood. METHODS: A thin film pressure transducer was deployed between the jaws of eight different laparoscopic instruments and a simulated tissue to study the forces generated at the tip of laparoscopic graspers and the effect of a change in angle of tissue tension at the interface between tissue and laparoscopic grasper. RESULTS: Pressure was concentrated at the tip of the instrument. Localized pressures increased on average from 210 kPa to 650 kPa as the angle of grasp was increased from 0 to 135 degrees. There was a wide variation between instruments with some exhibiting increases in tip pressure of a factor of eight as the angle was increased. CONCLUSION: High pressures are generated at the tip of laparoscopic graspers. Pressures increase as the angle of incidence of the grasper in relation to the tissue increases. The changes in pressure with change in angle are independent of load and handle pressure. PMID- 10030814 TI - Use of fine-needle aspiration cytology and frozen section examination in diagnosis of thyroid nodules. AB - BACKGROUND: With the advent of fine-needle aspiration cytology (FNAC), the role of frozen section (FS) in the management of non-toxic thyroid nodules has become uncertain. METHODS: During the period from January 1993 to December 1995, a total of 84 patients have undergone operative treatment for non-toxic thyroid nodules at the United Christian Hospital, Kowloon. The medical records of these patients were studied retrospectively. RESULTS: In the benign group, the diagnostic accuracy of FNAC was 94% and that of FS was 91%. If FNAC reported malignancy, the diagnostic accuracy was 70%. If FS reported malignancy, the report was accurate in 100%. Among the 43 cases reported as benign on FNAC, FS did not alter the surgical management in any case. In 10 cases reported as suspicious on FNAC, FS altered the surgical treatment in one (10%). However, among the 10 cases reported as malignant on FNAC, FS subsequently altered the surgical management in five cases (50%). In three cases of malignancy on FNAC, both FS and the final histopathology report showed benign disease. Hence, FS avoided overtreatment in three patients. CONCLUSION: Frozen section is indicated if pre-operative FNAC of the thyroid nodules suggests malignancy, in order to determine the extent of the operation and to avoid overtreatment of benign disease. However, FS can be omitted if FNAC is reported as benign or suspicious. PMID- 10030815 TI - Effects of adrenaline or endotoxin tolerance states on mesenteric blood flow in endotoxaemia. AB - BACKGROUND: Endotoxic shock is associated with release of catecholamines as well as decreased mesenteric vascular perfusion, which is thought to cause remote organ injury. Adrenaline tolerance was reported to decrease mortality in endotoxic shock and have cross-tolerance with endotoxin tolerance. Our aim was to investigate the effect of these two tolerance conditions on the lipopolysaccharide (LPS)-induced decrease in mesenteric blood flow (MBF). METHODS: Adrenaline tolerance was developed by injecting 0.03 mg/kg adrenaline to Swiss-albino mice, gradually increasing the dose to 2 mg/kg over 5 days. Endotoxin tolerance was developed by injecting saline for 4 days and LPS 1 mg/kg at the fifth day. Control animals were injected with saline for 5 days. At 72 h after completion of injections, half of the animals in each group were challenged with saline and the other half with 20 mg/kg LPS, at 0 h. Mesenteric blood flow was measured at 4 and 24 h. RESULTS: Neither endotoxin nor adrenaline tolerance prevented an LPS-induced decrease in MBF. CONCLUSION: A low dose of LPS prior to a higher dose does not prevent an LPS-induced decrease in MBF and may actually prime for a decrease. Also, catecholamines are not primary mediators of LPS induced decreases in MBF. PMID- 10030816 TI - An easy and effective method of cholangiography in laparoscopic cholecystectomy: laparoscopic cholecystocholangiography. AB - BACKGROUND: There is ample evidence that the incidence of operative cholangiography has declined since the introduction of laparoscopic cholecystectomy. It has been suggested that one of the reasons for this decline is the technical difficulty of cystic duct catheterization. A method of cholangiography which does not require such catheterization has been developed by others. This paper examines the ease and effectiveness of operative cholangiography performed by direct puncture of the gall-bladder. METHODS: A retrospective study was made of the records of 380 consecutive patients who underwent attempted laparoscopic cholecystectomy. After exclusion of patients in whom laparoscopic cholecystectomy was abandoned in favour of open cholecystectomy and those patients in whom operative cholangiography was not attempted, the records of 325 patients were available to the study. The operation notes of each patient were studied to determine whether, in the operator's opinion, a successful cholangiogram had been obtained. RESULTS: There were 290 patients in whom cholangiography was attempted using direct gall-bladder puncture (cholecystocholangiography (CCC)). There were 35 patients in whom cholangiography was attempted via cystic duct cannulation (CDC). Cholecystocholangiography was successful in 86% of those cases in which it was attempted. Cystic duct cannulation was successful in 83% of those cases in which it was attempted. CONCLUSION: Cholecystocholangiography is a valid alternative to cystic duct catheterization in its ability to achieve intra-operative cholangiography in the setting of laparoscopic cholecystectomy. PMID- 10030817 TI - New release of the Boonpong laparoscopic camera holder. AB - BACKGROUND: A voice-activated robotic arm named AESOP (automated endoscopic system for optimal positioning) has enabled the view through the laparoscopic camera to be kept in focus, but is very expensive. There is thus a need for a cheap, manually controlled, laparoscopic camera holder. METHODS: The original prototype utilized the principle of an adjustable desk lamp. This holder proved steady at any required angle. To protect the camera shaft, this was inserted through the wider part of a cut end 10 mm port before fixation in the holder. To improve manoeuvrability, a 'floating arm' was adopted between the table clamp and the holder. Subsequent developments included reduction in size of the modified desk lamp and water heating of the inverted protective sheath to minimize lens fogging. Pre-operatively, the holder is sterilized for 15 min in glutaraldehyde solution, while the floating arm is autoclaved. RESULTS: The instrument has been used in 42 laparoscopic operations in which a steady, well-focused view of the operating field has been attained. CONCLUSION: The instrument is easily and cheaply constructed. It can be adapted to hold other endoscopic instruments as in anorectal laser surgery, or to hold the laparoscopic camera when this is used to perform microsurgery without a microscope. It is named 'the Boonpong laparoscopic camera holder' in memory of a Thai hero under whose Dunlop-Boonpong Scholarship the author has had the opportunity to gain some Australian surgical experience. PMID- 10030818 TI - The return to Coree: the surgical connection. AB - Samuel Wilson purchased Coree in 1865. In 1874 he donated 30000 pound sterling to Melbourne University to build the Wilson Hall, used for ceremonial occasions including medical graduation. Samuel McCaughey purchased Coree in 1881. In 1919 he left large bequests used by Sydney University to found the first Chair of Surgery. This was held by Frances Percival Sandes from 1921 to 1928. David McCaughey died of general peritonitis at Coree in 1899, his son Samuel married Una McKellar who was Thomas Dunhill's step-daughter. Thomas Dunhill, pioneer thyroid surgeon, gave the hand of his stepgranddaughter, Unity McCaughey, to Murray Pheils in London in 1941. Roy McCaughey created the McCaughey Institute at Coree in 1945 in memory of his nephew Michael McCaughey who was killed in action in New Guinea. Pioneering work in ovum transfer and in vitro fertilization in sheep was carried out at Coree by Neil Moore from 1959 to 1971. Roy McCaughey left a bequest to the Royal Australasian College of Surgeons in 1972, this was used to endow the Sir Roy McCaughey Scholarship in 1995. PMID- 10030819 TI - Basingstoke replies again: comment. PMID- 10030820 TI - Food for thought: Basingstoke revisited again: a gourmand's delight or food poisoning?: Comment. PMID- 10030821 TI - Melioidosis of the prostate. PMID- 10030822 TI - Management of Dieulafoy's disease with combined endoscopy and laparoscopic gastric wedge resection. PMID- 10030823 TI - Metastatic deposits in Paget's disease of bone. PMID- 10030824 TI - Pseudo Rontals tenotomy. PMID- 10030825 TI - Torticollis following adenotonsillectomy. PMID- 10030826 TI - Prothrombin activation in rabbits. AB - The suitability of rabbit prothrombin activation fragment F 1.2 as a marker for the activation of the coagulation system was tested. Monoclonal antibodies to rabbit F 1.2 were raised, and a competitive F 1.2 ELISA was developed. Within the detection limit of the ELISA, no increase in rabbit F 1.2 was detected upon recalcification of plasma, whereas human F 1.2 increased 1500-fold. The apparent lack of F 1.2 formation in rabbit serum was confirmed by immunoblotting analysis of endogenous and biotin-labeled prothrombin. Meizothrombin and the B-chain of thrombin were the only prothrombin fragments detectable. In contrast, labeled human prothrombin formed, in addition, prethrombin 2 and F 1.2 in both human and rabbit serum. In contrast, rabbit F 1.2 formation could be demonstrated using purified rabbit prothrombin and factor Xa. These observations raise the possibility that rabbit prothrombin is less susceptible than the human counterpart to factor Xa cleavage at the 271/272 peptide bond. Thus, the primary structure of rabbit prothrombin was deduced by cDNA sequencing. While the 320/321 Xa cleavage site giving rise to meizothrombin was identical in rabbit and human prothrombin, the flanking region of the 271/272 Xa sensitive site contained a six amino acid deletion in the rabbit sequence. Taken together, these observations suggest that the observed differences between human and rabbit prothrombin activation may be due to different susceptibilities of the two Xa cleavage sites rather than plasma or serum cofactor(s). PMID- 10030827 TI - Increased serum levels and sinusoidal expression of thrombomodulin in acute liver damage. AB - Thrombomodulin (TM) is a surface glycoprotein of endothelial cells involved in both anticoagulation and antifibrinolysis. In this study, we assessed the clinical significance of TM in acute liver damage by using a rat model induced by intraperitoneal injection of D-galactosamine (Gal-N). Serum TM levels were measured with enzyme immunoassay utilizing rabbit anti-rat TM antibody. Simultaneously, immunohistochemical examination was performed using the same antibody. Serum TM levels increased significantly after the injection of Gal-N compared with preinjection levels, peaking from 48 to 72 hours after injection and normalizing by 168 hours. Changes in parenchymal damage were synchronized with changes of TM, and changes of TM levels mirrored changes of liver weight. In immunohistochemical examination, TM immunoreactivity was observed only on the endothelial surfaces of both the artery and portal vein within Glisson's sheath in controls. After injection of Gal-N, TM immunoreactivity was gradually intensified, especially around the necrotic area and the central veins. These findings disappeared with improvement of parenchymal damage. Both the increase of serum TM levels and intensified TM immunoreactivity in the liver were synchronized with acute liver parenchymal damage induced by Gal-N. These findings on TM are related to endothelial damage with parenchymal necrosis and liver regeneration interacting with both homeostasis of microcirculation and healing of parenchymal damage. PMID- 10030828 TI - Coagulation and fibrinolysis during laparoscopic cholecystectomy. AB - Laparoscopic surgery appears to be less traumatic to the patient than open surgery, but its influence upon coagulation and fibrinolysis is incompletely elucidated. Our aim was to measure markers of coagulation and fibrinolysis before, during. and after laparoscopic cholecystectomy (LC). Blood samples drawn on admission, on four occasions during operation as well as 2 hours after operation and on the first postoperative day in 50 patients undergoing elective LC were analyzed for prothrombin fragment 1+2 (F1+2), soluble fibrin (SF), D dimer (DD), fibrin degradation products (FbDP), tissue-type plasminogen activator (tPA) activity and antigen, and plasminogen activator inhibitor (PAI) activity and antigen. F1+2, SF, DD, and FbDP levels increased significantly after LC. Differences between pre- and postoperative PAI and tPA levels were not significant apart from a transient increase in tPA antigen levels. tPA activity was significantly increased during operation. PMID- 10030829 TI - Oral absorption and clearance of partially depolymerized fucosyl chondroitin sulfate from sea cucumber. AB - Partially depolymerized holothurian glycosaminoglycan (DHG), a fucosyl chondroitin sulfate chains isolated from sea cucumber, was administered by the intravenous and oral routes to experimental animal. After intravenous injection, clearance of DHG, as measured by the postcolumn HPLC, displayed complex kinetics that were not dose dependent. DHG was excreted unchanged in the urine. No degradation products of DHG were detected by either gel filtration or anion exchange HPLC at any time in plasma, indicating that administered DHG is not catabolyzed by mammalian. Anion exchange chromatographic behavior of DHG excreted into urine after oral administration showed that partial desulfation might occur through intestinal absorption. After oral administration of DHG (50 mg/kg), 0.1% of the dose was found in urine collected for 24 hours. More than 5% of intravenously administered DHG (1 mg/kg) was excreted into urine in 24 hours. These results are suggesting that orally administered macromolecules such as DHG are absorbed in the gastrointestinal tract. PMID- 10030830 TI - Cilostazol inhibits the expression of activation-dependent membrane surface glycoprotein on the surface of platelets stimulated in vitro. AB - Cilostazol is a newly developed antiplatelet drug that has been widely applied for clinical use. Its antiplatelet action appears to be mainly related to inhibition of intracellular phosphodiesterase activity. Our study was designed to investigate inhibitory effects of cilostazol on the expression of activation dependent platelet membrane surface glycoproteins. We performed flow cytometric analysis using monoclonal antibodies, PAC-1 (antibody against activation dependent epitope of GPIIb/IIIa), anti-CD62P (P-selectin), and anti-CD63. In vitro ADP stimulation of platelets taken from seven healthy volunteers produced significant increases in the mean channel fluorescence intensities (MFI) for PAC 1 (148% increase) and CD62P (43% increase) but did not increase in that for CD63. The enhanced MFI for CD62P was suppressed to the control level by pretreatment with 1 microM (88% suppression), 3 microM (94% suppression), and 10 microM (95% suppression) of cilostazol. However, that of PAC-1 was suppressed to a lesser degree (12, 16, and 21% suppressions, respectively). Cilostazol may inhibit P selectin release from alpha-granule, rather than activation-dependent conformational change of GPIIb/IIIa in platelets. Cilostazol inhibits cellular interaction among platelets, leukocytes, and vascular endothelial cells mediated by P-selectin. PMID- 10030831 TI - Endotoxin enhances in vitro platelet aggregability in whole blood. PMID- 10030832 TI - Assessment of platelet activity by measuring platelet-derived substances in plasma from patients with acute myocardial infarction: surprising lessons from the GUSTO-III Platelet Study. PMID- 10030833 TI - Modification of the genetic program of human alveolar macrophages by adenovirus vectors in vitro is feasible but inefficient, limited in part by the low level of expression of the coxsackie/adenovirus receptor. AB - Robust expression of genes transferred by adenovirus (Ad) vectors depends upon efficient entry of vectors into target cells. Cells deficient in the coxsackie/adenovirus receptor (CAR) are difficult targets for Ad-mediated gene transfer. We hypothesized that low levels of CAR expression may be responsible, in part, for the relative inefficiency of Ad-mediated gene transfer to human alveolar macrophages (AMs). CAR gene expression was detected in human AMs by reverse transcription-polymerase chain reaction and at low levels by Northern analysis. Indirect immunofluorescence showed specific, low-intensity surface staining for CAR, but at levels below those found on the positive-control A549 human lung epithelial cell line. Consistent with this, AMs expressed Ad vector transgenes 100 to 1,000-fold less efficiently than A549 cells, as assessed using the beta-galactosidase reporter (chemiluminescence assay) and green fluorescent protein (fluorescence microscopy and flow cytometry). At high multiplicity of infection, AMs from an HIV+ individual could be transduced with an AdIFNgamma vector to secrete detectable human interferon-gamma. Ad transgene expression by AMs was blocked by capsid fiber protein, suggesting that CAR is required in the pathway for productive Ad entry into alveolar macrophages. To confirm that Ad transgene expression by AMs is limited by low levels of CAR expression, cells were infected with an Ad vector containing the CAR complementary DNA (cDNA). Enhanced expression of CAR protein was demonstrated by indirect immunofluorescence, and the CAR cDNA-transduced cells showed 5-fold enhancement of subsequent Ad transgene expression. These observations demonstrate that human AMs can be targets for Ad-mediated gene transfer, but that efficiency of transgene expression is limited, at least in part, by low levels of CAR expression. PMID- 10030834 TI - Formation of multinucleated giant cells in the mouse lung is promoted in the absence of interleukin-12. AB - The formation of multinucleated giant cells (MGCs) in an in vivo model of pulmonary inflammation was investigated to determine whether these cells are the result of a dominant T helper (Th) 1 or Th2 cytokine environment. We report that knockout (KO) mice with a disrupted interleukin (IL)-12 p40 gene exposed to the helminth Schistosoma mansoni had abundant and very large MGCs (> 50 microm) in their lungs concurrent with extensive eosinophilia and a population of large macrophages. Many of the MGCs and macrophages appeared to have phagocytosed eosinophils as part of a clearance process. The KO mice also had a strongly polarized Th2 immune response as judged by elevated levels in the lungs of messenger RNA (mRNA) transcripts for IL-4, IL-5, IL-6, and IL-13, but decreased levels of mRNA for interferon-gamma (IFN-gamma) and tumor necrosis factor-alpha (TNF-alpha). In addition, cells recovered by bronchoalveolar lavage from the airways of these mice secreted a Th2-biased profile of cytokines upon restimulation in vitro with parasite antigen. In contrast, wild-type C57BL/6 or KO mice treated with recombinant IL-12 had a polarized Th1 phenotype with elevated levels of IFN-gamma and TNF-alpha mRNA in the lungs, and an airway cell population that secreted abundant IFN-gamma. Very few MGCs were detected in these mice, and there was an absence of pulmonary eosinophilia. We conclude that the formation of MGCs in our model is promoted in the absence of IL-12 and is linked instead to the abundance of Th2 cytokines, notably IL-4 and IL-13. PMID- 10030835 TI - Antigen-induced airway hyperresponsiveness, pulmonary eosinophilia, and chemokine expression in B cell-deficient mice. AB - Murine models of allergen-induced pulmonary inflammation share many features with human asthma, including the development of antigen-induced pulmonary eosinophilia, airway hyperresponsiveness, antigen-specific cellular and antibody responses, the elaboration of Th2 cytokines (interleukin [IL]-4 and IL-5), and the expression of chemokines with activity for eosinophils. We examined the role of B cells and antigen-specific antibody responses in such a model by studying the histopathologic and physiologic responses of B cell-deficient mice compared with wild-type controls, following systemic immunization and airway challenge with ovalbumin (OVA). Both OVA-challenged wild-type and B cell-deficient mice developed (1) airway hyperresponsiveness, (2) pulmonary inflammation with activated T cells and eosinophils, (3) IL-4 and IL-5 secretion into the airway lumen, and (4) increased expression of the eosinophil active chemokines eotaxin and monocyte chemotactic protein-3. There were no significant differences in either the pathologic or physiologic responses in the B cell-deficient mice compared with wild-type mice. These data indicate that B cells and antigen specific antibodies are not required for the development of airway hyperresponsiveness, eosinophilic pulmonary inflammation, and chemokine expression in sensitized mice following aerosol challenge with antigen. PMID- 10030836 TI - Immunolocalization of CD34 in nasal polyposis. Effect of topical corticosteroids. AB - Airway inflammation in patients with nasal polyps is characterized by the increased presence of eosinophils, the numbers of which are reduced after treatment with topical corticosteroids. Because eosinophilic responses in the airways are in part due to eosinophil progenitor differentiation, we hypothesized that CD34, a cell surface, sialomucinlike glycoprotein that specifically marks hemopoietic progenitors and endothelium, would be expressed in nasal polyp tissue. We sought to identify CD34(+) leukocytes or endothelial cells in nasal polyps. We also investigated the effect of the topical corticosteroid budesonide on the numbers of CD34(+) cells and vessels in nasal polyps. To accomplish this, we performed immunostaining for CD34 protein in tissue sections of nasal polyps from topical steroid-treated and -untreated groups of patients, as well as from one patient before and after systemic corticosteroid therapy. We also examined myeloid colony formation by isolated polyp mononuclear cells, and performed flow cytometry to detect the presence of CD34(+)/CD45(+) cells within these isolated populations. We also examined the in vitro effects of steroids on human umbilical vein endothelial cell (HUVEC) expression of CD34. We detected CD34-immunoreactive mononuclear cells and blood vessels in the lamina propria of all nasal polyps. CD34(+) mononuclear cells resembled immature hemopoietic cells morphologically. Mononuclear cell fractions from polyps contained myeloid colony-forming cells and cells bearing CD45, a pan-leukocyte marker, as well as CD34, and gated as true hemopoietic blast cells. The numbers of CD34(+) cells and CD34(+) vessels in steroid-treated nasal polyps were significantly higher than in steroid-untreated nasal polyps (15.67 +/- 2.08 cells/10 hpf, versus 5.33 +/- 1.36 cells/10 hpf, P = 0.002; 101.25 +/- 6.24 vessels/0.5 mm2 of lamina propria, versus 57.22 +/- 8.00 vessels/0.5 mm2 of lamina propria, P = 0.0008, respectively). A similar upregulation of CD34 immunostaining, especially for mononuclear cells, was observed in one patient after systemic corticosteroid therapy. Steroid treatment in vitro of HUVECs did not result in enhanced CD34 expression. Both CD34(+)/CD45(+) mononuclear cells and CD34(+) endothelial cells are present within nasal polyps, with higher numbers in patients who have received topical corticosteroid treatment. Because enhancement of CD34 expression was not seen in cultured umbilical vein endothelial cells treated in vitro with corticosteroid, the findings of the study suggest that in nasal polyp tissue, steroids enhance numbers of CD34(+) progenitors and endothelial cells via indirect mechanisms. PMID- 10030837 TI - Quantitation and localization of ENaC subunit expression in fetal, newborn, and adult mouse lung. AB - The newborn lung is cleared of fetal liquid by active Na+ transport. The heterotrimeric (alpha, beta, gamma) epithelial Na+ channel, ENaC, mediates this process. To understand the role of individual ENaC subunits in Na+ transport during development, we quantified murine ENaC (mENaC) subunit messenger RNA (mRNA) expression levels of fetal, neonatal, and adult mouse lung by Northern blot analysis and studied regional expression by in situ hybridization. alphamENaC and gammamENaC mRNA expression increased sharply in late fetal gestation and reached near-adult levels by Day 1 of postnatal life. betamENaC expression increased more gradually through late fetal and early postnatal life and increased progressively until adulthood. In situ hybridization studies showed similar localization patterns of alphamENaC and gammamENaC subunit expression in fetal and postnatal lung. gammamENaC and alphamENaC subunits were initially localized to fetal lung bud tubules and by late gestation both subunits were expressed in all regions (acinar and bronchiolar) of the distal lung epithelium. betamENaC was detected from 16 d gestation onward and was expressed most intensely in small airways. There was little expression of betamENaC in the alveolar region. In postnatal lung all three subunits were expressed intensely in small airways. In adult lung, alphamENaC and gammamENaC were expressed in a pattern consistent with an alveolar type II (ATII) cell distribution. The timing of quantitative changes in mENaC subunit expression is consistent with a role of Na+ transport in liquid clearance of the perinatal lung. Intense expression of mENaC subunits in medium and small airway epithelium and in ATII cells suggests that these regions are a primary location for liquid absorption in the perinatal and postnatal murine lung. PMID- 10030838 TI - IFN-gamma potentiates the release of TNF-alpha and MIP-1alpha by alveolar macrophages during allergic reactions. AB - Viral infections play an important role in the exacerbation of asthma. The production of interferons (IFNs) is well known to limit viral spread, but IFN gamma can also prime alveolar macrophages to release more inflammatory cytokines, such as tumor necrosis factor-alpha (TNF-alpha) and macrophage inflammatory protein-1alpha (MIP-1alpha). Given the importance of these cytokines, we have investigated the effect of IFN-gamma on their release by alveolar macrophages during stimulation by immunoglobulin (Ig)E/anti-IgE. Alveolar macrophages from normal or Nippostrongylus brasiliensis-infected rats, the latter having increased numbers of low-affinity receptors for IgE (Fcepsilon RII) on their alveolar macrophages, were treated with IgE for 2 h and stimulated with anti-IgE for 18 h. The increase of TNF-alpha release (153 +/- 48 pg/10(6) cells) by IgE/anti-IgE occurred only with alveolar macrophages from infected rats. The messenger RNA level for TNF-alpha in rat alveolar macrophages was also increased by stimulation with IgE/anti-IgE. Treatment with IFN-gamma prior to stimulation with IgE/anti IgE showed a time- and concentration-dependent increase of TNF-alpha release. Interestingly, IgE/anti-IgE treatment did not stimulate the release of MIP-1alpha (15 +/- 5 pg/10(6) cells), but IFN-gamma treatment alone and with IgE /anti-IgE significantly increased and potentiated MIP-1alpha release (98 +/- 40 pg/10(6) cells) by alveolar macrophages, respectively. These results suggest that IFN gamma produced at times such as during viral infections primes alveolar macrophages for enhanced release of inflammatory mediators during allergic reactions, thereby contributing to the inflammatory process. PMID- 10030839 TI - Tumor necrosis factor-alpha stimulates mucin secretion and cyclic GMP production by guinea pig tracheal epithelial cells in vitro. AB - Tumor necrosis factor (TNF)-alpha, a pluripotent cytokine implicated in the pathogenesis of airway inflammation, has been shown to provoke hypersecretion of mucin by airway epithelial cells in vitro. In this study, we investigated potential signaling pathways mediating TNF-alpha-induced mucin secretion using guinea pig tracheal epithelial (GPTE) cells in air-liquid interface culture. Exogenously applied TNF-alpha (human recombinant) stimulated mucin secretion in a concentration-dependent manner, with maximal effects at 10 to 15 ng/ml (286 to 429 U/ml). The pathway of stimulated secretion appeared to involve generation of intracellular nitric oxide (NO), activation of soluble guanylate cyclase (GC-S), production of cyclic guanosine monophosphate (cGMP), and activation of cGMP dependent protein kinase (PKG). TNF-alpha increased production of nitrite and nitrate by GPTE cells; both mucin secretion and cGMP production were attenuated by NG-monomethyl-L-arginine (1 mM), a competitive inhibitor of nitric oxide synthase (NOS), or by the GC-S inhibitor LY83583 (50 microM); and mucin secretion in response to TNF-alpha or to the cGMP analogue dibutyryl cGMP (100 and 500 microM) was attenuated by the specific PKG inhibitor KT5823 (1 microM). Increased mucin secretion and increased cGMP production in response to TNF-alpha both appeared to be mediated by a phospholipase C that hydrolyzes phosphatidylcholine (PC-PLC), and by protein kinase C (PKC), since both responses were attenuated by either D609 (10 and 20 microg/ml), a specific PC-PLC inhibitor, or by each of three PKC inhibitors: Calphostin C (0.3 and 0.5 microM), bisindoylmaleimide (GF 109203X, Go 6850; 20 nM), or Ro31-8220 (10 microM). Collectively, the results suggest that TNF-alpha stimulates secretion of mucin by GPTE cells via a mechanism(s) dependent on PC-PLC and PKC, and involving activation of NOS, generation of NO, production of cGMP, and activation of PKG. PMID- 10030840 TI - Keratinocyte growth factor enhances maturation of fetal rat lung type II cells. AB - Keratinocyte growth factor (KGF) or fibroblast growth factor (FGF)-7, a peptide produced by stromal cells and in particular by lung mesenchyme, has recently been shown to influence early lung morphogenesis and to be a mitogen for fetal and adult alveolar type II cells. Although contradictory findings have been reported regarding its effects on surfactant protein expression, its effects on surfactant phospholipids have not been studied. We investigated the effects of KGF on the synthesis of surfactant components by cultured fetal rat type II cells isolated during the late gestational period, when surfactant accumulates in preparation for extrauterine life. We show that KGF is a potent stimulus of surfactant phospholipid synthesis, particularly for the major component of surfactant, disaturated phosphatidylcholine (DSPC). KGF increased choline incorporation into DSPC in a dose-dependent manner up to 25 ng/ml (1.3 x 10(-9) M), and this effect was greater for surfactant than for nonsurfactant DSPC. KGF was several times more potent in this respect than acidic FGF at the same molar concentration. KGF, similar to epidermal growth factor, also stimulated acetate incorporation and increased the surfactant phospholipid and DSPC content of cultured cells twofold. These effects correlated with increased choline phosphate cytidylyltransferase activity and increased fatty acid synthase activity and gene expression. KGF also induced a dose-dependent stimulation of surfactant protein-A, -B, and -C gene expression, leading to a 2- to 3-fold increase in their messenger RNAs. KGF therefore stimulates the synthesis of all surfactant components in developing type II cells at the time of surfactant accumulation. Its secretion by lung fibroblasts may thus be an important factor in promoting the maturation of fetal lung epithelium and the synthesis of sufficient surfactant. The results suggest that KGF could provide a new therapeutic agent for the management of the immature or injured lung. PMID- 10030841 TI - Prostaglandin-E2 counteracts interleukin-1beta-stimulated upregulation of platelet-derived growth factor alpha-receptor on rat pulmonary myofibroblasts. AB - The platelet-derived growth factor (PDGF) alpha-receptor (PDGF-Ralpha) is upregulated during lung fibrogenesis, and induction of PDGF-Ralpha on cultured lung myofibroblasts by interleukin (IL)-1beta results in an increased mitogenic response to PDGF. Because IL-1beta stimulates prostaglandin (PG) E2 production, we investigated whether IL-1beta could upregulate PDGF-Ralpha via a PGE2 dependent mechanism. IL-1beta increased the production of PGE2 by rat lung myofibroblasts and the cyclooxygenase (COX) inhibitor indomethacin blocked IL 1beta-induced PGE2 production. However, indomethacin did not inhibit IL-1beta stimulated upregulation of [125I]PDGF-AA binding sites, indicating that PDGF Ralpha induction does not require PGE2 synthesis. Instead, PGE2 downregulated PDGF-Ralpha protein and messenger RNA expression, and counteracted the IL-1beta stimulated increase in [125I]PDGF-AA binding. Pretreatment of cells with indomethacin or the COX-2 specific inhibitor NS-398 attenuated the suppressive effect of exogenous PGE2 on PDGF-Ralpha, indicating that endogenous PGE2 released by IL-1beta treatment also contributed to downregulation of PDGF-Ralpha. PDGF Rbeta expression was not altered by IL-1beta or PGE2. Pretreatment of myofibroblasts with IL-lbeta increased PDGF-stimulated mitogenesis, and this effect was blocked by coincubation with PGE2. In contrast, PGE2 enhanced epidermal growth factor- or basic fibroblast growth factor-2-stimulated cell proliferation approximately 50%. Because IL-1beta upregulates both PGE2 production and PDGF-Ralpha expression, these data suggest that PGE2 functions in a negative feedback loop to limit expression of PDGF-Ralpha and suppress PDGF stimulated myofibroblast proliferation. PMID- 10030842 TI - Endothelial nitric oxide synthase as a potential susceptibility gene in the pathogenesis of emphysema in alpha1-antitrypsin deficiency. AB - A role for endothelial nitric oxide synthase (NOS3) in the susceptibility of individuals with alpha1-antitrypsin (alpha1AT) deficiency to destructive lung disease was evaluated. Six polymorphic sites were identified within the NOS3 gene (i.e., -924A/G, -788C/T, -691C/T, 774C/T, 894G/T, and 1998C/G). The genotype distribution was determined in 339 patients and 94 control individuals. Frequency of the 774T allele in severely affected individuals was 0.417 versus 0.269 in control subjects (P = 0.018), whereas the 894T allele frequency was 0.427 versus 0.280 in control subjects (P = 0.024). Patients with less severe lung disease had the 774T and 894T allele frequencies of 0.289 and 0.344, respectively, similar to frequencies in a control group (P > 0.3). No direct correlation between pulmonary function and five other NOS3 polymorphisms was observed. Thus, functional allelic variants that are in linkage disequilibrium with the 774C/T and 894G/T may be present in the specified genomic area. These data are consistent with a modulatory role for NOS3 in destructive lung disease associated with alpha1AT deficiency. PMID- 10030843 TI - The role of alpha4 (CD49d) and beta2 (CD18) integrins in eosinophil and neutrophil migration to allergic lung inflammation in the Brown Norway rat. AB - We investigated the role of beta2 (CD18) and alpha4 (CD49d) integrins in eosinophil and neutrophil recruitment to lung parenchyma and bronchoalveolar lavage fluid (BALF) of allergen-challenged Brown Norway (BN) rats. Challenge of sensitized BN rats with ovalbumin induced an eosinophil- and neutrophil-rich infiltrate in BALF at 24 h, accompanied by an increase in BALF protein content. Treatment with either the TA-2 monoclonal antibody (mAb) against alpha4 (as an F[ab']2 fragment) or the WT.3 mAb against beta2 integrin significantly reduced eosinophil and neutrophil accumulation in BALF by 54 to 66% and eosinophil accumulation in the parenchyma by 48%. A significant difference in effect was observed between mAb TA-2 in intact immunoglobulin G or F(ab)2 form. Combined treatment with mAbs WT.3 plus TA-2 (F[ab]2) virtually abolished eosinophil accumulation in BALF and in the parenchyma, and reduced neutrophil accumulation in BALF by 91%. In contrast, neutrophil accumulation in the lung was not inhibited by these mAb treatments. The increase in BALF protein concentration was significantly inhibited by TA-2 (by 40%) and by WT.3 plus TA-2 in combination (71% inhibition). We conclude that eosinophil and neutrophil migration into the air space in allergic lung inflammation is partially CD18 (beta2)- and CD49d (alpha4)- dependent and that alpha4 integrins mediate essentially all of the CD18 independent migration. Similarly, eosinophil accumulation in the parenchyma is completely alpha4 and CD18 (beta2) integrin-dependent. In marked contrast, neutrophil accumulation in the lung in this allergen model can occur independently of both alpha4 and beta2 integrins. PMID- 10030844 TI - Human neutrophils secrete gelatinase B in vitro and in vivo in response to endotoxin and proinflammatory mediators. AB - Bacterial sepsis is characterized by a systemic inflammatory state, with activation of numerous cell types. Phagocytes participate in this phenomenon by secreting various proinflammatory cytokines and enzymes. Matrix metalloproteinases (MMPs) such as gelatinases are produced by phagocytes and are thought to play an important role in processes of cell transmigration and tissue remodeling. In this work, we show that endotoxin (lipopolysaccharide [LPS]) and other inflammatory mediators, such as tumor necrosis factor (TNF), interleukin-8, and granulocyte colony-stimulating factor, induce a rapid (within 20 min) release of gelatinase-B (MMP-9) zymogen in whole human blood, as determined by gelatin zymography. The polymorphonuclear neutrophil was identified as the cell responsible for this rapid secretion, as a result of the release of preformed enzymes stored in granules. Normal human subjects given LPS intravenously showed a similar pattern of proMMP-9 secretion, with maximum plasma levels reached 1.5 to 3 h after LPS administration (P = 0.0009). Prior administration of TNF receptor:Fc, a potent TNF antagonist, to subjects given LPS, only partially blunted the release of proMMP-9 (P = 0.033). Ibuprofen, a cyclooxygenase inhibitor, did not alter this pattern of release. Increased levels of proMMP-9 and proMMP-2, as well as activated forms of MMP-9, were found in plasma from two patients with gram-negative sepsis. The levels of MMPs paralleled the severity of clinical condition and a marker of the severity of sepsis, plasma procalcitonin. These data indicate that MMPs are released in whole blood in response to various inflammatory mediators and that they could serve as sensitive and early markers for cell activation during the course of bacterial sepsis. PMID- 10030845 TI - Pertussis toxin-induced lung edema. Role of manganese superoxide dismutase and protein kinase C. AB - The mechanism by which pertussis toxin (Ptx) causes lung edema is not clear. We investigated the role of pulmonary manganese superoxide dismutase (MnSOD) and protein kinase C (PKC) in Ptx-induced lung edema. We demonstrated that intraperitoneal injection of Ptx at a concentration of 5 microg/100 g body weight caused a similar degree of lung edema in 2 d, as measured by lung wet weight/dry weight ratio, in heterozygous MnSOD gene (Sod2)-knockout mice (Sod2(+/-)) and in their wild-type littermates (Sod2(+/+)). The level of lung MnSOD activity in Sod2(+/-) mice was approximately half that of Sod2(+/-) mice. Ptx had no effect on levels of lung MnSOD messenger RNA, immunoreactive protein, or enzyme activity in either Sod2(+/+) or Sod2(+/-) mice. Ptx also had no effect on lung copper-zinc SOD, catalase, and glutathione peroxidase activities in these mice. On the other hand, Ptx caused the activation of lung PKC, for example, by translocation of a 72-kD PKC isoform from the cytosolic fraction to the membrane fraction. Pretreatment of mice with bisindolylmaleimide, a PKC inhibitor, prevented both the Ptx-induced activation of PKC and lung edema. These data suggest that Ptx induced lung edema in mice is, at least in part, due to the activation of lung PKC. PMID- 10030846 TI - Synergistic effects of interleukin-4 or interleukin-13 and tumor necrosis factor alpha on eosinophil activation in vitro. AB - Increased concentrations of tumor necrosis factor-alpha (TNF-alpha), interleukin (IL)-4, and IL-13 have been measured in bronchoalveolar lavage fluid (BALF) of patients with asthma following allergen provocation. In addition, these cytokines have also been reported to activate eosinophils in vitro. Although cytokine interactions have been postulated in the activation of eosinophils, the combined effects of cytokines on eosinophil activation remain poorly understood. Because activation of eosinophils has been regarded as a crucial event in the pathogenesis of asthmatic inflammation, we tested the hypothesis that IL-4 and IL 13 could enhance the effects of TNF-alpha on eosinophil activation. For this purpose, eosinophils from normal donors were purified and cultured in the presence of IL-4 or IL-13 and TNF-alpha. Eosinophil survival and surface expression of CD69 were assessed by flow cytometry. There was a concentration- and time-dependent upregulation in CD69 expression as well as eosinophil survival when eosinophils were incubated with IL-13, IL-4, or TNF-alpha. However, eosinophil viability and CD69 expression increased synergistically when eosinophils were incubated with IL-13 or IL-4 in the presence of TNF-alpha. This synergistic effect of IL-4 and IL-13 on CD69 expression was not limited to TNF alpha but was also observed with IL-5. Our study provides evidence that IL-4 can activate eosinophils in a similar fashion as does IL-13. Furthermore, this study shows that the addition of IL-4 or IL-13 to TNF-alpha or IL-5 has synergistic effects on eosinophil activation, suggesting that the combined effects of different cytokines present in BALF following allergen provocation can enhance eosinophil activation in vitro. PMID- 10030847 TI - Effects of cyclosporin A and dinactin on T-cell proliferation, interleukin-5 production, and murine pulmonary inflammation. AB - We compared the effects of cyclosporin A (CSA) and a macrotetrolide antibiotic, dinactin, on human T-cell proliferation and cytokine production induced by stimulation of the T-cell receptor alone (monoclonal antibody [mAb] directed against CD3) or in combination with costimulatory signals (mAbs directed against CD3 and CD28). These agents were also examined in a murine model of interleukin (IL)-5-mediated pulmonary inflammation. Dinactin inhibited T-cell proliferation induced by IL-2, by mAb to CD3, and by mAbs to CD3 plus alpha-CD28 with identical dose-response curves (IC50 = 10-20 ng/ml). Dinactin inhibited cytokine production with IC50 values of 10 ng/ml for IL-4 and IL-5 and 30 or 60 ng/ml for interferon gamma or IL-2, respectively. Unlike CSA, exogenous IL-2 did not alter the dinactin-mediated effects on T cells, and nuclear run-on and steady-state messenger RNA (mRNA) analysis showed that dinactin inhibited cytokine production through a post-transcriptional mechanism. CSA selectively blocked T-cell receptor induced T-cell proliferation and cytokine production (IC50 = 10 ng/ml). Under costimulatory conditions, IL-5 synthesis was only minimally inhibited by high concentrations of CSA, and at CSA concentrations of less than 125 ng/ml, IL-5 was significantly increased above control values. Dinactin and CSA reduced pulmonary eosinophilia when administered within 1 d of airway antigen challenge. Of the cytokine mRNAs examined in the lungs of CSA-pretreated, antigen-challenged mice, IL-5 mRNA levels were the least reduced, paralleling the resistance of IL-5 to CSA observed in vitro and suggesting a role for CD28 in the in vivo induction of IL-5. PMID- 10030848 TI - Bacterial lipopolysaccharide induction of the prostaglandin G/H synthase 2 gene causes thromboxane-dependent pulmonary hypertension in rabbits. AB - Two genes encode proteins with prostaglandin G/H synthase (PGHS) activity. PGHS-1 is primarily a constitutively expressed gene, whereas inflammatory agents such as bacterial lipopolysaccharide (LPS) endotoxin rapidly induce the PGHS-2 gene in leukocytes. Both PGHS-1 and PGHS-2 are rate-limiting enzymes for the production of prostaglandins and thromboxane following release of arachidonic acid by phospholipases. We previously reported that LPS perfusion into the circulation of isolated perfused rabbit lung (IPL) results in thromboxane-dependent pulmonary hypertension and lung edema when the LPS-primed lung is subsequently stimulated with platelet activating factor (PAF) (J. Clin. Invest. 1990;85:1135). In this study, we showed that the mechanism by which LPS primes IPL for enhanced production of thromboxane and pulmonary hypertension in response to PAF depends on specific upregulation of the PGHS-2 gene in the rabbit lung. LPS perfusion of IPL induced PGHS-2 gene expression, which correlated with the conversion of free arachidonic acid to thromboxane-B2 (TXB2) and the onset of pulmonary hypertension. LPS-induced PGHS-2 expression, TXB2 release, and pulmonary hypertension were inhibited by actinomycin D (an inhibitor of transcription) and cycloheximide (an inhibitor of protein synthesis). The constitutively expressed PGHS-1 remained unchanged with LPS perfusion, and did not convert free arachidonic acid to TXB2, suggesting that PGHS-1 does not contribute to the induction of pulmonary hypertension by LPS. These studies reveal a pathogenic role for induction of PGHS-2 in lung injury. PMID- 10030849 TI - Respiratory carcinoma cell lines. MUC genes and glycoconjugates. AB - Lung carcinoma cell lines are being used in many laboratories to study various airway epithelial functions, including mucin gene expression. To identify model systems for investigating regulation of MUC5/5AC gene expression and secretion of MUC5/5AC mucins in airway epithelial cells, we evaluated the expression of several mucin genes in six carcinoma cell lines of respiratory tract origin. RNA was extracted from A549, Calu-3, NCI H292, Calu-6, RPMI 2650, and A-427 cells; MUC1, MUC2, MUC4, MUC5/5AC, and MUC5B messenger RNA (mRNA) expression was determined. By Northern analyses, all cell lines expressed MUC1 mRNA, whereas MUC2 mRNA was not detectable in any of the cell lines. RPMI 2650 cell lines expressed only MUC1 mRNA. NCI-H292 cells expressed MUC4 and low levels of MUC5/5AC mRNA. Calu-3 and A549 cells expressed MUC5/5AC mRNA; A549 cells also expressed MUC5B mRNA. Glycoconjugates secreted by lung carcinoma cells were also examined. By wheat germ lectin analysis, Calu-3, H292, and A549 cells secreted high molecular weight glycoproteins having N-acetylglucosamine and/or sialic acid moieties. Western blot analyses with an anti-MUC5:TR-3A antibody demonstrated that Calu-3 and A549 cells secreted MUC5/5AC mucins. All six carcinoma cell lines secreted large, radiolabeled, sulfated macromolecules; the majority were proteoglycans that were digested by hyaluronidase. However, Calu-3 cells also secreted sulfated high molecular-weight glycoproteins that were immunoprecipitated by anti-MUC5:TR-3A antibody. These studies demonstrated that Calu-3 and A549 cell lines expressed high and moderate amounts of MUC5/5AC mRNA and MUC5/5AC mucins, whereas H292 cells expressed lesser amounts. These cell lines should prove useful for studies of MUC5/5AC gene expression and MUC5/5AC biosynthesis, trafficking, and secretions in airway epithelial cells. PMID- 10030850 TI - Opioids accelerate fetal rat lung maturation in vitro. AB - Infants born to heroin- and cocaine-addicted mothers have been reported to have a lower incidence of respiratory distress syndrome (RDS) compared with nonaddicted infants. However, it is not known whether these are direct drug-mediated effects or secondary phenomena. We therefore investigated the effect of opioids and cocaine on fetal rat lung maturation in vitro. Using 18- to 20-d fetal rat lung explants and 20-d fetal type II cells, we measured the effect of varying concentrations (1 x 10(-8) to 1 x 10(-3) M) of heroin, morphine, methadone, and the nonopioid cocaine on the rate of choline incorporation into phosphatidylcholine (PC) and disaturated PC. We also analyzed the morphology of 19-d explants after exposure to opioids. Significant increases in rate of choline incorporation were noted in 19- and 20-d explants using 1 x 10(-3) M heroin, 1 x 10(-3) M morphine, and 1 x 10(-4) M methadone (P < 0. 005). No acceleratory effect was seen with cocaine. Morphologic analysis of the three opioid-treated groups revealed a significant (192 to 251%) increase in type II pneumocytes and lamellar bodies per alveolar lining cell (P < 0.01). Choline incorporation into PC by type II cells was also significantly increased by opioids (P < 0. 01); lactate dehydrogenase release and cell viability were not affected by opioid treatment. These data indicate that high-dose opioids have an acceleratory effect on biochemical and morphologic parameters of fetal lung maturation in vitro. The lack of in vitro acceleration with cocaine suggests that any cocaine-related reduction in the incidence of RDS is a secondary effect. PMID- 10030851 TI - Long-lasting effects of chronic ozone exposure on rat nasal epithelium. AB - Ozone, the principal oxidant pollutant in photochemical smog, causes airway epithelial injury in the upper and lower respiratory tract of laboratory animals. We have recently reported that long-term inhalation exposure to ozone causes mucous-cell metaplasia (MCM) in the surface epithelium lining the nasal airways of F344 rats. The principal objective of the present study was to determine the persistence of ozone-induced MCM in the nasal epithelium after the end of a chronic exposure. Male F344/N rats were exposed to 0, 0.25, or 0.5 ppm ozone, for 8 h/d, 7 d/wk for 13 wk. Animals were killed 8 h, 4 wk, or 13 wk after the end of the chronic exposure. Ozone-related alterations in the nasal epithelium were qualitatively and quantitatively characterized through histochemistry, image analysis, and morphometric techniques. Some rats were exposed for an additional 8 h to 0.5 ppm ozone at 13 wk after the end of the chronic exposure to determine whether previous ozone exposure results in persistent changes in the sensitivity of nasal epithelium to acute injury. At the end of the chronic exposure, hyperplasia was present in the nasal epithelium of rats exposed to 0.25 and 0.5 ppm ozone. By 13 wk postexposure, this proliferative alteration was still evident only in the rats exposed to 0.5 ppm ozone. Ozone-induced MCM with associated intraepithelial mucosubstances was evident only in the nasal tissues of rats exposed to 0.5 ppm ozone. Though attenuated, these alterations in the nasal mucous apparatus were still detectable at 13 wk after the end of the exposure. At this same time after the chronic exposure, an acute (8 h) exposure to 0.5 ppm ozone induced an additional increase of mucosubstances in the nasal epithelium of rats previously exposed to 0.5 ppm ozone, but not in rats chronically exposed to 0 or 2.5 ppm ozone. The persistent nature of the ozone-induced MCM in rats documented in this report suggests that ozone exposure may have the potential to induce similar long-lasting alterations in the airways of humans. PMID- 10030853 TI - Minimally invasive surgery: introduction PMID- 10030852 TI - ATP modulates anti-IgE-induced release of histamine from human lung mast cells. AB - Adenosine 5'-triphosphate (ATP) is released from the cytoplasm under physiologic and pathophysiologic conditions and enters the extracellular space, where it acts on a group of recently cloned cell-surface receptors termed P2-purinoceptors (subtypes P2X and P2Y). We examined the effects of extracellular ATP, uridine triphosphate (UTP), the stable ATP analogues alpha,betamethylene-ATP (alpha,betamATP), beta,gammamethylene-ATP (beta,gammamATP), and 2-methylthio-ATP (2mSATP), and adenosine (10(-6)-10(-3) M) on histamine release from human lung mast cells (HLMC) induced by anti-IgE and the calcium ionophore A23187. None of the nucleotides or adenosine directly induced histamine release. Adenosine exhibited a bimodal effect, enhancing histamine release at 10(-6) to 10(-4) M (P > 0.05, NS) and inhibiting it at 10(-3) M (P < 0.05). ATP (10(-4) M) enhanced anti-IgE-induced histamine release (10.9 +/- 2.7% to 19. 2 +/- 2.9%, n = 20, P < 0.01), but not ionophore A23187-induced histamine release (n = 10). The adenine nucleotides consistently enhanced anti-IgE-induced histamine release; the rank order for this action was: ATP > 2mSATP > alpha,betamATP > beta,gammamATP, suggesting mediation by a P2Y-purinoceptor subtype. The selective P2X purinoceptor antagonist pyridoxalphosphate-6-azophenyl-2', 4'-disulfonic acid failed to influence the effect of ATP, further supporting P2Y-purinoceptor mediation of anti-IgE-induced histamine release. UTP, an agonist at P2Y purinoceptors, also significantly enhanced anti-IgE-induced histamine release. Application of the reverse transcription-polymerase chain reaction indicated that HLMC constitutively express the messenger RNAs encoding the P2Y1- and P2Y2 purinoceptor subtypes, and not that encoding the P2X7-purinoceptor (i.e., P2Z), a subtype implicated in ATP-induced histamine release in rodent peritoneal mast cells. The data produced in the study suggest that ATP plays an important modulatory role in histamine release from HLMC, and that it may therefore be mechanistically involved in human allergic/asthmatic reactions. PMID- 10030854 TI - Laparoscopic cholecystectomy, a treatment for gallstones: from idea to reality. PMID- 10030855 TI - Origin of laparoscopic cholecystectomy in the USA: personal experience. PMID- 10030856 TI - Laparoscopic cholecystectomy for biliary tract emergencies: state of the art. AB - Although laparoscopic cholecystectomy is unusually safe and well tolerated in patients with routine symptomatic cholelithiasis, it can become a formidable procedure when used to manage biliary tract emergencies. Optimally, a reasoned and cautious approach and a low threshold for conversion can avoid major complications. One such emergency, acute cholecystitis, may be particularly hazardous because of the relatively common finding of severe inflammation with dense adhesions to adjacent viscera and gallbladder necrosis. Special modifications of technique may be required. Overall, urgent operation (within 72 hours) results in an acceptably low mortality (0.3%) but a somewhat higher conversion rate (16%) and longer hospital stay (3 days). Unnecessary delays may result in more adhesions and an increased level of operative difficulty. In patients who are at an especially high risk because of co-morbid disease, percutaneous cholecystostomy is an appropriate alternative strategy. Biliary pancreatitis may be associated with high mortality (9%) and has an unpredictable course. Accordingly, a multidisciplinary approach that may include both gastroenterologists and radiologists is generally advisable. Because common bile duct (CBD) stones are present in more than 20% of patients who present with biliary pancreatitis, endoscopic retrograde cholangiopancreatography (ERCP) can be used effectively on a selective basis during the preoperative or postoperative period; the preferred timing continues to be somewhat controversial. As an alternative approach, laparoscopic CBD exploration is gradually gaining wider acceptance. In eight reported series using a variety of techniques for stone extraction, major complications were infrequent (10%), and the conversion rate was low (5%). Acute suppurative cholangitis is a more fulminant problem that is best managed by expeditious ERCP with removal of all intraductal stones. Resuscitation should be continued until complete; laparoscopic cholecystectomy can follow at an appropriate interval. PMID- 10030858 TI - Minimally invasive surgery for inguinal hernia. AB - The use of minimally invasive techniques in surgery for inguinal hernias has become an established approach to inguinal hernia repair. A brief history of laparoscopic hernia surgery is presented, including evolution of techniques. Several prospective randomized trials comparing open repairs with laparoscopic procedures are reviewed, and the results of the experience at the authors' institution are presented. Studies on the advantages of laparoscopic hernia repair vary, many showing advantages of the laparoscopic approach over open techniques. With continuing refinement of technique and efforts to minimize the cost differential, there should be a continuing role for minimally invasive hernia repair. PMID- 10030857 TI - Laparoscopic common bile duct exploration. AB - Laparoscopic cholecystectomy has become the procedure of choice for laparoscopically skilled surgeons when dealing with both chronic and acute cholecystitis. When choledocholithiasis is encountered in the treatment of these patients the skilled laparoscopist has several treatment options available to treat the patient in one stage and avoid the morbidity of endoscopic sphincterotomy. Although still controversial, laparoscopic common bile duct exploration has been shown to be safe, applicable, and cost-effective in the treatment of choledocholithiasis. This report details several laparoscopic treatment alternatives for choledocholithiasis. PMID- 10030859 TI - Laparoscopic surgery of the gastroesophageal junction. AB - Incompetence of the lower esophageal sphincter mechanism leads to gastroesophageal reflux (GER), which is the most common indication for surgery of the gastroesophageal junction. Evaluation, diagnosis, and the modern surgical treatment of GER are discussed. Evaluation of patients with severe heartburn include upper endoscopy to evaluate the general condition of the esophagus, stomach, and duodenum; an upper gastrointestinal contrast study for a complete anatomic view of the esophagus and stomach; esophageal manometry to evaluate the function of the esophagus; 24-hour pH monitoring to determine esophageal acid exposure; and a gastric emptying study selectively to determine the presence of a motility disorder. These studies most often prove the diagnosis of gastroesophageal reflux, hiatal hernia, Barrett's esophagus, peptic esophageal stricture, paraesophageal hernia, or achalasia. The laparoscopic approach to treatments for these include Nissen fundoplication, Toupet fundoplication, Collis gastroplasty with fundoplication, modified Heller myotomy, esophageal diverticulectomy, and revisional operations. These procedures are described in detail. The results of these operations indicate that they are safe and effective and should be considered the new gold standard for correction of gastroesophageal pathology. Laparoscopic surgery has revolutionized many procedures traditionally performed through a laparotomy. Although they are technically more difficult and require a significant amount of time and practice for the surgeon to become proficient, it is becoming apparent that for functional surgery of the gastroesophageal junction laparoscopy is the access of choice. PMID- 10030860 TI - Endoluminal surgery. AB - The development of laparoscopic surgery has provided minimally invasive surgeons with advanced laparoscopic instrumentation and high definition imaging. The resulting surgical expertise and technology has now been extended to gastric endoluminal surgery. Laboratory and clinical investigations have been initiated for various applications of this new form of surgery. Endoluminal gastric wall excision surgery is the most widely utilized and includes the removal of superficial gastric malignancies, benign gastric wall leiomyomas, and gastric polyps. Clinical experience has increased, and the initial results have been satisfactory. Pancreaticocystogastrostomy can be successfully performed using intraluminal surgery, but gastric wall bleeding and lack of fusion of the stomach to the cyst wall have complicated some cases. There are case reports of foreign body removal and intraluminal surgical procedures for patients with bleeding gastric ulcers. Of primary importance at this stage of development is the surgeon's familiarity with appropriate indications for gastric endoluminal surgery and the access devices currently available. Future considerations include the application of this approach to patients with gastroesophageal reflux disease, occult gastrointestinal bleeding, intractable bleeding from a duodenal ulcer, and multiinstitutional trials of gastric excision procedures. PMID- 10030861 TI - Laparoscopy and peripancreatic neoplasia. AB - Since its inception laparoscopy has been a valuable tool for diagnosis, and more recently it has become widely accepted as a medium for surgical intervention. In this light, the addition of minimally invasive techniques to the management of peripancreatic cancer has gained notable attention. Although most practitioners agree that there is some role for minimally invasive therapy, opinions vary as to the extent and significance these applications carry to the overall management of peripancreatic malignancies. PMID- 10030862 TI - Laparoscopic splenectomy. AB - Splenectomy is a powerful tool for treatment of hematologic disease, with 70% to 90% of patients achieving long-term improvement. In recent years laparoscopic splenectomy has gained acceptance as a viable alternative to open splenectomy. This review summarizes the indications for laparoscopic splenectomy, the operative techniques, and the most recent results. Laparoscopic splenectomy is evolving and may become the standard operative method for the treatment of the problem spleen. PMID- 10030863 TI - Laparoscopic adrenalectomy: new gold standard. AB - Nearly 600 cases of laparoscopic adrenalectomy have been described in the world literature, documenting the safety and effectiveness of the procedure. Comparative studies have demonstrated the advantages of the laparoscopic approach when compared to traditional open approaches to adrenalectomy, documenting a more rapid and comfortable recovery, shorter hospitalization, and fewer complications. Several techniques of laparoscopic adrenalectomy have been described. We prefer the transabdominal approach in the lateral decubitus position. Herein we report our experience with 28 adrenalectomies using this approach. Indications for adrenalectomy have been hyperaldosteronism (9), hypercortisolism (4), pheochromocytoma (3), incidentaloma (6), metastasis (3), lymphoma (1), angiomyolipoma (1), other (1). Average tumor size was 3.3 cm (1. 4-8.3 cm). Average operative time was 152 minutes (110-210 minutes), with left adrenalectomy taking slightly longer to perform than on the right (156 vs. 145 minutes). There were no intraoperative complications and one conversion to open adrenalectomy for a large metastatic lung cancer found to be invading the liver. One patient experienced left rib pain from a cannula site immediately at the costal margin. There were no other complications. Average length of hospitalization was 2.3 days (1-6 days). With this and others' experience, laparoscopic adrenalectomy has become the gold standard for adrenalectomy. This manuscript reviews the literature on laparoscopic adrenalectomy and describes the transabdominal lateral approach. PMID- 10030864 TI - Laparoscopic surgery of the colon and rectum. AB - The use of laparoscopic techniques in benign colorectal surgery has expanded over the past several years, but controversy continues to surround the use of laparoscopic resection in cases of colorectal carcinoma. Diagnostic laparoscopy, the creation of stomas, and limited resections are becoming reasonable indications for benign diseases. In cases of malignancy, resection through a conventional incision or a laparoscope must adhere to the same defined surgical oncologic principles. Current randomized trials comparing open resection to laparoscopic resection should address these concerns. Port-site recurrence remains a leading concern regarding the widespread acceptance of laparoscopic resection for colorectal carcinoma. This article focuses on the applications of laparoscopic colorectal surgery for malignant diseases. Further research in this area combined with advances in laparoscopic technology will be critical to the future successful application of laparoscopic surgery to colorectal carcinoma. PMID- 10030865 TI - Minimally invasive vascular surgery: review of current modalities. AB - The concept of a minimally invasive approach to the treatment of vascular pathology was realized nearly 30 years ago when Charles Dotter described dilatation of atherosclerotic stenoses. Since that time biotechnology and therapeutic innovation have progressed to the point where entire medical subspecialties are based on the endoluminal treatment of diseases of the blood vessels. The most rapid progress has been made in the area of endoluminal treatment of vascular lesions, with angioplasty, stent, and stent graft deployment becoming an increasingly common method of treating various vascular lesions. Extraluminal endoscopic treatment of vascular disease has been gaining popularity, particularly for management of perforator vein incompetence associated with venous stasis disorders. Endoscopic saphenous vein harvest has become an accepted method for minimizing the length of incision required for saphenectomy. Vascular imaging has followed similar trends, with more detailed information being derived from tiny intravascular ultrasonic catheters. This article summarizes the current state of minimally invasive vascular surgery to provide the reader with an understanding of the efficacy of the various modalities. It also discusses future directions in the field. PMID- 10030866 TI - Cost-effective minimally invasive surgery: What procedures make sense? AB - Because laparoscopic surgery has emerged during a time of medical cost consciousness, emphasis has been placed on the economic implications of this emerging field. The cost of these procedures, however, is just one component in determining their overall value to most of the stakeholders in the health care system. The value of a treatment is proportional to its appropriateness and quality per unit cost. Several confounding factors affect the variables in this equation and contribute to the difficulty in this type of assessment of an emerging technology. By understanding the mechanics of value assessment and certain caveats for specific procedures, the surgeon will be better able to determine what procedures makes sense (or are of value) in their practice and for their patients. PMID- 10030867 TI - Minimally invasive surgery: the next frontier. PMID- 10030869 TI - Curious new statistical prediction of quantum mechanics. PMID- 10030868 TI - Re: Chen, SC et al.: Abdominal sonography screening of clinically diagnosed or suspected appendicitis before surgery. World J. Surg. 22:449, 1998. PMID- 10030870 TI - Classical analog of pure-state quantum dynamics. PMID- 10030871 TI - New method to measure the relativistic doppler shift: First results and a proposal. PMID- 10030872 TI - Equation of motion of a stringlike dislocation. PMID- 10030873 TI - Measurement of the ratio of cross sections for neutrino and antineutrino scattering from electrons. PMID- 10030875 TI - (e,e' gamma ) measurements on the 4.439-MeV state of 12C. PMID- 10030874 TI - Experimental limits on the nucleon lifetime for two- and three-body decay modes. PMID- 10030876 TI - Search for anomalous fragments of 56Fe using plastic nuclear track detectors. PMID- 10030877 TI - Effect of surface dynamical fluctuations on light scattering by a nearby dipole. PMID- 10030880 TI - Pressure-induced critical phenomena of a microemulsion system. PMID- 10030878 TI - Axial magnetic fields in laser-produced plasmas. PMID- 10030879 TI - Stabilization of interchange modes in mirror plasma devices by radio-frequency sideband coupling. PMID- 10030882 TI - Spin-glass model of crystal surfaces. PMID- 10030881 TI - Critical behavior near a vanishing miscibility gap. PMID- 10030883 TI - Towards an explanation of the 3.4-power dependence of the viscosity on molecular weight. PMID- 10030884 TI - Sensitivity-enhanced electron-holographic interferometry and thickness measurement applications at atomic scale. PMID- 10030885 TI - Study of Si(111) surfaces by optical second-harmonic generation: Reconstruction and surface phase transformation. PMID- 10030886 TI - Screening properties of a metal surface at low frequencies and finite wave vectors. PMID- 10030887 TI - NMR study of the chemisorption bond of carbon monoxide on platinum. PMID- 10030888 TI - Classification of disorder and extrinsic order in polymers by resonant Raman scattering. PMID- 10030889 TI - Commensurability and defect-induced phason gaps in incommensurate systems. PMID- 10030890 TI - Initial stages of oxide formation on rhodium field emitters. PMID- 10030892 TI - Quantum gravity in two dimensions: Exact solution of the Jackiw model. PMID- 10030893 TI - Renormalized trajectory for O(3) Heisenberg model. PMID- 10030894 TI - Large-n limit of SU(n) quantum "spin" chains. PMID- 10030895 TI - Induced Chern-Simons terms at high temperatures and finite densities. PMID- 10030896 TI - Composite quarks and nonstandard bosons in p-barp collisions. PMID- 10030898 TI - Band termination at very high spin in 158Yb. PMID- 10030897 TI - Quasivibrational bands at high spins in 158Yb. PMID- 10030899 TI - Evidence for a nucleon-nucleus spin-spin interaction in 9Be. PMID- 10030900 TI - Particle propagation in quasiclassical models of relativistic heavy-ion collisions. PMID- 10030901 TI - Stopping atoms with laser light. PMID- 10030902 TI - Laser manipulation of atomic beam velocities: Demonstration of stopped atoms and velocity reversal. PMID- 10030903 TI - Laser-cooled-atomic frequency standard. PMID- 10030904 TI - Total capture and line-emission cross sections for C PMID- 10030905 TI - Observation of electric quadrupole decay in Xe45+ and Xe44+ PMID- 10030906 TI - Optical stark effect in the two-photon spectrum of NO. PMID- 10030907 TI - Precision measurement of transition energies and Lamb shifts in two-electron argon and potassium in solar-flare spectra. PMID- 10030908 TI - Production of squeezed states in the interaction between electromagnetic radiation and an electron gas. PMID- 10030909 TI - Possibility of direct observation of quantum jumps. PMID- 10030910 TI - Nonlinear stability of drift-tearing modes. PMID- 10030911 TI - Light-scattering study of the nematic twist constant near the smectic-A transition. PMID- 10030912 TI - Simultaneous magnetic-deformation and light-scattering study of bend and twist elastic-constant divergence at the nematic-smectic-A phase transition. PMID- 10030913 TI - Concentration profile of a dissolved polymer near the air-liquid interface: X-ray fluorescence study. PMID- 10030914 TI - Diffusion-limited aggregation in two dimensions. PMID- 10030915 TI - Measurement of interionic potentials in solids using deep-inelastic neutron scattering. PMID- 10030916 TI - Stabilization of bcc Co via epitaxial growth on GaAs. PMID- 10030917 TI - New ordered structure for the H-saturated Si(100) surface: The (3 x 1) phase. PMID- 10030918 TI - Hard-sphere glass and the density-functional theory of aperiodic crystals. PMID- 10030919 TI - Scaling in spin-glasses. PMID- 10030920 TI - Final-state effects in the Eu LsubIII-edge spectrum of EuPdsub2Psub2. PMID- 10030921 TI - Effect of melting of the metallic component on the anomalous far-infrared absorption of superconducting Sn particle composites. PMID- 10030922 TI - Two classes of composite energy bands in solids. PMID- 10030923 TI - Peak mobility of silicon metal-oxide-semiconductor systems. PMID- 10030924 TI - New kinetic percolation model with diffusion-limited growth. PMID- 10030925 TI - Comment on " epsilon expansion for the conductivity of a random resistor network" PMID- 10030926 TI - Harris et al. respond. PMID- 10030927 TI - Comment on "Pyroelectric materials as electronic pulse detectors of ultraheavy nuclei" PMID- 10030928 TI - Energy-density correlation functions in the two-dimensional Ising model with a line defect. PMID- 10030929 TI - Scaling behavior of windows in dissipative dynamical systems. PMID- 10030930 TI - Simulation of electric breakdown and resulting variant of percolation fractals. PMID- 10030932 TI - One-dimensional iterative maps and intramolecular rate processes. PMID- 10030931 TI - Nonperturbative effects in quantum field theory on curved spaces. PMID- 10030933 TI - Possible tests and improvements for Monte Carlo renormalization-group studies. PMID- 10030934 TI - Chiral fermions from compactification of O(32) and and E(8) x E(8) string theories. PMID- 10030935 TI - Search for single photons from supersymmetric particle production. PMID- 10030937 TI - Quantization of asymmetric shapes in nuclei. PMID- 10030936 TI - phi-meson production as a probe of the quark-gluon plasma. PMID- 10030938 TI - Measurement of T20 for the reaction 1H(dpol, gamma ) 3He and D-state effects in 3He. PMID- 10030939 TI - Signature-dependenct proton alignments at high rotational frequency and the persistence of proton pairing correlations. PMID- 10030940 TI - Dispersion relation and the low-energy behavior of the heavy-ion optical potential. PMID- 10030941 TI - Mean-field calculations of fluctuations in nuclear collisions. PMID- 10030942 TI - Threshold excitation of short-lived atomic inner-shell hole states with synchrotron radiation. PMID- 10030943 TI - Photoionization yield spectra below the atomic ionization limit in xenon. PMID- 10030945 TI - Calculation of a P- andT-nonconserving weak interaction in Xe and Hg with many body perturbation theory. PMID- 10030944 TI - Anomalous effects in very small-angle electron-potassium differential scattering measurements. PMID- 10030946 TI - Effects of autoionization on the alignment of Cd+(4d95s2 >thinsp;2D5/2) in the range 680-710 A PMID- 10030947 TI - Thermalization of neutral-beam-injected ions by lower hybrid waves in Jupiter's magnetosphere. PMID- 10030948 TI - Absolute amplitude and growth time of electron plasma waves excited by two laser beams. PMID- 10030949 TI - Microwave generation from filamentation and vortex formation within magnetically confined electron beams. PMID- 10030951 TI - Periodic spinodal decomposition: Light scattering in the phase-separating and disordered regimes. PMID- 10030950 TI - Energy dependence of inelastic electron scattering cross section by surface vibrations: Experimental measurement and theoretical interpretation. PMID- 10030952 TI - Novel magnetic field dependence of the coupling of excitations between two fermion fluids. PMID- 10030953 TI - Non-Ohmic transport in the magnetic-field-induced charge-density-wave phase of graphite. PMID- 10030954 TI - Measurement of conduction-electron spin relaxation due to rare gases physisorbed on a lithium surface. PMID- 10030955 TI - Monte Carlo study of high-energy electrons in silicon dioxide. PMID- 10030956 TI - First-principles calculation of the electric field gradient of Li3N. PMID- 10030957 TI - Effect of inelastic processes on resonant tunneling in one dimension. PMID- 10030959 TI - Comment on "High-spin-state spectroscopy with the reaction 88Sr( rho pol, pi )89Zr" PMID- 10030958 TI - Relativistic cosmologies with closed, locally homogeneous spatial sections. PMID- 10030960 TI - Vigdor et al. respond. PMID- 10030962 TI - Lamotte responds. PMID- 10030961 TI - Comment on "High-resolution proton NMR in amorphous Si:H: Spectroscopic direct observation of molecular hydrogen and reinterpretation of the narrow line" PMID- 10030963 TI - Spin oscillations in polarized gases. PMID- 10030964 TI - Comment on "Measurement of thermodynamic parameters of graphite by pulsed-laser melting and ion channeling" PMID- 10030966 TI - Phase-space eikonal method for treating wave equations. PMID- 10030968 TI - Vector-meson mass generation by chiral anomalies. PMID- 10030967 TI - Is the rho meson a dynamical gauge boson of hidden local symmetry? PMID- 10030969 TI - Effective-action expansion in perturbation theory. PMID- 10030970 TI - Hunting for the intermediate-mass Higgs boson in a hadron collider. PMID- 10030971 TI - Multiple-scattering approach to pion double charge exchange at 50 MeV. PMID- 10030972 TI - Transverse response functions in deep inelastic electron scattering for 40Ca, 48Ca, and 56Fe. PMID- 10030974 TI - Coherent and incoherent echo spectroscopy with extended-time excitation. PMID- 10030973 TI - Observation of Lambda -hypernuclei in the reaction 12C( pi +,K+) 1 Lambda 2C. PMID- 10030975 TI - Observation of radiation-pressure trapping of particles by alternating light beams. PMID- 10030976 TI - Circular dichroism in photoelectron angular distributions from oriented linear molecules. PMID- 10030977 TI - Nonlinear global Alfven eigenmodes. PMID- 10030978 TI - Evidence for a novel chemisorption bond: Formate (HCO2) on Cu(100). PMID- 10030979 TI - Phonon anomalies in Nb3Sn. PMID- 10030981 TI - Frequency behavior of the second-sound damping in the smectic-A phase of octylcyanobiphenyl: Evidence for the divergence of viscosities. PMID- 10030982 TI - Molecular clustering in a two-dimensional metal-ammonia solution. PMID- 10030980 TI - Monte Carlo renormalization-group study of the dynamics of an unstable state. PMID- 10030983 TI - Model-independent structure determination of the InSb(111)2 x 2 surface with use of synchrotron x-ray diffraction. PMID- 10030985 TI - Binding of shallow donor impurities in quantum-well structures. PMID- 10030984 TI - Mobility modulation of the two-dimensional electron gas via controlled deformation of the electron wave function in selectively doped AlGaAs-GaAs heterojunctions. PMID- 10030986 TI - Excitations in incommensurate biphenyl: Proton spin-lattice relaxation. PMID- 10030987 TI - ESR spectra of Er3+ in SmB6 single crystals: Dynamic Jahn-Teller effect in a mixed-valence compound. PMID- 10030988 TI - Spins in Si:P close to the metal-insulator transition. PMID- 10030989 TI - Dynamic M-shell effects in the ultraviolet absorption spectrum of metallic potassium. PMID- 10030990 TI - Picosecond time-resolved photoemission study of the InP(110) surface. PMID- 10030992 TI - Defects in a nonlinear pseudo one-dimensional solid. PMID- 10030993 TI - 55Mn NMR study of the collective excitations in spin-glasses. PMID- 10030994 TI - Attractive interaction and pairing in fermion systems with strong on-site repulsion. PMID- 10030991 TI - Femtosecond dynamics of resonantly excited excitons in room-temperature GaAs quantum wells. PMID- 10030995 TI - Low-frequency relaxation in Ising spin-glasses. PMID- 10030996 TI - Fractal sandstone pores: Implications for conductivity and pore formation. PMID- 10030997 TI - Comment on "Effects of relative energy contributions in a two-interaction transition" PMID- 10030998 TI - Reiss responds. PMID- 10030999 TI - Identification of zero-sound attenuation satellites in 3He-B. PMID- 10031000 TI - AsGa-induced dichroism in GaAs. PMID- 10031001 TI - Meyer, Spaeth, and Scheffler respond. PMID- 10031003 TI - Hedega PMID- 10031002 TI - Comment on "Theory for the anomalous M4,5VV Auger spectrum for dilute palladium in silver" PMID- 10031006 TI - Fractional statistics of the vortex in two-dimensional superfluids. PMID- 10031007 TI - Statistical properties of the spectrum of the two-level system. PMID- 10031008 TI - Classical diffusion on Eden trees. PMID- 10031010 TI - Conformal invariance and the Yang-Lee edge singularity in two dimensions. PMID- 10031009 TI - Energy-level statistics of integrable quantum systems. PMID- 10031011 TI - Meson theory of the dirac impulse approximation. PMID- 10031012 TI - Measurement of in-band transition probabilities at high spin. PMID- 10031013 TI - Consistent-Q formalism in odd-A nuclei. PMID- 10031014 TI - Convection patterns: Time evolution of the wave-vector field. PMID- 10031015 TI - Time dependence of flow patterns near the convective threshold in a cylindrical container. PMID- 10031016 TI - Diagnosis of strong beam-plasma turbulence conditions from electromagnetic emission. PMID- 10031017 TI - Mode-beating model of ac helicity injection. PMID- 10031018 TI - Electron acceleration in high-frequency longitudinal waves, Doppler-shifted ponderomotive forces, and Landau damping. PMID- 10031019 TI - Coexistence of different short-range-ordered spin fluctuations in Ce1-x(La,Y)xSb. PMID- 10031020 TI - Computer generation of structural models of amorphous Si and Ge. PMID- 10031021 TI - Dynamic scaling in the kinetics of clustering. PMID- 10031022 TI - Pressure changes and magnetostriction in finite magnetic fields in 3He and other normal fermi liquids. PMID- 10031023 TI - Relation between shear instability and liquid structure in alkali halides. PMID- 10031024 TI - Nonlinear transmission of zero sound in superfluid 3He-A: A saturation of the pair-breaking attenuation mechanism. PMID- 10031025 TI - Continuum percolation of rods. PMID- 10031026 TI - Limits of the fractal dimension for irreversible kinetic aggregation of gold colloids. PMID- 10031027 TI - Kinetics of formation and mean shape of branched polymers. PMID- 10031028 TI - Scaling of the excess energy in thermodynamically unstable solutions. PMID- 10031029 TI - Observation of structure-induced surface vibrational resonances on metal surfaces. PMID- 10031030 TI - Chemical-potential measurements and phase diagram of a pseudoternary solid: LixCuyMo6S8. PMID- 10031031 TI - Giant magnetic interaction (Condon domains) in two dimensions. PMID- 10031033 TI - Observation of f-band hybridization gap in the anomalous rare-earth compound YbAl3. PMID- 10031032 TI - Unusual metastable-quenching spectrum of K/Ni(111) and its explanation by a new quenching mechanism. PMID- 10031034 TI - Direct probing of the spatial distribution of the maximum Josephson current in a superconducting tunnel junction. PMID- 10031036 TI - Classical diffusion of particles in a random potential. PMID- 10031035 TI - Can gamma quanta really be captured by pulsar magnetic fields? PMID- 10031037 TI - Heinrichs responds. PMID- 10031038 TI - Comment on "Quantum effects on four-dimensional space-time symmetries" PMID- 10031039 TI - Comment on "Statistical scission model of fission-fragment angular distributions" PMID- 10031040 TI - Rossner, Huizenga, and Schroder respond: PMID- 10031041 TI - Comment on "Solitons in superfluid 3He-A: Bound states on domain walls" PMID- 10031042 TI - Ho et al. respond. PMID- 10031044 TI - Benguigui responds. PMID- 10031043 TI - Comment on "Experimental study of the elastic properties of a percolating system. PMID- 10031045 TI - Response to parametric modulation near an instability. PMID- 10031047 TI - Search for fractional charges in niobium and tungsten. PMID- 10031046 TI - Planar theory made variational. PMID- 10031048 TI - Simulations and speculations on gauge theories with many fermions. PMID- 10031049 TI - Massive gross-neveu model: A rigorous perturbative construction. PMID- 10031050 TI - Double analog transition 14C( pi +, pi -) 14O at 50 MeV. PMID- 10031051 TI - Deformation of heated nuclei observed in the statistical decay of the giant dipole resonance. PMID- 10031052 TI - Atomic inner-shell excitation induced by coherent motion of outer-shell electrons. PMID- 10031053 TI - Correspondence between electron binding energy and chemisorption reactivity of iron clusters. PMID- 10031055 TI - Three-dimensional reconnection between two colliding magnetized plasmas. PMID- 10031054 TI - Development of viscous fingering patterns. PMID- 10031056 TI - Long-wavelength oscillations in an inhomogeneous one-component plasma. PMID- 10031057 TI - Dynamical transition in a dense fluid approaching structural arrest. PMID- 10031058 TI - Origins of thixotropy. PMID- 10031059 TI - Phenomenological theory of icosahedral incommensurate ("quasiperiodic") order in Mn-Al alloys. PMID- 10031060 TI - Elasticity and dislocations in pentagonal and icosahedral quasicrystals. PMID- 10031061 TI - Mean-field theory of quasicrystalline order. PMID- 10031062 TI - Third sound in 4He adsorbed on Nuclepore. PMID- 10031063 TI - Observation of microwave transition from an on-center to off-center ionic configuration. PMID- 10031064 TI - Evidence of a square two-dimensional solid of methane physisorbed on the (100) surface of magnesium oxide. PMID- 10031065 TI - Phase diagram of selenium adsorbed on the Ni(100) surface: A physical realization of the Ashkin-Teller model. PMID- 10031066 TI - Atom location by axial-electron-channeling analysis. PMID- 10031067 TI - Chemisorption of H on magnetic Ni(001). PMID- 10031068 TI - Adsorption site, adsorption energy and normal vibration frequency of H on Ni(100) via total-energy calculations. PMID- 10031070 TI - Localization of the surface plasmon polariton caused by random roughness and its role in surface-enhanced optical phenomena. PMID- 10031069 TI - Observation of surface-enhanced magnetic order and magnetic surface reconstruction on Gd(0001). PMID- 10031071 TI - Optical-phonon emission in ballistic transport through microchannels of InGaAs. PMID- 10031072 TI - Existence of a Lifshitz point in incommensurate RbH3(SeO3)2. PMID- 10031073 TI - Hot-electron spectroscopy of GaAs. PMID- 10031074 TI - Long-range quasielastic scattering of low-energy electrons by conduction-band surface plasmons on Si(111)7 x 7. PMID- 10031075 TI - Origin of the peaked structure in the conductance of one-dimensional silicon accumulation layers. PMID- 10031076 TI - Theory of spin-polarized photoemission from nonmagnetic metals: Platinum. PMID- 10031077 TI - Weakly localized behavior in quasi-one-dimensional Li films. PMID- 10031078 TI - Some rigorous results for the Anderson model. PMID- 10031079 TI - N-color Ashkin-Teller model in the large-N limit. PMID- 10031080 TI - Comment on "Einstein equations in vacuum as integrability conditions" PMID- 10031081 TI - Chinea responds. PMID- 10031082 TI - Comment on "Statistical scission model of fission-fragment angular distributions" PMID- 10031083 TI - Rossner, Huizenga, and Schroder respond: PMID- 10031084 TI - Repeated contractive-state position measurements and the standard quantum limit. PMID- 10031085 TI - Levinson's theorem and the nodes of zero-energy wave functions for potentials with repulsive Coulomb tails. PMID- 10031087 TI - Dissipative quantum tunneling in a biased double-well system at finite temperatures. PMID- 10031086 TI - Quantum tunneling rates for asymmetric double-well systems with Ohmic dissipation. PMID- 10031088 TI - Intermittent chaos and low-frequency noise in the driven damped pendulum. PMID- 10031089 TI - Transition from regular to irregular spectra in quantum billiards. PMID- 10031091 TI - Measurement of tau lifetime and branching ratios. PMID- 10031092 TI - Measurement of the CP-nonconservation parameter epsilon '/ epsilon. PMID- 10031090 TI - Electroweak effects in e+e---> tau + tau - at 29 GeV. PMID- 10031093 TI - Measurement of epsilon '/ epsilon in the neutral Kaon system. PMID- 10031094 TI - High-spin evolution of quasicontinuum gamma radiation in 156Er. PMID- 10031095 TI - Deuteron photodisintegration differential cross section between 100 and 220 MeV. PMID- 10031097 TI - Higher-order correlations in spectra of complex systems. PMID- 10031096 TI - Transverse form factors for 13C(e,e) 13C g.s. and 13C(e,e') 13C(15.11 MeV). PMID- 10031098 TI - Electron-pair creation on the uranium nucleus. PMID- 10031099 TI - Charged particle exclusive analysis of relativistic U PMID- 10031101 TI - Laser scattering from dense cesium plasmas. PMID- 10031100 TI - Absorption physics at 351 nm in spherical geometry. PMID- 10031102 TI - Statistical theory of cubic langmuir turbulence. PMID- 10031103 TI - Decay time and instability measurements of plasmas generated by intense relativistic electron beams. PMID- 10031105 TI - Cooperative transport effects in electron-irradiated glasses. PMID- 10031104 TI - Observations of toroidal coupling for low-n Alfven modes in the TCA tokamak. PMID- 10031106 TI - New molecular-dynamics method for metallic systems. PMID- 10031108 TI - First observation of the undulation mode in birefringent microemulsions by quasielastic light scattering. PMID- 10031107 TI - Diffusivity of hydrogen in tantalum between 15 and 30 K. PMID- 10031109 TI - Effects of thermal fluctuations on systems with small surface tension. PMID- 10031110 TI - X-ray scattering study of the smectic-A1 to smectic-A2 transition. PMID- 10031111 TI - Two-dimensional electron-positron momentum measurement at a copper single-crystal surface. PMID- 10031112 TI - Positron on positroniumlike surface state on Al(100)? PMID- 10031113 TI - Observation of bulk and edge magnetoplasmons in a two-dimensional electron fluid. PMID- 10031115 TI - Evidence for an incommensurate high-field phase in the spin-Peierls system tetrathiafulvalene-AuS4C4(CF3) 4. PMID- 10031114 TI - Dynamical Hall effect in a two-dimensional classical plasma. PMID- 10031116 TI - Flicker (1/f) noise in percolation networks: A new hierarchy of exponents. PMID- 10031117 TI - Molecular diffusion in a microemulsion. PMID- 10031118 TI - Spatial self organization of surface structure during an oscillating catalytic reaction. PMID- 10031119 TI - Saturation of continuum-continuum transitions in multiphoton absorption. PMID- 10031121 TI - Comment on "Dislocation-loop theory of the nematic-smectic A-smectic C multicritical point" PMID- 10031120 TI - Comment on "Quasicrystals: A new class of ordered structures" PMID- 10031122 TI - Grinstein and Toner respond. PMID- 10031123 TI - Fractals with local bridges. PMID- 10031124 TI - Comment on "Fractons and the fractal structure of proteins" PMID- 10031125 TI - Helman et al. respond. PMID- 10031127 TI - Destruction of invariant tori as an eigenvalue problem. PMID- 10031128 TI - Symplectically invariant WKB wave functions. PMID- 10031129 TI - Resonance widths and positions by an algebraic approach. PMID- 10031131 TI - Soft hard scattering in the teraelectronvolt range. PMID- 10031130 TI - Measurement of the strong-coupling constant alpha s to second order for 22 <= sqrt s <= 46.78 GeV. PMID- 10031132 TI - Number of neutrinos in the standard model and its extensions to supersymmetry. PMID- 10031133 TI - Anomalous positron peaks from supercritical collision systems. PMID- 10031135 TI - K0 (K-bar 0)-->2 gamma decays: Phenomenology and CP nonconservation. PMID- 10031134 TI - SU(2) beta function with and without dynamical fermions. PMID- 10031136 TI - Microcanonical determination of effective-spin models for finite-temperature QCD. PMID- 10031138 TI - Nucleus-nucleus potential inside the strong-absorption radius from 16O PMID- 10031139 TI - alpha decay of neutron-deficient odd-Bi nuclei: Shell-model intruder states in Tl and Bi isotopes. PMID- 10031137 TI - Observation of tau -lepton decay to five charged particles. PMID- 10031140 TI - Experimental determination of the ground-state inversion splitting in H3O+ PMID- 10031141 TI - Polarization correlation of the two photons emitted by metastable atomic deuterium: A test of Bell's inequality. PMID- 10031142 TI - 3P1-orientation velocity-changing collision kernels studied by isolated multipole echoes. PMID- 10031143 TI - Observation of bistable reflectivity of phase conjugated signal through intracavity nearly degenerate four-wave mixing. PMID- 10031144 TI - Squeezing pattern in resonance fluorescence from a regular N-atom system. PMID- 10031145 TI - Frustrated optical instability: Self-induced periodic and chaotic spatial distribution of polarization in nonlinear optical media. PMID- 10031147 TI - Nonuniversal nu from a van der Waals theory of the wetting transition. PMID- 10031146 TI - Parametric self-enhancement of the spontaneous decay of sound in superfluid helium. PMID- 10031148 TI - New type of cholesteric liquid crystal. PMID- 10031149 TI - Specific heat of two-dimensional electrons in GaAs-GaAlAs multilayers. PMID- 10031150 TI - Effect of criticality on wetting layers. PMID- 10031151 TI - Theory of ballistic aggregation. PMID- 10031153 TI - Donor states in hydrogenated amorphous silicon and germanium. PMID- 10031152 TI - Symmetry criterion for the lack of a stable fixed point in the renormalization group recursion relations. PMID- 10031154 TI - Specular boundary scattering and electrical transport in single-crystal thin films of CoSi2. PMID- 10031155 TI - Method for direct determination of the effective correlation energy of defects in semiconductors: Optical modulation spectroscopy of dangling bonds. PMID- 10031156 TI - Evidence for resonant tunneling of electrons via sodium ions in silicon dioxide. PMID- 10031157 TI - Theory of magnetic and structural ordering in iron. PMID- 10031158 TI - New look at the mechanism for alkali-metal promotion. PMID- 10031160 TI - Density of low-energy vibrational states in a protein solution. PMID- 10031159 TI - Electron localization in alkali-halide clusters. PMID- 10031161 TI - Evolution of cosmic strings. PMID- 10031162 TI - Simulations of high-Mach-number collisionless perpendicular shocks in astrophysical plasmas. PMID- 10031165 TI - Statistical behavior in deterministic quantum systems with few degrees of freedom. PMID- 10031163 TI - Evidence for a high-energy cosmic-ray spectrum cutoff. PMID- 10031166 TI - New approach to the statistical properties of energy levels. PMID- 10031168 TI - Evidence of heavy-neutrino emission in beta decay. PMID- 10031167 TI - Search for right-handed currents by means of muon-spin rotation. PMID- 10031169 TI - Inclusive decay of B mesons into charged D. PMID- 10031171 TI - Nuclear effect from quark clustering and constituent-quark Fermi motion and mass. PMID- 10031170 TI - Reaction Mo+Mo between 12 and 18.8 MeV/u: Approaching the limits of the deep inelastic process. PMID- 10031173 TI - Multiple ionization of a Hartree atom by intense laser pulses. PMID- 10031172 TI - Theoretical proof that most nuclei must have positive electric quadrupole moments. PMID- 10031174 TI - Continuous-wave two-photon spectroscopy of the 1S-2S transition in hydrogen. PMID- 10031175 TI - Experimental evidence for subradiance. PMID- 10031176 TI - Spin-rotation interaction of noble-gas alkali-metal atom pairs. PMID- 10031177 TI - Optical guiding in a free-electron laser. PMID- 10031179 TI - Adsorbate-induced soft-phonon reconstruction of the Ni(100) surface. PMID- 10031178 TI - Pressure dissociation of solid nitrogen under 1 Mbar. PMID- 10031180 TI - Landau theory of surface segregation and phase transitions in binary alloys with fcc crystal structure. PMID- 10031181 TI - Beyond the rigid-ion approximation with spherically symmetric ions. PMID- 10031182 TI - Pattern formation resulting from faceted growth in zone-melted thin films. PMID- 10031183 TI - Concentration profile of polymer solutions near a solid wall. PMID- 10031184 TI - Production of enhanced liquid 3He magnetization by dynamic nuclear polarization. PMID- 10031185 TI - Anisotropies in the above-bandgap optical spectra of cubic semiconductors. PMID- 10031186 TI - Observation of a C-1s core exciton in diamond. PMID- 10031187 TI - Comment on "Role of electronic processes in epitaxial re- crystallization of amorphous semiconductors" PMID- 10031190 TI - Relation between the chiral anomaly and the quantized Hall effect. PMID- 10031189 TI - Neutron microscope. PMID- 10031191 TI - Direct measurement of charmed D+ and D0 semileptonic branching ratios. PMID- 10031193 TI - Implications of a systematic study of the CERN monojets for supersymmetry. PMID- 10031192 TI - Hierarchal mass scales in lattice gauge theories with dynamical, light fermions. PMID- 10031194 TI - Baryon mass inequalities in quark models. PMID- 10031195 TI - Possible unified interpretation of heavy nuclei. PMID- 10031196 TI - Mass-asymmetric barriers from excitation functions for complex-fragment emission. PMID- 10031197 TI - Multiple inner-shell vacancies in laser-irradiated Au plasma. PMID- 10031198 TI - Far-wing absorption profiles of a reactive collision: Mg+H PMID- 10031199 TI - Application of the Schwinger principle to direct excitation of atoms or ions by impact of bare nuclei at intermediate velocities. PMID- 10031200 TI - Measurement of time delays in the parametric production of photon pairs. PMID- 10031201 TI - Limits to concentration by passive means. PMID- 10031203 TI - Stimulated mode conversion at lower-hybrid frequencies. PMID- 10031202 TI - Parametric interaction of modulated intense relativistic electron beams with high voltage gaps. PMID- 10031205 TI - Critical Ising spin dynamics on percolation clusters. PMID- 10031204 TI - Excess noise for driven diffusive systems. PMID- 10031206 TI - Experiments on quantum and thermal desorption from 4He films. PMID- 10031208 TI - Continuous and first-order wetting transitions of hcp 4He crystals. PMID- 10031207 TI - Diffuse ferroelectric phase transition and long-range order of dilute KTa1 xNbxO3. PMID- 10031209 TI - Energy-loss rates for hot electrons and holes in GaAs quantum wells. PMID- 10031210 TI - Resistance of small metallic loops. PMID- 10031211 TI - Comment on "Active zone of growing clusters: Diffusion-limited aggregation and the Eden model" PMID- 10031212 TI - Plischke and Racz respond. PMID- 10031213 TI - Surface thickness in the Eden model. PMID- 10031214 TI - Plischke and Racz respond. PMID- 10031215 TI - Stochastic ionization of electrically polarized, hydrogen Rydberg atoms. PMID- 10031216 TI - Comment on "Eden model in many dimensions" PMID- 10031217 TI - Comment on Angelidis's universality claim. PMID- 10031219 TI - Classical hard-sphere fluid in infinitely many dimensions. PMID- 10031220 TI - Hydrogen in metallic alloys as an example of a lattice gas with random field and random bonds. PMID- 10031221 TI - Saddle-point variational method for the Dirac equation. PMID- 10031223 TI - Physical spectrum of compactified strings. PMID- 10031222 TI - Lambda production in e+e- annihilation at 29 GeV. PMID- 10031224 TI - Evidence for muon production by particles from Cygnus X-3. PMID- 10031225 TI - Experimental consequences of a horizontal gauge model for CP nonconservation. PMID- 10031226 TI - Muonic atoms with vacant electron shells. PMID- 10031227 TI - Spectral-spatial diffusion of resonantly trapped phonons. PMID- 10031228 TI - Photoemission from ordered physisorbed adsorbate phases: N2 on graphite and CO on Ag(111). PMID- 10031230 TI - Reversible amorphization in laser-quenched titanium alloys. PMID- 10031229 TI - Possibility of a field-induced hexagonal blue phase in cholesteric liquid crystals. PMID- 10031232 TI - Resonance Raman scattering by confined LO and TO phonons in GaAs-AlAs superlattices. PMID- 10031231 TI - Elastic properties of glasses. PMID- 10031233 TI - Interface vibrational modes in GaAs-AlAs superlattices. PMID- 10031235 TI - Adsorption phenomena at the surface of silica spheres in a binary liquid mixture. PMID- 10031234 TI - Vibrational phase relaxation at surfaces: CO on Ni(111). PMID- 10031236 TI - Classification of axisymmetric vortices in 3He-A. PMID- 10031237 TI - Critical behavior of the isotropic ferromagnetic quantum Heisenberg chain. PMID- 10031238 TI - Nuclear magnetic resonance on oriented 111In in a hcp Gd single crystal. PMID- 10031239 TI - Correlation of Schottky-barrier height and microstructure in the epitaxial Ni silicide on Si(111). PMID- 10031240 TI - Investigation of the magnitude and range of the Ruderman-Kittel interaction in SmRh4B4 and ErRh4B4. PMID- 10031241 TI - Temporal phase transition in the three-dimensional random-field Ising model. PMID- 10031242 TI - Sub-picosecond time-resolved Raman spectroscopy of LO phonons in GaAs. PMID- 10031243 TI - Diverging characteristic lengths at critical disorder in thin-film superconductors. PMID- 10031244 TI - Rate expression incorporating interaction between reactants: Application to the zero-order desorption spectra. PMID- 10031245 TI - Simple realization of the inflationary expansion of the universe. PMID- 10031246 TI - Comment on "Induced Chern-Simons terms at high temperatures and finite densities" PMID- 10031247 TI - Comment on "Ion-dynamics effects on hydrogenic Stark profiles in hot and dense plasmas" PMID- 10031248 TI - Stamm et al. Respond. PMID- 10031249 TI - Comment on "Substrate-induced orientational order in the isotropic phase of liquid crystals" PMID- 10031251 TI - Where is the continuum in lattice quantum chromodynamics? PMID- 10031252 TI - Massless Lattice phi44 theory: A nonperturbative control of a renormalizable model. PMID- 10031254 TI - Submillisecond on-line mass separation of nonvolatile radioactive elements: An application of charge exchange and thermalization processes of primary recoil ions in helium. PMID- 10031255 TI - Formation of A=12 Sigma - hypernucleus from K- absorption at rest; Observation of a Sigma - spin-orbit doublet of narrow widths. PMID- 10031253 TI - Direct photon production in e+e- annihilation. PMID- 10031256 TI - Exploding foil technique for achieving a soft x-ray laser. PMID- 10031257 TI - Demonstration of a soft x-ray amplifier. PMID- 10031258 TI - Surface roughness of water measured by x-ray refelctivity. PMID- 10031259 TI - Hydrodynamic theory of the glass transition. PMID- 10031260 TI - Local atomic structure of a clean surface by surface-extended x-ray absorption fine structure: Amorphized Si. PMID- 10031262 TI - Magnetic susceptibility of 3He adsorbed on sintered silver powder. PMID- 10031261 TI - Energy transfer at surfaces: Asymmetric line shapes and the electron-hole-pair mechanism. PMID- 10031264 TI - Analog of small Holstein polaron in hydrogen-bonded amide systems. PMID- 10031263 TI - Observation of surface melting. PMID- 10031265 TI - Conduction-band and surface-state critical points in SI: An inverse-photoemission study. PMID- 10031266 TI - Hopping exponential band tails. PMID- 10031267 TI - Evidence for multiple mechanisms contributing to the transition temperature in metallic spin-glasses. PMID- 10031268 TI - Nonperturbative critical behavior of random-fields systems. PMID- 10031271 TI - Statistical mechanical origin of the entropy of a rotating, charged black hole. PMID- 10031269 TI - Effect of quantum fluctuations on I-V curves of overdamped Josephson junctions. PMID- 10031272 TI - Model for maximal CP nonconservation. PMID- 10031274 TI - Supersymmetric quantum mechanics and large-N expansions. PMID- 10031273 TI - Measurement of p-barp and pp elastic scattering in the dip region at sqrt s =53 GeV. PMID- 10031275 TI - Variational calculation of the bound-state wave function in : lambda ( phi6- phi4)2: PMID- 10031276 TI - Exact renormalization for the Gross-Neveu model of quantum fields. PMID- 10031278 TI - Experimental consequences of family unification. PMID- 10031277 TI - Observation of three P states in the radiative decay of Upsilon (2S). PMID- 10031279 TI - KL-KS mass difference and supersymmetric left-right-symmetric theories. PMID- 10031280 TI - Relativistic impulse approximation, nuclear currents, and the spin-difference function. PMID- 10031282 TI - Subthreshold pion production: An intranuclear N-N collision interpretation. PMID- 10031281 TI - High angular momentum components in the subbarrier fusion of heavy ions. PMID- 10031283 TI - Electron correlation and binding effects in measured electron-scattering cross sections of CO2. PMID- 10031284 TI - Bifurcation in degenerate four-wave mixing in liquid suspensions of microspheres. PMID- 10031285 TI - Invasion percolation in an etched network: Measurement of a fractal dimension. PMID- 10031286 TI - Self-generated loss of coherency in Brillouin scattering and reduction of reflectivity. PMID- 10031287 TI - New evidence concerning the Griffiths first sum rule for tricritical light scattering. PMID- 10031288 TI - Experiments on magnetically driven superflow in 3He-A1. PMID- 10031289 TI - Localization of third sound by a disordered substrate. PMID- 10031290 TI - Photofragmentation of Mass-Resolved Si2-12+ clusters. PMID- 10031291 TI - Structure determination of the formate intermediate on Cu(110) by use of x-ray absorption fine-structure measurements. PMID- 10031292 TI - Onset of droplet aggregation from self-diffusion measurements in microemulsions. PMID- 10031293 TI - 3He-A textures and ultrasonic attenuation. PMID- 10031294 TI - Frozen-phonon total-energy determination of structural surface phase transitions: W(001). PMID- 10031295 TI - Calculation of neutrino flux from Cygnus X-3. PMID- 10031296 TI - Microwave background anisotropy and decaying-particle models for a flat universe. PMID- 10031297 TI - Comment on "Study of scaling in hadronic production of dimuons" PMID- 10031298 TI - Delocalization transition of a classical two-dimensional Coulomb lattice. PMID- 10031299 TI - Puzzling aspect of quantum field theory in curved space time. PMID- 10031300 TI - Monojets from family unification. PMID- 10031302 TI - Is perturbation theory the asymptotic expansion in lattice gauge theories? PMID- 10031303 TI - Outward effective mass of quark and baryon magnetic moments. PMID- 10031301 TI - Search for monojet production in e+e- annihilation. PMID- 10031305 TI - Two 17-keV Majorana neutrinos? PMID- 10031304 TI - Test of neutrino oscillations using atmospheric neutrinos. PMID- 10031306 TI - Majorans revisited. PMID- 10031307 TI - Ultralow-background study of neutrinoless double beta decay of 76Ge; new limit on the Majorana mass of nu e. PMID- 10031309 TI - Investigation of K-shell electron capture in 158Tb. PMID- 10031308 TI - Bound on time-reversal noninvariance in the nuclear Hamiltonian. PMID- 10031310 TI - Isospin dependence of s-wave pion absorption in the A=3 nuclei. PMID- 10031311 TI - Solar neutrino detection: Experimental determination of Gamow-Teller strengths via the 98Mo and 115In (p,n) reactions. PMID- 10031312 TI - Spontaneous emission from an excited atom in the presence of N atoms and M modes. PMID- 10031313 TI - Magnetohydrodynamical equilibrium and the shear Alfven continuum in nonaxisymmetric toroidal geometry. PMID- 10031314 TI - Cyclotron resonance in a noneutral plasma. PMID- 10031315 TI - Ion-Bernstein-wave heating in the JIPPT-II-U tokamak plasma. PMID- 10031316 TI - Relativistic plasma-wave excitation by collinear optical mixing. PMID- 10031317 TI - Thermal transport in very dilute mixtures of 3He in 4He near the superfluid transition. PMID- 10031318 TI - Nonuniversal jumps and the Kosterlitz-Thouless transition. PMID- 10031319 TI - Incident-angle dependence of catastrophic dechanneling for strained-layer superlattices. PMID- 10031320 TI - Orientational order in liquids: A possible scenario of freezing. PMID- 10031321 TI - Direct photoemission study of the antibonding surface-state band on Ge(111)2 x 1. PMID- 10031322 TI - Nonlocality in the two-dimensional plasmon dispersion. PMID- 10031323 TI - Compound formation at Cu-In thin-film interfaces detected by perturbed gamma - gamma angular correlations. PMID- 10031325 TI - Comment on "Three-cocycle in mathematics and physics" PMID- 10031324 TI - Superconductivity in high-pressure metallic phases of Si. PMID- 10031328 TI - Absence of the Kosterlitz-Thouless fixed points in the Migdal-Kadanoff recursion formulas. PMID- 10031326 TI - Jackiw responds. PMID- 10031329 TI - Limits for spatial anisotropy by use of nuclear-spin-polarized 9Be+ ions. PMID- 10031330 TI - Differences between lattice and continuum percolation transport exponents. PMID- 10031331 TI - Violation of causality in relativistic quantum theory? PMID- 10031332 TI - Measurement of the electron asymmetry in the beta decay of polarized Sigma - hyperons. PMID- 10031334 TI - Bifurcation and dynamical symmetry breaking in a renormalization-group-improved field theory. PMID- 10031333 TI - Gauge-invariant analysis of spontaneous symmetry breaking of an SU(5) adjoint scalar model. PMID- 10031335 TI - Vorton method in three-dimensional hydrodynamics. PMID- 10031336 TI - Measurement and instability analysis of three-dimensional anisotropic electron distribution functions. PMID- 10031337 TI - Tunneling of dislocation kinks and the effect of dissipation. PMID- 10031339 TI - Frequency-dependent noise in avalanche processes. PMID- 10031338 TI - Structure of rapidly quenched Al-Mn. PMID- 10031340 TI - Quasicritical behavior and first-order transition in the d=3 random-field Ising model. PMID- 10031341 TI - Spatial variations in the superconductivity of Nb3Sn measured by low-temperature tunneling microscopy. PMID- 10031342 TI - Plasmons in layered films. PMID- 10031343 TI - Strain-induced two-dimensional electron gas in selectively doped Si/SixGe1-x superlattices. PMID- 10031345 TI - Superconducting proximity effect in the native inversion layer on InAs. PMID- 10031344 TI - Upper critical field in p-wave superconductors with broken symmetry. PMID- 10031346 TI - Origin of broadband noise in charge-density-wave conductors. PMID- 10031347 TI - Can the universe be charged? PMID- 10031348 TI - Universality among scalar spin systems. PMID- 10031349 TI - Barma and Fisher respond. PMID- 10031350 TI - Defense of the standard quantum limit for free-mass position. PMID- 10031351 TI - New diffraction experiment on the electrostatic Aharonov-Bohm effect. PMID- 10031352 TI - Noise without noise: A new Monte Carlo method. PMID- 10031353 TI - Search for monojet production in e+e- annihilation. PMID- 10031354 TI - High-order strong-coupling calculation of the ground-state energy density in supersymmetric field theory. PMID- 10031355 TI - Superstrings at high temperature. PMID- 10031356 TI - Measurement of the branching fraction for tau --->5 pi +/-( pi 0) nu tau and an upper limit on the nu tau mass. PMID- 10031357 TI - Is supersymmetric origin of monojets viable? PMID- 10031359 TI - Square versus roll pattern at convective threshold. PMID- 10031360 TI - Velocity-vorticity patterns in turbulent flow. PMID- 10031358 TI - Neutral-pion photoproduction on the deuteron. PMID- 10031361 TI - Increased hot-electron production at quarter-critical density in long-scale length laser-plasma interactions. PMID- 10031362 TI - Mechanical properties of oxygen multilayers on graphite. PMID- 10031363 TI - Energetics of silicide interface formation. PMID- 10031365 TI - Identification of chalcogen point-defect sites in silicon by total-energy calculations. PMID- 10031364 TI - Stage transformation and staging disorder in graphite intercalation compounds. PMID- 10031366 TI - Electrical-conductivity fluctuations near the percolation threshold. PMID- 10031367 TI - Helium scattering from a krypton film on graphite. PMID- 10031368 TI - Two energy scales in CePd3. PMID- 10031369 TI - Observation of magnetic-field-induced superconductivity in a heavy-fermion antiferromagnet: CePb3. PMID- 10031370 TI - Energy transport and size effects in the photoluminescence of amorphous germanium/amorphous-silicon multilayer structures. PMID- 10031371 TI - Comment on "Predicted modifications in the direct and indirect gaps of tetrahedral semiconductors" PMID- 10031372 TI - Rompa and Schuurmans respond. PMID- 10031373 TI - Comment on "Accelerated diffusion in Josephson junctions and related chaotic systems" PMID- 10031375 TI - Measuring the dimension of space time. PMID- 10031376 TI - Phase structure of systems of self-avoiding surfaces. PMID- 10031377 TI - Change of scale for nucleons in nuclei from quasielastic electron scattering. PMID- 10031378 TI - Exclusive production of K+K- pi + pi - in photon-photon collisions. PMID- 10031379 TI - Production of phi and F(1970)--> phi pi in e+e- annihilation at 29 GeV. PMID- 10031381 TI - Energy-momentum sum rule and the anomalous behavior of the structure functions of nuclear targets. PMID- 10031380 TI - Continuum dimuon production in p-bar-W collisions at 125 GeV/c. PMID- 10031382 TI - Charged multiplicity of hadronic events containing heavy-quark jets. PMID- 10031385 TI - E2 effective charges of g9/2 nucleons derived from quadrupole moments of high spin isomers in 88,90,91Zr and 90,92,94Mo. PMID- 10031383 TI - Structural changes in 156Er at high spins. PMID- 10031384 TI - Collective accelerator for electrons. PMID- 10031387 TI - Observation of a laser-assisted ionization of the He(2(1)S,2(3)S)+He PMID- 10031386 TI - First observation of magnetically trapped neutral atoms. PMID- 10031388 TI - Hugoniot measurements for laser-generated shock waves in aluminum. PMID- 10031390 TI - Early stage of phase-separation processes in FeCr and AlZn alloys. PMID- 10031389 TI - Plasma distribution function in a superthermal radiation field. PMID- 10031391 TI - High-resolution scanning-ion-microprobe study of graphite and its intercalation compounds. PMID- 10031392 TI - Observation of a soliton reconstruction of Au(111) by high-resolution helium-atom diffraction. PMID- 10031394 TI - First-principles total-energy calculation for a single adatom on a crystal. PMID- 10031395 TI - Nonlinear current fluctuations in a metallic resistor at low temperatures. PMID- 10031393 TI - Observation of resonant impurity states in semiconductor quantum-well structures. PMID- 10031396 TI - Spectroscopic evidence for the 5f Coulomb interaction in UAl2 and UPt3. PMID- 10031397 TI - Site symmetry and ground-state characteristics for the oxygen donor in silicon. PMID- 10031398 TI - Is Bekenstein's conjecture true for charged black holes? PMID- 10031401 TI - Dynamics-independent null experiment for testing time-reversal invariance. PMID- 10031399 TI - Comment on fractal aggregates in sputter-deposited films. PMID- 10031402 TI - Lattice results on the meson electric form factor. PMID- 10031404 TI - Dinucleus: A doorway to heavy-ion fusion. PMID- 10031403 TI - pp vs p-barp: From intersecting storage rings to superconducting supercollider. PMID- 10031405 TI - Observation of low-energy Z oscillations in total electron-capture cross sections for bare projectiles colliding with H and H2. PMID- 10031406 TI - Measurement of the total energy radiated by 150-GeV electrons in a Ge crystal. PMID- 10031407 TI - Direct calculation of absolute free energy for lattice systems by Monte Carlo sampling of finite-size dependence. PMID- 10031408 TI - Specific-heat spectroscopy of the glass transition. PMID- 10031409 TI - Tunneling images of germanium surface reconstructions and phase boundaries. PMID- 10031410 TI - Observation of new short-wavelength collective excitations in heavy water by coherent inelastic neutron scattering. PMID- 10031412 TI - Quasiperiodic patterns. PMID- 10031411 TI - Au(110) (1 x 2)-to-(1 x 1) phase transition: A physical realization of the two dimensional Ising model. PMID- 10031413 TI - Magnetoresistance fluctuations in mesoscopic wires and rings. PMID- 10031414 TI - Observation of h/e Aharonov-Bohm oscillations in normal-metal rings. PMID- 10031415 TI - Prediction of strongly enhanced two-dimensional ferromagnetic moments on metallic overlayers, interfaces, and superlattices. PMID- 10031416 TI - Spin separation in a metal overlayer. PMID- 10031417 TI - Pinning and roughening of domain walls in Ising systems due to random impurities. PMID- 10031418 TI - Effects of dissipation and temperature on macroscopic quantum tunneling. PMID- 10031419 TI - Dissociative chemisorption of CH4 on W(110): Dramatic activation by initial kinetic energy. PMID- 10031420 TI - Improved astronomical limits on the neutrino mass. PMID- 10031421 TI - Quantum measurement problem and quantum fluids. PMID- 10031423 TI - Comment on "Experimental study of multiple scattering in x-ray absorption near edge structure" PMID- 10031422 TI - Leggett and Garg respond. PMID- 10031424 TI - Bunker and Stern respond. PMID- 10031426 TI - Williams, Kubler, and Terakura respond. PMID- 10031428 TI - Three-cocycle in mathematics and physics. PMID- 10031425 TI - Electronic structure of NiO. PMID- 10031429 TI - Strange attractor in the Ising model with competing interactions on the Cayley tree. PMID- 10031430 TI - Monte Carlo analysis of the SO(3) lattice gauge theory and the critical dimensionality of space-time. PMID- 10031431 TI - Parity nonconservation in elastic p alpha scattering and the determination of the weak meson-nucleon coupling constants. PMID- 10031432 TI - Nuclear alignment and magnetic moments of 133Xe, 133Xem, and 131Xem by spin exchange with optically pumped 87Rb. PMID- 10031433 TI - Interpretation of fission-fragment angular distributions in heavy-ion fusion reactions. PMID- 10031434 TI - Threshold double photoexcitation of argon with synchrotron radiation. PMID- 10031435 TI - Collision-induced Hanle resonances of kilohertz width in phase-conjugate four wave light mixing. PMID- 10031436 TI - Evidence for collisional damping in high-energy Raman-scattering experiments at 0.26 microm. PMID- 10031437 TI - Anomalous pressure dependence of the torsional levels in solid nitromethane. PMID- 10031438 TI - Micromechanism for metallic-glass formation by solid-state reactions. PMID- 10031439 TI - Long-range order in AlxGa1-xAs. PMID- 10031440 TI - Evidence for intrinsic angular momentum in superfluid 3He-A. PMID- 10031441 TI - New exact results for the Potts model. PMID- 10031442 TI - Direct observation of intraionic and interconfigurational excitations in an intermediate-valence compound by Raman spectroscopy. PMID- 10031443 TI - Photoinduced surface charge distribution on TiO2. PMID- 10031444 TI - Picosecond photoluminescence: A probe of band-tail thermalization in amorphous semiconductors. PMID- 10031445 TI - Prism-coupled light emission from tunnel junctions. PMID- 10031447 TI - Thermodynamic, transport, and excitation properties of Ce impurities in a model metal: Kondo resonance and universality in the mixed-valent regime. PMID- 10031446 TI - Neutron-scattering measurement of the spin-wave spectra for nickel. PMID- 10031448 TI - Nonexponential relaxation of conductance near semiconductor interfaces. PMID- 10031449 TI - Finite-size studies of the incompressible state of the fractionally quantized Hall effect and its excitations. PMID- 10031450 TI - Magnetic-field-induced localization transition in HgCdTe. PMID- 10031451 TI - Comment on "Nucleation of 3He-B from the A phase: A cosmic-ray effect?" PMID- 10031453 TI - Photocarrier dynamics in a-Si:H: Effects of bias illumination. PMID- 10031452 TI - Leggett responds. PMID- 10031455 TI - Zeldov and Weiser respond. PMID- 10031454 TI - Effect of bias illumination on photoinduced absorption decay in a-Si:H. PMID- 10031456 TI - Comment on "Optical bias control of dispersive relaxations in a-Si = H" PMID- 10031458 TI - Comment on "String-dominated universe" PMID- 10031457 TI - Pfost, Vardeny, and Tauc respond. PMID- 10031461 TI - Measurement of the relativistic Doppler shift in neon. PMID- 10031462 TI - Quantization of the Hall conductance for general, multiparticle Schrodinger Hamiltonians. PMID- 10031463 TI - Diffusion and localization of a particle in a periodic potential coupled to a dissipative environment. PMID- 10031464 TI - Indefinitely growing self-avoiding walk. PMID- 10031465 TI - Test of models for parton fragmentation by means of three-jet events in e+e- annihilation at sqrt s-bar=29 GeV. PMID- 10031467 TI - Supergravitational radiative corrections to the gauge hierarchy. PMID- 10031466 TI - Lambda production in e+e- annihilation at 29 GeV. PMID- 10031468 TI - Limit on lepton nonconservation and neutrino mass from double beta decay. PMID- 10031470 TI - Microscopic theory of pion production and sidewards flow in heavy-ion collisions. PMID- 10031469 TI - Precise 3H-3He mass difference for neutrino mass determination. PMID- 10031471 TI - High-resolution inelastic electron scattering and the isoscalar nature of the M1 transition to the J pi =1(+) state at Ex=5.846 MeV in 208Pb. PMID- 10031473 TI - Theoretical estimates of the rates of radioactive decay of radium isotopes by 14C emission. PMID- 10031472 TI - Discovery of radioactive decay of 222Ra and 224Ra by 14C emission. PMID- 10031474 TI - Final-state interactions between noncompound light particles for 16O-induced reactions on 197Au at E/A=25 MeV. PMID- 10031476 TI - Laser intensity for maximum yield in multiphoton ionization. PMID- 10031475 TI - Population of triaxial rotor levels in 182Os. PMID- 10031477 TI - Diffusionlike aspects of multiphoton absorption in electrically polarized highly excited hydrogen atoms. PMID- 10031478 TI - Spectroscopy of Al PMID- 10031479 TI - Quasi-Penning resonances of a Rydberg electron in crossed electric and magnetic fields. PMID- 10031480 TI - Higher-order squeezing of a quantum field. PMID- 10031482 TI - Anomalous dispersion in disparate-mass gas mixtures. PMID- 10031481 TI - Squeezing in a Rydberg atom maser. PMID- 10031483 TI - Ultrasonic study of the breakdown of conventional hydrodynamics in the smectic-A phase of terephthal-bis-p-p'-butylaniline (TBBA). PMID- 10031484 TI - Entanglements of semidilute polymer rods. PMID- 10031485 TI - Transition to oscillatory convection in a 3He-superfluid-4He mixture. PMID- 10031486 TI - Shear-viscosity behavior near the double critical point of the mixture 3 methylpyridine, water, and heavy water. PMID- 10031488 TI - Origin of the difference of the coverage-dependent vibrational shift for S on Ni(100) and O on Ni(100). PMID- 10031487 TI - Adsorbate structure determination using surface vibrational spectroscopy. PMID- 10031489 TI - Resistance fluctuations due to hydrogen diffusion in niobium thin films. PMID- 10031490 TI - Ising model in a quenched random field: Critical exponents in three dimensions from high-temperature series. PMID- 10031491 TI - Microscopic theory of impurity-defect reactions and impurity diffusion in silicon. PMID- 10031492 TI - Comment on "Models of hierarchically constrained dynamics for glassy relaxation" PMID- 10031493 TI - Palmer et al. respond. PMID- 10031494 TI - Comment on "Pressure narrowing of ac Stark-broadened multiphoton spectra" PMID- 10031495 TI - Li, Porter, and Johnson respond. PMID- 10031496 TI - Comment on "Critical cone in phonon-induced desorption of helium" PMID- 10031497 TI - Evaluation of critical exponents on the basis of stochastic quantization. PMID- 10031498 TI - Uncertainty, entropy, and the statistical mechanics of microscopic systems. PMID- 10031499 TI - Masses, widths, and leptonic widths of the higher upsilon resonances. PMID- 10031500 TI - Observation of new structure in the e+e- cross section above the Upsilon (4S). PMID- 10031501 TI - Physical CP phase and maximal CP nonconservation. PMID- 10031502 TI - Scales of deconfinement? PMID- 10031503 TI - gamma Z kinetic mixing as signal of a higher scale. PMID- 10031504 TI - Evidence of anomalous behavior of relativistic alpha particles emitted in 12C emulsion interaction at 4.5 GeV/nucleon. PMID- 10031505 TI - Strong angular momentum effects in near-barrier fusion reactions. PMID- 10031506 TI - Statistical emission of 2He from highly excited nuclear systems. PMID- 10031507 TI - Attempts to produce superheavy elements by fusion of 48Ca with 248Cm in the bombarding energy range of 4.5-5.2 MeV/u. PMID- 10031508 TI - Strong angular correlation of bound electrons revealed by resonant two-color, three-photon ionization of barium. PMID- 10031510 TI - Quantum interference effect for two atoms radiating a single photon. PMID- 10031509 TI - Collision-strength shift in electron-impact single and double ionization of Sb and Bi ions. PMID- 10031511 TI - Photoelectron angular distributions for near-threshold two-photon ionization of cesium and rubidium atoms. PMID- 10031512 TI - Towards numerical solutions of the Schrodinger equation for diatomic molecules. PMID- 10031513 TI - Analytical model for large-scale turbulence. PMID- 10031514 TI - Nonlinear Landau heating by ion-Bernstein waves in magnetically confined fusion plasmas. PMID- 10031516 TI - Correlated motions in glasses studied by coherent inelastic neutron scattering. PMID- 10031515 TI - Time-resolved NMR study of self-diffusion in the cholesteric phase. PMID- 10031517 TI - Absence of phase separation for fluids in three dimensions. PMID- 10031519 TI - Pair interaction from structural data for dense classical liquids. PMID- 10031518 TI - Critical adsorption of a pure fluid on a graphite substrate. PMID- 10031520 TI - Analytical solutions for diffusion on fractal objects. PMID- 10031522 TI - Polarization-dependent resonances in electronically induced ion desorption via adsorbate-core excitations on metal surfaces. PMID- 10031521 TI - Quasielastic light scattering from diamond. PMID- 10031523 TI - Observation of surface optical phonons in NaF(001) by inelastic He-atom scattering. PMID- 10031524 TI - Interaction potential between a helium atom and metal surfaces. PMID- 10031525 TI - Anderson localization and the theory of dirty superconductors. PMID- 10031526 TI - Upper critical magnetic field of the heavy-fermion superconductor UBe13. PMID- 10031527 TI - Magnetic order and other phase transitions in mixed-valent YbPd. PMID- 10031528 TI - Predicted solar neutrino rates in the Q-nuclear solar model. PMID- 10031529 TI - Comment on the Dirac bracket. PMID- 10031530 TI - Godfrey responds. PMID- 10031532 TI - Comment on "What is the mass of an exciton?" PMID- 10031531 TI - Comment on "Exotic nuclear decay of 223Ra by emission of 14C nuclei" PMID- 10031533 TI - Why quantum diffusion is nondissipative. PMID- 10031534 TI - Soliton motion in the case of a nonzero reflection coefficient. PMID- 10031535 TI - Heterotic string. PMID- 10031536 TI - Light-meson spectrum with a Nambu-Goldstone pion. PMID- 10031538 TI - Quantum electrodynamic energy shifts of quarks bound in a cavity. PMID- 10031537 TI - Single-particle momentum distribution at high energies and concept of partition temperature. PMID- 10031539 TI - Measurement of the real-to-imaginary ratio of the p-barp forward-scattering amplitudes. PMID- 10031540 TI - Charged D production in e+e- annihilation at 29 GeV and a limit on D0-D-bar 0 mixing. PMID- 10031542 TI - Monojets from Z decay without extra neutrinos or Higgs particles. PMID- 10031541 TI - Monojets from Z decay at CERN and PETRA. PMID- 10031543 TI - Giant M1 resonance in Pb. PMID- 10031545 TI - Observation of a relativistic, bistable hysteresis in the cyclotron motion of a single electron. PMID- 10031544 TI - Role of memory effects on the spreading width of a collective state in extended time-dependent Hartree-Fock theory. PMID- 10031546 TI - Vibrational temperature of O2 + and N2 + drifting at elevated E/N in helium. PMID- 10031548 TI - Highly spin-polarized photoemission near threshold from physisorbed xenon and krypton atoms. PMID- 10031547 TI - Nonresonant electron transfer and projectile K-electron excitation in ion-atom collisions. PMID- 10031549 TI - One-atom maser. PMID- 10031550 TI - External noise can suppress the onset of spatial turbulence. PMID- 10031552 TI - Orientational ordering and melting of molecular H2 in an a-Si matrix: NMR studies. PMID- 10031551 TI - Two-dimensional simulations of single-frequency and beat-wave laser-plasma heating. PMID- 10031553 TI - Rippled relaxation in the (110) surface of the ordered metallic alloy NiAl. PMID- 10031554 TI - Instabiltiy of the CsCl structure in ionic solids at high pressures. PMID- 10031555 TI - Experimental evidence for surface roughening in two dimensions. PMID- 10031557 TI - Collective-excitation gap in the fractional quantum Hall effect. PMID- 10031556 TI - Scaling of the metastability boundary of a d=2 random-field Ising system. PMID- 10031558 TI - Determination of the surface conductivity of ultrathin metallic films on Si(111) by high-resolution electron-energy-loss spectroscopy. PMID- 10031560 TI - Image states: Binding energies, effective masses, and surface corrugation. PMID- 10031559 TI - Cascade of metal-insulator transitions for electrons in the Frenkel-Kontorova chain. PMID- 10031561 TI - Sticking probability of H2 and HD on noble-metal surfaces. PMID- 10031563 TI - Comments on "General theory for quantum statistics in two dimensions" PMID- 10031562 TI - Creation and ESR identification, in single crystals, of synthetic analogs of the S=(1/2) states of the Fe4S4 cores of the reduced ferredoxins and oxidized high potential proteins. PMID- 10031564 TI - Vector polarization in reactions with spin-1 particles. PMID- 10031566 TI - Moss et al. respond. PMID- 10031565 TI - Comment on "Observation of a noise-induced phase transition with an analog simulator" PMID- 10031567 TI - Comment on "Resonant microwave absorption of selected DNA molecules" and "Observation of low-lying Raman bands in DNA by tandem interferometry" PMID- 10031569 TI - Collisions in the classical limit: The vanishing-potential theorem. PMID- 10031570 TI - Invariants polynomial in momenta for integrable Hamiltonians. PMID- 10031571 TI - Accelerated diffusion in Josephson junctions and related chaotic systems. PMID- 10031572 TI - Critical dimension of string theories in curved space. PMID- 10031573 TI - Upper bound on the tau -neutrino mass from the previously unobserved decay mode tau -->KK pi nu tau. PMID- 10031574 TI - Inclusive production of Omega - and Omega -bar + by KL0-carbon interactions in the energy range 80-280 GeV/c. PMID- 10031575 TI - Relation between the spin and the size of a skyrmion. PMID- 10031576 TI - Inclusive pion double charge exchange in 16O and 40Ca. PMID- 10031577 TI - Possible solution to the entropy puzzle in heavy-ion collisions. PMID- 10031579 TI - Role of meson-exchange currents in the charge form factor of 6Li. PMID- 10031578 TI - Boson densities in the germanium isotopes and inelastic electron scattering. PMID- 10031581 TI - Extension of supersymmetry in nuclear structure. PMID- 10031580 TI - Magnetic form factor of the deuteron. PMID- 10031582 TI - Direct observation of electronic intramolecular energy transfer through a large energy gap. PMID- 10031583 TI - Modified generalized valence-bond method: A simple correction for the electron correlation missing in generalized valence-bond wave functions; Prediction of double-well states for Cr2 and Mo2. PMID- 10031584 TI - Application of new lower-bound techniques to the spectra of Li and Li+ PMID- 10031585 TI - Numerical solution of the time-dependent Dirac equation with application to positron production in heavy-ion collisions. PMID- 10031586 TI - Tricritical phenomena in rotating Couette-Taylor flow. PMID- 10031587 TI - Coherent ringing in superfluorescence. PMID- 10031588 TI - New class of instabilities in passive optical cavities. PMID- 10031589 TI - Electron-beam guiding and phase-mix damping by a laser-ionized channel. PMID- 10031590 TI - Multichannel scattering studies of the spectra and spatial distribution of tokamak microturbulence. PMID- 10031591 TI - Acceleration of electrons by the interaction of a bunched electron beam with a plasma. PMID- 10031592 TI - Effect of nonlinear collective processes on the confinement of a pure-electron plasma. PMID- 10031594 TI - Inelastic neutron scattering in epoxy resins: The phonon-fracton density of states and the specific heat. PMID- 10031593 TI - Fractal aggregates in sputter-deposited NbGe2 films. PMID- 10031596 TI - Adsorption-site location by transmission channeling: Deuterium on Ni(100). PMID- 10031595 TI - Wetting layers and dispersion forces for a fluid in contact with a vertical wall. PMID- 10031597 TI - Post-collision interactions in M2,3-shell energy-loss, autoionization, and Auger spectra of Cr and Fe by electron impact near threshold. PMID- 10031599 TI - Lifetime of an electron-hole plasma of silicon in the picosecond range. PMID- 10031598 TI - New interpretation of spin-wave behavior in nickel. PMID- 10031600 TI - Quantum noise and the threshold of hearing. PMID- 10031602 TI - Undecidability and intractability in theoretical physics. PMID- 10031601 TI - Long-time tails in the velocity autocorrelation function of hard-rod binary mixtures. PMID- 10031603 TI - Formal scattering theory by an algebraic approach. PMID- 10031604 TI - Mass and anomalous magnetic moment of an electron between two conducting parallel plates. PMID- 10031605 TI - Deformation of the nucleon and delta in excited states. PMID- 10031606 TI - Topological charge in SU(2) lattice gauge theory. PMID- 10031607 TI - Differences between proton- and pi --induced production of the charmonium chi states. PMID- 10031608 TI - pp and pp-bar elastic scattering at sqrt s =0.55 to 40 TeV. PMID- 10031609 TI - Origin of elastic pp polarization at large angles. PMID- 10031610 TI - Measurement of the total hadronic cross section in virtual photon-photon interactions. PMID- 10031611 TI - Axial currents in nuclei and the skyrmion size. PMID- 10031612 TI - Search for anomalous fragments in 1.8A-GeV 40Ar reactions in nuclear emulsions. PMID- 10031614 TI - Low-lying isovector collective states and the interacting-boson model. PMID- 10031613 TI - Properties of the 208Po(0(+),T=22) double isobaric analog state. PMID- 10031615 TI - New atomic mechanism for positron production in heavy-ion collisions. PMID- 10031616 TI - Completely quantal treatment of the van der Waals forces between atoms: Application to positronium. PMID- 10031617 TI - Observation of the metastable negative argon ion Ar- PMID- 10031618 TI - Observation of high-angular-momentum Rydberg states of H2 in a fast beam. PMID- 10031619 TI - Experiment with stored 0.7-MeV ions: Observation of stability properties of a nonthermal plasma. PMID- 10031621 TI - Nucleation of cavitons in strong langmuir turbulence. PMID- 10031620 TI - Observation and analysis of maser activity in a tokamak plasma. PMID- 10031623 TI - Pinned incommensurate structure of cesium intercalated graphite. PMID- 10031622 TI - Nonlinear driven reconnection in the reversed-field pinch. PMID- 10031624 TI - Dimer-plus-chain structure for the SI(100)-c(4 x 2) surface. PMID- 10031625 TI - Analysis of light-scattering measurements near a cloud point. PMID- 10031626 TI - Time-resolved nonlinear spectroscopy of a fermi doublet: The { nu 1,2 nu 2} Fermi resonance in CO2 solid. PMID- 10031627 TI - Real-space determination of atomic structure and bond relaxation at the NiSi2 Si(111) interface. PMID- 10031628 TI - Critical localization in two-dimensional Landau quantization. PMID- 10031629 TI - Nuclear Bragg diffraction of synchrotron radiation in yttrium iron garnet. PMID- 10031630 TI - Absence of an intermediate phase for a general class of one-component ferromagnetic models. PMID- 10031632 TI - Comments on the convexity properties of the baryon spectrum. PMID- 10031631 TI - Spin correlations in a concentrated metallic spin-glass. PMID- 10031633 TI - Random-Alloy splitting of Cu levels in GaAs1-xPx. PMID- 10031634 TI - Composition-dependence of deep impurity levels in alloys. PMID- 10031635 TI - Samuelson et al. respond. PMID- 10031639 TI - Quantum mechanics versus macroscopic realism: Is the flux there when nobody looks? PMID- 10031640 TI - Quantum irregular spectrum in a corresponding classically chaotic lattice spin system. PMID- 10031641 TI - Off-shell model for threshold pionic eta production on a nucleon and for eta N scattering. PMID- 10031642 TI - Gluonic excitations of mesons: Why they are missing and where to find them. PMID- 10031643 TI - Spectral flow and the anomalous production of fermions in odd number of dimensions. PMID- 10031644 TI - Measurements of Gamow-Teller strength distributions in masses 13 and 15. PMID- 10031645 TI - Inelastic proton scattering as a test of the new collective-"current" M1 mode in deformed nuclei. PMID- 10031646 TI - Experimental angular-resolved photoelectron spectroscopy of free oriented CH3I molecules. PMID- 10031647 TI - Microwave radiation from a high-gain free-electron laser amplifier. PMID- 10031649 TI - Conversion of wave energy to magnetic field energy in a plasma torus. PMID- 10031648 TI - Transition x rays from medium-energy electrons. PMID- 10031650 TI - Kinetic energies in quantum solids. PMID- 10031651 TI - Nonunique structure of metastable (GaSb)1-x(Ge2)x alloys. PMID- 10031652 TI - High-momentum-transfer inelastic neutron scatterins from liquid helium-3. PMID- 10031653 TI - Measurement of elasticity and conductivity of a three-dimensional percolation system. PMID- 10031654 TI - Hydrogen-induced strain modulation in Nb-Ta superlattices. PMID- 10031656 TI - Search for a transition in the three-dimensional PMID- 10031655 TI - Integrated x-ray-scattering intensity measurement of the order parameter at the nematic-to-smectic-A phase transition. PMID- 10031657 TI - Critical behavior of three-dimensional Ising spin-glass model. PMID- 10031658 TI - Short-range magnetic order near the Curie temperature iron from spin-resolved photoemission. PMID- 10031660 TI - Resolved forward Brillouin scattering in optical fibers. PMID- 10031659 TI - Na-induced bonding and bond-length changes for CO on Pt(111): A near-edge x-ray absorption fine-structure study. PMID- 10031661 TI - Surface photoelectric effect for thin metal overlayers. PMID- 10031662 TI - Predicted Raman intensities for bulk and surface plasmons of a layered electron gas. PMID- 10031663 TI - Rapid solvent-induced recombination and slow energy relaxation in a simple chemical reaction: Picosecond studies of iodine photodissociation in CCl4. PMID- 10031664 TI - Theory of phase separation in micellar solutions. PMID- 10031665 TI - Fourier path-integral Monte Carlo methods: Partial averaging. PMID- 10031666 TI - Dispersed ionic conductors and percolation theory. PMID- 10031668 TI - Period-doubling systems as small-signal amplifiers. PMID- 10031667 TI - Average arrival time of wave pulses through continuous random media. PMID- 10031670 TI - Baryons as solitons in the effective Lagrangian of spontaneously broken chiral symmetry. PMID- 10031669 TI - Symmetric kicked self-oscillators: Iterated maps, strange attractors, and symmetry of the phase-locking Farey hierarchy. PMID- 10031671 TI - Bolometric detection of neutrinos. PMID- 10031672 TI - Wolfenstein polarization observables for the reaction ppolp-->p PMID- 10031673 TI - Naturally light Higgs doublet in supersymmetric E6 grand unified theory. PMID- 10031674 TI - Observation of B production in e+e- interactions above the b-flavor threshold. PMID- 10031675 TI - QCD at large Nc-Skyrme or the bag? PMID- 10031676 TI - Cyclotron motion in a microwave cavity: Possible shifts of the measured electron g factor. PMID- 10031677 TI - Three-dimensional viscous confinement and cooling of atoms by resonance radiation pressure. PMID- 10031678 TI - New mechanism for resonant dt micro formation and epithermal effects in muon catalyzed fusion. PMID- 10031679 TI - Transition from second- to first-order dipole-dipole interaction in the excited EuSr molecule. PMID- 10031680 TI - Measuring Maxwell's displacement current inside a capacitor. PMID- 10031681 TI - Demonstration of self-pulsing instability and transitions to chaos in single-mode and multimode homogeneously broadened Raman laser. PMID- 10031682 TI - Observation of inhibited spontaneous emission. PMID- 10031683 TI - Growth and quasistabilization of large-scale spikes on laser beams in self focusing media. PMID- 10031685 TI - Measurement of absolute growth rates and saturation phenomena for stimulated Brillouin scattering in a CO2-laser-irradiated plasma. PMID- 10031684 TI - Recharging of the ohmic-heating transformer by means of lower-hybrid current drive in the ASDEX tokamak. PMID- 10031686 TI - Electron temperature and density measurements by harmonic electron cyclotron emissions from doublet-III tokamak plasma. PMID- 10031688 TI - Critical phenomena in randomly stirred fluids. PMID- 10031687 TI - Hose-induced current enhancement associated with beam propagation. PMID- 10031689 TI - Lattice dynamics from phonon imaging. PMID- 10031691 TI - Ion-induced desorption by high-energy (600 keV) hydrogen clusters. PMID- 10031690 TI - Ultrahigh pressures: Optical observations and Raman measurements of hydrogen and deuterium to 1.47 Mbar. PMID- 10031692 TI - Density-functional formalism: Sources of error in local-density approximations. PMID- 10031694 TI - Propagating plasma mode in thin superconducting filaments. PMID- 10031693 TI - Spin-glass response time in Ag:Mn: Exponential temperature dependence. PMID- 10031695 TI - ESR study of electrochemical doping in the conducting polymer polypyrrole. PMID- 10031697 TI - Type II supernovae in 12Mcirdot and 15Mcirdot stars: The equation of state and general relativity. PMID- 10031696 TI - Solar-neutrino oscillations. PMID- 10031698 TI - Range of validity of the Einstein relation. PMID- 10031699 TI - Cates responds. PMID- 10031700 TI - Comment on "Number of neutrinos in the standard model and its extensions to supersymmetry" PMID- 10031701 TI - Comment on "Mass and anomalous magnetic moment of an electron between two conducting parallel plates" PMID- 10031703 TI - Lichten and Robatino respond. PMID- 10031702 TI - Comment on "New atomic mechanism for positron production in heavy-ion collisoins" PMID- 10031704 TI - Half-flux periodicity in arrays. PMID- 10031705 TI - Pannetier et al. respond. PMID- 10031706 TI - Determination of the effective correlation energy of defects in semiconductors. PMID- 10031707 TI - Comment on "Transition-temperature oscillations in thin superconducting films" PMID- 10031708 TI - Interaction of helium with a corrugated surface. PMID- 10031709 TI - Takada and Kohn respond. PMID- 10031710 TI - Continuum dissolution and the relativistic many-body problem: A solvable model. PMID- 10031711 TI - Mass scales of the string unification. PMID- 10031712 TI - Commutator of the quark mass matrices in the standard electroweak model and a measure of maximal CP nonconservation. PMID- 10031713 TI - Constants of motion for a spin-(1/2) particle in the field of a dyon. PMID- 10031715 TI - Gamow-Teller strength function in 71Ge via the (p,n) reaction at medium energies. PMID- 10031714 TI - Baryon production in e+e- annihilation at sqrt s =29 GeV: Clusters or diquarks? PMID- 10031717 TI - Elastic scattering of alpha particles and the phase of the nucleon-nucleon scattering amplitude. PMID- 10031716 TI - Weak decay of 1 Lambda 2C and 1 Lambda 1B hypernuclei. PMID- 10031718 TI - Fission decay of reaction products with A <~ 150. PMID- 10031719 TI - Vibrational frame transformation for electron-molecule scattering. PMID- 10031721 TI - Polarization of 21Ne by spin exchange with optically pumped Rb vapor. PMID- 10031720 TI - Phase effects in bichromatic field interactions with a two-level atom. PMID- 10031722 TI - Reptation and tube renewal in entangled polymer solutions. PMID- 10031723 TI - Measurement of the Lyapunov spectrum from a chaotic time series. PMID- 10031724 TI - Suppression of amplified spontaneous emission by the four-wave mixing process. PMID- 10031725 TI - Crafted pulses for the uniform suppression of a region in a coherent spectrum. PMID- 10031726 TI - Turbulence in a cylindrical container of argon near threshold of convection. PMID- 10031727 TI - Subcritical magnetohydrodynamic turbulence. PMID- 10031729 TI - 7 x 7 reconstruction of Ge(111) surfaces under compressive strain. PMID- 10031728 TI - New types of phase separation behavior during the crystallization process in polymer blends with phase diagram. PMID- 10031730 TI - Gelation of polymer solutions: An experimental verification of the scaling behavior of the size distribution function. PMID- 10031732 TI - High transparency of classically opaque metallic films. PMID- 10031731 TI - Tunneling between two strongly coupled superlattices. PMID- 10031733 TI - Completely polarized electrons emitted from polycrystalline iron upon pulsed laser irradiation. PMID- 10031734 TI - Inelastic processes in Ne+ and Ar+ collisions with Mg and Y surfaces leading to scattered-ion fractions and vacuum-ultraviolet photon emission. PMID- 10031735 TI - Dynamic spin organization in dilute magnetic systems. PMID- 10031736 TI - Resonant Raman scattering by spin-density fluctuations in n-type germanium. PMID- 10031738 TI - Exact solution of a four-site d-electron problem: The nickel-metal photoemission spectrum. PMID- 10031737 TI - Aharonov-Bohm effect for the quantum Hall conductivity on a disordered lattice. PMID- 10031739 TI - Observation of size effect in the quantum hall regime. PMID- 10031740 TI - Quantum oscillations in normal-metal networks. PMID- 10031743 TI - Commensurate-incommensurate transitions with quenched random impurities. PMID- 10031741 TI - New quantum photoconductivity and large photocurrent gain by effective-mass filtering in a forward-biased superlattice p-n junction. PMID- 10031745 TI - Renormalization of mappings of the two-torus. PMID- 10031744 TI - Novel phase diagram for self-avoiding walks (polymers). PMID- 10031746 TI - Novel baryon resonances in the Skyrme model. PMID- 10031747 TI - Charm production in neutron-nucleon interactions. PMID- 10031748 TI - Unusual behavior of projectile fragments from the interaction of copper with relativistic Ar ions. PMID- 10031749 TI - Photodissociation of single H2O quantum states in the first absorption band: Complete characterization of OH rotational and Lambda -doublet state distributions. PMID- 10031750 TI - Half-quantum vortices in superfluid 3He-A. PMID- 10031751 TI - Direct observation of discommensuration arrays in NbTe4 by means of low temperature electron microscopy. PMID- 10031752 TI - Intrinsic surface-induced optical anisotropies of cubic crystals: Local-field effect. PMID- 10031753 TI - Inertial dynamics of charge-density waves in TaS3 and NbSe3. PMID- 10031754 TI - Local-density-functional calculation of the pressure-induced metallization of BaSe and BaTe. PMID- 10031756 TI - Ni-Pt phase diagram: Experiment and theory. PMID- 10031755 TI - Monte Carlo studies of the dynamics of quantum many-body systems. PMID- 10031757 TI - Non-Lorentzian noise at semiconductor interfaces. PMID- 10031758 TI - Giant conductivity resonance in the spin-density-wave state of an organic conductor. PMID- 10031759 TI - Monte Carlo study of critical relaxation near a surface. PMID- 10031760 TI - Antiferromagnetic spin fluctuations in the heavy-fermion superconductor UPt3. PMID- 10031761 TI - Observation of spin-polarized photoelectron diffraction. PMID- 10031763 TI - Do Davydov solitons exist at 300 K? PMID- 10031762 TI - 4s valence level of adsorbed K atoms probed by metastable-He deexcitation spectroscopy. PMID- 10031766 TI - Simple approach to N-level quantum systems in arbitrary fields: The "time-slicer" PMID- 10031765 TI - Curvature-induced asymptotic freedom. PMID- 10031768 TI - Resonant scattering and charm showers in ultrahigh-energy neutrino interactions. PMID- 10031767 TI - Decay B--> psi X. PMID- 10031769 TI - Spin-dependent potentials in SU(3) lattice gauge theory. PMID- 10031770 TI - Search for anomalous fragments produced in collisions with heavy target nuclei and in delta Z = 1 peripheral interactions. AB - We exposed a stack of CR39 track detectors containing Ag foils to a 1.7 GeV/nucleon 56Fe beam and investigated the anomalous mean-free-path effect. Neither the whole set of 7517 nor a subset of 2542 interacting fragments produced probably in the Ag target show an effect. By combining the data of this and an earlier experiment we can also exclude an effect for 3219 interacting fragments produced in delta Z = 1 collisions. PMID- 10031772 TI - Testing of QCD plasma formation by dilepton spectra in relativistic nuclear collisions. PMID- 10031771 TI - Capture amplitudes in the reaction 12C( alpha, gamma ) 16O at stellar energies. PMID- 10031773 TI - Electric quadrupole moment of the 211Rn (63/2)- isomer: Absence of core deformation at very high spins. PMID- 10031774 TI - Observation of the double isobaric analog transition 18O( pi +, pi -) 18Ne at 50 MeV. PMID- 10031775 TI - Selective excitation of dressed atomic states by use of phase-controlled optical fields. PMID- 10031776 TI - Oscillator strength measurements of even-parity autoionizing resonances by combined synchrotron-radiation-laser excitation. PMID- 10031777 TI - Exact quantum-mechanical study of three-dimensional four-atom collisional processes in a model system. PMID- 10031778 TI - Squeezing of quantum fluctuations via atomic coherence effects. PMID- 10031780 TI - Current rampup by lower-hybrid waves in the PLT tokamak. PMID- 10031779 TI - Bistable solitons. PMID- 10031781 TI - Point-defect diffusion from coherent quasielastic neutron scattering. PMID- 10031782 TI - Si(001) Dimer structure observed with scanning tunneling microscopy. PMID- 10031783 TI - Observation of low-energy excitations in KBr(1-x)(CN)x by Brillouin scattering. PMID- 10031785 TI - Experimental demonstration of the role of anisotropy in interfacial pattern formation. PMID- 10031784 TI - Interaction of atomic hydrogen with undersaturated helium films. PMID- 10031786 TI - lambda -shaped ultrasound-attenuation peak in superconducting (U,Th)Be13. PMID- 10031788 TI - Electronic structure, total energies, and abundances of the elementary point defedts in GaAs. PMID- 10031787 TI - Observation of transitions between electronic states at the (111) A-face of CdTe by electrolyte electroreflectance. PMID- 10031789 TI - Singlet exciton fusion in molecular solids: A direct subpicosecond determination of time-dependent annihilation rates. PMID- 10031791 TI - Density-functional calculations of the cohesive energy of condensed matter in very strong magnetic fields. PMID- 10031790 TI - Observation of the resonant optical Stark effect in a semiconductor. PMID- 10031792 TI - Comment on "Critical behavior of a binary mixture of protein and salt water" PMID- 10031794 TI - Evidence for Ising-type critical phenomena in two-dimensional percolation. PMID- 10031795 TI - New actions for superstrings. PMID- 10031796 TI - General action principle for supersymmetric particles. PMID- 10031797 TI - Critical behavior of two-dimensional systems with continuous symmetries. PMID- 10031798 TI - Multiplicity fluctuation and single-particle spectrum in two-jet events in e+e- annihilation. PMID- 10031799 TI - Evidence for nonnucleonic effects in the threshold electrodisintegration of the deuteron at high momentum transfer. PMID- 10031800 TI - Nuclear deexcitation via the electronic-bridge mechanism. PMID- 10031801 TI - Relationship between Gamow-Teller transition probabilities and (p,n) cross sections at small momentum transfers. PMID- 10031802 TI - Production of pions in a coherent state in heavy-ion collisions. PMID- 10031803 TI - Evolution of nucleus-nucleus collision mechanisms from the barrier to beyond the Fermi energy. PMID- 10031804 TI - Collectivity of the superdeformed bands in 152Dy. PMID- 10031805 TI - Observation of the first Tz=-(5/2) nuclide, 35Ca, via its beta -delayed two proton emission. PMID- 10031807 TI - Elastic small-angle electron scattering by He, Ne, and Ar at 35 keV. PMID- 10031806 TI - Accurate theoretical beta -decay energy spectrum of the tritium molecule and its neutrino mass dependence. PMID- 10031808 TI - Small-angle elastic differential scattering cross section for 25-keV electrons scattering from helium. PMID- 10031809 TI - Parameters of the luminous region surrounding deuterium pellets in the Princeton Large Torus tokamak. PMID- 10031812 TI - Hydrodynamic shifts in the NMR spectrum of 3He-B. PMID- 10031810 TI - Magnetic and structural properties of single-crystal rare-earth Gd-Y superlattices. PMID- 10031811 TI - Anisotropy and cluster growth by diffusion-limited aggregation. PMID- 10031814 TI - First-principles theory of quasiparticles: Calculation of band gaps in semiconductors and insulators. PMID- 10031813 TI - Deep-level impurities: A possible guide to prediction of band-edge discontinuities in semiconductor heterojunctions. PMID- 10031815 TI - Has a cosmological neutrino background from gravitational stellar collapse been detected? PMID- 10031816 TI - Spin waves in spin-polarized quantum gases. PMID- 10031817 TI - Ruckenstein and Levy respond. PMID- 10031819 TI - First-order transition in doped polyacetylene. PMID- 10031818 TI - Comment on "Electrical-conductivity fluctuations near the percolation threshold" PMID- 10031822 TI - Semiclassical instability of compactification. PMID- 10031821 TI - N-dependent fractional statistics of N vortices. PMID- 10031823 TI - Fractal basin boundaries and homoclinic orbits for periodic motion in a two-well potential. PMID- 10031824 TI - Does coupling to a condensed phase increase or decrease tunneling? PMID- 10031825 TI - Monte Carlo renormalization group in the large-N limit. PMID- 10031826 TI - Probing the desert with fermion masses. PMID- 10031828 TI - F-spin multiplets and supersymmetry in nuclei. PMID- 10031827 TI - Inclusive neutron spectra at 0 degrees from the reactions Pb(Ne,n)X and NaF(Ne,n)X at 390 and 790 MeV per nucleon. PMID- 10031829 TI - Quasicrystal with one-dimensional translational symmetry and a tenfold rotation axis. PMID- 10031830 TI - Optical studies of nitrogen to 130 GPa. PMID- 10031832 TI - Dynamics of concentration fluctuations for a micellar solution. PMID- 10031831 TI - Surface extended x-ray-absorption fine structure of low-Z adsorbates studied with fluorescence detection. PMID- 10031833 TI - Smectic-A phase with two collinear incommensurate density modulations. PMID- 10031835 TI - Dominant influence of beam-induced interface rearrangement on solid-phase epitaxial crystallization of amorphous silicon. PMID- 10031834 TI - Flory approach to the enhancement factor in polymer statistics. PMID- 10031836 TI - Real-space determination of atomic structure of the Si(111)- sqrt 3 sqrt 3 R30 degrees -Au surface by low-energy alkali-ion scattering. PMID- 10031837 TI - Magnetization of hcp solid 3He. PMID- 10031838 TI - Dynamic features of superfluid turbulence near the second critical heat current. PMID- 10031839 TI - Theoretical evidence for low-spin ground states of early interstitial and late substitutional 3d transition-metal ions in silicon. PMID- 10031840 TI - First-principles interatomic potentials in transition metals. PMID- 10031841 TI - Identification of anomalous muonium in semiconductors as a vacancy-associated center. PMID- 10031842 TI - Optically induced magnetization in a diluted magnetic semiconductor: Hg1-xMnxTe. PMID- 10031843 TI - Determination of the surface phonon dispersion relations for monolayer, bilayer, trilayer, and thick Kr(111) films physisorbed on Ag(111) by inelastic He scattering. PMID- 10031845 TI - Superconducting-quasiparticle interface states. PMID- 10031844 TI - Low-energy excitations in alpha - and gamma -Ce observed by photoemission. PMID- 10031846 TI - Generation of surface excitations on dielectric spheres by an external electron beam. PMID- 10031848 TI - Direct approach to resolve the solar-neutrino problem. PMID- 10031847 TI - Storing infinite numbers of patterns in a spin-glass model of neural networks. PMID- 10031852 TI - Energy-level quantization in the zero-voltage state of a current-biased Josephson junction. PMID- 10031851 TI - Chaos-order-chaos transitions in a two-dimensional Hamiltonian system. PMID- 10031853 TI - Quantitative study of the effect of the environment on macroscopic quantum tunneling. PMID- 10031854 TI - New Langevin equations for a translating and simultaneously rotating asymmetric top. PMID- 10031855 TI - Production of massive muon pairs in pi --nucleus collisions. PMID- 10031856 TI - Nuclear magnetic moment of 207Tl. PMID- 10031857 TI - Continuum electron emission from collisions of 0.1-3.2-MeV Kr ions with Xe targets. PMID- 10031858 TI - Energy and radiative lifetime of the 5d96s2 2D5/2 state in Hg II by Doppler-free two-photon laser spectroscopy. PMID- 10031859 TI - Observation of triplet nd autoionizing Rydberg states in H2. PMID- 10031860 TI - Autoionizing Rydberg states in triplet molecular hydrogen. PMID- 10031861 TI - New biased-reptation model for charged polymers. PMID- 10031862 TI - H2 dissociation at metal surfaces. PMID- 10031863 TI - Amorphous-to-quasicrystalline transformation in the solid state. PMID- 10031864 TI - Formation of icosahedral Al(Mn) by directed energy processes. PMID- 10031865 TI - Low-temperature state of UCu5: Formation of heavy electrons in a magnetically ordered material. PMID- 10031866 TI - Submicrocrystallites and the orientational proximity effect. PMID- 10031867 TI - 3He film flow: Two-dimensional superfluidity. PMID- 10031868 TI - Magnetic field dependence of activation energies in the fractional quantum Hall effect. PMID- 10031870 TI - Stimulation of tunneling by a high-frequency field: Decay of the zero-voltage state in Josephson junctions. PMID- 10031869 TI - Observation of Aharonov-Bohm electron interference effects with periods h/e and h/2e in individual micron-size, normal-metal rings. PMID- 10031871 TI - Exchange-correlation-induced "negative effective U" PMID- 10031872 TI - Universal conductance fluctuations in metals. PMID- 10031873 TI - Far-infrared absorption of silver-particle composites. PMID- 10031875 TI - Dynamics on ultrametric spaces. PMID- 10031874 TI - Solitons and fractional spectral dimensionality in the dilute S=(1/2) anisotropic XY chain. PMID- 10031876 TI - Layer-by-layer band structure of physisorbed Xe on Al(111). PMID- 10031878 TI - Distorted 4f-5d hybridization as a Jahn-Teller phenomenon. PMID- 10031877 TI - Production of high, long-lasting, dynamic proton polarization by way of photoexcited triplet states. PMID- 10031879 TI - Comment on "Fusion of polarized deuterons" PMID- 10031881 TI - Comment on "Relativistic plasma-wave excitation by collinear optical mixing" PMID- 10031880 TI - Fick and Hofmann respond. PMID- 10031882 TI - Clayton et al. respond. PMID- 10031885 TI - Nonperturbative bounds on < phin> in cutoff ( lambda phin)d field theory. PMID- 10031883 TI - Concentration scaling for spin-glasses with multiple magnetic impurities. PMID- 10031886 TI - Study of the mixed symmetry J pi =2(+) states in 156Gd with inelastic electron scattering. PMID- 10031887 TI - Accurate density functional for the energy: Real-space cutoff of the gradient expansion for the exchange hole. PMID- 10031888 TI - Fast-wave current drive in a toroidal plasma. PMID- 10031889 TI - Energy transduction in pellet-injected plasmas. PMID- 10031891 TI - Almost critical behavior of the anchoring energy at the interface between a nematic liquid crystal and a SiO substrate. PMID- 10031890 TI - Observation of second sound in superfluid 3He-B. PMID- 10031892 TI - Boundary-layer formulation of dendritic growth: Existence of a family of steady state needle solutions. PMID- 10031893 TI - Roughening of stepped metal surfaces. PMID- 10031894 TI - Extended x-ray isochromat fine structure of Cu. PMID- 10031895 TI - Comment on "Diffusion limited aggregation in two dimensions" PMID- 10031897 TI - Two scaling regimes for complete wetting by critical layers. PMID- 10031896 TI - Fractal dimension in a percolation model of fluid displacement. PMID- 10031898 TI - Nightingale and Indekeu respond. PMID- 10031899 TI - Comment on "Two energy scales in CePd3" PMID- 10031900 TI - Lawrence, Thompson, and Chen respond. PMID- 10031901 TI - Complement to the Wigner-Kirkwood expansion. PMID- 10031902 TI - Diffusion-controlled annihilation in the presence of particle sources: Exact results in one dimension. PMID- 10031903 TI - New route to optical chaos: Successive-subharmonic-oscil- lation cascade in a semiconductor laser coupled to an external cavity. PMID- 10031904 TI - Chiral-symmetry breaking in 2+1 dimensions. PMID- 10031905 TI - Hamilton-Jacobi formalism and wave equations for strings. PMID- 10031906 TI - Observation of J/ psi radiative decay to pseudoscalar omega omega. PMID- 10031908 TI - Isovector-meson contributions in the Dirac-Hartree-Fock approach to nuclear matter. PMID- 10031907 TI - Total gamma -ray spectrum in 153Ho: From the yrast line into the continuum. PMID- 10031909 TI - Structural classification of AB2 molecules and A3 clusters from valence electron orbital radii. PMID- 10031910 TI - Collective rotor-vibrator spectra in alkaline earth atoms. PMID- 10031911 TI - Nuclear-spin noise. PMID- 10031912 TI - Period-doubling lasers as small-signal detectors. PMID- 10031913 TI - Incipient singularities in the Navier-Stokes equations. PMID- 10031914 TI - Amplification of stimulated soft x-ray emission in a confined plasma column. PMID- 10031915 TI - Enhanced magnetization of 3He in contact with small copper particles by the excitation of 63Cu NMR. PMID- 10031917 TI - Direct imaging of a novel silicon surface reconstruction. PMID- 10031916 TI - Electron mobility on thin He films. PMID- 10031918 TI - Quasiperiodic GaAs-AlAs heterostructures. PMID- 10031919 TI - Monte Carlo study of the nematic-to-smectic-A transition. PMID- 10031920 TI - Observaton of scattering in an amorphous metal. PMID- 10031921 TI - Diffusion of solitons in the antiferromagnetic chains of (CD3)4NMnCl3: A study by neutron spin echo. PMID- 10031923 TI - Surface-enhanced alloy effects in Hg1-xCdxTe: (100) surface states and the site dependent coherent-potential approximation. PMID- 10031922 TI - Many-body effects in atomic-collision cascades. PMID- 10031924 TI - Interfacial charge-spin coupling: Injection and detection of spin magnetization in metals. PMID- 10031925 TI - Molecular tunneling measured by dipole-dipole-driven nuclear magnetic resonance. PMID- 10031926 TI - Calculations for cosmic axion detection. PMID- 10031927 TI - Cosmic strings and the correlations of Abell clusters. PMID- 10031928 TI - Comment on "Investigation of the magnitude and range of the Ruderman-Kittel interaction in SmRh4B4 and ErRh4B4" PMID- 10031929 TI - Comment on "Investigation of the magnitude and range of the Ruderman-Kittel interaction in SmRh4B4 and ErRh4B4" PMID- 10031930 TI - Terris, Gray, and Dunlap respond. PMID- 10031932 TI - Hamiltonian structure of the higher-order corrections to the Korteweg-de Vries equation. PMID- 10031933 TI - Dealing with truncation in Monte Carlo renormalization-group calculations. PMID- 10031934 TI - A dependence of charm production. PMID- 10031935 TI - Hard scattering with exclusive reactions: pi -p elastic scattering and rho -meson production. PMID- 10031937 TI - Space-time local symmetry of string field theory. PMID- 10031936 TI - Decay distribution of high-transverse-momentum rho mesons. PMID- 10031938 TI - Precision Measurement of Electroweak Effects in e+e---> micro+ micro- at sqrt s =29 GeV. PMID- 10031940 TI - Relativistic description of baryon magnetic moments. PMID- 10031939 TI - Observation of an enhancement in p-barp--> pi + pi - and p-barp-->K+K- cross sections at p-bar momentum of ~500 MeV/c. PMID- 10031942 TI - Equations of motion for the heterotic string theory from the conformal invariance of the sigma model. PMID- 10031941 TI - tau leptonic branching ratios and a search for Goldstone-boson decay. PMID- 10031943 TI - Flux limit of cosmic-ray magnetic monopoles from a fully coincident superconducting induction detector. PMID- 10031944 TI - Langevin simulation including dynamical quark loops. PMID- 10031945 TI - Determination of the spreading width for the collective transition strength at finite temperature. PMID- 10031947 TI - Distribution of collective magnetic multipole strength as a measure of neutron proton symmetry breaking. PMID- 10031946 TI - Energy and mass dependence of low-energy pion single charge exchange to the isobaric analog state. PMID- 10031950 TI - Was the Livermore x-ray laser pumped by recombination? PMID- 10031949 TI - Observation of polarized optical radiation following electron capture into slow, highly ionized neon. PMID- 10031948 TI - Measurement of x-ray and gamma -ray intensities following the fusion of d microd and p microd. PMID- 10031951 TI - Periodic collapse and long-time evolution of strong Langmuir turbulence. PMID- 10031952 TI - Percolation in an oil-continuous microemulsion. PMID- 10031953 TI - Dynamic slowing-down and nonexponential decay of the density correlation function in dense microemulsions. PMID- 10031954 TI - Pore-scale viscous fingering in porous media. PMID- 10031955 TI - Do interactions raise or lower a percolation threshold? PMID- 10031956 TI - Ginzburg-Landau-Gor'kov equations, currents, and electromagnetic properties of coexisting charge density wave superconductors. PMID- 10031957 TI - Observation of direct vibrational excitation in gas-surface collisions: NO on Ag(111). PMID- 10031958 TI - Measurements of macroscopic quantum tunneling out of the zero-voltage state of a current-biased Josephson junction. PMID- 10031959 TI - Experimental band structure of Na. PMID- 10031961 TI - State-to-state molecular-beam scattering of vibrationally excited NO from cleaved LiF(100) surfaces. PMID- 10031960 TI - Photoemission from the charge-density wave in Na and K. PMID- 10031962 TI - Nutation sequences for magnetic resonance imaging in solids. PMID- 10031963 TI - Midgap state in nearly commensurate charge-density waves. PMID- 10031964 TI - Thermal conductivity of 1T-TaS2 and 2H-TaSe2. PMID- 10031965 TI - Interpretation of the solar 48Ca/46Ca abundance ratio and the correlated Ca-Ti isotopic anomalies in the EK-1-4-1 inclusion of the Allende meteorite. PMID- 10031966 TI - Inelastic electron-phonon scattering and time-resolved laser-induced phase transformation in aluminum. PMID- 10031967 TI - Comment on "Anticorrugating effect of hybridization on the helium diffraction potential for metal surfaces" PMID- 10031968 TI - Diffusion-limited aggregation with disaggregation. PMID- 10031969 TI - Rigorous derivation of reaction-diffusion equations with fluctuations. PMID- 10031970 TI - Method of averaging and the quantum anharmonic oscillator. PMID- 10031971 TI - Inclusive charged-particle distribution in nearly threefold-symmetric three-jet events at Ec.m. PMID- 10031972 TI - Deconfining phase transition and the continuum limit of lattice quantum chromodynamics. PMID- 10031973 TI - Production dynamics of the Upsilon in proton-nucleon interactions. PMID- 10031974 TI - Time distributions for underground muons from the direction of Cygnus X-3. PMID- 10031975 TI - Determination of sin2 theta W and rho in deep-inelastic neutrino-nucleon scattering. PMID- 10031976 TI - Hot toroidal and bubble nuclei. PMID- 10031977 TI - Surface effects in cluster calculations of energy profiles of muonium in diamond. PMID- 10031978 TI - Autoionization inhibited by internal interferences. PMID- 10031979 TI - Double-electron loss of 0.5-MeV H- PMID- 10031980 TI - Breakdown of the Born-Oppenheimer approximation in the calculation of electric hyperpolarizabilities. PMID- 10031981 TI - Observation of chaos in a frequency-modulated CO2 laser. PMID- 10031983 TI - Dislocation energies in rare-gas monolayers on graphite. PMID- 10031982 TI - Temporally and spatially resolved x-ray emission from a collapsing-gas-shell Z pinch plasma. PMID- 10031984 TI - Interatomic potentials for silicon structural energies. PMID- 10031985 TI - Critical exponents near the lower consolute point of nonionic micellar solutions. PMID- 10031987 TI - Low-temperature acoustic properties of (KBr)1-x(KCN)x in the orientationally disordered state. PMID- 10031988 TI - Surface reaction dynamics via temperature modulation: Applications to the oxidation of carbon monoxide on the Pt(110)-(1 x 2) surface. PMID- 10031986 TI - Diffusion properties of the muon-produced soliton in trans-polyacetylene. PMID- 10031990 TI - Survival probability for kinetic self-avoiding walks. PMID- 10031989 TI - Exponential temperature dependence of the thermal boundary conductance between sintered silver and 3He-B in the region of low normal fluid density. PMID- 10031991 TI - Tunneling images of atomic steps on the Si(111)7 x 7 surface. PMID- 10031993 TI - Structure and dynamics of a metallic glass: Molecular-dynamics simulations. PMID- 10031992 TI - Real-space observation of surface states on Si(111)7 x 7 with the tunneling microscope. PMID- 10031994 TI - X-ray studies of tilted hexatic phases in thin liquid-crystal films. PMID- 10031995 TI - Coexistence of spin-glass and antiferromagnetic orders in the Ising system Fe0.55Mg0.45Cl2. PMID- 10031996 TI - Theory of vortex interaction with thermoelectric fields in a thin-film superconductor. PMID- 10031997 TI - Observation of a new thermoelectric effect in superconducting thin films. PMID- 10031998 TI - Image planes and surface states. PMID- 10031999 TI - Experimental investigation of trapped sine-Gordon solitons. PMID- 10032000 TI - Failure of the classical field model of Mossbauer spectroscopy. PMID- 10032001 TI - Broken symmetries in a one-dimensional half-filled band with arbitrarily long range Coulomb interactions. PMID- 10032002 TI - Injected-hot-electron transport in GaAs. PMID- 10032003 TI - Subpicosecond spectral hole burning due to nonthermalized photoexcited carriers in GaAs. PMID- 10032004 TI - Spin susceptibility of the two-dimensional electron gas with open Fermi surface under magnetic field. PMID- 10032005 TI - Detection of magnetic moments of Ni and Fe atoms on the surface of Pb. PMID- 10032006 TI - Strong magnetic dichroism predicted in the M4,5 x-ray absorption spectra of magnetic rare-earth materials. PMID- 10032007 TI - Unitarity constraints on the nondegenerate-Majorana-neutrino model. PMID- 10032008 TI - Modified generalized valence-bond method: Prediction of double-well states for Cr2 and Mo2. PMID- 10032009 TI - Kinetic growth models. PMID- 10032010 TI - Majid et al. respond. PMID- 10032013 TI - Approximation scheme for the quantum Liouville equation using phase-space distribution functions. PMID- 10032012 TI - Experiments to detect possible weak violations of special relativity. PMID- 10032014 TI - Measurements of Cabibbo-suppressed hadronic decays of charmed D+ and D0 mesons. PMID- 10032015 TI - Limits on charm production in hadronic interactions near threshold. PMID- 10032016 TI - Fluctuation effects in hot quark matter: Precursors of chiral transition at finite temperature. PMID- 10032017 TI - Signals of CP nonconservation in hyperon decay. PMID- 10032018 TI - Dimuons from gauge fermions produced in pp-bar collisions. PMID- 10032019 TI - New nu constraints on Majorana mass matrices. PMID- 10032020 TI - Derivation of inelasticity distribution for hadron-hadron collisions in a gluon gluon interaction picture. PMID- 10032021 TI - Nuclear temperatures and the population of particle-unstable states of 6Li in 40Ar-induced reactions on 197Au at E/A=60 MeV. PMID- 10032022 TI - Scintillation from slow protons: A probe of monopole detection capabilities. PMID- 10032023 TI - Possible quasimolecular bands in 32S. PMID- 10032025 TI - Electric-field-induced interferences in autoionizing resonances. PMID- 10032024 TI - Interference narrowing at crossings of sodium Stark resonances. PMID- 10032026 TI - Wake formation by megaelectronvolt-per-nucleon bare H and He ions in large hydrocarbon molecules? PMID- 10032028 TI - Amplitude-dependent properties of a hydrodynamic soliton. PMID- 10032027 TI - Scaling behavior of dilute polymer solutions in elongational flows. PMID- 10032029 TI - Competing instabilities in a rotating layer of mercury heated from below. PMID- 10032030 TI - Three-dimensional self-organization of a magnetohydrodynamic plasma. PMID- 10032031 TI - Theory of the hcp-fcc transition in metals. PMID- 10032032 TI - Nonlinear theory of domain walls and the anomalies of intercalation kinetics. PMID- 10032034 TI - Direct observation of two-dimensional, dynamic clustering and ordering with colloids. PMID- 10032033 TI - In-plane jump diffusion of Li in LiC6. PMID- 10032035 TI - Vacuum tunneling current from an adsorbed atom. PMID- 10032036 TI - Magnetic x-ray scattering studies of holmium using synchro- tron radiation. PMID- 10032037 TI - Mean square displacement of a tracer particle in a hard-core lattice gas. PMID- 10032038 TI - Origin of glass formation. PMID- 10032039 TI - Light-scattering study of a polymer nematic liquid crystal. PMID- 10032040 TI - Evidence for Anderson-Brinkman-Morel-type state in a heavy-fermion superconductor from ultrasonic attenuation. PMID- 10032042 TI - The photino, the sun, and high-energy neutrinos. PMID- 10032041 TI - NMR study of the charge-density wave in Rb0.30MoO3 single crystal. PMID- 10032043 TI - Structural stability of crystalline compounds. PMID- 10032044 TI - Pettifor and Podloucky respond. PMID- 10032045 TI - Oscillatory structures in GaAs/(AlGa)As tunnel junctions. PMID- 10032047 TI - Many-particle translational symmetries of two-dimensional electrons at rational Landau-level filling. PMID- 10032048 TI - Two-cocycle of a Kac-Moody group. PMID- 10032049 TI - Quasiperiodically forced damped pendula and Schrodinger equations with quasiperiodic potentials: Implications of their equivalence. PMID- 10032050 TI - One-loop finiteness in O(32) open-superstring theory. PMID- 10032051 TI - Subalgebras of loop algebras and symmetries of the Kadomtsev-Petviashvili equation. PMID- 10032052 TI - Experimental limits on the free-proton lifetime for two- and three-body decay modes. PMID- 10032054 TI - Anomalous ultraviolet divergences and renormalizability of the light-cone gauge. PMID- 10032055 TI - General solution of the chiral Schwinger model. PMID- 10032053 TI - Precise measurements of the leptonic branching ratios of the tau lepton. PMID- 10032056 TI - Does the Cabibbo angle vanish in Fermi matrix elements of high-J states? PMID- 10032057 TI - Chemical effect on the 2D5/2: 2D3/2 branching ratio of the 5d photoionization of Pb. PMID- 10032058 TI - Inhibited spontaneous emission by a Rydberg atom. PMID- 10032059 TI - Mechanisms for multiple ionization of atoms by strong pulsed lasers. PMID- 10032060 TI - Observation of fluorescence of the HeH molecule. PMID- 10032061 TI - Self-reflected wave inside a very dense saturable absorber. PMID- 10032062 TI - Excitation of coherent phonon polaritons with femtosecond optical pulses. PMID- 10032063 TI - Universality of the Kosterlitz-Thouless transition in 4He films as function of thickness. PMID- 10032064 TI - Observation of singular diameters in the coexistence curves of metals. PMID- 10032065 TI - Origin of the singular diameter in the coexistence curve of a metal. PMID- 10032066 TI - Direct observations of the (1 x 2) surface reconstruction on the Pt(110) plane. PMID- 10032067 TI - Local structure at Mn sites in icosahedral Mn-Al quasicrystals. PMID- 10032068 TI - Dynamical phase transitions in hierarchical structures. PMID- 10032069 TI - Time-of-flight energy and mass analysis of metal-helide ions and their formation and dissociation. PMID- 10032070 TI - Composition, structure, and electric field variations in photodeposition. PMID- 10032071 TI - Three-dimensional and relativistic effects in layered 1T-TiSe2. PMID- 10032072 TI - Solution of the Kondo problem by diagrammatic methods. PMID- 10032073 TI - Electron holographic observations of the electrostatic field associated with thin reverse-biased p-n junctions. PMID- 10032074 TI - Direct observation of ballistic transport in GaAs. PMID- 10032075 TI - Identification of the 0.82-eV electron trap, EL2 in GaAs, as an isolated antisite arsenic defect. PMID- 10032077 TI - 1/f noise of granular metal-insulator composites. PMID- 10032076 TI - Magnetoplasmon excitations from partially filled Landau levels in two dimensions. PMID- 10032078 TI - Quantum Hall effect in a two-dimensional electron-hole gas. PMID- 10032080 TI - Nonexistence of a chiral Schwinger model. PMID- 10032079 TI - Random field critical behavior: Finite-size effects. PMID- 10032081 TI - Jackiw and Rajaraman respond. PMID- 10032082 TI - Heavy-neutrino emission. PMID- 10032083 TI - Comment on "Two-dimensional pressure of 4He monolayers: First-order melting of the incommensurate solid" PMID- 10032084 TI - Hurlbut and Dash respond. PMID- 10032085 TI - Fisher renormalization at the smectic-A1 to smectic-A2 transition in a mixture. PMID- 10032087 TI - Microwave ionization of hydrogen atoms: Experiment vs classical dynamics. PMID- 10032088 TI - Depinning by quenched randomness. PMID- 10032089 TI - Lepton-nucleus deep-inelastic scattering. PMID- 10032090 TI - Complex Langevin simulation of the SU(3) spin model with nonzero chemical potential. PMID- 10032091 TI - Microchips as precision quantum-electrodynamic probes. PMID- 10032093 TI - Solution of the strong CP problem by color exchange. PMID- 10032092 TI - Regularities of fermion masses and mixing angles and their extension to the fourth generation. PMID- 10032094 TI - Exclusive production of higher-generation hadrons and form-factor zeros in quantum chromodynamics. PMID- 10032095 TI - Tritium electromagnetic form factors. PMID- 10032096 TI - Is there a consistent theory of large-amplitude collective motion? PMID- 10032097 TI - Role of deformation in the intrusion of the h9/2 levels below the Z=82 proton shell. PMID- 10032098 TI - Quantum oscillator in a blackbody radiation field. PMID- 10032099 TI - Generalized oscillator strengths for 4s 2S-->4p 2P transition in Cu: Comparison of experiment and theory. PMID- 10032101 TI - Ultranarrow nonlinear optical resonances in solids. PMID- 10032100 TI - Observation of quadrupole and hexadecapole moments of the electronic charge cloud produced in electron-loss collisions. PMID- 10032102 TI - Controlled evolution of highly elongated tokamak plasmas. PMID- 10032103 TI - High-power microwave generation from a virtual cathode device. PMID- 10032104 TI - Conditional eddies, or clumps, in ion-beam-generated turbulence. PMID- 10032105 TI - Incommensurate morphology of calaverite (AuTe2) crystals. PMID- 10032106 TI - New texture with flow in 3He-A. PMID- 10032108 TI - Diffuse LEED and surface crystallography. PMID- 10032107 TI - Observation of a Kohn anomaly in the surface-phonon dispersion curves of Pt(111). PMID- 10032110 TI - Tricritical and critical-end-point behavior of interfacial tensions in fluid mixtures. PMID- 10032109 TI - Problem of universality in phase transitions on hierarchical lattices. PMID- 10032111 TI - Glassy to icosahedral phase transformation in Pd-U-Si alloys. PMID- 10032112 TI - Possible resolution of the angular momentum paradox: Fractional charge, twist, and topology in 3He-A. PMID- 10032114 TI - Density waves in high magnetic fields: A metal-insulator transition. PMID- 10032113 TI - High-temperature SiO2 decomposition at the SiO2/Si interface. PMID- 10032115 TI - Bistability and metastability of the gallium vacancy in GaAs: The actuator of EL2? PMID- 10032116 TI - Novel interference effects between parallel quantum wells. PMID- 10032117 TI - Lifetime of image surface states. PMID- 10032118 TI - Observation of nonlinear electrical transport at the onset of a Peierls transition in an organic conductor. PMID- 10032120 TI - Hot electron relaxation in GaAs quantum wells. PMID- 10032119 TI - Metal-insulator transition in quench-condensed AlxGe1-x: "Scaling" and tunneling experiments. PMID- 10032121 TI - Diffuse cosmic gamma-ray background as a probe of cosmological gravitino regeneration and decay. PMID- 10032122 TI - Comment on "Renormalization, unstable manifolds, and the fractal structure of mode locking" PMID- 10032123 TI - Comment on "High-momentum-transfer inelastic neutron scattering from liquid helium-3" PMID- 10032124 TI - Sokol et al. respond. PMID- 10032127 TI - Monte Carlo method for quantum spins using boson world lines. PMID- 10032125 TI - Comment on "Structure of rapidly quenched Al-Mn" PMID- 10032128 TI - Exact dynamically convergent calculations of the frequency-dependent density response function. PMID- 10032130 TI - Electric dipole moment of the electron and CP nonconservation in muon decay. PMID- 10032129 TI - Gravitomagnetic pole and mass quantization. PMID- 10032131 TI - Naturalness for multiscalar models and radiative stability. PMID- 10032132 TI - Induced angular momentum in (2+1)-dimensional QED. PMID- 10032133 TI - Derivative expansion of the effective action. PMID- 10032134 TI - Monopoles on strings. PMID- 10032135 TI - First observation and cross-section measurement of nu e+e---> nu e+e- PMID- 10032136 TI - Slow and fast high-spin sequences in 158Er. PMID- 10032137 TI - Observation of squeezed states generated by four-wave mixing in an optical cavity. PMID- 10032138 TI - Long-time impurity confinement as a precursor to disruptions in ohmically heated tokamaks. PMID- 10032139 TI - Comparison of the radial potential profile measured in a tokamak to predictions of stochastic magnetic field theory. PMID- 10032140 TI - Magnetic field and nonlocal transport in laser-created plasmas. PMID- 10032141 TI - Critical behavior of binary liquid mixtures of deuterated and protonated polymers. PMID- 10032143 TI - Spontaneous Raman scattering from shocked water. PMID- 10032142 TI - Dynamics of semidilute polymer rods: An alternative to cages. PMID- 10032144 TI - Precursor-mediated molecular chemisorption and thermal desorption: The interrelationships among energetics, kinetics, and adsorbate lattice structures. PMID- 10032145 TI - Extinction of the Kapitza anomaly for phonons along the surface normal direction. PMID- 10032147 TI - Zigzag disclinations in biaxial nematic liquid crystals. PMID- 10032146 TI - Continuous ferroelastic phase transition of a KBr:KCN mixed crystal. PMID- 10032148 TI - Momentum distribution of 3He. PMID- 10032149 TI - Critical kinetics of volume phase transition of gels. PMID- 10032150 TI - Bond orientational order in the randomly diluted elastic network. PMID- 10032151 TI - Magnetic excitations in amorphous germanium studied by high-field calorimetry. PMID- 10032152 TI - Pressure-induced valence change of Eu in Eu(Pd0.8Au0.2)2Si2: Collapse of magnetic order. PMID- 10032153 TI - Unified approach for molecular dynamics and density-functional theory. PMID- 10032154 TI - Quantum Monte Carlo simulation of high-field electron transport: An application to silicon dioxide. PMID- 10032155 TI - Observation of a collective mode in superconducting UBe13. PMID- 10032156 TI - Probing the wave function of a surface state in Ag(111): A new approach. PMID- 10032157 TI - 1/f noise and grain-boundary diffusion in aluminum and aluminum alloys. PMID- 10032158 TI - In situ Mossbauer analysis of hyperfine interactions near Fe(110) surfaces and interfaces. PMID- 10032159 TI - Cascade of field-induced phase transitions in the organic metal tetramethyltetraselenafulvalenium perchlorate PMID- 10032160 TI - Exact inequality for random systems: Application to random fields. PMID- 10032161 TI - Bridging the "pressure gap" between ultrahigh-vacuum surface physics and high pressure catalysis. PMID- 10032162 TI - Comment on "High-resolution scanning-ion-microprobe study of graphite and its intercalation compounds" PMID- 10032163 TI - Hwand and Levi-Setti respond. PMID- 10032164 TI - Diffusion on self-avoiding walks with bridges. PMID- 10032166 TI - Unbroken quantum realism, from microscopic to macroscopic levels. PMID- 10032167 TI - Morphology of a class of kinetic growth models. PMID- 10032168 TI - Suppression of singularities by the g55 field with mass and classical vacuum polarization in a classical Kaluza-Klein theory. PMID- 10032169 TI - JWKB connection-formula problem revisited via Borel summation. PMID- 10032171 TI - Experimental predictions of lattice and perturbative quantum chromodynamics. PMID- 10032170 TI - Statistical mechanics of probabilistic cellular automata. PMID- 10032172 TI - Search for quark deconfinement: Strangeness production in pp, dd, p alpha, and alpha alpha collisions at sqrt sNN =31.5 and 44 GeV. PMID- 10032173 TI - Evidence against a stable dibaryon from lattice QCD. PMID- 10032174 TI - Limits on like-sign dilepton production in nu micro interactions. PMID- 10032175 TI - Yukawa couplings in superstring compactification. PMID- 10032177 TI - Cross sections for monopole-induced proton decay in SU(5). PMID- 10032176 TI - Measurement of Sigma - production polarization and magnetic moment. PMID- 10032178 TI - Low-energy-electron attachment to oxygen clusters produced by nozzle expansion. PMID- 10032179 TI - New concepts of metallic bonding based on valence-bond ideas. PMID- 10032180 TI - Anticrossing spectroscopy of Rydberg atoms using blackbody radiation. PMID- 10032181 TI - Instabilities of a homogeneously broadened laser. PMID- 10032182 TI - Pattern selection near the onset of convection: The Eckhaus instability. PMID- 10032183 TI - Observation of large amplitude, narrow-band density fluctuations in the interior region of an Ohmic tokamak plasma. PMID- 10032184 TI - Inductance effect of runaways on lower-hybrid-current ramping. PMID- 10032185 TI - Acceleration of beam ions during major-radius compression in the tokamak fusion test reactor. PMID- 10032186 TI - Sticking of molecular hydrogen on a cold Cu(100) surface. PMID- 10032187 TI - Experimental investigation of beta 1-H on W(100) using high-resolution electron energy-loss spectroscopy: Bond distances, scattering mechanisms, and impact scattering selection rules. PMID- 10032188 TI - Oxygen on Fe(100): An initial-oxidation study by spin-polarized Auger spectroscopy. PMID- 10032189 TI - Three-photon spectroscopy of exciton polaritons in alkali halides. PMID- 10032190 TI - Relation of random and competing nonrandom couplings for spin-glasses. PMID- 10032191 TI - Lifetime enhancement of two-dimensional excitons by the quantum-confined Stark effect. PMID- 10032192 TI - Model for the E2' center in alpha quartz. PMID- 10032194 TI - Galactic antiprotons from photinos. PMID- 10032193 TI - Catalytic promotion and poisoning: All-electron local-density-functional theory of CO on Ni(001) surfaces coadsorbed with K or S. PMID- 10032195 TI - Energy-level statistics of integrable quantum systems. PMID- 10032198 TI - Rare kaon decay K+--> pi +l+l- PMID- 10032197 TI - Classical transport in modulated structures. PMID- 10032199 TI - Domain walls in superstring models. PMID- 10032201 TI - Unstable neutrinos from gravitational stellar collapse and Cygnus X-3. PMID- 10032200 TI - Order of the deconfining transition for finite-temperature QCD in the presence of dynamical quarks. PMID- 10032202 TI - Pion structure as observed in the reaction pi -N--> micro+ micro-X at 80 GeV/c. PMID- 10032203 TI - CP nonconservation in Bs0 decays: A searching ground for new physics. PMID- 10032204 TI - String-generated gravity models. PMID- 10032205 TI - Subthreshold kaon production as a probe of the nuclear equation of state. PMID- 10032206 TI - Giant Gamow-Teller excitation of 148Dy populated in beta + decay. PMID- 10032207 TI - Interpretation of the breakup reaction dp-->ppn in the incident-deuteron-momentum range 2.0-3.7 GeV/c in terms of free Np scattering. PMID- 10032208 TI - t20 in pi +d elastic scattering between 118 and 148 MeV. PMID- 10032209 TI - Measurements of interaction cross sections and nuclear radii in the light p-shell region. PMID- 10032210 TI - Measurement of parity nonconservation in atomic cesium. PMID- 10032211 TI - Fluctuation spectroscopy by tunable energy compensation: Application to radiator reorientation kernels. PMID- 10032212 TI - Viscous fingering fractals in porous media. PMID- 10032213 TI - Observation of weak localization of light in a random medium. PMID- 10032214 TI - Weak localization and coherent backscattering of photons in disordered media. PMID- 10032215 TI - Dipole activity of surface phonons on Si(111)2 x 1. PMID- 10032216 TI - Observation of singly quantized dissipation events obeying the Josephson frequency relation in the critical flow of superfluid 4He through an aperture. PMID- 10032217 TI - Persistent currents and dissipation in the A and B phases of liquid 3He. PMID- 10032219 TI - Spontaneous spin polarization of photoelectrons from GaAs. PMID- 10032218 TI - Molecular theory on the entanglement effect of rodlike polymers. PMID- 10032220 TI - ESR in a heavy-fermion alloy (UBe13) doped with local moments. PMID- 10032221 TI - Phenomenological aspects of heavy fermions. PMID- 10032223 TI - Observation of isolated carbon atoms and the study of their mobility on Pt clusters by NMR. PMID- 10032222 TI - Superconducting and magnetic transitions in the heavy-fermion system URu2Si2. PMID- 10032224 TI - Relativistic cosmic-ray spectra in the fully nonlinear theory of shock acceleration. PMID- 10032226 TI - Markov-Tree model of intrinsic transport in Hamiltonian systems. PMID- 10032227 TI - Measurement of the Wigner function. PMID- 10032228 TI - Study of inclusive KS0, Lambda, and Lambda -bar production in diffractive gamma p interactions. PMID- 10032229 TI - Truncated QCD shower calculation of heavy-quark production in pp-bar collisions with B0-B-bar 0 mixing. PMID- 10032230 TI - Spontaneous breakdown of parity as the origin of isospin breaking. PMID- 10032231 TI - Duality-invariant equidistance between the units of electric and magnetic charge. PMID- 10032232 TI - Signatures for horizontal gauge bosons in very energetic hadronic collisions. PMID- 10032233 TI - Chiral loops in pi 0, eta 0--> gamma gamma and eta - eta ' mixing. PMID- 10032234 TI - Lattice calculation of weak matrix elements. PMID- 10032235 TI - Hybrid stochastic differential equations applied to quantum chromodynamics. PMID- 10032236 TI - Effects of extra light Z bosons in unified and superstring models. PMID- 10032238 TI - Time-dependent Dirac equation with relativistic mean-field dynamics applied to heavy-ion scattering. PMID- 10032237 TI - Evidence for a direct three-nucleon pion-absorption process. PMID- 10032239 TI - Photon antibunching and squeezing for a single atom in a resonant cavity. PMID- 10032241 TI - Global universality at the onset of chaos: Results of a forced Rayleigh-Benard experiment. PMID- 10032240 TI - Quantum fluctuations, pump noise, and the growth of laser radiation. PMID- 10032242 TI - Correlated spontaneous-emission lasers: Quenching of quantum fluctuations in the relative phase angle. PMID- 10032243 TI - In situ observation of a roughening transition of the (1012-bar) satellite crystal surface of modulated ( (CH3)4N)2ZnCl4. PMID- 10032244 TI - Kinetics of stage ordering and stage transitions. PMID- 10032245 TI - Prediction of high-energy spin-wave excitation in iron. PMID- 10032246 TI - Translational mass of an exciton. PMID- 10032247 TI - Charge-density-wave depinning: A dynamical critical phenomenon? PMID- 10032248 TI - Orientational and isotope effects in field dissociation by atomic tunneling of compound ions. PMID- 10032250 TI - Causality of the linearized relativistic Boltzmann equationp. PMID- 10032251 TI - Could Goldstone bosons generate an observable 1/R potential? PMID- 10032252 TI - Deconfinement for SU(2) gauge theory in 2+1 dimensions. PMID- 10032254 TI - Resolution of any interacting-boson-model Hamiltonian into intrinsic and collective parts. PMID- 10032253 TI - Characterization of gross-structure resonances in angular-momentum-mismatched channels in heavy-ion collisions. PMID- 10032255 TI - Local density-functional theory of frequency-dependent linear response. PMID- 10032257 TI - Propagative phase dynamics for systems with Galilean invariance. PMID- 10032256 TI - Structure and bonding in small silicon clusters. PMID- 10032258 TI - Modulation of intense relativistic electron beams by an external microwave source. PMID- 10032259 TI - Harmonic phase conjugation in liquid suspensions of microparticles via higher order gratings. PMID- 10032260 TI - Relaxation of spheromak plasmas toward a minimum-energy state and global magnetic fluctuations. PMID- 10032261 TI - Diffusivity of Ni in an amorphous Ni-Zr alloy. PMID- 10032262 TI - Experimental evidence of linear ordering of deuterium in alpha -LuDx. PMID- 10032263 TI - Coulomb splittings in glasses. PMID- 10032264 TI - Crystal and quasicrystal structures in Al-Mn-Si alloys. PMID- 10032265 TI - Quantum dynamics and statistics of vortices in two-dimensional superfluids. PMID- 10032266 TI - Thermodynamic polydispersity and the Flory exponent. PMID- 10032267 TI - Composition-dependent hydrogen motion in a random alloy, VxNb1-xH0.2: From localized motion at V atoms to long-range hydrogen diffusion. PMID- 10032268 TI - Fractal structure of TiH2 aggregates in a CuTi matrix. PMID- 10032269 TI - Observation of molecular reorientation at a two-dimensional-liquid phase transition. PMID- 10032271 TI - Direct measurement of Thouless's length-dependent conductance on a submicron length scale. PMID- 10032270 TI - Novel surface phase transition in nematic liquid crystals: Wetting and the Kosterlitz-Thouless transition. PMID- 10032272 TI - Density of states for a two-dimensional Penrose lattice: Evidence of a strong Van Hove singularity. PMID- 10032273 TI - Scaling behavior in the charge-density-wave conductivity of niobium triselenide. PMID- 10032274 TI - Roughening by impurities at finite temperatures. PMID- 10032277 TI - Discrete model of chemical turbulence. PMID- 10032275 TI - Huse, Henley, and Fisher respond. PMID- 10032278 TI - Geometric symmetry breaking. PMID- 10032279 TI - A priori definition of maximal CP nonconservation. PMID- 10032280 TI - Where are the BB-bar mixing effects observable in the Upsilon region? PMID- 10032281 TI - Emission spectra of bound helium hydride. PMID- 10032282 TI - Phase winding and flow alignment in freely suspended films of smectic-C liquid crystals. PMID- 10032283 TI - Measurements of persistent melting-pressure depression during melting of polarized 3He. PMID- 10032284 TI - Correlations and droplet growth. PMID- 10032286 TI - Superheating of small solid-argon bubbles in aluminum. PMID- 10032285 TI - Quasielastic peak in electron scattering from metallic surfaces. PMID- 10032287 TI - Superfluidity of 4He confined in microscopic bubbles in copper. PMID- 10032288 TI - Magnetic structure of Gd-Y single-crystal alloys from neutron diffraction and magnetization measurements. PMID- 10032290 TI - Experimental proof of impurity Auger recombination in silicon. PMID- 10032289 TI - Antivortex paramagnetism in the magnetic-field-induced superconducting state of EuxSn1-xMo6S8. PMID- 10032291 TI - Metastable molecular precursor for the dissociative adsorption of oxygen on Si(111). PMID- 10032292 TI - Spontaneous magnetic order induced by an intratriplet mode in the dimerized singlet-ground-state system Cs3Cr2I9. PMID- 10032293 TI - Aperiodic magnetoresistance oscillations in narrow inversion layers in Si. PMID- 10032294 TI - Field-theoretical approach to the dynamical many-polaron system in one spatial dimension. PMID- 10032295 TI - f-f excitations by resonant electron-exchange collisions in rare-earth metals. PMID- 10032297 TI - Latent-image generation by deposition of monodisperse silver clusters. PMID- 10032296 TI - Disruptive scattering effect on the indirect spin-spin interaction in metals. PMID- 10032299 TI - Spin-dependent forces in heavy-quark systems. PMID- 10032298 TI - Probing the desert with boson and fermion masses. PMID- 10032301 TI - Sherwin, Hall, and Zettl respond. PMID- 10032300 TI - Comment on "Chaotic ac conductivity in the charge-density-wave state of (TaSe4)2I. PMID- 10032302 TI - Tricritical point in random-field Ising model. PMID- 10032303 TI - Field theory for nonlinear critical relaxation near a surface. PMID- 10032304 TI - New formula for gravitational radiation energy loss in general relativity. PMID- 10032305 TI - Time evolution and eigenstates of a quantum iterative system. PMID- 10032306 TI - Absence of first-order phase transition in SU(5) lattice gauge theory with renormalization-group-improved action. PMID- 10032307 TI - Renormalization of g-boson effects in the interacting-boson Hamiltonian. PMID- 10032308 TI - Transfer cross sections for 58Ni PMID- 10032309 TI - Time-resolved laser spectroscopy on high-lying states in neutral oxygen. PMID- 10032310 TI - Electric birefringence of critical micellar solutions. PMID- 10032311 TI - Surface memory effects in liquid crystals: Influence of surface composition. PMID- 10032312 TI - Noise scaling in continuum percolating films. PMID- 10032313 TI - Two-photon photoemission via image-potential states. PMID- 10032315 TI - First-order transition to a metallic state in polyacetylene: A strong-coupling polaronic metal. PMID- 10032314 TI - Mean-field theory of the Potts glass. PMID- 10032316 TI - Resolution of the nature of the ferromagnetic state in ternary EuRh3B2: Giant Mossbauer quadrupole splitting. PMID- 10032317 TI - Unusual Eu valence and magnetic behavior in EuxRh3B2. PMID- 10032319 TI - Transport processes via localized states in thin a-Si tunnel barriers. PMID- 10032318 TI - Binding energy and spectral width of Si 2p core excitons in SixGe1-x alloys. PMID- 10032320 TI - Optical investigation of hole and electron subbands in HgTe-CdTe superlattices. PMID- 10032322 TI - Comment on "Consistent inference of probabilities for reproducible experiments" PMID- 10032321 TI - Spectrum of the cosmic background radiation at millimeter wavelengths. PMID- 10032323 TI - Tikochinsky, Tishby, and Levine respond. PMID- 10032324 TI - Pulse propagation in an absorbing film. PMID- 10032325 TI - Measurement of the formation and evolution of a strange attractor in a laser. PMID- 10032326 TI - Renormalization, unstable manifolds, and the fractal structure of mode locking. PMID- 10032327 TI - Phase transitions in finite systems: Influence of geometry on approach towards bulk critical behavior. PMID- 10032328 TI - Sensitive dependence on parameters in nonlinear dynamics. PMID- 10032329 TI - Density of pseudoscalar states: Evidence for valence glue. PMID- 10032330 TI - Analyzing powers in pi +p elastic scattering at intermediate energies. PMID- 10032331 TI - Renormalizing the nonrenormalizable. PMID- 10032332 TI - Couplings and scales in superstring models. PMID- 10032333 TI - Mixed alignment in the osmium-iridium region. PMID- 10032334 TI - Faddeev Calculation of three-nucleon force contribution to triton binding energy. PMID- 10032335 TI - Bound-free ultraviolet emission from triatomic hydrogen. PMID- 10032336 TI - High n Rydberg atoms and external fields. PMID- 10032337 TI - Heliumlike titanium spectra produced by electron-cyclotron-heated tokamak plasmas. PMID- 10032338 TI - Surface-charge-density relaxation of Ni(113). PMID- 10032340 TI - Collective modes in simple liquids: A semiempirical model. PMID- 10032339 TI - Charge-density waves observed with a tunneling microscope. PMID- 10032341 TI - Oblique-roll electrohydrodynamic instability in nematics. PMID- 10032342 TI - Line shifts in electron channeling radiation from lattice vibrations. PMID- 10032344 TI - Theory for the anomalous Hall constant of mixed-valence systems. PMID- 10032343 TI - Formation of a metallic glass by thermal decomposition of Fe(CO)5. PMID- 10032345 TI - Band gaps and electronic structure of transition-metal compounds. PMID- 10032346 TI - Hot electrons and energy transport in metals at millikelvin temperatures. PMID- 10032347 TI - Lattice vibrations in the strong electron-phonon-interaction system BaPb1-xBixO3 studied by Raman scattering. PMID- 10032348 TI - Localization and size effects in single-crystal Au films. PMID- 10032349 TI - New gapless modes in the fractional quantum Hall effect of multicomponent fermions. PMID- 10032350 TI - Nonlinear gravitational clustering in cosmology. PMID- 10032351 TI - Comment on "Evidence for intrinsic angular momentum in superfluid 3He-A" PMID- 10032353 TI - Comment on "Magnetic-field-induced localization transition in HgCdTe" PMID- 10032352 TI - Hall responds. PMID- 10032354 TI - Rosenbaum et al. respond. PMID- 10032355 TI - Constants of motion and the variational equations. PMID- 10032356 TI - Origins of randomness in physical systems. PMID- 10032357 TI - Ashkin-Teller and Gross-Neveu models: New relations and results. PMID- 10032359 TI - Production of new particles in heavy-ion collisions. PMID- 10032358 TI - A dependence of the inclusive production of hadrons with high transverse momenta. PMID- 10032361 TI - Supersymmetry and ultrahigh-energy cosmic rays. PMID- 10032360 TI - Search for micro-e conversion in Ti. PMID- 10032362 TI - Leptons and "horizontal" neutral scalar bosons from topological particle theory. PMID- 10032363 TI - Skyrmion interactions at short distances. PMID- 10032365 TI - Experimental determination of the energy level of Be-(1s22s2p2) 4P. PMID- 10032366 TI - Total cross-section measurements for positrons and electrons colliding with potassium. PMID- 10032364 TI - Electromagnetic excitation of aligned 7Li nuclei. PMID- 10032367 TI - Chaotic dynamics in a periodically excited air jet. PMID- 10032369 TI - Experimental observation of a codimension-two bifurcation in a binary fluid mixture. PMID- 10032368 TI - Traveling waves and chaos in convection in binary fluid mixtures. PMID- 10032370 TI - Effects of finite ion Larmor radius on high-n ballooning instability in tokamaks. PMID- 10032371 TI - Local power conservation for linear wave propagation in an inhomogeneous plasma. PMID- 10032372 TI - New ordered state between crystalline and amorphous in Ni-Cr particles. PMID- 10032373 TI - New result in surface segregation of Ni-Cu binary alloys. PMID- 10032374 TI - Theory of spin-polarized secondary electrons in transition metals. PMID- 10032375 TI - Critical behavior of the Hall conductivity at the metal-insulator transition. PMID- 10032377 TI - Fractal model for the ac response of a rough interface. PMID- 10032376 TI - Electron-stimulated desorption of neutral NO from Ni: State-specific resonance ionization detection. PMID- 10032378 TI - Arsenic-terminated Ge(111): An ideal 1 x 1 surface. PMID- 10032379 TI - Nonlinear excitations on a quantum ferromagnetic chain. PMID- 10032380 TI - Strings in two-dimensional classical XY models. PMID- 10032381 TI - Direct determination of electron band energies by transmission interference in thin films. PMID- 10032382 TI - Comment on "Microwave background anisotropy and decaying-particle models for a flat universe" PMID- 10032384 TI - Node-avoiding Levy flight: A numerical test of the epsilon expansion. PMID- 10032386 TI - Permanent quark confinement in four-dimensional hierarchical lattice gauge theories of Migdal-Kadanoff type. PMID- 10032385 TI - Numerical corrections of Wu's coefficients for scattering of high-frequency waves from spheres and cylinders. PMID- 10032387 TI - Polarization effects in rho 0-meson production in antiproton-proton interactions at 22.4, 12, and 5.7 GeV/c. PMID- 10032388 TI - Measurement of the ratio Gamma (KL--> pi + pi -)/ Gamma (KL--> pi l nu ) for KL with 65 GeV/c laboratory momentum. PMID- 10032389 TI - Measurement of the topological branching fractions of the tau lepton. PMID- 10032391 TI - Proton ground-state correlations in 48Ca. PMID- 10032390 TI - Determination of the nucleon structure by means of the weak neutral current. PMID- 10032393 TI - Correlations between preequilibrium nucleons. PMID- 10032392 TI - Mass-asymmetric fission of light nuclei. PMID- 10032395 TI - Relativistic impulse approximation for meson-nucleus scattering in the Kemmer Duffin-Petiau formalism. PMID- 10032394 TI - Correlated spin orientations in 12C PMID- 10032397 TI - Pressure-induced cubic to tetragonal transition in CsI. PMID- 10032396 TI - Fixed winding number and the quasiperiodic route to chaos in a convective fluid. PMID- 10032398 TI - Role of relaxation in epitaxial growth: A molecular-dynamics study. PMID- 10032399 TI - Long-range icosahedral orientational order and quasicrystals. PMID- 10032400 TI - Singlet to triplet conversion of metastable He atoms during deexcitation at a Cs covered surface. PMID- 10032401 TI - 4f Photoemission from rare-earth systems. PMID- 10032402 TI - Approach a la Borland to multidimensional localization. PMID- 10032403 TI - Wave functions derived by quantum modeling of the electron density from coherent x-ray diffraction: Beryllium metal. PMID- 10032404 TI - Localization effects in thin potassium wires. PMID- 10032405 TI - Small-angle Rayleigh scattering in CCl4 subjected to a temperature gradient. PMID- 10032409 TI - Are random fractal clusters isotropic? PMID- 10032406 TI - Nonequilibrium distribution in reactive systems. PMID- 10032411 TI - Critical Ising spin dynamics near the percolation threshold. PMID- 10032410 TI - Chaos and Husimi distribution function in quantum mechanics. PMID- 10032412 TI - Universality classes for spreading phenomena: A new model with fixed static but continuously tunable kinetic exponents. PMID- 10032414 TI - Fat fractals on the energy surface. PMID- 10032413 TI - Role of irreversibility in stabilizing complex and nonergodic behavior in locally interacting discrete systems. PMID- 10032415 TI - Measurement of e+e---> micro+ micro-: A test of electroweak theories. PMID- 10032416 TI - Generalized supersymmetric quantum mechanics. PMID- 10032417 TI - Grand unification of three light generations. PMID- 10032418 TI - Fermion mass matrix and strong CP solution in SU(5). PMID- 10032419 TI - Theoretical spectral distributions and total cross sections for neutral subthreshold pion production in carbon-carbon collisions. AB - With use of a recently developed particle-hole theory for pion production from coherent isobar formation and decay, calculations of total cross sections and kinetic-energy distributions for neutral subthreshold pions produced in carbon carbon collisions at incident energies below 100 MeV/nucleon are made and compared with recent experimental data. PMID- 10032420 TI - Measurement of 14N( gamma, pi +)14C (g.s.) at 200 MeV: A test of the distorted wave impulse approximation for charged-pion photoproduction below the Delta (1232) resonance. PMID- 10032421 TI - Spin dependence in superelastic electron scattering from Na(3P). PMID- 10032422 TI - Threshold behavior near an electronic shape resonance: Analysis of the He(3P) threshold in He- photodetachment and determination of the He(2(3)S) electron affinity. PMID- 10032423 TI - Dispersion of nonlinear susceptibilities of Ar, N2, and O2 measured and compared. PMID- 10032424 TI - Flicker noise in frequency fluctuations of lasers. PMID- 10032426 TI - Nonlocal energy deposition in high-intensity laser-plasma interactions. PMID- 10032425 TI - Light polarization of a quasi-isotropic laser with optical feedback. PMID- 10032428 TI - Phase determination of forbidden x-ray reflections in V3Si by virtual Bragg scattering. PMID- 10032427 TI - Observations of the spatial evolution of a potential hump into a strong double layer in a high-voltage straight plasma discharge. PMID- 10032429 TI - New ground state for the Splay-Freedericksz transition in a polymer nematic liquid crystal. PMID- 10032430 TI - Hypersound observations of glass fluctuations. PMID- 10032431 TI - Migration of helium atoms in copper at 25 K. PMID- 10032432 TI - Role of long-wavelength degrees of freedom in the rod-to-coil transition in polymers. PMID- 10032433 TI - Photoemission from a superlattice and a single quantum well. PMID- 10032434 TI - Dependence of 1/f noise on defects induced in copper films by electron irradiation. PMID- 10032435 TI - Coherent-voltage oscillations induced by sliding-charge-density waves: Interface or bulk phenomenon? PMID- 10032436 TI - Noise and chaos in a fractal basin boundary regime of a Josephson junction. PMID- 10032437 TI - Effect of core polarization on the plasma frequency of Cd, In, and Sn. PMID- 10032438 TI - Cyclotron-resonance-induced nonequilibrium phase transition in n-GaAs. PMID- 10032439 TI - Energy level of the 0 to + charge transition of substitutional manganese in silicon. PMID- 10032441 TI - Observation of order-disorder transitions in strained-semiconductor systems. PMID- 10032442 TI - Structure of constrained Hamiltonian systems and Becchi-Rouet-Stora symmetry. PMID- 10032440 TI - Quantum theory of activated events in presence of long-time memory. PMID- 10032443 TI - New standard-model test for future colliders. PMID- 10032444 TI - Symmetry breaking in the lattice Abelian Higgs model. PMID- 10032445 TI - Spin and parity analysis of KK-bar pi system in the D and E/iota regions. PMID- 10032446 TI - Quaternionic quantum field theory. PMID- 10032447 TI - Top-quark mass in grand-unified theories with intermediate scales. PMID- 10032449 TI - Search for the circular polarization of the 1081-keV gamma ray in 18F. PMID- 10032448 TI - Parity mixing of 0(+) and 0(-) levels in 18F. PMID- 10032450 TI - Experimental search for a heavy neutrino in the beta spectrum of 35S. PMID- 10032451 TI - Fission and particle decay of cold compound nuclei with high angular momentum. PMID- 10032452 TI - Atomic effects and heavy-neutrino emission in beta decay. PMID- 10032453 TI - Deformation of very light rare-earth nuclei. PMID- 10032454 TI - One- and two-photon dissociation of Na2: Angular, velocity, and internal-state distributions of atomic fragments studied by Doppler spectroscopy. PMID- 10032455 TI - Intermolecular Coriolis and centrifugal forces in chiral molecules: Laboratory frame differences between enantiomers and racemic mixtures. PMID- 10032457 TI - Nonlinear kinetic transport of electrons and magnetic field in laser-produced plasmas. PMID- 10032456 TI - Enhanced four-wave mixing by use of frequency-shifted optical waves in photorefractive BaTiO3. PMID- 10032458 TI - Frequency scaling of the lower-hybrid-current-drive density limit in tokamak plasmas. PMID- 10032459 TI - Laser-induced freezing. PMID- 10032461 TI - New experimental finding in two-dimensional dendritic crystal growth. PMID- 10032460 TI - Self-consistent calculation of the q dependence of the electron-phonon coupling in aluminum. PMID- 10032462 TI - Electronic damping of hydrogen vibration on the W(100) surface. PMID- 10032463 TI - Unit-cell structure of rapidly cooled Al-Mn alloys with icosahedral symmetry. PMID- 10032464 TI - Excitation of hydrogen motion inside a nickel vacancy. PMID- 10032465 TI - Fluctuation driven first-order phase transition, below four dimensions, in the random-field Ising model with a Gaussian random-field distribution. PMID- 10032466 TI - Nature of single-localized-electron states derived from tunneling measurements. PMID- 10032467 TI - Evidence for magnetism in the low-temperature charge-density-wave phase of NbSe3. PMID- 10032468 TI - Elastic scattering of exciton polaritons by neutral impurities. PMID- 10032469 TI - First observation of a magnetic-exchange-induced valence transition. PMID- 10032471 TI - Charge-density excitation on a lateral surface of a semiconductor superlattice and edge plasmons of a two-dimensional electron gas. PMID- 10032470 TI - Density of states and de Haas-van Alphen effect in two-dimensional electron systems. PMID- 10032472 TI - Frequency-shifted polaron coupling in Ga0.47In0.53As heterojunctions. PMID- 10032473 TI - Spatial and temporal structure of chaotic instabilities in an electron-hole plasma in Ge. PMID- 10032474 TI - Gravitational-wave emission from rotating gravitational collapse. PMID- 10032475 TI - Comment on "Mass and lifetime limits on supersymmetric particles from a proton beam-dump experiment" PMID- 10032477 TI - A universal 1/f power spectrum as the accumulation point of wave turbulence. PMID- 10032478 TI - Quantum tunneling using discrete-time operator difference equations. PMID- 10032479 TI - Exploratory numerical study of discrete quantum gravity. PMID- 10032480 TI - Transient chaos in dissipatively perturbed near-integrable Hamiltonian systems. PMID- 10032481 TI - Variational approach to quantum statistical mechanics of nonlinear systems with application to sine-Gordon chains. PMID- 10032482 TI - Spin-dependent forces in heavy-quark systems. PMID- 10032483 TI - Renormalization-group constraints in supersymmetric theories. PMID- 10032485 TI - Quantum holonomy and the chiral gauge anomaly. PMID- 10032486 TI - Rapidly convergent lower bounds for the Schrodinger-equation ground-state energy. PMID- 10032484 TI - Lambda c production from e+e- annihilation in the Upsilon energy region. PMID- 10032487 TI - Axisymmetric hollowing instability of an intense relativistic electron beam propagating in air. PMID- 10032488 TI - Thermal barrier formation and plasma confinement in the axisymmetrized tandem mirror GAMMA 10. PMID- 10032489 TI - New theory of transport due to like-particle collisions. PMID- 10032490 TI - Enhancement of the plasma potential by fluctuating electric fields near the ion cyclotron frequency. PMID- 10032491 TI - Silver films condensed at 300 and 90 K: Scanning tunneling microscopy of their surface topography. PMID- 10032492 TI - Velocity of longitudinal sound and F2s in liquid 3He. PMID- 10032493 TI - Crystallography of In on GaAs(110): Possible relationship of laterally inhomogeneous structure of Fermi-level pinning. PMID- 10032494 TI - Anomalous low-temperature susceptibility of solid 3He at high molar volumes. PMID- 10032495 TI - Phonon-fracton crossover on fractal lattices. PMID- 10032496 TI - Magnetization study of the field-induced transitions in tetramethyltetraselenafulvalenium perchlorate, (TMTSF)2ClO4. PMID- 10032497 TI - Direct and exchange contributions in inelastic scattering of spin-polarized electrons from iron. PMID- 10032499 TI - Microscopic mechanism of hydrogen passivation of acceptor shallow levels in silicon. PMID- 10032498 TI - Band-overlap metallization of cesium iodide. PMID- 10032500 TI - Semirelativistic behavior of electrons in InSb in crossed magnetic and electric fields. PMID- 10032501 TI - Electron interferometry at crystal surfaces. PMID- 10032503 TI - Gutzwiller variational approximation to the heavy-fermion ground state of the periodic Anderson model. PMID- 10032502 TI - Tunneling spectroscopy and inverse photoemission: Image and field states. PMID- 10032504 TI - Origin of the oscillation in current-voltage characteristics of GaAs-AlGaAs tunnel junctions. PMID- 10032505 TI - Dielectric study of percolation phenomena in a microemulsion. PMID- 10032506 TI - Macroscopic quantum tunneling in quasi one-dimensional metals. I. Experiment. PMID- 10032507 TI - Macroscopic quantum tunneling in quasi one-dimensional metals. II. Theory. PMID- 10032508 TI - Spin-glass state of a randomly diluted granular superconductor. PMID- 10032509 TI - Josephson-junction array in an irrational magnetic field: A superconducting glass? PMID- 10032510 TI - Magnetizaton of amorphous iron-nickel-phosphorous alloys near the percolation threshold. PMID- 10032511 TI - Occupancy-probability scaling in diffusion-limited aggregation. PMID- 10032512 TI - Comment on "Consistent inference of probabilities for reproducible experiments" PMID- 10032513 TI - Tikochinsky, Tishby, and Levine respond. PMID- 10032514 TI - Reanalysis of the Eoumltvos experiment. PMID- 10032516 TI - Renormalization of charge in Villain lattice gauge theory. PMID- 10032515 TI - How does the SU(2) x U(1) symmetry break in the early Universe? PMID- 10032517 TI - High-energy behavior of multiparticle distributions and their bounds. PMID- 10032518 TI - Measurement of the K0(896) radiative width. PMID- 10032519 TI - Radiative corrections to beta decay and the possibility of a fourth generation. PMID- 10032520 TI - Astrophysical constraints on the couplings of axions, majorons, and familons. PMID- 10032521 TI - Phenomenological mass limits on extra Z of E6 superstrings. PMID- 10032523 TI - Nuclear response function in the Mori formalism. PMID- 10032522 TI - Lifetime measurements of neutron-rich light isotopes 14Be and 17C. PMID- 10032524 TI - Observation of high-n Rydberg series (7 micro+ micro- and on D0-D-bar0 mixing. PMID- 10032551 TI - Skyrmions in the presence of vector mesons. PMID- 10032550 TI - Possible evidence for a radiatively decaying neutrino. PMID- 10032552 TI - Upper limit on the tau-neutrino mass. PMID- 10032554 TI - Anomalous positron peaak in heavy-ion collisions. PMID- 10032553 TI - Precision measurement of the mass difference & PMID- 10032555 TI - Detection of nuclear magnetic resonance on oriented 193mPtFe via the anisotropy of characteristic x rays. PMID- 10032556 TI - Calculation of magic numbers and the stability of small Si clusters. PMID- 10032557 TI - Nonadiabatic electron heating at high-Mach-number perpendicular shocks. PMID- 10032558 TI - Density-functional theory of freezing of hard-sphere mixtures into substitutional solid solutions. PMID- 10032560 TI - Observation of subharmonic routes to chaos in parallel-pumped spin waves in yttrium iron garnet. PMID- 10032559 TI - Role of surface molecular reactions in influencing the growth mechanism and the nature of nonequilibrium surfaces: A Monte-Carlo study of molecular-beam epitaxy. PMID- 10032561 TI - "Melting" of frustrated spins: Mechanism for reentrant ferromagnetic-spin-glass behavior. PMID- 10032563 TI - Spin-glass on a Bethe lattice. PMID- 10032562 TI - Anisotropy of transverse sound in the heavy fermion superconductor UPt3. PMID- 10032564 TI - Quenched phonon -drag in silicon microcontacts. PMID- 10032565 TI - Spin-density-wave transition in dilute YGd single crystals. PMID- 10032566 TI - Collective detection of motion in the presence of noise. PMID- 10032568 TI - Comment on the giant quadrupole interaction in EuxRh3B2. PMID- 10032567 TI - Comment on "New ground state for the Splay-Freedericksz transition in a polymer nematic liquid crystal" PMID- 10032569 TI - Shaheen et al. respond. PMID- 10032571 TI - Skyrmions and vector mesons. PMID- 10032572 TI - Precise determination of PMID- 10032574 TI - The sdg interacting-boson model applied to 168Er. PMID- 10032573 TI - Spectroscopy with the singlet deuteron reaction 12C( alpha,dS=0)14N at 50 MeV. PMID- 10032575 TI - Near-threshold resonance enhancement of neon valence satellites studied with synchrotron radiation. PMID- 10032577 TI - Ultrafast modulation spectroscopy. PMID- 10032576 TI - Experimental studies of a diamagnetic multiplet in odd Rydberg states of lithium. PMID- 10032578 TI - Observation of high-order solitons directly produced by a femtosecond ring laser. PMID- 10032579 TI - Semiclassical theory of light detection in the presence of feedback. PMID- 10032580 TI - Continuum percolation in an interacting system: Exact solution of the Percus Yevick equation for connectivity in liquids. PMID- 10032581 TI - Depth-controlled grazing-incidence diffraction of synchrotron x radiation. PMID- 10032582 TI - Cooling-rate dependence for the spin-glass ground-state energy: Implications for optimization by simulated annealing. PMID- 10032584 TI - Solution to the inertial-drag paradox for a fluid in a porous medium. PMID- 10032583 TI - Information on adsorbate positions from low-energy recoil scattering: Adsorption of hydrogen on Pt. PMID- 10032585 TI - Elasticlike contribution of electric origin to the distortion free energy of nematics. PMID- 10032586 TI - Theory of single-atom imaging in the scanning tunneling microscope. PMID- 10032587 TI - Sharp diffraction maxima from an icosahedral glass. PMID- 10032588 TI - Exact finite-size effects in surface tension. PMID- 10032589 TI - Correlation-induced reentry in impure superconductors. PMID- 10032590 TI - Dephasing time in disordered systems. PMID- 10032591 TI - Quasiperiodic transitions to chaos of instabilities in an electron-hole plasma excited by ac perturbations at one and at two frequencies. PMID- 10032593 TI - Femtosecond excitation of nonthermal carrier populations in GaAs quantum wells. PMID- 10032592 TI - Energy dependence of the single-particle self-energy correction for Ge and Si. PMID- 10032594 TI - Electromechanical properties of charge-density-wave conductors. PMID- 10032595 TI - One-dimensional conduction in the two-dimensional electron gas in a GaAs-AlGaAs heterojunction. PMID- 10032596 TI - New method to study spin conversion of a nuclear-spin rotor with low tunnel splitting. PMID- 10032597 TI - Sliding conductivity without voltage oscillations in niobium triselenide. PMID- 10032598 TI - Evidence for Ising-type critical phenomena in two-dimensional percolation. PMID- 10032599 TI - Comment on "Pair interaction from structural data of dense classical liquids" PMID- 10032600 TI - Levesque, Weis, and Reatto respond. PMID- 10032601 TI - Gallium vacancy and EL2 in GaAs. PMID- 10032602 TI - Baraff and Schluter respond. PMID- 10032603 TI - Improved bounds on the dimension of space-time. PMID- 10032604 TI - Long-range spin-orbit potential. PMID- 10032605 TI - Measurement of the direct photon spectrum from the Upsilon (1S). PMID- 10032606 TI - Search for supermassive magnetic monopoles using mica crystals. PMID- 10032607 TI - Dilaton and chiral-symmetry breaking. PMID- 10032608 TI - Anomalously broad spin distributions in sub-barrier fusion reactions. PMID- 10032609 TI - Equation of state of nuclear matter in the relativistic Dirac-Brueckner approach. PMID- 10032610 TI - Screening effects in multielectron ionization of heavy atoms in intense laser fields. PMID- 10032611 TI - Corona formation and range lengthening in intense-ion-beam-target interaction. PMID- 10032612 TI - Space potential distribution in the ISX-B tokamak. PMID- 10032613 TI - Energy transfer in the plasma wake-field accelerator. PMID- 10032614 TI - Experimental observation of bounce-resonance Landau damping in an axisymmetric mirror plasma. PMID- 10032615 TI - Dendritic and fractal patterns in electrolytic metal deposits. PMID- 10032617 TI - Layer hopping by chains in polymeric smectics? PMID- 10032616 TI - Morphology and microstructure in electrochemical deposition of zinc. PMID- 10032618 TI - Experimental and theoretical evidence for a strong anisotropy of the surface Debye-Waller factor as determined for a monolayer of cobalt on copper (111) by surface extended x-ray-absorption fine structure. PMID- 10032619 TI - Polymorphism of silica and ice. PMID- 10032621 TI - Direct observation of the threshold for electron heating in silicon dioxide. PMID- 10032620 TI - Proposed experimental realization of Anderson localization in random and incommensurate artificially layered systems. PMID- 10032622 TI - Experimental proof for coordination-dependent valence of Tm metal. PMID- 10032624 TI - Dynamical screening of hot carriers in semiconductors from a coupled molecular dynamics and ensemble Monte Carlo simulation. PMID- 10032623 TI - Vortex dynamics and phase transitions in a two-dimensional array of Josephson junctions. PMID- 10032625 TI - Critical behavior of the three-dimensional dilute Ising antiferromagnet in a field. PMID- 10032626 TI - Dynamic core-hole screening effects in the C-KVV Auger line shape of graphite. PMID- 10032627 TI - Possible explanation of the solar-neutrino puzzle. PMID- 10032628 TI - Comment on "Measurements of interaction cross sections and nuclear radii in the light p-shell region" PMID- 10032629 TI - Comment on "Energy transduction in pellet-injected plasmas" PMID- 10032630 TI - Mayers responds. PMID- 10032632 TI - Salomaa and Volovik respond. PMID- 10032631 TI - Comment on "Half-quantum vortices in superfluid 3He-A" PMID- 10032633 TI - Comment on "Role of long-wavelength degrees of freedom in the rod-to-coil transition in polymers" PMID- 10032634 TI - Goldenfeld and Halley respond. PMID- 10032637 TI - Quantum instability of de Sitter space. PMID- 10032638 TI - Theory of chaos in surface waves: The reduction from hydrodynamics to few dimensional dynamics. PMID- 10032639 TI - Detecting Higgs-boson decays into Z pairs. PMID- 10032640 TI - Skyrmion solutions to the Weinberg-Salam model. PMID- 10032642 TI - Bound on the mass and coupling of the hyperphoton by particle physics. PMID- 10032641 TI - Scale-invariant hypercolor model and a dilaton. PMID- 10032643 TI - Experimental signals for hyperphotons. PMID- 10032645 TI - Meson multiplicity versus energy in relativistic nucleus-nucleus collisions. PMID- 10032644 TI - Lambda production in e+e- annihilations at 29 GeV: Comparison with Lund-model predictions. PMID- 10032646 TI - Characterization of hot compound nuclei from binary decay into complex fragments. PMID- 10032647 TI - Twentieth-order perturbation study of the nonadiabatic electric polarizabilities for H2 + via the perturbational-variational Rayleigh-Ritz formalism. PMID- 10032649 TI - Resonant photodetachment of the positronium negative ion. PMID- 10032648 TI - Spin-dependent superelastic scattering from pure angular momentum states of Na(3P). PMID- 10032651 TI - Convection in a binary mixture heated from below. PMID- 10032650 TI - Invariance of the spectrum of light on propagation. PMID- 10032652 TI - Multiple-quantum NMR study of clustering in hydrogenated amorphous silicon. PMID- 10032653 TI - Concept of collective pinning applied to solution hardening of crystals. PMID- 10032654 TI - Local defect structure of highly mobile deuterium in niobium. PMID- 10032655 TI - Acoustic properties of solid 3He at low temperatures. PMID- 10032656 TI - Observation of a simple lithium-associated electron trap in crystalline SiO2. PMID- 10032657 TI - Model for columnar microstructure of thin solid films. PMID- 10032658 TI - Stability of ordered bulk and epitaxial semiconductor alloys. PMID- 10032659 TI - Phase transition in the Ruderman-Kittel-Kasuya-Yosida model of spin-glass. PMID- 10032660 TI - Photoemission-based photovoltage probe of semiconductor surface and interface electronic structure. PMID- 10032661 TI - Acoustic attenuation due to domain walls in anisotropic superconductors, with application to U1-xThxBe13. PMID- 10032662 TI - Superconductivity and localization in the presence of strong spin-orbit scattering. PMID- 10032663 TI - Giant moments in palladium. PMID- 10032664 TI - Are four- and six-monopole configurations singled out? PMID- 10032665 TI - Comment on "Properties of the 208Po(0(+),T=22) double isobaric analog state" PMID- 10032666 TI - Splay rigidity in the diluted central-force elastic network. PMID- 10032669 TI - Novel relativistic effect important in accelerators. PMID- 10032667 TI - Wang and Harris respond. PMID- 10032670 TI - Equilibrium in periodically time-dependent two-level systems. PMID- 10032671 TI - Is Hilbert space too large? PMID- 10032672 TI - Tricritical ratio of length scales in D=4 Abelian Higgs model. PMID- 10032673 TI - New precision determination of the pi - mass from pionic x-rays. PMID- 10032675 TI - Precise determination of the nucleon radius in 3He. PMID- 10032674 TI - Tensor polarization of the deuteron in elastic e-d scattering. PMID- 10032676 TI - Electron-ejection asymmetries by molecular orientation following K-shell excitation of CO. PMID- 10032677 TI - Long-range ion-atom interactions studied by field-dissociation spectroscopy of molecular ions. PMID- 10032678 TI - Generation of thermal muonium in vacuum. PMID- 10032679 TI - Experimental study and analysis of the lithium atom in the presence of parallel electric and magnetic fields. PMID- 10032681 TI - Coherent excitation of phonon polaritons in a centrosymmetric crystal. PMID- 10032680 TI - Coherent backscattering of light by disordered media: Analysis of the peak line shape. PMID- 10032682 TI - Icosahedral symmetry in a metallic phase observed by field-ion microscopy. PMID- 10032683 TI - Intrinsic properties of the two-point functions of the solid-on-solid interface. PMID- 10032684 TI - Direct observation of the charge-density wave in potassium by neutron diffraction. PMID- 10032685 TI - Temperature-gradient-induced open-circuit electric currents in charge-density wave condensates. PMID- 10032686 TI - Quantum interference effects in lithium ring arrays. PMID- 10032688 TI - Permeability measurements during the sol-gel transition: Direct determination of the nu exponent. PMID- 10032687 TI - Determination of interface states for CaF2/Si(111) from near-edge x-ray absorption measurements. PMID- 10032689 TI - Lattice-gas automata for the Navier-Stokes equation. PMID- 10032691 TI - Vardeny and Tauc respond. PMID- 10032690 TI - Correlations and defect energies. PMID- 10032692 TI - Comment on "Identification of anomalous muonium in semiconductors as a vacancy associated center" PMID- 10032693 TI - Sahoo, Mishra, and Das respond. PMID- 10032695 TI - Input states for enhancement of fermion interferometer sensitivity. PMID- 10032697 TI - Circle maps and mode locking in the driven electrical conductivity of barium sodium niobate crystals. PMID- 10032696 TI - Mathematical models of hysteresis. PMID- 10032699 TI - Infinite conservation laws in the one-dimensional Hubbard model. PMID- 10032698 TI - O(n) matrix spin model with unusual critical behavior in the limit n--> PMID- 10032700 TI - Hyperspin and hyperspace. PMID- 10032701 TI - Supercurrent anomaly in the N=1 self-interacting Wess-Zumino model and supersymmetric Yang-Mills theory: Derivation from the anomalous-vacuum expectation-value approach. PMID- 10032702 TI - Basis-independent tests of CP nonconservation in fermion-mass matrices. PMID- 10032703 TI - Quark polarization from W+/- decay asymmetry. PMID- 10032705 TI - Identification of four new neutron-rich rare-earth isotopes. PMID- 10032704 TI - Decay of very hot nuclei. PMID- 10032706 TI - Dissociation channels for multiply charged clusters. PMID- 10032707 TI - Phase-space approach to the density-functional calculation of Compton profiles of atoms and molecules. PMID- 10032709 TI - Double-helix current drive for tokamaks. PMID- 10032708 TI - Structure of C3 as measured by the Coulomb-explosion technique. PMID- 10032710 TI - Gain measurements from start-up and spectrum of a Raman free-electron laser oscillator. PMID- 10032711 TI - Divergence of the Chapman-Enskog expansion. PMID- 10032712 TI - Laser implosion of high-aspect-ratio targets produces thermonuclear neutron yields exceeding 1012 by use of shock multiplexing. PMID- 10032714 TI - Adsorbate-induced surface stress: Phonon anomaly and reconstruction on Ni(001) surfaces. PMID- 10032713 TI - Experimental evidence of continuous melting of ethylene on graphite. PMID- 10032715 TI - Calorimetry of bcc solid 3He through the nuclear magnetic ordering temperature in a magnetic field. PMID- 10032716 TI - Large-scale properties and collapse transition of branched polymers: Exact results on fractal lattices. PMID- 10032717 TI - Oblique roll instability in an electroconvective anisotropic fluid. PMID- 10032718 TI - Bounds on the size of ultrametric structures. PMID- 10032719 TI - Ordered phase of short-range Ising spin-glasses. PMID- 10032720 TI - CdTe-HgTe (1-bar 1-bar 1-bar) heterojunction valence-band discontinuity: A common anion-rule contradiction. PMID- 10032721 TI - Kossel images as direct manifestations of the gap structure of the dispersion surface for colloidal crystals. PMID- 10032722 TI - Infrared behavior and finite-size effects in inflationary cosmology. PMID- 10032723 TI - Critical exponents of the Heisenberg spin chain. PMID- 10032724 TI - Schlottmann responds. PMID- 10032725 TI - Inequality for the infinite-cluster density in Bernoulli percolation. PMID- 10032726 TI - Macroscopic T nonconservation: Prospects for a new experiment. PMID- 10032727 TI - Anisotropic N=3 Ashkin-Teller model: A realization of the supersymmetric Kosterlitz-Thouless transition. PMID- 10032728 TI - Sensitivity of a Hopf bifurcation to multiplicative colored noise. PMID- 10032729 TI - Resonance due to a local spin rotator in high-energy accelerators. PMID- 10032731 TI - Polarization effects in exclusive hadron scattering. PMID- 10032730 TI - Observation of a narrow enhancement in phiKK and phi pi pi final states produced in 400-GeV p-N interactions. PMID- 10032732 TI - QCD-Electroweak interference in vector-boson production. PMID- 10032733 TI - Flavor-changing Yukawa coupling in the standard model and muon polarization in KL -> micro micro-bar. PMID- 10032734 TI - Quark-diagram analysis of two-body charm decays. PMID- 10032736 TI - Entropy production in heavy-ion collisions. PMID- 10032735 TI - Nonlinear sigma model from two-dimensional QCD. PMID- 10032737 TI - Resonant electron-transfer relaxation observed in fluorine K-Auger spectra. PMID- 10032739 TI - Observation of multiple-electron processes in ionization of Xe6+ by electron impact. PMID- 10032738 TI - Measurement of the angular correlation between recoil velocity and angular momentum vectors in molecular photodissociation. PMID- 10032740 TI - Observation of collision-induced subnatural Zeeman-coherence linewidths in the Doppler limit. PMID- 10032741 TI - Relativistic two-photon emission: Lifetime of the 2 1S0 state of helium-like Kr34+ PMID- 10032742 TI - Gain on free-bound transitions by stimulated radiative recombination. PMID- 10032743 TI - Reynolds number scaling of cellular automaton hydrodynamics. PMID- 10032744 TI - Cellular-automata supercomputers for fluid-dynamics modeling. PMID- 10032745 TI - Consequences of time-reversal symmetry for the electric field scaling of transport in stellarators. PMID- 10032746 TI - Extreme swelling of a lyotropic lamellar liquid crystal. PMID- 10032747 TI - 3He-4He mixture films: The 4He coverage dependence of the 3He binding energy. PMID- 10032749 TI - Thermal-conductivity studies near the smectic-A-hexatic-B transition in a liquid cyrstal compound. PMID- 10032748 TI - Temperature dependence of molecular spinning and tumbling fluctuations in the nematic phase. PMID- 10032750 TI - Dipolar and quadrupolar freezing in (KBr)1-x(KCN)x. PMID- 10032751 TI - Dynamical structure factor of amorphous germanium. PMID- 10032752 TI - Broken icosahedral symmetry: A quasicrystalline structure for cholesteric blue phase III. PMID- 10032753 TI - Quasicrystalline textures of cholesteric liquid crystals: Blue phase III? PMID- 10032754 TI - First-principles calculation of the electronic structure of nonperiodic solids: Application to a-Si:H. PMID- 10032755 TI - CdF2:In - A critical positive test of the Toyozawa model of impurity self trapping. PMID- 10032756 TI - Apriori predictions of phase transitions in KCaF3 and RbCaF3: Existence of a new ground state. PMID- 10032757 TI - Fractal-like exciton kinetics in porous glasses, organic membranes, and filter papers. PMID- 10032758 TI - Spin-polarized electron tunneling study of an artificially layered superconductor with internal magnetic field: EuO-Al. PMID- 10032759 TI - Comment on " phi-meson production as a probe of the quark-gluon plasma" PMID- 10032760 TI - Superlattice effects on confined phonons. PMID- 10032761 TI - Comment on "Resonance Raman scattering by confined LO and TO phonons in GaAs-AlAs superlattices" PMID- 10032762 TI - Sood et al. respond. PMID- 10032763 TI - Exact renormalization group for dynamical phase transitions in hierarchical structures. PMID- 10032764 TI - Teitel and Domany respond. PMID- 10032768 TI - Could there be a Planck-scale unitary bootstrap underlying the superstring? PMID- 10032765 TI - Comment on "Landau-Lifshitz equation of ferromagnetism: Exact treatment of the Gilbert damping" PMID- 10032769 TI - Laser-induced axion photoproduction. PMID- 10032770 TI - Lifetimes of the charmed particles D+/-, F+/-, and Lambda c+ produced by neutrinos. PMID- 10032771 TI - Lifetime of D0 charmed mesons produced in neutrino interactions. PMID- 10032772 TI - Measurement of the F-meson lifetime. PMID- 10032773 TI - Left-right asymmetry in inverse pi - photoproduction from a transversely polarized proton target. PMID- 10032775 TI - Periodic orbits of the time-dependent Hartree-Fock equations. PMID- 10032774 TI - Gamma decay of isovector giant resonances built on highly excited states in 111Sn. PMID- 10032776 TI - Chemical dependence of low-energy beta decays as a contribution to resolution of 241Pu half-life anomaly. PMID- 10032778 TI - Light-pressure cooling of a crystal. PMID- 10032777 TI - Effects of finite geometry on the wave number of Taylor-vortex flow. PMID- 10032779 TI - Nonsteady end effects in Hele-Shaw cells. PMID- 10032780 TI - High-gain, long-pulse free-electron-laser oscillator. PMID- 10032781 TI - Rayleigh scattering and weak localization. PMID- 10032782 TI - Control of phase matching and nonlinear generation in dense media by resonant fields. PMID- 10032783 TI - Control of radial potential profile and nonambipolar ion transport in an electron cyclotron resonance mirror plasma. PMID- 10032784 TI - Consequences of bond-orientational order on the macroscopic orientation patterns of thin tilted hexatic liquid-crystal films. PMID- 10032785 TI - Interpenetrating incommensurately modulated lattices with icosahedral symmetry. PMID- 10032786 TI - Icosahedral-phase formation by solid-state interdiffusion. PMID- 10032787 TI - Effect of surface ionization on wetting layers. PMID- 10032788 TI - Structural study of low-temperature-implanted Ni and Pd hydrides. PMID- 10032789 TI - Diffusion to finite-size traps. PMID- 10032790 TI - Observation of long-wavelength interface phonons in a GaAs/AlGaAs superlattice. PMID- 10032791 TI - Resonant interaction of plasmons and intersubband resonances in a two-dimensional electron system. PMID- 10032792 TI - Observation of the triplet excited state of a conjugated-polymer crystal. PMID- 10032793 TI - NMR evidence of the Frohlich mode in Rb0.30MoO3. PMID- 10032794 TI - Quasi one-dimensional conduction in multiple, parallel inversion lines. PMID- 10032796 TI - Spin-lattice relaxation of very pure solid o-D2. PMID- 10032795 TI - Evidence of intrinsic extended pi -bonding band and metalliclike behavior in undoped and doped electropolymerized poly(3-methylthiophene) films. PMID- 10032797 TI - Ultrasonic attenuation in clean anisotropic superconductors. PMID- 10032798 TI - The half-life of 80Zn: The first measurement for an r-process waiting-point nucleus. PMID- 10032799 TI - Two-point correlation for rich clusters of galaxies. PMID- 10032800 TI - Comment on "Predicting the proton mass from pi pi scattering data" PMID- 10032802 TI - Toward a proof of entropy increase in the presence of quantum black holes. PMID- 10032803 TI - One-parameter class of solutions in the chiral Schwinger model. PMID- 10032805 TI - Deuteron as a soliton in the Skyrme model. PMID- 10032804 TI - Decay D0--> phiK-bar0. PMID- 10032807 TI - Iterative maps for bistable excitation of two-level systems. PMID- 10032806 TI - Anisotropic alpha emission from on-line separated isotopes. PMID- 10032808 TI - Production of multiply charged ions by strong uv laser pulses: Theoretical evidence for stepwise ionization. PMID- 10032810 TI - Inhibition of atomic phase decays by squeezed light: A direct effect of squeezing. PMID- 10032809 TI - Atomic autoionization following very fast dissociation of core-excited HBr. PMID- 10032811 TI - Orientational phase transition in the system pyridine/Ag(111): A near-edge x-ray absorption fine-structure study. PMID- 10032812 TI - Electronic and structural properties of a twin boundary in Si. PMID- 10032813 TI - Effective potentials: A new approach and new results for one-dimensional systems with competing length scales. PMID- 10032814 TI - Statics and dynamics of the diffusion-limited polymerization of the conducting polymer polypyrrole. PMID- 10032815 TI - Structure, stability, and origin of (2perp) phases on Si(100). PMID- 10032817 TI - Phase transition studies of germanium to 1.25 Mbar. PMID- 10032816 TI - Microscopic mechanisms governing alkali-metal transport in electron-irradiated glasses. PMID- 10032818 TI - Noise-driven sidebranching in the boundary-layer model of dendritic solidification. PMID- 10032819 TI - Elastic properties of charge-density-wave conductors: ac-dc electric field coupling. PMID- 10032820 TI - Three-spin interaction in CsMn0.28Mg0.72Br3. PMID- 10032821 TI - Sensitivity of the conductance of a disordered metal to the motion of a single atom: Implications for 1/f noise. PMID- 10032822 TI - Interface fluctuations in disordered systems: 5- epsilon expansion and failure of dimensional reduction. PMID- 10032823 TI - Density-functional treatment of an exactly solvable semiconductor model. PMID- 10032824 TI - Surface electronic structure of Si(111)-(7x7) resolved in real space. PMID- 10032826 TI - Magnetic ground state of CePb3. PMID- 10032825 TI - Magnetic resonance of 160Tb oriented in a terbium single crystal at low temperatures. PMID- 10032827 TI - Alkali-metal promotion of a dissociation precursor: N2 on Fe(111). PMID- 10032828 TI - Interaction of two collisionless shocks. PMID- 10032829 TI - Comment on "Nonlinear gravitational clustering in cosmology." PMID- 10032830 TI - Time-dependent density-functional theory: Conceptual and practical aspects. PMID- 10032831 TI - Monte Carlo simulation of self-avoiding surfaces in three dimensions. PMID- 10032832 TI - Wave-packet evolution and quantization. PMID- 10032833 TI - Current-mass ratios of the light quarks. PMID- 10032834 TI - Electromagnetic form factors in the Skyrme model. PMID- 10032835 TI - Tests of time-reversal symmetry in compound-nucleus reactions. PMID- 10032836 TI - Nonperturbative treatment of excitation and ionization in U92+ +U91+ collisions at 1 GeV/amu. PMID- 10032838 TI - Inverse hook method for measuring oscillator strengths. PMID- 10032837 TI - A critical test of many-body theory: The photoionization cross section of Cl as an example of an open-shell atom. PMID- 10032839 TI - Velocity selection and the Saffman-Taylor problem. PMID- 10032840 TI - Analytic theory of the selection mechanism in the Saffman-Taylor problem. PMID- 10032841 TI - Shape selection of Saffman-Taylor fingers. PMID- 10032843 TI - Direct observation of anomalous electron diffusion due to small-scale magnetic turbulence in a tokamak. PMID- 10032844 TI - High-aspect-ratio laser-fusion targets driven by 24-beam uv laser radiation. PMID- 10032842 TI - Current drive by fast magnetosonic waves near the lower hybrid frequency in the JIPP T-IIU tokamak. PMID- 10032845 TI - Vibration eigenmodes and size of microcrystallites in glass: Observation by very low-frequency Raman scattering. PMID- 10032846 TI - Order electricity and surface orientation in nematic liquid crystals. PMID- 10032847 TI - Icosahedrally related decagonal quasicrystal in rapidly cooled Al-14-at.%-Fe alloy. PMID- 10032848 TI - Adsorbate induced Rayleigh phonon gap of p(2x2)O/Pt(111). PMID- 10032850 TI - Long-period stacking transitions in intercalated graphite. PMID- 10032849 TI - Scale invariance and the group structure of quasicrystals. PMID- 10032851 TI - Structure of copper microclusters isolated in solid argon. PMID- 10032852 TI - Tricritical effect of attractive and repulsive forces on a single polymer coil in a poor solvent. PMID- 10032853 TI - Diophantine equation for the Hall conductance of interacting electrons on a torus. PMID- 10032854 TI - Density-functional theory for random alloys: Total energy within the coherent potential approximation. PMID- 10032855 TI - Discrete plasmons in finite semiconductor multilayers. PMID- 10032857 TI - Grain-boundary resistance in polycrystalline metals. PMID- 10032856 TI - Ferromagnetism versus aniferromagnetism in face-centered-cubic iron. PMID- 10032858 TI - Quantum oscillations in the surface-acoustic-wave attenuation caused by a two dimensional electron system. PMID- 10032859 TI - Comment on "Microchips as precision quantum-electrodynamic probes." PMID- 10032860 TI - Comment on "Production mechanisms for a new neutral particle below 2 MeV." PMID- 10032861 TI - Arbitrary pulse shapes in the near-resonance Kapitza-Dirac effect. PMID- 10032862 TI - Low-frequency vibrational modes and the far-infrared dielectric loss in glasses. PMID- 10032863 TI - Comment about fractal sandstone pores. PMID- 10032864 TI - Katz and Thompson respond. PMID- 10032865 TI - Poisson clusters and Poisson voids. PMID- 10032866 TI - String in curved space: Use of spinor representation of a noncompact group. PMID- 10032868 TI - Deconfining phase transition in lattice QCD. PMID- 10032867 TI - Observation of a narrow KK-bar state in J/ psi radiative decays. PMID- 10032869 TI - Deconfinement and timelike quark loops. PMID- 10032870 TI - Definitive tests of the Sigma -nuclear spin-orbit splitting. PMID- 10032872 TI - Field effects on the Rydberg product-state distribution from dielectronic recombination. PMID- 10032871 TI - Modification of atomic collision dynamics by intense ultrashort laser pulses. PMID- 10032873 TI - Selective resonant photoionization processes near the Si 2p edge of tetramethylsilane. PMID- 10032874 TI - Observation of modulational instability in optical fibers. PMID- 10032876 TI - Statistical-mechanics approach to stability of current-carrying plasmas. PMID- 10032877 TI - Trapped-electron stochasticity induced by frequency-modulated waves. PMID- 10032875 TI - Magnetically insulated inertial fusion: A new approach to controlled thermonuclear fusion. PMID- 10032878 TI - Intensity measurements of the forbidden line 975 A PMID- 10032879 TI - Faceting at the silicon (100) crystal-melt interface: Theory and experiment. PMID- 10032881 TI - Measurements of CsI band-gap closure to 93 GPa. PMID- 10032880 TI - Concentration dependence and temperature dependence of hydrogen tunneling in Nb(OH)x. PMID- 10032882 TI - Thermodynamic study of the competition between superconductivity and magnetism in ErRh4B4. PMID- 10032884 TI - Observation of a new universal resistive behavior of two-dimensional superconductors in a magnetic field. PMID- 10032883 TI - Study of local environment in quasicrystalline Al86Mn14 by Mossbauer effect. PMID- 10032885 TI - Electronic states at silicide-silicon interfaces. PMID- 10032886 TI - Longitudinal-field micro+ spin relaxation via quadrupolar level-crossing resonance in Cu at 20 K. PMID- 10032888 TI - Periodicity of the Aharonov-Bohm effect in normal-metal rings. PMID- 10032887 TI - Partially gapped Fermi surface in the heavy-electron superconductor URu2Si2. PMID- 10032889 TI - Volume magnetostriction of rare-earth metals with unstable 4f shells. PMID- 10032891 TI - Origin of nonuniversality in micellar solutions. PMID- 10032890 TI - Self-diffusion of a molecule in porous Vycor glass. PMID- 10032892 TI - Comment on "Instability of the electron-hole plasma in silicon" PMID- 10032893 TI - Comment on Are there "visible" axions? PMID- 10032894 TI - Diffusion in a random potential: Hopping as a dynamical consequence of localization. PMID- 10032895 TI - Change of the adiabatic invariant due to separatrix crossing. PMID- 10032896 TI - Electric dipole moment of 3He. PMID- 10032898 TI - Cosmic production of quarkonium? PMID- 10032897 TI - Lattice gauge-Higgs theories with local PMID- 10032899 TI - Study of three-prong tau decays and determination of the A1 parameters. PMID- 10032900 TI - Search for nonspectator decays of the D0. PMID- 10032901 TI - Direct measurements of charmed-D-meson hadronic branching fractions. PMID- 10032902 TI - Line functionals and string field theory. PMID- 10032904 TI - Some crucial predictions of compositeness for the experiments at 100-GeV e+e- colliders. PMID- 10032903 TI - Stability analysis of M4 >= 2 >= 2 >= 2 in the ten-dimensional Einstein/Maxwell theory. PMID- 10032905 TI - Dynamics of low-energy antiproton annihilation in nuclei as inferred from inclusive proton and pion measurements. PMID- 10032907 TI - Collisional narrowing of a fine-structure Raman transition. PMID- 10032906 TI - Theoritical study of alignment and orientation in Li+ + He collisions. PMID- 10032908 TI - Structural, electronic, and chemisorption properties of small aluminum clusters. PMID- 10032910 TI - Generation, detection, and application of high-intensity photon number eigenstate fields. PMID- 10032909 TI - Shear thickening and turbulence in simple fluids. PMID- 10032911 TI - Plasma current generation and sustainment by electron cyclotron waves, in the WT 2 tokamak. PMID- 10032912 TI - Investigations of the angular distribution of parametrically driven ion acoustic waves. PMID- 10032913 TI - Experimental study of the principles governing tokamak transport. PMID- 10032915 TI - Monovacancy formation enthalpy in silicon. PMID- 10032914 TI - Symmetry and stability of icosahedral and other quasicrystalline phases. PMID- 10032917 TI - Dangling bond in a-Si:H. PMID- 10032916 TI - Structure of random porous materials: Silica aerogel. PMID- 10032918 TI - CO chemisorption on Ni(110): Effect on surface magnetism. PMID- 10032919 TI - Excitonic mobility edge in GaAsxP1-x. PMID- 10032921 TI - Density-functional theory for excited states in a quasi-local-density approximation. PMID- 10032920 TI - Metastable defects in amorphous-silicon thin-film transistors. PMID- 10032923 TI - Phase transitions in finite systems. PMID- 10032922 TI - Local-field effect on the surface conductivity of adsorbed overlayers. PMID- 10032924 TI - Singh and Pathria respond. PMID- 10032925 TI - Comment on "Role of memory effects on the spreading width of a collective state in extended time-dependent Hartree-Fock theory" PMID- 10032927 TI - Dynamic transition in a hierarchical Ising system. PMID- 10032928 TI - Statistical mechanics of the sine-Gordon equation. PMID- 10032929 TI - Dissipative quantum and classical Liouville mechanics of the anharmonic oscillator. PMID- 10032930 TI - Constraints on massive neutrinos in pi -->e nu decay. PMID- 10032932 TI - Unimolecular decomposition of sputtered Aln +, Cun +, and Sin + clusters. PMID- 10032931 TI - Polarization of Lambda 's and Lambda -bar 's in pp, p-barp, and K-p interactions at 176 GeV/c. PMID- 10032933 TI - Free-electron laser and laser electron acceleration based on the megagauss magnetic fields in laser-produced plasmas. PMID- 10032935 TI - Experimental demonstration of controlled collective ion acceleration with the ionization-front accelerator. PMID- 10032934 TI - Stimulated Raman scattering in the presence of filamentation in underdense plasmas. PMID- 10032936 TI - X-ray study of fluctuations near the nematic-smectic-A-smectic-C multicritical point. PMID- 10032938 TI - Critical wetting with short-range forces: Is mean-field theory valid? PMID- 10032937 TI - Light scattering measurements in the 7-barS5-8OCB nematic-smectic-A-smectic-C liquid crystal system. PMID- 10032939 TI - Formation of an icosahedral phase by solid-state reaction. PMID- 10032940 TI - Superconducting-normal phase boundary of a fractal network in a magnetic field. PMID- 10032942 TI - Comprehensive theory of flow properties of 3He moving through superfluid 4He in capillaries. PMID- 10032941 TI - Orientational freezing in KCN-KBr studied by magnetic resonance. PMID- 10032943 TI - Bonding geometry and H vibrations on W(001). PMID- 10032945 TI - Practical method for highly accurate large-scale surface calculations. PMID- 10032944 TI - H and W(001) surface reconstructions: Local bonding to surface states. PMID- 10032946 TI - Onset of global phase coherence in Josephson junction arrays: A dissipative phase transition. PMID- 10032948 TI - Observation by optically detected magnetic resonance of Frenkel pairs in irradiated ZnSe. PMID- 10032947 TI - dc conductivity mechanisms in amorphous group-IV semiconductors. PMID- 10032949 TI - Triad anisotropy and magnetization reversal by 180 degrees domain wall in reentrant Ni79Mn21. PMID- 10032950 TI - Commensurate and incommensurate vortices in two-dimensional xy models. PMID- 10032951 TI - Observation of a positron mobility threshold in gaseous helium. PMID- 10032952 TI - Electron-ion interactions and ionization in a polar solvent. PMID- 10032953 TI - Comment on "Classical hard-sphere fluid in infinitely many dimensions" PMID- 10032954 TI - Frisch, Rivier, and Wyler respond. PMID- 10032955 TI - Location of renormalization-group fixed points. PMID- 10032956 TI - Swendsen responds. PMID- 10032959 TI - Curious properties of quantum ensembles which have been both preselected and post selected. PMID- 10032960 TI - Relationship between classical motion in random media and quantum localization. PMID- 10032961 TI - Upper limit on any intermediate-range force associated with baryon number. PMID- 10032963 TI - Further tests and possible interpretations of a suggested new vectorial interaction. PMID- 10032962 TI - Hypercharge fields and Eotvos-type experiments. PMID- 10032964 TI - Some quantum corrections to Calabi-Yau compactification. PMID- 10032965 TI - Unexpected entrance channel effects in the decay of the compound nucleus 156Er. PMID- 10032966 TI - 218Ra alpha reduced width and its consequences for alpha clustering in the heavy elements. PMID- 10032967 TI - Reaction 12C(e,e'p) in the dip region. PMID- 10032969 TI - Criteria for initiation of tokamak disruptions. PMID- 10032968 TI - First observation of the E2 nuclear-resonance effect in antiprotonic atoms. PMID- 10032970 TI - Growth of fractally rough colloids. PMID- 10032971 TI - Supercooling of liquid hydrogen. PMID- 10032972 TI - f-wave effects in superfluid 3He PMID- 10032973 TI - Phason gap in substitutionally disordered incommensurate systems. PMID- 10032975 TI - One-dimensional fractional quantized Hall effect. PMID- 10032974 TI - Alloy-stabilized semiconducting and magnetic zinc-blende phase of MnTe. PMID- 10032976 TI - Switching and phase-slip centers in charge-density-wave conductors. PMID- 10032977 TI - Universal conductance fluctuations in narrow Si accumulation layers. PMID- 10032978 TI - Isomer shifts and their relation to charge transfer in dilute Fe alloys. PMID- 10032979 TI - Electron-phonon interaction in optical absorption at the Si(111)2 x 1 surface. PMID- 10032980 TI - Accurate exchange-correlation potential for silicon and its discontinuity on addition of an electron. PMID- 10032981 TI - Metal-insulator transition in semimagnetic semiconductors. PMID- 10032982 TI - Comment on the sign in the reanalysis of the Eotvos experiment. PMID- 10032983 TI - Fischbach et al. respond. PMID- 10032985 TI - Fischbach et al. respond. PMID- 10032984 TI - Comment on "Reanalysis of the Eotvos experiment" PMID- 10032987 TI - Hadron pT correlations in quark jets. PMID- 10032986 TI - Comment on "Curious properties of quantum ensembles which have been preselected and post-selected" PMID- 10032988 TI - Survival probability for kinetic self-avoiding walks and inherent scaling invariance and universality of the Flory approximation. PMID- 10032989 TI - Pietronero responds. PMID- 10032990 TI - Comment on "Fractons and the fractal structure of proteins" PMID- 10032991 TI - Anomalous reflection exhibited by a generalized resonance-tunneling equation. PMID- 10032992 TI - Dynamical stability of quantum "chaotic" motion in a hydrogen atom. PMID- 10032993 TI - Interferometric measurement of neutron Fizeau effect. PMID- 10032994 TI - Resolution of the operator-ordering problem by the method of finite elements. PMID- 10032995 TI - Fourier transform: A tool to measure statistical level properties in very complex spectra. PMID- 10032996 TI - Exact integrability of the one-dimensional Hubbard model. PMID- 10032997 TI - Interacting parastrings. PMID- 10032998 TI - Amplitude for n-gluon scattering. PMID- 10032999 TI - Search for the decay micro+-->e+ gamma. PMID- 10033001 TI - Double-photon decay in xenon atoms. PMID- 10033000 TI - Sensitivity of ppol PMID- 10033002 TI - Theory for the transient statistics of a dye laser. PMID- 10033003 TI - Skin currents and compound sawteeth in tokamaks. PMID- 10033005 TI - Experimental measurements of phase space. PMID- 10033004 TI - Measurements of strong electron core heating during Alfven-wave heating on the TCA tokamak. PMID- 10033006 TI - Solute trapping: Comparison of theory with experiment. PMID- 10033007 TI - Rigidity percolation and molecular clustering in network glasses. PMID- 10033008 TI - Family of exponents for Laplace's equation near a polymer. PMID- 10033009 TI - Rigid backbone: A new geometry for percolation. PMID- 10033011 TI - Fracture behavior of a solid with random porosity. PMID- 10033010 TI - Integrated fractal analysis of silica: Adsorption, electronic energy transfer, and small-angle x-ray scattering. PMID- 10033012 TI - Magnetic field penetration depth in the heavy-electron superconductor UBe13. PMID- 10033013 TI - Raman scattering by coupled layer plasmons and in-plane two-dimensional single particle excitations in multi-quantum-well structures. PMID- 10033015 TI - ac susceptibility study of the d=3 random-field critical dynamics. PMID- 10033014 TI - Monte Carlo method for magnetic impurities in metals. PMID- 10033016 TI - Stretched-exponential dielectric relaxation in a charge-density-wave system. PMID- 10033017 TI - Giant-oscillator-strength effect on excitonic optical nonlinearities due to localization. PMID- 10033018 TI - Novel electron tunneling behavior at staging dislocations and the residual resistance of graphite intercalation compounds. PMID- 10033019 TI - Unbinding transitions of interacting membranes. PMID- 10033021 TI - Shnidman responds. PMID- 10033020 TI - Comment on "Origin of nonuniversality in micellar solutions." PMID- 10033023 TI - Ihm responds. PMID- 10033022 TI - Comment on "Origin of the oscillation in current-voltage characteristics of GaAs AlGaAs tunnel junctions" PMID- 10033024 TI - Comment on "Observation of low-energy excitations in KBr1-x(CN)x by Brillouin scattering." PMID- 10033026 TI - Gravitino decay and the cosmic gamma-ray background. PMID- 10033025 TI - Walton, Vanderwal, and Hu respond. PMID- 10033027 TI - Olive and Silk respond. PMID- 10033028 TI - Kinetic phase transitions in an irreversible surface-reaction model. PMID- 10033029 TI - Towards the continuum limit of lattice gauge theory with dynamical fermions. PMID- 10033031 TI - Electrically charged vortices in non-Abelian gauge theories with Chern-Simons term. PMID- 10033030 TI - Flux limit of cosmic-ray magnetic monopoles from a multiply discriminating superconducting detector. PMID- 10033032 TI - Charge-symmetry breaking in neutron-proton elastic scattering. PMID- 10033034 TI - Modular invariance and one-loop finiteness of five-point amplitudes in type-II and heterotic string theories. PMID- 10033033 TI - Test of charge symmetry in neutron-proton elastic scattering at 477 MeV. PMID- 10033035 TI - Empirical evidence for an SO(7) fermion dynamical symmetry in nuclei. PMID- 10033037 TI - Isomorphism of dc-field-induced interference and laser-induced effects in autoionization. PMID- 10033036 TI - Experimental investigation of double-beta decay in 82Se. PMID- 10033038 TI - Suppression of multiphoton ionization with circularly polarized coherent light. PMID- 10033039 TI - Diamagnetism of the hydrogen atom in the quasi-Landau regime. PMID- 10033041 TI - Precision spectroscopy of the nf triplet Rydberg states of H2 and determination of the triplet ionization potential. PMID- 10033040 TI - Fractional quantization of molecular pseudorotation in Na3. PMID- 10033042 TI - Behavior of the chemical potential of neutral atoms in the limit of large nuclear charge. PMID- 10033043 TI - Saturation of Penning ionization at small distances probed by coincidence techniques. PMID- 10033044 TI - Production of very-low-energy highly charged ions by synchrotron radiation. PMID- 10033045 TI - Giant resonances in the electron-impact ionization of heavy atoms and ions. PMID- 10033046 TI - Onset of oscillatory convection in a binary fluid mixture. PMID- 10033047 TI - Theory of the orbitron maser. PMID- 10033048 TI - Saturation of beat-excited plasma waves by electrostatic mode coupling. PMID- 10033049 TI - Fractal growth of crystalline phospholipid domains in monomolecular layers. PMID- 10033051 TI - Lower critical dimension of metallic vector spin-glasses. PMID- 10033050 TI - Local structure of S impurities in GaAs. PMID- 10033052 TI - Some exact results for the electric correlation functions of the eight-vertex model. PMID- 10033053 TI - Percolation in superconductive networks. PMID- 10033054 TI - Comment on "Van der Waals stabilization of bubbles" PMID- 10033055 TI - Wentzell responds. PMID- 10033056 TI - Periodic splay-twist Freedericksz transition in nematic liquid crystals. PMID- 10033057 TI - Molecular dynamics and ab initio total energy calculations. PMID- 10033058 TI - Comparison of an exact fermion Monte Carlo algorithm with the pseudofermion method using staggered fermions. PMID- 10033059 TI - String propagation in a tachyon background. PMID- 10033060 TI - Limitations of heterotic superstring phenomenology. PMID- 10033061 TI - Search for light short-lived particles in radiative upsilon decays. PMID- 10033062 TI - Upper limits for the production of light short-lived neutral particles in radiative Upsilon decay. PMID- 10033064 TI - Linear and nonlinear theory of Cherenkov maser operation in the intense relativistic beam regime. PMID- 10033063 TI - Coexistence of prolate and oblate structures up to spin 40 PMID- 10033065 TI - Nonlinear reflection and refraction of planar ion-acoustic plasma solitons. PMID- 10033067 TI - Vibrational anomalies are not generally due to fractal geometry: Comments on proteins. PMID- 10033066 TI - Thermodynamic criteria for grain-boundary melting; A molecular-dynamics study. PMID- 10033068 TI - Observation of a magnetic antiphase domain structure with long-range order in a synthetic Gd-Y superlattice. PMID- 10033069 TI - Observation of two length scales for the critical fluctuations of RbCaF3. PMID- 10033070 TI - Rate-theory model of polymer crystallization. PMID- 10033071 TI - Asymmetric melting and freezing kinetics in silicon. PMID- 10033072 TI - Cooperative ring exchange and the fractional quantized Hall effect in an incompressible fluid. PMID- 10033073 TI - New method to calculate the muon polarization function. PMID- 10033074 TI - Electron mass tunneling along the growth direction of (Al,Ga)As/GaAs semiconductor superlattices. PMID- 10033076 TI - Enhanced superconductivity in quasi-two-dimensional systems. PMID- 10033075 TI - Spin anisotropy of ferromagnetic films. PMID- 10033077 TI - Negative absolute mobility of minority electrons in GaAs quantum wells. PMID- 10033078 TI - Electronic states on a Penrose lattice. PMID- 10033079 TI - Towards a self-consistent determination of the mixing parameters in the Anderson model: An application to the 4f-excitation spectra of YbP. PMID- 10033080 TI - "Dressed excitons" in a multiple-quantum-well structure: Evidence for an optical Stark effect with femtosecond response time. PMID- 10033081 TI - Nonreciprocal optical reflection of the uniaxial antiferromagnet MnF2. PMID- 10033082 TI - Band lineups at II-VI heterojunctions: Failure of the common-anion rule. PMID- 10033083 TI - Work function of a transition-metal surface with submonolayer alkali-metal coverage. PMID- 10033084 TI - Realization of a Witten critical theory in (CH3)4NMnCl3. PMID- 10033086 TI - Casati, Chirikov, and Guarneri respond. PMID- 10033085 TI - Energy level statistics of integrable quantum systems. PMID- 10033087 TI - Comment on "Fractal structure of TiH2 aggregates in a CuTi matrix" PMID- 10033088 TI - Dependence of superconducting transition temperature on pressure in primitive hexagonal Si. PMID- 10033091 TI - Density-functional theory and freezing of simple liquids. PMID- 10033092 TI - Angular momentum for diatoms described by gauge fields. PMID- 10033094 TI - Pion-nucleon form factors in the unitary three-body model for NN scattering. PMID- 10033095 TI - E1 and E2/E0 form factors and strength distributions from 28Si (e,e'p) and 28Si (e,e' alpha ) coincidence scattering. PMID- 10033093 TI - Observation of the decay B-->FX. PMID- 10033096 TI - Resolution of the fusion window anomaly in heavy-ion collisions. PMID- 10033097 TI - Shelved optical electron amplifier: Observation of quantum jumps. PMID- 10033098 TI - Erratic motion in a convective optical flow. PMID- 10033099 TI - Enhancement of long-scale magnetic fields in spatially random-phased laser illumination of a CH foil. PMID- 10033100 TI - Laser-target interaction with induced spatial incoherence. PMID- 10033101 TI - Flute stabilization due to ponderomotive force created by an rf field with a variable gradient. PMID- 10033102 TI - Generalized viscoelastic theory of the glass transition for strongly coupled, classical, one-component plasmas. PMID- 10033103 TI - Role of chemical potentials in surface reconstruction: A new model and phase transition of GaAs(111)2x2. PMID- 10033104 TI - Complete wetting on "strong" substrates: Xe/Pt(111). PMID- 10033105 TI - Observation of spin-triplet states for double donors in silicon. PMID- 10033106 TI - Terms linear in k in the band structure of zinc-blende-type semiconductors. PMID- 10033107 TI - Critical behavior of the nonlinear sigma model with a free surface: The "ordinary" transition in 2+ epsilon dimensions. PMID- 10033108 TI - Surface plasmon cross coupling in molecular fluorescence near a corrugated thin metal film. PMID- 10033109 TI - Higher-order angular dependence of the positive-muon Knight shift in bismuth. PMID- 10033110 TI - Direct observation of adsorbate-induced band-gap states on GaAs(110). PMID- 10033112 TI - Evidence of hot-electron transfer into an upper valley in GaAs. PMID- 10033111 TI - Observation of low-energy micro+ emission from solid surfaces. PMID- 10033113 TI - Metallization of CsI. PMID- 10033114 TI - Evidence for 4f-ligand dehybridization in the evolution of heavy-fermion behavior in the series CeCu2-xNixSi2. PMID- 10033116 TI - Magnetic coupling of surface adlayers: Gd on Fe(100). PMID- 10033115 TI - Universal conductance fluctuations in silicon inversion-layer nanostructures. PMID- 10033117 TI - Spin-dominated inflation in the Einstein-Cartan theory. PMID- 10033118 TI - Model-independent structure determination of the InSb(111)2 x 2 surface. PMID- 10033119 TI - Bohr et al. respond. PMID- 10033120 TI - Thermoelectric generation of magnetic flux in thin-film superconductors. PMID- 10033121 TI - Garland et al. respond. PMID- 10033122 TI - Comment on "Reliability of low-energy electron diffraction for studies of surface order-disorder phenomena" PMID- 10033123 TI - Moritz and Lagally respond. PMID- 10033124 TI - Charged-meson pair production in gamma gamma interactions. PMID- 10033125 TI - Evidence for a new state produced in antiproton annihilations at rest in liquid deuterium. PMID- 10033126 TI - Difference spectra: Dominance of two-body cascades in antiproton-neutron annihilations at rest. PMID- 10033127 TI - Particle production in the central rapidity region of ultrarelativistic nuclear collisions. PMID- 10033128 TI - Confinement criterion for QCD with dynamical quarks. PMID- 10033129 TI - Applicability of asymptotic QCD for exclusive processes. PMID- 10033130 TI - Correlation between domain boundaries and surface steps: A scanning-tunneling microscopy study on reconstructed Pt(100). PMID- 10033132 TI - Measurement of the silicon (111) surface contraction. PMID- 10033131 TI - Davydov splitting of crystal-field excitations and magnetic phonon splitting in PrF3. PMID- 10033133 TI - Surface phonons of the superconducting materials NbC(100) and TaC(100). PMID- 10033134 TI - Observation of two-dimensional compositional ordering of a carbon monoxide and argon monolayer mixture physisorbed on graphite. PMID- 10033136 TI - Proton Fermi-contact coupling constants from local-density-functional theory: Application to the soliton in polyacetylene. PMID- 10033135 TI - Observation of a low-temperature resonance peak in ultrasonic attenuation of UPt3. PMID- 10033137 TI - Infrared-optical properties of gas-evaporated gold blacks: Evidence for anomalous conduction on fractal structures. PMID- 10033139 TI - Cosmic quarkonium: A probe of dark matter. PMID- 10033138 TI - Long-range incommensurate magnetic order in a Dy-Y multilayer. PMID- 10033140 TI - Comment on "Sensitive dependence on parameters in nonlinear dynamics" and on "Fat fractals on the energy surface" PMID- 10033141 TI - Farmer and Umberger respond. PMID- 10033142 TI - Comment on "Fractal model for the ac response of a rough interface" PMID- 10033144 TI - Dynamic symmetries in scattering. PMID- 10033145 TI - High-dimension chaotic attractors of a nonlinear ring cavity. PMID- 10033146 TI - Measurement of the Lense-Thirring drag on high-altitude, laser-ranged artificial satellites. PMID- 10033147 TI - Test of the special-relativistic Doppler formula at beta =0.84. PMID- 10033148 TI - Theory of a two-level system strongly interacting with a degenerate Fermi gas. PMID- 10033149 TI - Study of a quantum fermi-acceleration model. PMID- 10033150 TI - Geometrical constraints and equations of motion in extended supergravity. PMID- 10033151 TI - Weak mixing angles from semileptonic decays in the quark model. PMID- 10033152 TI - Production mechanisms for a new neutral particle below 2 MeV. PMID- 10033153 TI - Complex Langevin solution of the Schwinger model. PMID- 10033154 TI - Correlation properties of unresolved gamma rays from high-spin states. PMID- 10033156 TI - Asymptotic normalization constants for 3H-->n+d and triton binding energy. PMID- 10033155 TI - Bimodal symmetric fission observed in the heaviest elements. PMID- 10033157 TI - "Heisenberg core" in classical-trajectory Monte Carlo calculations of ionization and charge exchange. PMID- 10033158 TI - van der Waals force between positronium and hydrogenic atoms: Finite-mass corrections. PMID- 10033159 TI - Rydberg spectroscopy of H2 via stepwise resonant two-photon ion-pair (H++H PMID- 10033160 TI - Measurement of Stark amplitudes alpha, beta in the 6(2)P1/2-->7(2)P1/2 transition in atomic thallium. PMID- 10033161 TI - Radial viscous fingers and diffusion-limited aggregation: Fractal dimension and growth sites. PMID- 10033162 TI - Nonthermal electron velocity distribution measured by electron cyclotron emission in Alcator C tokamak. PMID- 10033163 TI - Virtual-cathode oscillator emission by a pinched diode. PMID- 10033165 TI - Path-integral computation of the low-temperature properties of liquid 4He. PMID- 10033164 TI - Direct observation of critical phenomena by incoherent neutron scattering. PMID- 10033166 TI - Preservation of a 7 x 7 periodicity at a buried amorphous Si/Si(111) interface. PMID- 10033168 TI - Vortices with spontaneously broken axisymmetry in 3He-B. PMID- 10033167 TI - Identification of vortices in superfluid 3He-B. PMID- 10033169 TI - Metastable angular distributions from electron-stimulated desorption. PMID- 10033170 TI - Experimental evidence for the Haldane gap in a spin-1 nearly isotropic, antiferromagnetic chain. PMID- 10033171 TI - Observation of a true interface state in strained-layer Cu adsorption on Ru(0001). PMID- 10033172 TI - Global phase coherence in two-dimensional granular superconductors. PMID- 10033173 TI - Heat capacity of a condensed electron system in the dilute metal n-Hg0.8Cd0.2Te. PMID- 10033174 TI - Direct observation of ensemble averaging of the Aharonov-Bohm effect in normal metal loops. PMID- 10033175 TI - Pressure dependence of the low-temperature specific heat of the heavy-fermion compound CeAl3. PMID- 10033176 TI - Low-frequency modes in proteins: Use of the effective-medium approximation to interpret the fractal dimension observed in electron-spin relaxation measurements. PMID- 10033178 TI - Mughabghab responds. PMID- 10033177 TI - Comment on "Evidence for a nucleon-nucleus spin-spin interaction in 9Be" PMID- 10033180 TI - Comment on "Photoelectron angular distributions for near-threshold two-photon ionization of cesium and rubidium atoms" PMID- 10033179 TI - Comment on "Quantization of asymmetric shapes in nuclei" PMID- 10033181 TI - Hydrogen-acceptor pairs in silicon. PMID- 10033182 TI - Assali and Leite respond. PMID- 10033184 TI - Resonances of chaotic dynamical systems. PMID- 10033186 TI - Renormalization-group approach for electronic structure. PMID- 10033185 TI - Mass generation by merons in quantum spin chains and the O(3) sigma model. PMID- 10033187 TI - Scaling and critical slowing down in random-field Ising systems. PMID- 10033189 TI - Role of string excitation in the last stages of black-hole evaporation. PMID- 10033188 TI - Quantum tunneling, dissipation, and fluctuations. PMID- 10033190 TI - Hadron dynamics in the three-flavor Skyrme model. PMID- 10033191 TI - Phenomenology and cosmology with superstrings. PMID- 10033192 TI - Can the skyrmion model be a good description of the nucleon? PMID- 10033193 TI - Covariant second quantization of superstrings. PMID- 10033194 TI - Observation of correlated narrow-peak structures in positron and electron spectra from superheavy collision systems. PMID- 10033195 TI - Muon Coulomb capture in aqueous solutions and the controversy between the large mesonic-molecule model and the transfer model. PMID- 10033196 TI - Shapes of rotating free drops: Spacelab experimental results. PMID- 10033197 TI - Relativistic nonlinear optics of a single cyclotron electron. PMID- 10033198 TI - X-ray study of high-density amorphous water. PMID- 10033199 TI - Polarization and tilt-angle measurements near the smectic-A-chiral-smectic-C transition of p-(n-decyloxybenzylidene)-p-amino-(2-methyl-butyl)cinnamate (DOBAMBC). PMID- 10033200 TI - Periodic quasicrystal. PMID- 10033201 TI - Wetting in random systems. PMID- 10033202 TI - Electric field dependence of local-defect reactions in semiconductors. PMID- 10033203 TI - Observation of a correlation length finite-size effect in Rayleigh scattering from thin critical fluid films. PMID- 10033204 TI - Ferroelastic phase transition in two-dimensional molecular solids. PMID- 10033205 TI - Ultrasound as a sensitive probe of f-wave pairing fluctuations in 3He-A. PMID- 10033207 TI - Spin-dependent photoemission intensities from solids. PMID- 10033206 TI - Observation of magnetic instabilities in dilute Pr, Nd, and Pm systems. PMID- 10033208 TI - Adsorbate ionicity and surface-dipole-moment changes: Cluster-model studies of Cl/Cu(100) and F/Cu(100). PMID- 10033211 TI - Sharp photon-induced np-->(n+1)s resonances in Xe and Kr monolayers observed by spin-resolved electron spectroscopy. PMID- 10033209 TI - Infrared and polarization anomalies in the optical spectra of modulation-doped semiconductor quantum-well structures. PMID- 10033210 TI - Influence of s-d exchange interaction on the conductivity of Cd1-xMnxSe:In in the weakly localized regime. PMID- 10033212 TI - Subharmonic and chaotic response of periodically driven extrinsic Ge photoconductors. PMID- 10033214 TI - Classical-trajectory studies of electron- or photon-stimulated desorption from ionic solids. PMID- 10033213 TI - Symmetric arsenic dimers on the Si(100) surface. PMID- 10033215 TI - Electronic structure and phase stability of LiZnAs: A half ionic and half covalent tetrahedral semiconductor. PMID- 10033216 TI - Corrections to the one-dimensional density of states: Observation of a Coulomb gap? PMID- 10033217 TI - Adsorbate-induced reconstruction of the Ni(100) surface. PMID- 10033219 TI - Comment on "Large long-time tails and shear waves in dense classical liquids" PMID- 10033218 TI - Rahman responds. PMID- 10033221 TI - Limiting quasienergy statistics for simple quantum systems. PMID- 10033222 TI - Test of scaling exponents for percolation-cluster perimeters. PMID- 10033225 TI - Baryogenesis and the gravitino problem in superstring models. PMID- 10033224 TI - Slow-monopole search with large-area helium-gas propor- tional-counter array. PMID- 10033223 TI - Observation of a new charmed meson. PMID- 10033226 TI - Mechanism for understanding small neutrino mass in superstring theories. PMID- 10033227 TI - Solution to the neutrino-mass problem in superstring E6 theory. PMID- 10033228 TI - Electric and magnetic dipole transitions to bound states in 206Pb. PMID- 10033229 TI - Quasielastic nucleon transfer and the heavy-ion interaction potential. PMID- 10033230 TI - Measurement of the 1S-2S frequency in atomic hydrogen. PMID- 10033231 TI - Interferometric measurement of the 1S1/2-2S1/2 transition frequency in atomic hydrogen. PMID- 10033232 TI - Synchrotron radiation studies of the Ar 3s-1 binding-energy spectrum: A comparison of experimental intensities and theory. PMID- 10033233 TI - Observation of unexpected density effects in muon-catalyzed d-t fusion. PMID- 10033234 TI - Autodetachment spectroscopy of metastable He2 - PMID- 10033236 TI - New exact solutions and bifurcations in the spatial distribution of polarization in third-order nonlinear optical interactions. PMID- 10033235 TI - Bragg resonance of light in optical superlattices. PMID- 10033237 TI - Electromagnetic field cascading in the beat-wave generation of plasma waves. PMID- 10033238 TI - Real-space observation of pi -bonded chains and surface disorder on Si(111)2 x 1. PMID- 10033239 TI - Kapitza conductance between gaseous atomic hydrogen and liquid helium. PMID- 10033240 TI - Structural instability of ultrafine particles of metals. PMID- 10033241 TI - Commensurate, incommensurate and rotated Xe monolayers on Pt(111): A He diffraction study. PMID- 10033242 TI - Critical and noncritical roughening of surfaces. PMID- 10033244 TI - New empirical model for the structural properties of silicon. PMID- 10033243 TI - Helium on graphite: Low-temperature desorption kinetics and sticking coefficient. PMID- 10033245 TI - Molecular imaging of tobacco mosaic virus lyotropic nematic phases. PMID- 10033246 TI - Evidence for the coexistence of charge- and spin-density waves in 2H-TaS2. PMID- 10033247 TI - Modifications of hopping transport due to electrostatically enhanced Coulomb repulsion. PMID- 10033248 TI - Universal disorder-induced transition in the resistivity behavior of strongly coupled metals. PMID- 10033250 TI - Pulsed-laser irradiated silicon studied by time-resolved x-ray absorption (90-300 eV). PMID- 10033249 TI - Inverse-photoemission spectroscopy at the metal-electrolyte interface. PMID- 10033251 TI - Frequency-dependent response of pinned charge-density-wave condensates: Classical versus quantum description. PMID- 10033252 TI - NMR study of the structure and motion of charge density waves in NbSe3. PMID- 10033254 TI - Photogeneration of confined soliton pairs (bipolarons) in polythiophene. PMID- 10033253 TI - Magnetic-field-induced transition and quantum oscillations in tetramethyltetraselenafulvalenium perrhenate, (TMTSF)2ReO4. PMID- 10033255 TI - Reference levels for heterojunctions and Schottky barriers. PMID- 10033256 TI - Localization of quasienergy eigenfunctions in action space. PMID- 10033257 TI - Chaotic Rabi oscillations under quasiperiodic perturbation. PMID- 10033258 TI - Search for anomalous single-photon production at the e+e- storage ring PEP. PMID- 10033259 TI - Quantization of topological mass in the presence of a magnetic pole. PMID- 10033260 TI - Compactification of closed bosonic strings. PMID- 10033261 TI - Initial temperature and thermalization time in heavy-ion collisions. PMID- 10033262 TI - Antinucleon charge-exchange reaction as a probe of longitudinal spin excitations. PMID- 10033264 TI - Observation of interference between quadrupole and dipole transitions in low energy (2-eV) photoionization from a sodium Rydberg state. PMID- 10033263 TI - Negative-ion formation in Rydberg atom interactions (n=7-40). PMID- 10033266 TI - Coherence and decay of Rydberg wave Packets. PMID- 10033265 TI - Experimental proof of a || Delta m|| << j propensity rule in rotationally inelastic differential scattering. PMID- 10033267 TI - Theoretical model of inner-shell excitation by outer-shell electrons. PMID- 10033268 TI - Commensurate-incommensurate transition in nonequilibrium systems. PMID- 10033270 TI - Van der Waals stabilization of bubbles. PMID- 10033269 TI - Adiabatic expansion of a strongly correlated pure electron plasma. PMID- 10033271 TI - Pulsed melting of silicon (111) and (100) surfaces simulated by molecular dynamics. PMID- 10033272 TI - Restructuring of colloidal silica aggregates. PMID- 10033273 TI - Conformal invariance, the central charge, and universal finite-size amplitudes at criticality. PMID- 10033274 TI - Universal term in the free energy at a critical point and the conformal anomaly. PMID- 10033275 TI - Reconstruction of the W(110) surface induced by hydrogen adsorption. PMID- 10033276 TI - Resonant and kinematical enhancement of He scattering from LiF(001) surface and pseudosurface vibrational normal modes. PMID- 10033277 TI - Magnetic x-ray-scattering study of interfacial magnetism in a Gd-Y superlattice. PMID- 10033278 TI - Ultrafast heating of silicon on sapphire by femtosecond optical pulses. PMID- 10033279 TI - Nonequilibrium electron-hole plasma in GaAs quantum wells. PMID- 10033280 TI - Interstitial hydrogen and neutralization of shallow-donor impurities in single crystal silicon. PMID- 10033281 TI - Thermometric NMR of stable nuclei by low-temperature nuclear orientation. PMID- 10033282 TI - Carrier-concentration-induced ferromagnetism in PbSnMnTe. PMID- 10033283 TI - Chiral symmetry and chiral anomaly in an incommensurate charge-density-wave system. PMID- 10033286 TI - Must nonspherical collapse produce black holes? A gravitational confinement theorem. PMID- 10033284 TI - Fractal shape of hail clouds. PMID- 10033287 TI - Evidence for Aharonov-Bohm effect with magnetic field completely shielded from electron wave. PMID- 10033288 TI - Experimental measurement of the gamma -->3 pi coupling constant. PMID- 10033290 TI - Ratio of electric quadrupole to magnetic dipole amplitudes in the nucleon-delta transition. PMID- 10033289 TI - Inclusive phi production in B-meson decay. PMID- 10033291 TI - Evidence for higher-twist effects in hard pi p collisions at 200 GeV/c. PMID- 10033293 TI - Effective action in Monte Carlo calculations with dynamical fermions. PMID- 10033292 TI - Measurement of the branching fractions tau ---> rho - nu tau and tau --->K PMID- 10033294 TI - New determination of the deuteron binding energy and the neutron mass. PMID- 10033295 TI - Observation of an atomic Stark-electric-quadrupole interference. PMID- 10033296 TI - Diffraction of atoms by light: The near-resonant Kapitza-Dirac effect. PMID- 10033297 TI - Inductive postacceleration of charge- and current-neutralized, intense pulsed ion beam. PMID- 10033298 TI - Fast-wave current drive in the Irvine torus. PMID- 10033299 TI - Collapsing-caviton turbulence in one dimension. PMID- 10033300 TI - Observations of spheromak equilibria which differ from the minimum-energy state and have internal kink distortions. PMID- 10033302 TI - Soft-wall domain-growth kinetics of twofold-degenerate ordering. PMID- 10033301 TI - Generation of a strong magnetic field by an intense CO2 laser pulse. PMID- 10033303 TI - Scaling structure of the surface layer of diffusion-limited aggregates. PMID- 10033304 TI - Stability of the high-pressure body-centered-cubic phase of helium. PMID- 10033305 TI - Icosahedral crystals: Where are the atoms? PMID- 10033307 TI - Critical dynamics of diluted Ising systems. PMID- 10033306 TI - Reliability of low-energy electron diffraction for studies of surface order disorder phenomena. PMID- 10033308 TI - Cooperative ring exchange theory of the fractional quantized Hall effect. PMID- 10033309 TI - Novel electronic properties of a potassium overlayer on Si(001)-(2 x 1). PMID- 10033310 TI - Approximate electron removal energies in density-functional theory from post-hoc correction of local-spin-density eigenvalues. PMID- 10033311 TI - Stability analysis of a dense hard-sphere fluid subjected to large shearmdashshear-induced ordering. PMID- 10033312 TI - Dynamic scaling of growing interfaces. PMID- 10033313 TI - Realizations of magnetic-monopole gauge fields: Diatoms and spin precession. PMID- 10033314 TI - Global, uniform, semiclassical approximation to wave equations. PMID- 10033316 TI - Classical limit of Bethe-Ansatz thermodynamics for the sine-Gordon system. PMID- 10033315 TI - Threshold behavior and Levinson's theorem for two-dimensional scattering systems: A surprise. PMID- 10033318 TI - Length-twist parameters in string path integrals. PMID- 10033317 TI - Detecting "secret" quantum numbers. PMID- 10033319 TI - Dynamical generation of Majorana masses for gauginos. PMID- 10033320 TI - Beta-decay asymmetry of the neutron and gA/gV. PMID- 10033321 TI - Detection of the silyl radical SiH3 by infrared diode-laser spectroscopy. PMID- 10033322 TI - Multiorder stokes emission from micrometer-size droplets. PMID- 10033324 TI - First-principles calculation of surface phonons on the Al(110) surface. PMID- 10033323 TI - Atomic force microscope. PMID- 10033325 TI - Fermi resonance in the phonon spectra of copper halides. PMID- 10033327 TI - Theory of shear-induced melting of colloidal crystals. PMID- 10033326 TI - Explosive recombination of compressed spin-polarized hydrogen. PMID- 10033328 TI - Thermodynamics of a narrow-band Bose gas on a lattice. PMID- 10033329 TI - Surface precursor to magnetic-domain nucleation observed by secondary-electron spin polarization. PMID- 10033331 TI - Ionicity and the structural stability of solids. PMID- 10033330 TI - Very-low-temperature resistivity anomaly in KRb, KNa, and LiMg alloys. PMID- 10033332 TI - Electron emission induced by cluster bombardment of metallic surfaces. PMID- 10033333 TI - Observation of impurity cyclotron resonance in Hg1-xCdxTe. PMID- 10033334 TI - Spin-density-wave transitions in a magnetic field. PMID- 10033335 TI - Quantum percolation in magnetic fields. PMID- 10033336 TI - Magnetic tuning of the metal-insulator transition for uncompensated arsenic-doped silicon. PMID- 10033337 TI - Effect of gold impurities on the critical properties of CuMn spin-glasses. PMID- 10033338 TI - Possible mechanism for generating almost isothermal baryon-density perturbations. PMID- 10033339 TI - Search for high-energy muons from Cygnus X-3. PMID- 10033342 TI - Quantum mechanical manifestation of cantori: Wave-packet localization in stochastic regions. PMID- 10033340 TI - Comment on "Outward effective mass of quark and baryon magnetic moments" PMID- 10033343 TI - Periodically pulsed spin dynamics: Scaling behavior of semiclassical wave functions. PMID- 10033344 TI - Algebraic approach to dissociation from bound states. PMID- 10033345 TI - Generating quantum mechanical superpositions of macroscopically distinguishable states via amplitude dispersion. PMID- 10033346 TI - Brownian dynamics close to a wall studied by photon correlation spectroscopy from an evanescent wave. PMID- 10033348 TI - Feeble intermediate-range forces from higher dimensions. PMID- 10033347 TI - Equivalence of active and passive gravitational mass using the moon. PMID- 10033349 TI - Critical dimensions of spinning strings on group manifolds from Fujikawa's method. PMID- 10033350 TI - Phenomenologically consistent discrete symmetries in superstring theories. PMID- 10033351 TI - Quark vacuum polarization and the Luscher term. PMID- 10033352 TI - Numerical determination of the QCD beta function. PMID- 10033354 TI - Neutral-meson-antimeson mixing for a heavy isosinglet quark constituent. PMID- 10033353 TI - Monte Carlo calculation of the spin-dependent potentials for heavy-quark spectroscopy. PMID- 10033355 TI - Experimental limit on iota --> gamma gamma and the interpretation of the iota as a glueball. PMID- 10033356 TI - Exotic states in QED. PMID- 10033357 TI - Reaction 58Ni( pi +,2p) at 160 MeV. PMID- 10033359 TI - Equilibrium atomic structure: Rotating atoms. PMID- 10033358 TI - Effect of alignments on the shape of 158Yb. PMID- 10033360 TI - Sympathetic cooling of trapped ions: A laser-cooled two-species nonneutral ion plasma. PMID- 10033361 TI - Evidence for correlated double-electron capture in low-energy collisions of O6+ with He. PMID- 10033363 TI - Direct measurement of vortex diffusivity in thin films of 4He. PMID- 10033362 TI - Derivation of the equilibrium degree of polarization in high-energy electron storage rings. PMID- 10033364 TI - Nonequilibrium molecular-dynamics studies on the anisotropic viscosity of perfectly aligned nematic liquid crystals. PMID- 10033365 TI - New universality for spatially disordered cellular automata and directed percolation. PMID- 10033366 TI - Quantized layer growth at liquid-crystal surfaces. PMID- 10033367 TI - Orientational and positional order in a tilted hexatic liquid-crystal phase. PMID- 10033369 TI - Variable stoichiometry surface reconstructions: New models for GaAs(1-bar1-bar1 bar) (2 x 2) and ( sqrt 1-bar9-bar x sqrt 1-bar9-bar). PMID- 10033368 TI - Atomic structure of the (2 x 2) reconstructed GaAs(1-bar1-bar1-bar) surface: A multivacancy model. PMID- 10033370 TI - Charge-density-wave state in alpha -U: A multiple-domain and single-q structure. PMID- 10033371 TI - Differential anomalous-x-ray-scattering study of icosahedral and amorphous Pd58.8U20.6Si20.6. PMID- 10033372 TI - Transport processes in heavy-fermion superconductors. PMID- 10033373 TI - Wave-vector- and magnetic-field-dependent spin fluctuations in the heavy-fermion system CeCu6. PMID- 10033374 TI - Dissipation due to a "valley wave" channel in the quantum Hall effect of a multivalley semiconductor. PMID- 10033376 TI - Intermediate-frequency conduction in Si:As below the metal-insulator transition. PMID- 10033375 TI - Elementary excitations in the fractional quantum Hall effect and the spin reversed quasiparticles. PMID- 10033377 TI - Observation of resonant tunneling in silicon inversion layers. PMID- 10033378 TI - Spin-polarized photoemission study of epitaxial Fe(001) films on Ag(001). PMID- 10033379 TI - Time-resolved picosecond optical measurements of laser-excited graphite. PMID- 10033380 TI - Direct observation of spin waves above TC for nickel. PMID- 10033381 TI - Origin of surface states on Si(111)(7 x 7). PMID- 10033382 TI - Non-Abelian adiabatic phases and the fractional quantum Hall effect. PMID- 10033384 TI - Spectrum supersymmetry of Regge trajectories. PMID- 10033383 TI - Derivative expansion for the one-loop effective actions with internal symmetry. PMID- 10033385 TI - Have quasinuclear NN-bar bound states been discovered? PMID- 10033386 TI - Equilibration in orbiting reactions. PMID- 10033387 TI - Evidence for alpha-particle clustering in the 44Ti nucleus. PMID- 10033388 TI - Dissociative charge exchange of HeH+: An experimental study of the HeH molecule. PMID- 10033389 TI - Measurement of coherent transition x rays. PMID- 10033390 TI - Three-dimensional double layers inducing ion-cyclotron oscillations in a collisionless plasma. PMID- 10033391 TI - Evidence for viscosity reduction in moderately spin-polarized 3He. PMID- 10033392 TI - First observation of the universal periodic corrections to scaling: Magnetoresistance of normal-metal self-similar networks. PMID- 10033393 TI - Heat-capacity study of free-standing liquid-crystal films. PMID- 10033394 TI - Observation of doubly spin-polarized deuterium by electron-spin resonance. PMID- 10033395 TI - Formation of a new ordered structure of CaF2/Si(111) by ultraviolet irradiation. PMID- 10033396 TI - Integer optimization and zero-temperature fixed point in Ising random-field systems. PMID- 10033397 TI - Muon Knight shift in the heavy-fermion superconductors U1-xThxBe13, x=0 and 0.033. PMID- 10033399 TI - Electronic spectral density in heavy-fermion metals. PMID- 10033398 TI - Unusual angular and temperature dependence of the upper critical field in UPt3. PMID- 10033400 TI - Spectral broadening in biomolecules. PMID- 10033401 TI - Adiabatic conversion of solar neutrinos. PMID- 10033402 TI - Nonadiabatic level crossing in resonant neutrino oscillations. PMID- 10033406 TI - Critical exponent of chaotic transients in nonlinear dynamical systems. PMID- 10033405 TI - Quenched exponential decay. PMID- 10033407 TI - Improved estimate of the scalar-glueball mass. PMID- 10033408 TI - Study of lattice SU(N) QCD at finite baryon density. PMID- 10033409 TI - Evidence for two pseudoscalar resonances of eta pi + pi - system in the D(1285) and E/ iota regions. PMID- 10033410 TI - Collision-induced Ramsey resonances in Sm vapor. PMID- 10033411 TI - Experimental observation of a radiative wave generated in xenon by a laser-driven supercritical shock. PMID- 10033412 TI - Oscillatory surface relaxations in Ni, Al, and their ordered alloys. PMID- 10033414 TI - Mechanism for doping in Bi chalcogenide glasses. PMID- 10033413 TI - Fast mutual diffusion in polymer blends. PMID- 10033415 TI - Solitons and infrared-active modes in polyacetylene. PMID- 10033417 TI - Layerwise structure in the fcc {111} solid-liquid interface. PMID- 10033416 TI - Ultrasound propagation in sintered metal powder: Evidence for a crossover from phonons to fractons. PMID- 10033418 TI - Observation of (5 x 5) surface reconstruction on pure silicon and its stability against native-oxide formation. PMID- 10033419 TI - Fourier acceleration of relaxation processes in disordered systems. PMID- 10033420 TI - Deterministic, fractal defect structures in close packings of hard disks. PMID- 10033421 TI - Three-photon magnetoabsorption of excitons in alkali halides. PMID- 10033422 TI - Range and strength of pins collectively interacting with the flux-line lattice in type-II superconductors. PMID- 10033423 TI - Deexcitation model for sputtered excited neutral atoms. PMID- 10033424 TI - Some exact results for multiorientational "Ising-type" dipoles in transverse fields. PMID- 10033425 TI - Role of vortex strings in the three-dimensional O(2) model. PMID- 10033426 TI - New functional integral approach to strongly correlated Fermi systems: The Gutzwiller approximation as a saddle point. PMID- 10033427 TI - Crystal stability and structural transition pressures of sp-bonded solids. PMID- 10033428 TI - Soluble two-band model of fermions. PMID- 10033429 TI - Thermoelectric voltage between identical metals in a point-contact configuration. PMID- 10033430 TI - Statistical spectral and dynamical properties of two-level systems. PMID- 10033431 TI - Comment on "Detecting 'secret' quantum numbers." PMID- 10033432 TI - Rotation of time-dependent flow patterns near convective threshold. PMID- 10033433 TI - Ahlers and Cannell respond. PMID- 10033435 TI - Four-loopndashorder beta function for two-dimensional nonlinear sigma models. PMID- 10033436 TI - Vacuum spacetimes that admit no maximal slice. PMID- 10033437 TI - Dimensionality of strange attractors determined analytically. PMID- 10033438 TI - Characterization of chaos in a hybrid optically bistable device. PMID- 10033439 TI - Comparison of the particle flow in three-jet and radiative two-jet events from e+e- annihilation at Ec.m. PMID- 10033440 TI - Unique determination of the form-factor ratio in radiative pion decay. PMID- 10033441 TI - CP nonconservation in decays of W and Z bosons. PMID- 10033442 TI - Fusion reactions of polarized deuterons. PMID- 10033443 TI - Critical angle in electron capture. PMID- 10033444 TI - Conversion of Poisson photons into sub-Poisson photons by the action of electron feedback. PMID- 10033446 TI - Laser-surface adsorbate interactions: Thermal versus photoelectronic excitation of Mo(CO)6 on Si(111). PMID- 10033445 TI - Wakeless triple-soliton accelerator. PMID- 10033447 TI - Isotope-induced quantum-phase transitions in the liquid state. PMID- 10033449 TI - Observation of fourth vibrational overtone of hydrogen. PMID- 10033448 TI - Growth of breath figures. PMID- 10033450 TI - Distortion and peak broadening in quasicrystal diffraction patterns. PMID- 10033451 TI - Systematics of disorder in quasiperiodic material. PMID- 10033452 TI - Dissipative flow of liquid 4He in the limit of absolute zero. PMID- 10033453 TI - Evidence for smectic order in a fluid of hard parallel spherocylinders. PMID- 10033455 TI - Magnetic screening of Fe impurities in Mg. PMID- 10033454 TI - Layering and layer-critical-point transitions of ethylene on graphite. PMID- 10033456 TI - Observation of carrier localization in intentionally disordered GaAs/GaAlAs superlattices. PMID- 10033457 TI - First-principles electronic structure theory for semi-infinite semiconductors with applications to Ge(001)(2 x 1) and Si(001)(2 x 1). PMID- 10033459 TI - Bond breaking and the ionization of sputtered atoms. PMID- 10033458 TI - Dissociation-width-dependent radiative recombination of electrons and holes at widely split partial dislocations in silicon. PMID- 10033460 TI - Spatial and temporal patterns in high-power ferromagnetic resonance. PMID- 10033461 TI - Evidence for a quantum size effect of the conduction electrons during oxidation of Cs. PMID- 10033462 TI - Geometrical interpretation of momentum and crystal momentum of classical and quantum ferromagnetic Heisenberg chains. PMID- 10033464 TI - Nature of the bonding for chemisorbed CO. PMID- 10033463 TI - Motion of extreme Reissner-Nordstrom black holes in the low-velocity limit. PMID- 10033465 TI - Wimmer, Fu, and Freeman respond. PMID- 10033467 TI - Vandenbosch et al. respond. PMID- 10033466 TI - Comment on "Anomalously broad spin distributions in sub-barrier fusion reactions" PMID- 10033468 TI - Comment on "X-ray Compton-Raman scattering from atomic inner-shell electrons" PMID- 10033469 TI - Namikawa and Hosoya respond. PMID- 10033470 TI - Time ordering and the thermodynamics of strange sets: Theory and experimental tests. PMID- 10033471 TI - Exact solution to localized-induction-approximation equation modeling smoke ring motion. PMID- 10033473 TI - CP nonconservation at the Z0 peak. PMID- 10033472 TI - New infinities in two-dimensional nonlinear sigma models and consistent string propagation. PMID- 10033474 TI - Possible v-quark signatures at e+e- colliders. PMID- 10033475 TI - Characteristics of charm production by 400-GeV protons. PMID- 10033476 TI - Measurement of the Sigma - magnetic moment using the Sigma --->ne- nu -bar and Sigma --->n pi - decay modes. PMID- 10033477 TI - Constraints on iota --> gamma gamma provided by the topological susceptibility. PMID- 10033478 TI - Properties of the zeta (1480). PMID- 10033479 TI - Dynamical selection rules in NN-bar annihilation. PMID- 10033480 TI - Total cross section for deuteron photodisintegration between 15 and 75 MeV. PMID- 10033482 TI - Can an isovector dipole mode of nuclear collective motion give a signature duplicating that of an isoscalar monopole mode? PMID- 10033481 TI - Search for dispersive effects in elastic electron scattering from 12C. PMID- 10033483 TI - Boson images of fermion operators. PMID- 10033484 TI - Collisional excitation and decay of the 1P shape resonance of H- PMID- 10033485 TI - Forbidden transitions to atomic Rydberg states in optical collisions. PMID- 10033486 TI - Multielectron x-ray photoexcitation measurements in krypton. PMID- 10033487 TI - Precise theory of field enhancement of dielectronic recombination. PMID- 10033488 TI - Radiative lifetimes of argon molecules and dependence on internuclear distance. PMID- 10033489 TI - Polarization effects in collision-induced intramultiplet mixing for Ne PMID- 10033491 TI - Diffraction of low-energy ion-induced secondary electrons emitted in the forward direction from a solid foil. PMID- 10033490 TI - Giant-dipole-resonance absorption in atomic thorium by a novel two-laser technique. PMID- 10033492 TI - Effects of the Wannier ridge on secondary-electron spectra in proton-helium collisions. PMID- 10033493 TI - Laser guiding of electron beams in the advanced test accelerator. PMID- 10033494 TI - Electrical conductivity of a dense plasma. PMID- 10033495 TI - ac free-electron laser. PMID- 10033496 TI - Resonant sticking at surfaces. PMID- 10033498 TI - Structural unit in icosahedral MnAlSi and MnAl. PMID- 10033497 TI - Liquid-film instabilities in confined geometries. PMID- 10033499 TI - Hopping magnetoconduction and the random structure in quasi one-dimensional inversion layers. PMID- 10033501 TI - Elastic scattering in a normal-metal loop causing resistive electronic behavior. PMID- 10033500 TI - Superconductivity under pressure in (U1-xThx)Be13: Evidence for two superconducting states. PMID- 10033502 TI - Landau-Khalatnikov damping of ultrasound in heavy-fermion superconductors. PMID- 10033503 TI - de Haas-van Alphen effect in the heavy-electron compound CeCu6. PMID- 10033504 TI - Ultrafast phase relaxation of excitons via exciton-exciton and exciton-electron collisions. PMID- 10033505 TI - Density-wave instabilities and thermoelectric parameters in the alkali metals. PMID- 10033506 TI - Inverse photoemission of adsorbed xenon multilayers on Ru(001): Refutation of final-state screening effects. PMID- 10033508 TI - Laboratory simulation of direct positron annihilation in a neutral-hydrogen galactic environment. PMID- 10033507 TI - Optical third-harmonic generation in reflection from crystalline and amorphous samples of silicon. PMID- 10033509 TI - Cosmic strings and the large-scale structure of the Universe. PMID- 10033510 TI - Comment on "Local structure at Mn sites in icosahedral Mn-Al quasicrystals." PMID- 10033511 TI - Stern, Ma, and Bouldin respond. PMID- 10033513 TI - Role of modular invariance in evaluation of gauge and gravitational anomalies in the heterotic-string theory. PMID- 10033512 TI - Complete integrability in a quantum description of chaotic systems. PMID- 10033514 TI - Fourth-generation fermions and the existence of additional light weak bosons. PMID- 10033515 TI - Higgs-boson-Z0 associated production from fourth-generation quarks at supercollider energies. PMID- 10033516 TI - Skyrmions with rho and omega mesons as dynamical gauge bosons. PMID- 10033517 TI - Measurement of parity nonconservation in the proton-proton total cross section at 800 MeV. PMID- 10033518 TI - Multiple quark stripping in proton-nucleus collisions at 100 GeV. PMID- 10033519 TI - Cooling atoms with stimulated emission. PMID- 10033520 TI - Transient suppression of the Autler-Townes doublet. PMID- 10033521 TI - Observation of quantum jumps. PMID- 10033522 TI - Observation of quantum jumps in a single atom. PMID- 10033523 TI - Free sodium-water clusters. PMID- 10033524 TI - Near-threshold measurements of the C 1s satellites in the photoelectron spectrum of CO. PMID- 10033525 TI - Complementary branching ratios by satellite excitation. PMID- 10033526 TI - Divergence of the shear viscosity in classical fluids near solidification. PMID- 10033527 TI - Interfacial stability of immiscible displacement in a porous medium. PMID- 10033528 TI - Renormalization-group analysis of turbulence. PMID- 10033529 TI - Observation of forward Raman scattering in laser-produced plasmas. PMID- 10033530 TI - Production and identification of a collisionless, curvature-driven, trapped particle instability. PMID- 10033532 TI - Theory and simulation of freeze-fracture in cholesteric liquid crystals. PMID- 10033531 TI - Nucleation and growth of colloidal crystals. PMID- 10033533 TI - Diffusion of a flexible polymer in a random porous material. PMID- 10033535 TI - Observation of a Freedericksz transition in superfluid 3He-A. PMID- 10033534 TI - Measurement of the viscoelastic coefficients of main-chain nematic polymers by an NMR technique. PMID- 10033536 TI - Geometrical supercooling of liquids in porous glass. PMID- 10033537 TI - Formation of In-As complexes in silicon observed by the perturbed-angular correlation technique. PMID- 10033538 TI - Four-terminal phase-coherent conductance. PMID- 10033539 TI - Asymmetry in the magnetoconductance of metal wires and loops. PMID- 10033540 TI - Magnetic depopulation of 1D subbands in a narrow 2D electron gas in a GaAs:AlGaAs heterojunction. PMID- 10033541 TI - Local modes in anharmonic solids and the Kondo problem. PMID- 10033542 TI - Theory of electron band tails and the Urbach optical-absorption edge. PMID- 10033543 TI - Role of F-center diffusion in the electron-stimulated desorption of metal atoms from alkali halides. PMID- 10033544 TI - Two-successive transitions in uniaxially anisotropic spin-glasses. PMID- 10033545 TI - Study of solids by use of nonthermalized positrons. PMID- 10033546 TI - Resonant Raman scattering by crystal-violet molecules adsorbed on a smooth gold surface: Evidence for a charge-transfer excitation. PMID- 10033547 TI - Picosecond phase coherence and orientational relaxation of excitons in GaAs. PMID- 10033549 TI - Solar-neutrino problem and three-neutrino oscillations. PMID- 10033548 TI - New tools for solving the solar-neutrino problem. PMID- 10033550 TI - Dynamic scaling of Eden-cluster surfaces. PMID- 10033551 TI - Kardar, Parisi, and Zhang respond. PMID- 10033552 TI - Surface vibrational excitations on Si(001)(2 x 1). PMID- 10033553 TI - Allan and Mele respond. PMID- 10033554 TI - Comment on "Localization and size effects in single-crystal Au films" PMID- 10033555 TI - Chaudhari et al. respond. PMID- 10033557 TI - Fractional statistics in 2+1 dimensions through the Gaussian model. PMID- 10033556 TI - Chaos and interaction of atoms with self-consistent fields in the case of small coupling constant. PMID- 10033558 TI - New force or thermal gradient in the Eotvos experiment? PMID- 10033559 TI - Functional measure for lattice gravity. PMID- 10033560 TI - Renormalization flow in lattice QED. PMID- 10033561 TI - Construction of four-dimensional fermionic string models. PMID- 10033563 TI - Measurement of the 4.8-MeV 9B state width by the reaction 10B(3He, alpha )9B( alpha ) 5Li at E( 3He PMID- 10033562 TI - Measurement of the inclusive branching fraction tau ---> nu tau pi - pi 0+ neutral meson(s). PMID- 10033564 TI - Spectroscopic strength of 1f7/2 transitions deduced from the 51V(e,e'p)50Ti reaction. PMID- 10033566 TI - Size-selective depletion spectroscopy of predissociated states of Na3. PMID- 10033565 TI - Repolarization of negative muons by polarized 209Bi nuclei. PMID- 10033567 TI - Measurement of spin dependence in low-energy elastic scattering of electrons from lithium atoms. PMID- 10033568 TI - Influence of dielectronic recombination on fast heavy-ion charge states in plasma. PMID- 10033569 TI - High-resolution microwave spectroscopy of the 10G-10H Rydberg transition in H2. PMID- 10033570 TI - Propagation and dephasing of picosecond phonon polariton pulses in ammonium chloride. PMID- 10033571 TI - Three-dimensional analysis of coherent amplification and self-amplified spontaneous emission in free-electron lasers. PMID- 10033572 TI - Viscous fingers and diffusion-limited aggregates near percolation. PMID- 10033573 TI - Scalar-wave localization in a two-component composite. PMID- 10033574 TI - Coherent vortices and subharmonic interactions in the two-dimensional Navier Stokes equations. PMID- 10033575 TI - Nonlocal electron heat transport by not quite Maxwell-Boltzmann distributions. PMID- 10033577 TI - High-efficiency, magnetized, virtual-cathode microwave generator. PMID- 10033576 TI - High- beta plasmas in the PBX tokamak. PMID- 10033578 TI - Self-consistency constraints on turbulent magnetic transport and relaxation in a collisionless plasma. PMID- 10033579 TI - Formation of a dense branching morphology in interfacial growth. PMID- 10033581 TI - Long-range crossover and "nonuniversal" exponents in micellar solutions. PMID- 10033580 TI - Contributions of phasons and of low-energy excitations to the specific heat of the quasi one-dimensional (TaSe4)2I compound. PMID- 10033582 TI - Anion-ordering phase diagram of di(tetramethyltetraselena- fulvalenium) perrhenate (TMTSF)2ReO4. PMID- 10033583 TI - Grain-boundary melting transition in an atomistic simulation model. PMID- 10033584 TI - Focusing of negative ions by vortices in rotating 3He PMID- 10033585 TI - Interference phenomena and mode locking in the model of deformable sliding charge density waves. PMID- 10033586 TI - Evidence of the anomalous charge state 57Fe4+ in the nuclear decay of 57Co3+ PMID- 10033588 TI - Thermal-donor-related isoelectronic center in silicon which can bind up to four excitons. PMID- 10033587 TI - Coherent Primakoff effect: Pion creation in aligned crystals. PMID- 10033590 TI - Crossover from spin waves to quasilocalized excitations in the diluted antiferromagnet (Mn0.5Zn0.5)F2. PMID- 10033589 TI - Nonuniversality of the Mooij correlation-the temperature coefficient of electrical resistivity of disordered metals. PMID- 10033591 TI - Observation of an energy- and temperature-dependent carrier mass for mixed valence CePd3. PMID- 10033592 TI - One-component Fermi-liquid theory and the properties of UPt3. PMID- 10033593 TI - Alternative explanations of the Eotvos results. PMID- 10033594 TI - Comment on "Free-electron laser and laser electron acceleration based on the megagauss magnetic fields in laser-produced plasmas." PMID- 10033595 TI - Comment on "Universal disorder-induced transition in the resistivity behavior of strongly coupled metals." PMID- 10033598 TI - Complexity and the relaxation of hierarchical structures. PMID- 10033599 TI - Cellular automata, Langevin equations, and unstable states. PMID- 10033596 TI - Gurvitch responds. PMID- 10033600 TI - Finite-temperature behavior of lattice QCD with Wilson fermion action and its implication on spectroscopic studies. PMID- 10033601 TI - Time variation of Newton's gravitational constant in superstring theories. PMID- 10033602 TI - CP nonconservation at the unification scale. PMID- 10033603 TI - Calculation of atmospheric neutrino-induced backgrounds in a nucleon-decay search. PMID- 10033605 TI - Accurate verification of the conserved-vector-current and standard-model predictions. PMID- 10033604 TI - Observation of tensor and scalar mesons produced in e+e- annihilation at 29 GeV. PMID- 10033606 TI - Decay properties of giant multipole resonances: Collective doorways and statistical doorways. PMID- 10033607 TI - Subbarrier fusion with aligned 23Na ions. PMID- 10033608 TI - Quantum chaos and statistical properties of energy levels: Numerical study of the hydrogen atom in a magnetic field. PMID- 10033610 TI - Calculation of moments of dynamical systems describing turbulence. PMID- 10033609 TI - Nonperturbative bistability in periodic nonlinear media. PMID- 10033611 TI - Competing patterns in a convective binary mixture. PMID- 10033612 TI - Relativistic solitary-wave solutions of the beat-wave equations. PMID- 10033613 TI - Spinodal curve in highly asymmetrical polyelectrolytes. PMID- 10033614 TI - Crystallization of polysilane in binary Si:H alloys. PMID- 10033615 TI - First principles theoretical explanation of incommensurate behavior in Rb2ZnCl4. PMID- 10033616 TI - Dynamic scaling of cluster-mass distributions in kinetic colloid aggregation. PMID- 10033617 TI - Dynamics of two-dimensional melting on a periodic substrate. PMID- 10033618 TI - Observation of molecular H2 chemisorption on a nickel surface. PMID- 10033619 TI - Weak localization and light scattering from disordered solids. PMID- 10033621 TI - Renormalization-group study of one-dimensional quasiperiodic systems. PMID- 10033620 TI - Correlation between kinetic-energy transfer to rotation and to phonons in gas surface collisions of NO with Ag(111). PMID- 10033622 TI - Spin dynamics of nearly localized electrons. PMID- 10033623 TI - Dipole-induced changes of the band discontinuities at the SiO2-Si interface. PMID- 10033624 TI - Lattice relaxation accompanying carrier capture and emission by deep electronic levels in semiconductors. PMID- 10033625 TI - Effective magnetic moments of heavy fermions and the Wilson ratio for Kondo lattices. PMID- 10033626 TI - Isotope-induced symmetry change in dynamic semiconductor defects. PMID- 10033627 TI - Photomodulation spectroscopy of iodine-doped polyacetylene: Phase transition from soliton lattice to metal. PMID- 10033628 TI - Resonant microwave absorption by dissolved DNA. PMID- 10033629 TI - Model for the 5 March 1979 gamma-ray transient. PMID- 10033630 TI - Comment on nonaxisymmetric vortices in superfluid 3He-B. PMID- 10033631 TI - Thuneberg responds. PMID- 10033633 TI - Anisotropic superconductivity and ultrasound attenuation in U1-xThxBe13. PMID- 10033632 TI - Comment on "Complete wetting on 'strong' substrates: Xe/Pt(111)." PMID- 10033634 TI - Phenomenological quantization scheme in a nonlinear Schroumldinger equation. PMID- 10033636 TI - Restrictions on a 1.7-MeV axion from nuclear pair transitions. PMID- 10033635 TI - New limit on axion production in 800-GeV hadronic showers. PMID- 10033637 TI - Neutrino counting at e+e- colliders and E6 gauge theory. PMID- 10033639 TI - Is there an upper limit to fermion masses? PMID- 10033638 TI - World-sheet supersymmetry. PMID- 10033640 TI - Possible manifestation of quark-gluon plasma in multiplicity distributions from high-energy reactions. PMID- 10033642 TI - Strangeness and the baryon size. PMID- 10033641 TI - Mass shift of charmonium near deconfining temperature and possible detection in lepton-pair production. PMID- 10033643 TI - Evidence for scaling in lattice QCD at beta =5.7. PMID- 10033644 TI - Pion absorption on the diproton. PMID- 10033645 TI - Search for correlated narrow-peak structure in the two-photon spectrum from 6 MeV/nucleon U+Th collisions. PMID- 10033646 TI - Test of the Delta -hole model through the energy dependence of ( pi, pi ' gamma ) angular correlations on 12C. PMID- 10033647 TI - Single and double ionization of helium by fast antiproton and proton impact. PMID- 10033648 TI - Doppler-free two-photon polarization-spectroscopic measurement of the Stark broadened profile of the hydrogen L alpha line in a dense plasma. PMID- 10033649 TI - Theory of two-photon polarization spectroscopy of plasma-broadened hydrogen L alpha line. PMID- 10033650 TI - Universal short-wave instability of two-dimensional eddies in an inviscid fluid. PMID- 10033651 TI - Three-dimensional instability of elliptical flow. PMID- 10033653 TI - Large intensity fluctuations for wave propagation in random media. PMID- 10033652 TI - Inhibition of tunneling in optical bistability by a squeezed vacuum. PMID- 10033654 TI - High-efficiency extraction of microwave radiation from a tapered-wiggler free electron laser. PMID- 10033655 TI - Formation of a spatially ordered structure in a finite- beta edge plasma. PMID- 10033656 TI - Novel class of continuous phase transitions to incommensurate structures. PMID- 10033657 TI - Wetting of a disordered substrate: Exact critical behavior in two dimensions. PMID- 10033658 TI - Theory of the orientational glass state in M(CN)xX1-x mixed crystals. PMID- 10033659 TI - Order-parameter exponent beta 1 of a binary liquid mixture at a boundary. PMID- 10033660 TI - Breakdown of Eliashberg theory for two-dimensional superconductivity in the presence of disorder. PMID- 10033661 TI - Measurement of the charge-density-wave gap of NbSe3 from tunnel-junction spectra. PMID- 10033663 TI - Cluster dynamics in a dipolar glass. PMID- 10033662 TI - Residual energies after slow cooling of disordered systems. PMID- 10033664 TI - Singular volume dependence of transition-metal magnetism. PMID- 10033665 TI - Appearance of correlation effects in U intermetallics. PMID- 10033666 TI - Strong low-temperature photoemission peak in CeH2.7. PMID- 10033667 TI - Electron localization in quasicrystals. PMID- 10033669 TI - Resonant fast dynamo. PMID- 10033668 TI - Excited-atom production by electron bombardment of alkali halides. PMID- 10033670 TI - Late phase transitions and the spontaneous generation of cosmological density perturbations. PMID- 10033671 TI - Homogeneous cosmological models and new inflation. PMID- 10033672 TI - Approximation theory and the calculation of energies from divergent perturbation series. PMID- 10033673 TI - New variables for classical and quantum gravity. PMID- 10033674 TI - New determination of the asymptotic D-state-to-S-state ratio of the deuteron. PMID- 10033675 TI - Positron differential elastic-scattering cross-section measurements for argon. PMID- 10033676 TI - Experimental test of higher-order electron-capture processes in collisions of fast protons with atomic hydrogen. PMID- 10033677 TI - Angular distribution of fluorescence from photoionization-produced He+ (n=2). PMID- 10033678 TI - Observation of interference between C PMID- 10033679 TI - Supercontinuum generation in gases. PMID- 10033680 TI - Theoretical model of fishbone oscillations in magnetically confined plasmas. PMID- 10033682 TI - Near-surface generation of F centers by synchrotron radiation. PMID- 10033681 TI - Excitation of fast waves near the mean gyrofrequency. PMID- 10033684 TI - Diffusion without vacancies or interstitials: A new concerted exchange mechanism. PMID- 10033683 TI - Direct evidence for substitutional ion-implanted indium dopants in silicon. PMID- 10033685 TI - Onset of the critical velocity regime in superfluid 4He at low temperature. PMID- 10033686 TI - Calorimetric study of amorphization in planar, binary, multilayer, thin-film diffusion couples of Ni and Zr. PMID- 10033687 TI - Electron-hole pair creation by atomic scattering at surfaces. PMID- 10033688 TI - Electronic transport and depletion of quantum wells by tunneling through deep levels in semiconductor superlattices. PMID- 10033689 TI - Determination of surface-plasmon dispersion relation by ricochet photoemission. PMID- 10033690 TI - Ferromagnetic order at (100)p(1 x 1) surfaces of bulk paramagnetic vanadium. PMID- 10033691 TI - Second condensed phase of electron-hole plasma in Si. PMID- 10033692 TI - Implications of fractional occupation of adsorbate resonances on van der Waals interactions at surfaces. PMID- 10033693 TI - Resonant solar neutrino oscillation experiments. PMID- 10033694 TI - String-seeded spirals: Origin of rotation and the density of the halo. PMID- 10033695 TI - Energy dependence of polarization effects in exclusive hadron scattering. PMID- 10033698 TI - Characterization of fat fractals in nonlinear dynamical systems. PMID- 10033700 TI - Nonlinear density-matrix approach for the finite-temperature soliton problem. PMID- 10033699 TI - Low temperature behavior of a tunneling atom interacting with a degenerate electron gas. PMID- 10033701 TI - Universal scattering theorems for strongly interacting W's and Z's. PMID- 10033702 TI - Contribution to the muon anomaly from superstring-inspired models. PMID- 10033703 TI - Exact calculation of ff-->ffWW for the charged-current sector and comparison with the effective-W approximation. PMID- 10033704 TI - Top-quark detection at high-energy electron-positron colliders. PMID- 10033705 TI - Spin dependence in low-energy neutron-proton scattering. PMID- 10033706 TI - Polarized proton-proton bremsstrahlung. PMID- 10033707 TI - Reaction 6Li(e,e'd) 4He and the alpha -d momentum distribution in the ground state of 6Li. PMID- 10033708 TI - Spin-spin potentials in 27Alpol PMID- 10033709 TI - (6Li,6He) reaction as a probe of spin transfer strength. PMID- 10033710 TI - Improved oscillator phase locking by use of a modulated electron beam in a gyrotron. PMID- 10033711 TI - Adverse consequences of a moving vacuum-plasma boundary on axisymmetric ac helicity injection. PMID- 10033712 TI - Vanishing sticking probabilities and enhanced capillary flow of spin-polarized hydrogen. PMID- 10033713 TI - Low-frequency Raman scattering from fractal vibrational modes in a silica gel. PMID- 10033714 TI - Molecular-dynamics study of ionic motions and neutron inelastic scattering in alpha -AgI. PMID- 10033715 TI - Observations of the diffraction of evanescent x rays at a crystal surface. PMID- 10033716 TI - Experimental observation of forces acting during scanning tunneling microscopy. PMID- 10033717 TI - Isotope effects on interdiffusion in blends of normal and deuterated polymers. PMID- 10033718 TI - Unusual bifurcation of renormalization-group fixed points for interfacial transitions. PMID- 10033719 TI - Delayed nucleation at a weakly first-order transition. PMID- 10033720 TI - Molecular dissociation and shock-induced cooling in fluid nitrogen at high densities and temperatures. PMID- 10033721 TI - Collective rotation of molecules driven by the angular momentum of light in a nematic film. PMID- 10033723 TI - Dynamic coarsening of crystal surfaces by formation of macrosteps. PMID- 10033722 TI - Molecular-dynamics simulation of the phase behavior of AgI. PMID- 10033724 TI - Insights into metastable defects in semi-insulating GaAs from electronic Raman studies on nonequilibrium holes. PMID- 10033725 TI - Initial stages of trapping in a-Si:H observed by femtosecond spectroscopy. PMID- 10033726 TI - Layered magnetic structures: Evidence for antiferromagnetic coupling of Fe layers across Cr interlayers. PMID- 10033727 TI - Room-temperature optical nonlinearities in GaAs. PMID- 10033728 TI - Thermal-equilibrium defect processes in hydrogenated amorphous silicon. PMID- 10033729 TI - Evolution of two-dimensional soap-film networks. PMID- 10033731 TI - Molecular confinement in nanometer-size superlattice microstructures. PMID- 10033730 TI - Theory and model for martensitic transformations. PMID- 10033733 TI - Cherenkov radiation from optical pulses. PMID- 10033732 TI - How large can a star be? PMID- 10033736 TI - Inverse scattering and integrability in multidimensions. PMID- 10033738 TI - Superweak CP nonconservation arising from an underlying quarternionic quantum dynamics. PMID- 10033737 TI - Nonuniversality and breakdown of scaling in a two-component coagulation model. PMID- 10033739 TI - Effective Lagrangean for low-energy hadron physics. PMID- 10033740 TI - Measurement of elastic electron scattering from the proton at high momentum transfer. PMID- 10033741 TI - Search for a short-lived neutral particle produced in nuclear decay. PMID- 10033742 TI - Effect of the nuclear medium on the proton investigated with the 12C(e,e'p)11B reaction. PMID- 10033743 TI - Relative 3s spectroscopic strength in 206Pb and 208Pb studied with the (e,e'p) knockout reaction. PMID- 10033744 TI - Violence of heavy-ion reactions from neutron multiplicity: 11 to 20A MeV 20Ne+ 238U. PMID- 10033745 TI - Statistical "doorway" role of the dinucleus in heavy-ion deep-inelastic reactions. PMID- 10033746 TI - Quartet effects in rare-earth nuclei. PMID- 10033747 TI - Polarization pendello$uml-sung and the generation of circularly polarized x-rays with a quarter-wave plate. PMID- 10033748 TI - Self-consistent dynamolike activity in turbulent plasmas. PMID- 10033750 TI - High-pressure melting curve of KCl: Evidence against lattice-instability theories of melting. PMID- 10033749 TI - Rapid collapse of a plasma sawtooth oscillation in the JET tokamak. PMID- 10033751 TI - Wetting transition in liquid helium. PMID- 10033752 TI - Melting pressure and the phase diagram of magnetically ordered solid 3He. PMID- 10033753 TI - Microscopic theory of a fully polarized model Fermi liquid. PMID- 10033755 TI - Pressure dependence of spin-fluctuation effects in the specific heat of the heavy fermion superconductor UPt3. PMID- 10033754 TI - Many-body interactions in rare gases: Krypton and xenon. PMID- 10033756 TI - Observation of negative s-wave proximity effect in superconducting UBe13. PMID- 10033757 TI - Indirect phase detection of NMR spinor transitions. PMID- 10033758 TI - Critical behavior of an Ising spin-glass. PMID- 10033759 TI - Unusually low surface-recombination velocity on silicon and germanium surfaces. PMID- 10033760 TI - Calculation of thermodynamic properties and phase diagrams of binary transition metal alloys. PMID- 10033762 TI - Corrections to van der Waals forces. PMID- 10033761 TI - Deviation from Hubble flow, biased galaxy formation, and the mass density of the Universe. PMID- 10033764 TI - Normalization of distribution functions in nuclei. PMID- 10033763 TI - Au and Drachman respond. PMID- 10033765 TI - Shlomo et al. respond. PMID- 10033767 TI - Schwartz et al. respond. PMID- 10033766 TI - Quantum corrections to thermally activated decay in SQUID rings. PMID- 10033768 TI - Comment on "Sharp photon-induced np-->(n+1)s resonances in Xe and Kr monolayers observed by spin-resolved electron spectroscopy." PMID- 10033770 TI - Comment on "Low-energy excitations in alpha - and gamma -Ce observed by photoemission" PMID- 10033769 TI - Schonhense and Heinzmann respond. PMID- 10033771 TI - Patthey et al. respond. PMID- 10033772 TI - Comment on "Spin glass on a Bethe lattice." PMID- 10033773 TI - Comment on "Spin-glass on a Bethe lattice." PMID- 10033776 TI - Quantum nondemolition detection of optical quadrature amplitudes. PMID- 10033774 TI - Thouless responds. PMID- 10033777 TI - Diffusion and long-time tails in a two-dimensional site-percolation model. PMID- 10033779 TI - Boson stars: Gravitational equilibria of self-interacting scalar fields. PMID- 10033778 TI - Self-diffusion in a nonuniform model system. PMID- 10033780 TI - Supersymmetric compactification of the heterotic string on coset spaces. PMID- 10033781 TI - Strings on a group manifold, Kac-Moody groups, and anomaly cancellation. PMID- 10033782 TI - Heavy quarks and electroweak symmetry breaking. PMID- 10033784 TI - First capture of antiprotons in a Penning trap: A kiloelectronvolt source. PMID- 10033783 TI - Evidence for a spin-1 particle produced by two photons. PMID- 10033785 TI - Apparent anomalously short mean free paths observed in relativistic heavy-ion collisions. PMID- 10033786 TI - Microwave multiphoton transitions between Rydberg states of potassium. PMID- 10033787 TI - Direct observation of the second-order coherence of parametrically generated light. PMID- 10033789 TI - Direct transition to turbulence in rotating Benard convection. PMID- 10033788 TI - Generation of squeezed states by parametric down conversion. PMID- 10033790 TI - Interpretation of disruptions in tokamak simulations. PMID- 10033791 TI - Activated chemisorption: Internal degrees of freedom and measured activation energies. PMID- 10033792 TI - Dendritic solidification in narrow gaps and surface-pressure-induced wetting transition. PMID- 10033793 TI - Disassociation of cadmium-vacancy complexes within the displacement spike. PMID- 10033795 TI - Hydrogen-induced subsurface reconstruction of Cu(110). PMID- 10033794 TI - Low-frequency shear response of (KBr)1-x(KCN)x. PMID- 10033796 TI - Surface fractal dimension of small metallic particles. PMID- 10033797 TI - Pressure dependence of band offsets in an InAs-GaSb superlattice. PMID- 10033798 TI - Electronic structure of the superatom: A quasiatomic system based on a semiconductor heterostructure. PMID- 10033799 TI - New pore-size parameter characterizing transport in porous media. PMID- 10033801 TI - Raman scattering from nonresonant intercalant modes in stage-1 C-AsF5. PMID- 10033800 TI - Multi-ion screening in uncompensated semiconductors. PMID- 10033802 TI - Transport and thermal properties of heavy-fermion superconductors: A unified picture. PMID- 10033803 TI - Electronic structure of the Si(111)2 x 1 surface by scanning-tunneling microscopy. PMID- 10033804 TI - Structure and fractal dimension of protein-detergent complexes. PMID- 10033805 TI - Study of interfacial curvature in a three-component microemulsion with equal volume of water and oil. PMID- 10033806 TI - New channel in ortho-para hydrogen conversion. PMID- 10033807 TI - Ab initio calculation of coverage-dependent adsorption properties of H on Pd(001). PMID- 10033808 TI - Normal versus anomalous formate-copper surface bonding and the application of x ray-absorption fine-structure studies to molecular adsorption. PMID- 10033809 TI - Comment on "Anomalous low-temperature susceptibility of solid 3He at high molar volumes" PMID- 10033810 TI - Kumar and Sullivan respond. PMID- 10033811 TI - Comment on "Problem of universality in phase transitions on hierarchical lattices" PMID- 10033812 TI - Hu responds. PMID- 10033813 TI - Semiclassically based Monte Carlo evaluation of path integrals. PMID- 10033814 TI - Replica Monte Carlo simulation of spin glasses. PMID- 10033815 TI - Massive, unitary, renormalizable Yang-Mills theory without Higgs bosons. PMID- 10033816 TI - Evidence against asymptotic freedom from SU(2) lattice gauge theory. PMID- 10033818 TI - Clear evidence for a first-order chiral transition in QCD. PMID- 10033817 TI - New formulation for the lattice-fermion derivative. Locality and chirality without spectrum doubling. PMID- 10033819 TI - Nonrenormalization theorems in superstring theory. PMID- 10033820 TI - Evidence for coherent neutral-pion production by high-energy neutrinos. PMID- 10033821 TI - Chou-Yang model and hyperon-proton elastic scattering. PMID- 10033822 TI - Measurement of the 16O( pi +, pi 0p) reaction. PMID- 10033823 TI - Direct spin determination of on-line-separated isotopes by nuclear orientation and nuclear magnetic resonance. PMID- 10033824 TI - Transformation of symmetrization order to nuclear-spin magnetization by chemical reaction and nuclear magnetic resonance. PMID- 10033825 TI - Distance of excited-state formation in ion-surface collisions. PMID- 10033826 TI - New theoretical description of the carbon-carbon triple bond. PMID- 10033827 TI - Laser chaotic attractors in crisis. PMID- 10033828 TI - Spontaneous generation of Raman solitons from quantum noise. PMID- 10033829 TI - Confirmation of positron mobility edge in gaseous helium by Monte Carlo simulation. PMID- 10033830 TI - Bifurcation of magnetized electron transport in laser-produced plasmas. PMID- 10033831 TI - Existence and role of the precursor film in the spreading of polymer liquids. PMID- 10033832 TI - Solute trapping in silicon by lateral motion of {111} ledges. PMID- 10033833 TI - Glassy dynamics in icosahedral systems. PMID- 10033834 TI - Observations of the melting transition in thin lead films. PMID- 10033836 TI - Identification of the Ga interstitial in AlxGa1-xAs by optically detected magnetic resonance. PMID- 10033835 TI - Field adsorption of helium on tungsten. PMID- 10033837 TI - Phase diagram of Yukawa systems: Model for charge-stabilized colloids. PMID- 10033838 TI - Random strains and the structure of (Kbr)1-x(KCN)x mixed crystals. PMID- 10033839 TI - Dislocation generation in the two-dimensional Frenkel-Kontorova model at high stresses. PMID- 10033841 TI - Flow of polarized Fermi gases through narrow channels. PMID- 10033840 TI - Mistakes in quasilattices. PMID- 10033842 TI - Ordering at Si(111)/a-Si and Si(111)/SiO2 interfaces. PMID- 10033843 TI - Steric interactions in a model multimembrane system: A synchrotron x-ray study. PMID- 10033844 TI - Absorption blue shift in laser-excited semiconductor microspheres. PMID- 10033846 TI - Electron-energy-loss scattering near a single misfit dislocation at the GaAs/GaInAs interface. PMID- 10033845 TI - Anderson localization of electromagnetic waves in a dielectric medium of randomly distributed metal particles. PMID- 10033847 TI - Magnetic and nonmagnetic charge states in YbPd. PMID- 10033848 TI - Geometrical factors in enhanced photoyield from small metal particles. PMID- 10033849 TI - Superconductivity and phase transitions in compressed Si to 45 GPa. PMID- 10033850 TI - Critical end point in CeSb under uniaxial pressure parallel to PMID- 10033851 TI - Tunneling exchange, supersymmetry, and Riccati equations. PMID- 10033852 TI - Collective excitations and the dynamical Stark effect in a coherently driven exciton system. PMID- 10033854 TI - Quantum transport and surface scattering. PMID- 10033853 TI - Nuclear electric quadrupole induction of atomic polarization. PMID- 10033855 TI - Intractable computations with out local minima. PMID- 10033856 TI - Propagative phase dynamics. PMID- 10033857 TI - Distinguishing a quasicrystal from an icosahedral glass via lattice imaging. PMID- 10033858 TI - Stephens and Goldman respond. PMID- 10033862 TI - Possible instability for shear-induced order-disorder transitionp. PMID- 10033863 TI - Scaling of the 0sup++ glueball mass in SU(N) Hamiltonian lattice calculations. PMID- 10033864 TI - Finite-size results for SU(3) gauge theory. PMID- 10033865 TI - Exotic muon decay micro-->e+x. PMID- 10033866 TI - New quasi-Landau structure of highly excited atoms: The hydrogen atom. PMID- 10033868 TI - Oscillation of photoionization thresholds of small photolytic silver clusters on silver bromide grain surface. PMID- 10033869 TI - Fast magnetic dynamos in chaotic flows. PMID- 10033867 TI - Direct determination of the stereochemical structure of CH4+ PMID- 10033871 TI - Experimental evidence of MHD surface waves. PMID- 10033870 TI - Evidence for Lorenz-type chaos in a laser. PMID- 10033872 TI - Second sound in wave turbulence: A clue to the cause of anomalous plasma diffusivity. PMID- 10033873 TI - Scaling of incremental energy confinement time in the JFT-2M tokamak. PMID- 10033874 TI - Model for thermal transport in tokamaks. PMID- 10033875 TI - Hydrogen pairing and anisotropic potential for hydrogen isotopes in yttrium. PMID- 10033877 TI - Pressure dependence of the nematic-to-iostropic transition in the cesium perfluoro-octanoate lyotropic liquid crystal. PMID- 10033876 TI - Nuclear magnetic resonance in random fields: Cluster formation and local dynamics of a deuteron glass. PMID- 10033878 TI - Electron-microscope observation of the smectic-nematic transition in a lyotropic liquid crystal. PMID- 10033880 TI - Kossel diagrams show electric-field-induced cubic-tetragonal structural transition in frustrated liquid-crystal blue phases. PMID- 10033879 TI - Elastic properties of Langmuir-Blodgett films. PMID- 10033881 TI - Crystalline nucleation in deeply quenched liquids. PMID- 10033883 TI - Transient response of a tunneling device obtained from the Wigner function. PMID- 10033882 TI - Mossbauer spectroscopic evidence of angle-dependent intersystem crossing in LiNbO3:Fe3+ PMID- 10033884 TI - Observation of time evolution from resonant Raman scattering to excitonic polariton luminescence in ZnTe. PMID- 10033886 TI - Implications of the red-shift-number test for cosmology. PMID- 10033885 TI - Temporal association in asymmetric neural networks. PMID- 10033887 TI - Comment on "Reanalysis of the Eotvos experiment" PMID- 10033888 TI - Fischbach et al. respond. PMID- 10033889 TI - Comment on "New interaction for the enhancement of the Delta I=1/2 amplitude in weak decays" PMID- 10033891 TI - Comment on "Model for the underground muons associated with Cygnus X-3" PMID- 10033890 TI - Ma responds. PMID- 10033892 TI - Ruddick responds. PMID- 10033893 TI - Comment on "Commutator of the quark mass matrices in the standard electroweak model and a measure of maximal CP nonconservation" PMID- 10033894 TI - Jarlskog responds. PMID- 10033895 TI - Melting at grain boundaries and surfaces. PMID- 10033897 TI - Transition-strength fluctuations and the onset of chaotic motion. PMID- 10033898 TI - Kolmogorov-Arnol'd-Moser barriers in the quantum dynamics of chaotic systems. PMID- 10033900 TI - Quantum limit for successive position measurements. PMID- 10033899 TI - Time in quantum measurements. PMID- 10033901 TI - Thermal coefficients of quantum chromodynamics. PMID- 10033903 TI - Energy dependence of source sizes in nuclear interferometry. PMID- 10033902 TI - Limits to nu micro, nu e--> nu tau oscillations and nu micro, nu e--> tau - direct coupling. PMID- 10033904 TI - Correlated sources of heavy fragments in the Kr+Au reaction at 35 and 44 MeV/u. PMID- 10033905 TI - Intranuclear N-N collision model for the production of high-energy gamma rays in heavy-ion collisions. PMID- 10033906 TI - Damping of nuclear rotational motion at modest temperatures. PMID- 10033907 TI - Relativistic Hartree calculations for axially deformed nuclei. PMID- 10033908 TI - Spectroscopic observation of phase coexistence in SF6-Arn clusters for n=10-20. PMID- 10033909 TI - Laser-produced spectra and QED effects for Fe, Co, Cu, and Zn ions of Au, Pb, Bi, Th, and U. PMID- 10033910 TI - Lamb shift in heliumlike uranium (U90+). PMID- 10033911 TI - Quadratic Zeeman effect for nonhydrogenic systems: Application to the Sr and Ba atoms. PMID- 10033913 TI - Observation of a short-wavelength laser pumped by Auger decay. PMID- 10033912 TI - Traveling and standing waves in binary-fluid convection in finite geometries. PMID- 10033915 TI - Observation of a 10-meV Einstein oscillator mode on the Si(111) (2 x 1) surface. PMID- 10033916 TI - Tensor LEED: A technique for high-speed surface-structure determination. PMID- 10033914 TI - Detection of ferromagnetic domains in a two-dimensional nuclear-spin system. PMID- 10033917 TI - Isotope effects in the PdH system: Lattice dynamics of PdT0.7. PMID- 10033918 TI - Surface melting and roughening of adsorbed argon films. PMID- 10033919 TI - Surface polar ordering in a liquid crystal observed by optical second-harmonic generation. PMID- 10033920 TI - Physical realization of the parity anomaly in condensed matter physics. PMID- 10033922 TI - Anomalous surface-state penetration near a band edge. PMID- 10033921 TI - Realistic calculation of the indirect-exchange interaction in metals. PMID- 10033923 TI - Defects in amorphous silicon: A new perspective. PMID- 10033924 TI - Electrons at disordered surfaces and 1/f noise. PMID- 10033925 TI - Enhanced superconductivity by electron renormalization of a directly observed Brout-Visscher local phonon: Re in Mo1-xRex. PMID- 10033926 TI - Novel surface states and the quantum Hall effect in an anisotropic three dimensional system. PMID- 10033928 TI - Finite-size scaling and correlation lengths for disordered systems. PMID- 10033927 TI - Detection of soliton shape modes in polyacetylene. PMID- 10033929 TI - Experimental study of the A dependence of J/ psi photoproduction. PMID- 10033930 TI - Topological-exchange-current contribution to the deuteron magnetic form factor. PMID- 10033931 TI - Final-state-interaction analysis of inelastic electron scattering on 3He. PMID- 10033932 TI - Calculation of the shell-model potential from the optical-model potential. PMID- 10033933 TI - Lifetime measurements of high-spin states in 166Yb. PMID- 10033935 TI - Stark multiplets in molecular Rydberg states. PMID- 10033934 TI - Dynamics of ring polymers in the presence of fixed obstacles. PMID- 10033936 TI - Partial cross-section measurements for ionization of helium by positron impact. PMID- 10033938 TI - Two-photon transitions in atomic inner shells: Relativistic self-consistent-field calculation for Xe. PMID- 10033937 TI - Harpooning in surface scattering: O2 - formation in collisions of O2 + from Ag(111). PMID- 10033939 TI - Observation of resonant transfer and excitation to specific LS-coupled states in O5++He collisions by high-resolution, 0 degrees Auger-electron spectroscopy. PMID- 10033941 TI - Experimental observation of slow ion acoustic double layers. PMID- 10033940 TI - Formation of dynamical domains in a circular Couette system. PMID- 10033942 TI - Biatomic steps on (001) silicon surfaces. PMID- 10033943 TI - Geometrical structures of the Ge/Si(111) interface and the Si(111)(7 x 7) surface. PMID- 10033945 TI - Wall-induced orientational order of a liquid crystal in the isotropic phase - an evanescent-wave-ellipsometry study. PMID- 10033944 TI - Structure of high-density amorphous ice by neutron diffraction. PMID- 10033946 TI - Stability of dendritic crystals. PMID- 10033947 TI - Direct resolution and identification of the sublattices in compound semiconductors by high-resolution transmission electron microscopy. PMID- 10033948 TI - Normal displacements on a reconstructed silicon (111) surface: An x-ray-standing wave study. PMID- 10033949 TI - Modification of Pd77Si23 metallic glasses by picosecond laser annealing. PMID- 10033950 TI - Icosahedral quasicrystals and quantum structural diagrams. PMID- 10033951 TI - Effective mass of neutrons diffracting in crystals. PMID- 10033952 TI - Universality of quantum Hall effect: Topological invariant and observable. PMID- 10033954 TI - Mode condensation in a hierarchical system. PMID- 10033953 TI - Nonlinear behavior near the percolation metal-insulator transition. PMID- 10033955 TI - Half-flux-quantum magnetoresistance oscillations in disordered metal rings. PMID- 10033957 TI - Supersymmetric treatment of random disorder in the continuum model of polyacetylene. PMID- 10033956 TI - Evidence for structure-related induced anisotropy in amorphous CoTi soft ferromagnetic thin films. PMID- 10033958 TI - Gelation of colloidal silica. PMID- 10033960 TI - Comment on "Nonequilibrium periodic structures induced by rotating and static fields in a lyotropic nematic liquid crystal" PMID- 10033959 TI - Self-avoiding walks on a crumpled fractal. PMID- 10033963 TI - New limits on spatial anisotropy from optically-pumped sup201Hg and 199Hg. PMID- 10033965 TI - Is there a breakdown of quantum electrodynamics? PMID- 10033964 TI - Range of feeble forces from higher dimensions. PMID- 10033966 TI - Solution to the U(1) problem on a lattice. PMID- 10033967 TI - Study of baryon correlations in e+e- annihilation at 29 GeV. PMID- 10033968 TI - Precise measurement of neutral-pion photoproduction on the proton near threshold. PMID- 10033969 TI - Suppression of the two-neutrino double-beta decay by nuclear-structure effects. PMID- 10033970 TI - Inclusive pion double charge exchange in 4He. PMID- 10033971 TI - Pondermotive effects on angular distributions of photoelectrons. PMID- 10033973 TI - Oscillatory exchange of atoms between traps containing Bose condensates. PMID- 10033972 TI - Is a circular Rydberg atom stable in a vanishing electric field? PMID- 10033974 TI - Tricritical codimension-two point near the onset of convection in viscoelastic liquids. PMID- 10033975 TI - Detailed measurements of inelastic scattering in Anderson localization. PMID- 10033976 TI - Experimental study of the chemisorbed state of C2 H2, C2 H4, and C2 H6 on noble metal surfaces. PMID- 10033978 TI - Thermodynamic and electronic properties of alkali-metal atom fluids. PMID- 10033977 TI - Exact surface and wedge exponents for polymers in two dimensions. PMID- 10033979 TI - Impurity-quenched orientational epitaxy of Kr layers on Pt(111). PMID- 10033980 TI - X-ray determination of the substrate modulation potential for a two-dimensional Rb liquid in graphite. PMID- 10033981 TI - Gradient percolation in three dimensions and relation to diffusion fronts. PMID- 10033982 TI - Neutron scattering study of premartensitic behavior in Ni-Al alloys. PMID- 10033983 TI - From fractal to dendritic: Competition between diffusion and field. PMID- 10033984 TI - Resonant microwave absorption in superconductor-normal-superconductor junctions. PMID- 10033985 TI - Stress-induced doubly resonant Raman scattering in GaAs. PMID- 10033986 TI - Direct observation of ballistic electrons in silicon dioxide. PMID- 10033987 TI - 2Eg transitions in GaSb-AlSb quantum-well structures. PMID- 10033989 TI - Three-dimensional random-bond Ising model: Phase diagram and critical properties. PMID- 10033988 TI - Ferromagnetic order at surfaces of ultrathin epitaxial fcc gamma -Fe(111)p(11) films on Cu(111). PMID- 10033990 TI - Charged-soliton dynamics in trans-polyacetylene. PMID- 10033992 TI - Halfpap and Lindsay respond. PMID- 10033991 TI - Comment on "Rigidity percolation in the germanium-arsenic-selenium alloy system" PMID- 10033993 TI - Comment on "Interatomic forces in scanning tunneling microscopy: Giant corrugations of the graphite surface" PMID- 10033994 TI - Determination of 2e/h and h/e2 in SI units. PMID- 10033995 TI - Search for the rare decay micro+-->e+ gamma gamma. PMID- 10033996 TI - Search for high-mass narrow resonances in virtual photon-photon interactions. PMID- 10033997 TI - Average transverse momentum and energy density in high-energy nucleus-nucleus collisions. PMID- 10033998 TI - Direct mass measurements of neutron-rich light nuclei near N=20. PMID- 10033999 TI - Octupole deformation in neutron-rich barium isotopes. PMID- 10034000 TI - Rydberg atoms in uniform magnetic fields: Uncovering the transition from regularity to irregularity in a quantum system. PMID- 10034001 TI - Measured densities and rotational temperatures of metastable H2 in a multicusp ion source. PMID- 10034003 TI - Surface extended x-ray absorption fine-structure study of the O(2 x 1)/Cu(110) system: Missing-row reconstruction and anisotropy in the surface mean free path and in the surface Debye-Waller factor. PMID- 10034002 TI - Three-dimensional particle simulation of drift-wave fluctuations in a sheared magnetic field. PMID- 10034004 TI - Fast sound in two-component liquids. PMID- 10034006 TI - Electron tunneling into superconducting ZrN. PMID- 10034005 TI - Jump dynamics and the isotope effect in solid-state diffusion. PMID- 10034007 TI - Nonlinear dynamic susceptibilities at the spin-glass transition of Ag:Mn. PMID- 10034009 TI - Comment on "Universality of finite-size scaling: Role of the boundary conditions" PMID- 10034008 TI - Instability of the ideal tungsten (001) surface. PMID- 10034010 TI - Cabrera and Jullien respond. PMID- 10034011 TI - Comment on "Why quantum diffusion is nondissipative" PMID- 10034012 TI - Ramanathan responds. PMID- 10034013 TI - Comment on "Surface effects in cluster calculations of energy profiles of muonium diamond" PMID- 10034014 TI - Estreicher et al. responds. PMID- 10034015 TI - Observation of molecular vibrations in real time. PMID- 10034016 TI - Singularities and asymptotics in diffusion-limited aggregation. PMID- 10034017 TI - Turkevich and Scher respond. PMID- 10034018 TI - Patterns produced by precipitation at a moving reaction front. PMID- 10034019 TI - Tricritical points in three-dimensional XY model with mixed action. PMID- 10034020 TI - Purely cubic action for string field theory. PMID- 10034021 TI - New interaction for the enhancement of the Delta I=(1/2) amplitude in weak decays. PMID- 10034022 TI - From light to heavy quarkonia: An integrated Bethe-Salpeter view. PMID- 10034023 TI - Can the data from the CERN pp-bar collider limit gaugino masses? PMID- 10034024 TI - Precision measurement of sin2thetaW from semileptonic neutrino scattering. PMID- 10034026 TI - Experimental and theoretical determinations of the 5d photoionization cross section in laser-excited barium atoms between 15 and 150 eV photon energy. PMID- 10034025 TI - Nuclear collective flow as a function of projectile energy and mass. PMID- 10034027 TI - Light traps using spontaneous forces. PMID- 10034028 TI - Experimental observation of optically trapped atoms. PMID- 10034029 TI - Heavy-ion straggling: Possible evidence for inner-shell excitation. PMID- 10034030 TI - Femtosecond relaxation dynamics of large molecules. PMID- 10034031 TI - Order, disorder, and phase turbulence. PMID- 10034033 TI - Trapping of gun-injected plasma by a tokamak. PMID- 10034032 TI - Ion heating due to rotation and collision in magnetized plasma. PMID- 10034034 TI - Measurement of growth rates and temporal behavior of stimulated Raman scattering in a CO2-laser-produced plasma. PMID- 10034036 TI - Dynamics of the 3He A-B phase boundary. PMID- 10034035 TI - Velocity of propagation of the 3He-A-B interface in hypercooled 3He-A. PMID- 10034037 TI - Nonequilibrium periodic structures induced by rotating and static fields in a lyotropic nematic liquid crystal. PMID- 10034038 TI - Diffusion-limited growth of wetting layers. PMID- 10034039 TI - Indirect ionic interactions. PMID- 10034040 TI - Finite size effects on first order phase transitions: fcc binary alloys. PMID- 10034041 TI - Freeze-fracture electron-microscope observations of the blue phase III. PMID- 10034042 TI - Flux quantization on quasicrystalline networks. PMID- 10034043 TI - Incommensurate magnetic phase in EuAs3 with zone-boundary lock-in. PMID- 10034044 TI - Positron dynamics in rare-gas solids. PMID- 10034045 TI - Critical plasmons of a quasiperiodic semiconductor superlattice. PMID- 10034046 TI - Dynamics of NO molecular-beam scattering from a Ge surface. PMID- 10034048 TI - Universality of finite-size scaling: Role of the boundary conditions. PMID- 10034047 TI - Fully localized 3d-shell behavior of Fe ions in alkali-metal hosts. PMID- 10034049 TI - Third law of black-hole dynamics: A formulation and proof. PMID- 10034050 TI - 0++-2++ glueball mass ratio in non-Abelian gauge theories. PMID- 10034052 TI - Finite-basis-set approach to the Dirac-Hartree-Fock equations. PMID- 10034053 TI - Many-body corrections to the intermolecular interaction probed with atom-surface scattering. PMID- 10034051 TI - Pion and kaon pair production in photon-photon collisions. PMID- 10034054 TI - Low-energy electron-atom scattering: The case of near degeneracy. PMID- 10034055 TI - Comprehensive rate determinations in an electronic intramolecular collisional energy transfer: Delta E and Delta J propensity rules through a surprisal analysis. PMID- 10034056 TI - Observation of single-mode operation in a free-electron laser. PMID- 10034057 TI - Turbulent relaxation to a force-free field-reversed state. PMID- 10034058 TI - X-ray study of the nematic phase and smectic-A1-to-smectic-A phase transition in heptylphenyl nitrobenzoloxybenzoate (DB7NO2). PMID- 10034059 TI - Dipolar glass state in K1-xNaxTaO3. PMID- 10034060 TI - Anomalous corrugations in scanning tunneling microscopy: Imaging of individual states. PMID- 10034061 TI - Interatomic forces in scanning tunneling microscopy: Giant corrugations of the graphite surface. PMID- 10034062 TI - Observation of magnetic-field-induced first-order optical Freedericksz transition in a nematic film. PMID- 10034064 TI - Two-directional photoinduced crystallization in GeSe2 and SiSe2 glasses. PMID- 10034063 TI - Direct observation of atomic steps in the surface reconstruction of the Pt(110) plane. PMID- 10034065 TI - Anomalous diffraction profiles of alkali-halide-alkali-cyanide mixed crystals. PMID- 10034066 TI - Transient resonant light scattering in a disordered system. PMID- 10034067 TI - Structure and electronic states in disordered systems. PMID- 10034068 TI - Observation of interference oscillations in helium scattering from single surface defects. PMID- 10034069 TI - Coulomb gap in sodium tungsten bronzes. PMID- 10034070 TI - Relaxation times of k=0 rotons in pure parahydrogen crystals and roton scattering by orthohydrogen impurities. PMID- 10034071 TI - Time-dependent phenomena in a short-range Ising spin-glass Fe0.5Mn0.5TiO3. PMID- 10034072 TI - Optical emission properties of interface states for metals on III-V semiconductor compounds. PMID- 10034073 TI - Origin of middle-phase microemulsions. PMID- 10034074 TI - Low-frequency 1/f noise in the interplanetary magnetic field. PMID- 10034075 TI - Comment on "Induced angular momentum in (2+1)-dimensional QED" PMID- 10034076 TI - Paranjape responds. PMID- 10034079 TI - Deconfining and chiral transitions of finite-temperature quantum chromodynamics in the presence of dynamical quark loops. PMID- 10034077 TI - Comment on "Universality of the Kosterlitz-Thouless transition in 4He films as a function of thickness" PMID- 10034081 TI - Inconsistency of Feynman rules derived via path integration. PMID- 10034080 TI - Energy dependence of spin effects in p PMID- 10034082 TI - Solitons in a composite Higgs model of electroweak theory. PMID- 10034084 TI - How chiral solitons relate K-barN and pi N scattering. PMID- 10034083 TI - Origin of gauge invariance in string theory. PMID- 10034086 TI - Model for the underground muons associated with Cygnus X-3. PMID- 10034085 TI - Study of the decay tau ---> pi - pi - pi + nu tau. PMID- 10034087 TI - New model of b-quark interactions: A superstring alternative. PMID- 10034088 TI - Universal features of shape transitions in hot rotating nuclei. PMID- 10034090 TI - Compression modulus of nuclear matter and charge-distribution differences. PMID- 10034089 TI - Measurement of isospin mixing in 4He and its implications for charge-symmetry breaking. PMID- 10034091 TI - Entrance- and exit-channel effects and the suppression of neutron emission from 64Ni+92Zr-->156Er* PMID- 10034092 TI - High-energy gamma-ray emission in heavy-ion collisions. PMID- 10034093 TI - Deflection of nonequilibrium light particles by the nuclear mean field. PMID- 10034094 TI - Muon channeling in semiconductors: Evidence for pionium formation. PMID- 10034096 TI - Regularity and irregularity in spectra of the magnetized hydrogen atom. PMID- 10034095 TI - Observation of quadrupole and dipole diamagnetic shifts in atomic ground-state hyperfine structure. PMID- 10034097 TI - Weak localization of photons: Universal fluctuations and ensemble averaging. PMID- 10034099 TI - Instability of a thermal Stokes layer. PMID- 10034098 TI - Nonlinear power saturation and phase (wave refractive index) in a collective free electron laser amplifier. PMID- 10034100 TI - Energy confinement of lower-hybrid-current-driven tokamak plasmas. PMID- 10034101 TI - NMR in normal 3He using a meander-line coil. PMID- 10034103 TI - Strain-assisted epitaxial growth of new ordered compounds. PMID- 10034102 TI - Structure of aggregated gold colloids. PMID- 10034104 TI - Dispersive x-ray spectroscopy for time-resolved in situ observation of electrochemical inclusion of metallic clusters within a conducting polymer. PMID- 10034105 TI - General theory of inhomogeneous systems, using maximum entropy. PMID- 10034106 TI - Thermal donors in silicon: A study with ENDOR. PMID- 10034107 TI - Observation of switching and narrow-band noise in the condensed phase of a GaAs/Ga0.77Al0.23As heterojunction. PMID- 10034109 TI - Magnetic susceptibility and specific heat of an anisotropic spin-glass: EuxSr1 xAs3. PMID- 10034108 TI - Magnetic-field-induced carrier conversion in a charge-density-wave conductor. PMID- 10034110 TI - London penetration depth of heavy-fermion superconductors. PMID- 10034112 TI - One-dimensional electron-electron scattering with small energy transfers. PMID- 10034111 TI - Measurement of the energy gap in an organic superconductor: Evidence for extremely strong coupling. PMID- 10034113 TI - Surface roughening and the fractal nature of rocks. PMID- 10034114 TI - Active nonlinear ultralow-frequency generation in the ionosphere. PMID- 10034115 TI - Comment on the n= PMID- 10034116 TI - Comment on "Monopoles on strings." PMID- 10034117 TI - Hindmarsh and Kibble respond. PMID- 10034118 TI - Comment on "Bolometric detection of neutrinos." PMID- 10034119 TI - Comment on "Fractal dimension of dielectric breakdown." PMID- 10034120 TI - Niemeyer, Pietronero, and Wiesmann respond. PMID- 10034121 TI - Frequency-shifted polaron coupling in GaInAs heterojunctions. PMID- 10034122 TI - Comment on "Possible explanation of the solar-neutrino puzzle." PMID- 10034124 TI - Fractal dimension of cantori. PMID- 10034126 TI - Observable physics from superstring exotic particles: Small Dirac neutrino masses. PMID- 10034125 TI - Search for neutral particles in electron-beam-dump experiment. PMID- 10034127 TI - Loss of collectivity at high spin in 172W and a three-band interpretation of first yrast upbends. PMID- 10034128 TI - Emission of muonium into vacuum from a silica powder layer. PMID- 10034129 TI - Experimental study of charge transfer near a nuclear-scattering resonance. PMID- 10034130 TI - Polarization correlation study of the electron-impact excitation of neon and argon. PMID- 10034131 TI - Small-scale dynamics of high-Reynolds-number two-dimensional turbulence. PMID- 10034132 TI - Observation of photon antibunching in phase-matched multiatom resonance fluorescence. PMID- 10034134 TI - Eddy formation in obstructed fluid flow: A molecular-dynamics study. PMID- 10034133 TI - Broad-band parametric deamplification of quantum noise in an optical fiber. PMID- 10034135 TI - Measurements of the electric field distribution in high-power diodes. PMID- 10034136 TI - Strongly inhibited Rayleigh-Taylor growth with 0.25- microm lasers. PMID- 10034137 TI - Observations of centrally peaked impurity profiles following pellet injection in the Alcator-C tokamak. PMID- 10034138 TI - Optogalvanic observation of ionization waves in hollow-cathode discharges. PMID- 10034140 TI - Au(100) surface reconstruction. PMID- 10034139 TI - Anomalous currents to an electrode in a magnetoplasma. PMID- 10034141 TI - Structure of Au(110) determined with medium-energy-ion scattering. PMID- 10034142 TI - Kinetics of coagulation with fragmentation: Scaling behavior and fluctuations. PMID- 10034143 TI - Hydrogen diffusion mechanism in amorphous Pd85Si15H7.5: A neutron-scattering study. PMID- 10034144 TI - Roughening of low-angle grain boundaries. PMID- 10034146 TI - Observation of anomalous plasmon linewidth in the icosahedral Al-Mn quasicrystals. PMID- 10034145 TI - Anomalous time-of-flight distributions observed for argon implanted in silicon and resputtered by Ar+-ion bombardment. PMID- 10034147 TI - Raman spectroscopy of SiO2 glass at high pressure. PMID- 10034148 TI - Fractional quantization in ac conductance of Alx PMID- 10034149 TI - Transient analysis of ionic cluster emission from a silicon surface by nitrogen laser excitation. PMID- 10034150 TI - Theory of spin-polarized secondary-electron emission from ferromagnets. PMID- 10034152 TI - Observation of metal-insulator and metal-metal transitions in hydrogen iodide under pressure. PMID- 10034151 TI - Motionally dependent bound states in semiconductor quantum wells. PMID- 10034153 TI - Simple system with quasiperiodic dynamics: A spin in a magnetic field. PMID- 10034154 TI - Interactions of ultrahigh-energy neutrinos. PMID- 10034155 TI - Bistable solitons. PMID- 10034157 TI - Gibbsian surface segregation in Cu-Ni alloys. PMID- 10034156 TI - Kaplan responds. PMID- 10034159 TI - Comment on "Electron-ion interactions and ionization in a polar solvent" PMID- 10034158 TI - Sakurai responds. PMID- 10034160 TI - Determination of the wave field from scattering data. PMID- 10034161 TI - Exact solution of the Rabi Hamiltonian by known functions? PMID- 10034162 TI - Statistical mechanics of tethered surfaces. PMID- 10034163 TI - Spin-1/2 bosonization on compact surfaces. PMID- 10034164 TI - Trajectories of strings with rigidity. PMID- 10034165 TI - Tensor analyzing power in pi d elastic scattering. PMID- 10034166 TI - Pion absorption on T=1 nucleon pairs at T pi =70 MeV. PMID- 10034168 TI - Nonequilibrium population of magnetic substates and excitation-energy division in the decay of an orbiting complex. PMID- 10034167 TI - Observation of a discrete-line superdeformed band up to 60 PMID- 10034169 TI - Limitation of heavy-ion fusion: Fusion of aligned 23Na with 23Na. PMID- 10034171 TI - Generation of pair coherent states and squeezing via the competition of four-wave mixing and amplified spontaneous emission. PMID- 10034170 TI - New photoelectric ionization peak in the hydrogen atom. PMID- 10034172 TI - Standing-wave forward-backward gain asymmetry in optically pumped gas lasers. PMID- 10034173 TI - Tangential neutral-beam-driven instabilities in the Princeton beta experiment. PMID- 10034174 TI - Observation of one-dimensional second sound in superfluid helium. PMID- 10034175 TI - Critical behavior of the thermal conductance of 3He-4He mixture films at the Kosterlitz-Thouless transition. PMID- 10034176 TI - Rigidity percolation in the germanium-arsenic-selenium alloy system. PMID- 10034177 TI - Coulomb explosions in a metallic glass due to the passage of fast heavy ions? PMID- 10034179 TI - Wavelength selection in directional solidification. PMID- 10034178 TI - Near-metamagnetism of liquid 3He at high pressure. PMID- 10034180 TI - Nonlocal screening in metal surfaces. PMID- 10034181 TI - Self-similarity and fractal dimension of a roughening interface by Monte Carlo simulations. PMID- 10034182 TI - Anisotropic heat conduction in diacetylenes. PMID- 10034183 TI - Theoretical analysis of explosively propagating molten layers in pulsed-laser irradiated a-Si. PMID- 10034184 TI - Kondo bosons and the Kondo lattice: Microscopic basis for the heavy Fermi liquid. PMID- 10034185 TI - Picosecond surface electron dynamics on photoexcited Si(111)(2 x 1) surfacs surfaces. PMID- 10034187 TI - Metal-nonmetal transition in expanded liquid mercury. PMID- 10034186 TI - Quantum phase slips and superconductivity in granular films. PMID- 10034188 TI - Oxide-charge-induced localized states and screening in a model two-dimensional system. PMID- 10034189 TI - Proton tunneling with millielectronvolt energies at the Be-H acceptor complex in silicon. PMID- 10034190 TI - Superconducting tunneling in ultrathin Nb films. PMID- 10034191 TI - Magnetic equilibrium noise in spin-glasses: Eu0.4Sr0.6S. PMID- 10034192 TI - Density of localized states near the band edge of disordered systems. PMID- 10034193 TI - Nonlinear neural networks. PMID- 10034194 TI - Comment on "Saddle-point variational method for the Dirac equation." PMID- 10034195 TI - Evidence for Ising-type critical behavior in two-dimensional percolation. PMID- 10034197 TI - Phase coherence and quantized circulation transitions in superfluid helium. PMID- 10034196 TI - Jug responds. PMID- 10034198 TI - Avenel and Varoquaux respond. PMID- 10034199 TI - Compatibility of crystalline order and the quantized Hall effect. PMID- 10034201 TI - New universal scenarios for the onset of chaos in Lorenz-type flows. PMID- 10034202 TI - Spinning cosmic strings and quantization of energy. PMID- 10034204 TI - Observation of Berry's topological phase by use of an optical fiber. PMID- 10034203 TI - Manifestations of Berry's topological phase for the photon. PMID- 10034205 TI - Polymer network of fixed topology: Renormalization, exact critical exponent gamma in two dimensions, and D=4- epsilon. PMID- 10034207 TI - Measurement of the Sigma 0- Lambda transition magnetic moment. PMID- 10034206 TI - Comparison of the particle flow in qq-barg and qq-bar gamma events in e+e- annihilation. PMID- 10034208 TI - Hadron spectroscopy in lattice QCD with dynamical quark loops. PMID- 10034210 TI - Large muon- and electron-number nonconservation in supergravity theories. PMID- 10034209 TI - Chiral hierarchies and flavor-changing neutral currents in hypercolor. PMID- 10034211 TI - Atomic effects in low-energy beta decay: The case of tritium. PMID- 10034212 TI - Neutrinoless double- beta decay and its relation to pion double charge exchange. PMID- 10034213 TI - Differential cross section for coherent photon scattering from 4He at 180 MeV. PMID- 10034214 TI - Photodissociation of mass-selected (CO2)n - clusters: Evaporation leading to magic numbers in fragment-ion dstributions. PMID- 10034216 TI - Molecular description of two-electron atoms. PMID- 10034215 TI - Interfering resonances: Avoided crossings of autoionizing states in molecules. PMID- 10034217 TI - Many-electron effects in the shape of the Cl K alpha 1,2 x-ray emission lines. PMID- 10034218 TI - Observation of strong forward-backward asymmetries in electron emission from overlapping resonance states produced by transfer excitation in 2.5-3.5-MeV C3++He collisions. PMID- 10034220 TI - Multiple scattering noise in one dimension: Universality through localization length scaling. PMID- 10034219 TI - Hydrodynamic dispersion in network models of porous media. PMID- 10034221 TI - Divergence measurements of soft-x-ray laser beam. PMID- 10034222 TI - Small-scale plasma-density depletions in Arecibo high-frequency modification experiments. PMID- 10034223 TI - Multicriticality in hexatic-liquid crystals. PMID- 10034224 TI - Growth probability distribution in kinetic aggregation processes. PMID- 10034225 TI - New reconstructions on silicon (111) surfaces. PMID- 10034226 TI - Evidence for a relationship between the anisotropy of surface energy and surface reconstruction: Comparison of Pt(110) and Cu(110). PMID- 10034227 TI - Observation of a textural transformation associated with the A2-transition in superfluid 3He-A. PMID- 10034228 TI - Reentrant superfluidity in highly polarized liquid 3He. PMID- 10034229 TI - Critical dielectric behavior of micellar water below the cloud point of a water oil microemulsion. PMID- 10034230 TI - Experimental identification of charge relaxation rates in intermediate-valence compounds by phonon spectroscopy. PMID- 10034231 TI - Domain-wall interactions and spatially modulated phases. PMID- 10034232 TI - Dyon analogs in antiferromagnetic chains. PMID- 10034233 TI - Size effects of electrical breakdown in quenched random media. PMID- 10034234 TI - Anomalous Hall effect below the magnetic-field-induced metal-insulator transition in narrow-gap semiconductors. PMID- 10034235 TI - Frequency locking, quasiperiodicity, and chaos in extrinsic Ge. PMID- 10034236 TI - Observation of final-state screening in inverse photoemission from adsorbed xenon layers. PMID- 10034237 TI - Characterization of copper (100) surfaces by isolated indium-probe atoms via the electric field gradient. PMID- 10034239 TI - Calculated photoemission spectra of Na. PMID- 10034238 TI - Modification of the Fermi-surface instability in UPt3 by Th substitution. PMID- 10034240 TI - Interface-state measurements at Schottky contacts: A new admittance technique. PMID- 10034241 TI - Electron-electron scattering in nondegenerate semiconductors: Driving the anisotropic distribution toward a displaced Maxwellian. PMID- 10034242 TI - Comment on "Gravitomagnetic pole and mass quantization" PMID- 10034243 TI - Comment on "Gravitomagnetic pole and mass quantization" PMID- 10034244 TI - Minimax principle for the Dirac equation. PMID- 10034245 TI - Quantized currents and topological invariants for electrons in incommensurate potentials. PMID- 10034246 TI - Self-similarity of fluctuations in random multiplicative processes. PMID- 10034247 TI - Topological terms induced by finite temperature and density fluctuations. PMID- 10034248 TI - B-->Kl+l- and other rare B-meson decays. PMID- 10034250 TI - Precise test for the unitarized pion photoproduction impulse amplitude in exclusive nuclear reactions. PMID- 10034249 TI - WW production from pp collisions. PMID- 10034251 TI - Comprehensive calculations of the ( pi +,K+) reaction on 12C. PMID- 10034252 TI - Neutron-star masses as a constraint on the nuclear compression modulus. PMID- 10034254 TI - Computation of second-order many-body corrections in relativistic atomic systems. PMID- 10034253 TI - Definition of the shape parameter gamma in the interacting-boson model. PMID- 10034255 TI - Coincidence study of doubly differential cross sections: Projectile ionization in He+-He collisions. PMID- 10034256 TI - Structure of a one-component plasma in an external field: A molecular-dynamics study of particle arrangement in a heavy-ion storage ring. PMID- 10034257 TI - Suppression of sawtooth oscillations by lower-hybrid current drive in the ASDEX tokamak. PMID- 10034259 TI - Energy surfaces of polymeric sulfur: Structure and electronic properties. PMID- 10034258 TI - Quantum beats from nuclei excited by synchrotron radiation. PMID- 10034260 TI - Coulomb energy in pseudobinary alloys. PMID- 10034261 TI - Evidence for the Ir (100) surface reconstruction by field-ion microscopy. PMID- 10034262 TI - Synchrotron x-ray study of a Fibonacci superlattice. PMID- 10034263 TI - Nuclear ferromagnetism of two-dimensional 3He. PMID- 10034265 TI - Critical properties of a random anisotropy system a-DyNi: A new universality class in disordered systems? PMID- 10034264 TI - Spin-freezing process in a spin-glass: Cd0.6Mn0.4Te. PMID- 10034266 TI - Phase-transition behavior in a random-anisotropy system. PMID- 10034267 TI - Transition of local moments coupled to itinerant electrons in the quasi one dimensional conductor, copper phthalocyanine iodide. PMID- 10034268 TI - First-principles calculation of the residual electrical resistivity of random alloys. PMID- 10034269 TI - Reaction of Si(100) with NH3: Rate-limiting steps and reactivity enhancement via electronic excitation. PMID- 10034271 TI - Benguigui responds. PMID- 10034270 TI - Comment on "Experimental study of the elastic properties of a percolating system." PMID- 10034272 TI - Comment on "NMR study of the structure and motion of charge-density waves in NbSe3." PMID- 10034275 TI - Helicity-amplitude relations for vector-meson production from a skyrmion model. PMID- 10034276 TI - Effects of Z0 mixing with an E6 gauge boson at e+e- colliders. PMID- 10034278 TI - Electron-impact ionization of negatively charged water-cluster ions. PMID- 10034277 TI - Identification of higher representations of the U(6/4) supersymmetry in the nucleus 195Ir. PMID- 10034279 TI - Measurement of the average equilibrium charge of fast heavy ions in a solid by H+ emission at the exit surface. PMID- 10034281 TI - Solvable model of the beam-beam limit in e+e- colliding rings. PMID- 10034282 TI - Mercury injection in porous media: A resistance devil's staircase with percolation geometry. PMID- 10034280 TI - Collisionally aided coherent emission at an optical frequency. PMID- 10034284 TI - Laboratory observation of ion conics by velocity-space tomography of a plasma. PMID- 10034283 TI - Strong damping of stimulated Brillouin scattering in cavity structured targets. PMID- 10034285 TI - Beyond the pair-potential model of fluids at the liquid-vapor critical point. PMID- 10034286 TI - Apparent size of an atom in the scanning tunneling microscope as a function of bias. PMID- 10034287 TI - First-principles calculation of semiconductor-alloy phase diagrams. PMID- 10034288 TI - Calculations of the surface stress tensor at aluminum PMID- 10034289 TI - Chaotic nature of the spin-glass phase. PMID- 10034290 TI - Localized grain-boundary electronic states and intergranular fracture. PMID- 10034291 TI - Magneto-optical Kerr effect, enhanced by the plasma resonance of charge carriers. PMID- 10034293 TI - Dynamical conductivity of the GaAs two-dimensional electron gas at low temperature and carrier density. PMID- 10034292 TI - Order-disorder transitions in the melt morphology of laser-irradiated silicon. PMID- 10034294 TI - Modification of the electron-phonon interactions in GaAs-GaAlAs heterojunctions. PMID- 10034295 TI - Comment on emission of band-gap-energy positrons from surfaces of LiF, NaF, and other ionic crystals. PMID- 10034297 TI - Interacting field theory of relativistic point particles. PMID- 10034298 TI - Naturally small Dirac neutrino masses in superstring theories. PMID- 10034299 TI - Spin analysis of the chi b states. PMID- 10034300 TI - Color magnetism and the helicity-zero ( gamma vN--> Delta ) transition amplitude. PMID- 10034301 TI - Manifestation of the Berry phase in diabolic pair transfer in rotating nuclei. PMID- 10034303 TI - High resolution rotational spectroscopy of weakly bound ionic clusters: ArH3+, ArD3+ PMID- 10034302 TI - Collective oblate band in 131La due to the rotational alignment of h11/2 neutrons. PMID- 10034304 TI - Threshold behavior in single-photon double ionization of argon. PMID- 10034305 TI - Determination of the dipole moment of ArH+ from the rotational Zeeman effect by tunable far infrared laser spectroscopy. PMID- 10034306 TI - Observation of amplitude squeezing in a constant-current-driven semiconductor laser. PMID- 10034307 TI - High-temperature plasmas in a tokamak fusion test reactor. PMID- 10034308 TI - Phase separation of a binary liquid mixture in a porous medium. PMID- 10034309 TI - In situ observation of commensuration process of long-period superlattice in the Ag-Mg alloys. PMID- 10034310 TI - High-energy-neutron vibrational spectroscopy on beta -V2H. PMID- 10034311 TI - Description of the dodecagonal quasicrystal by a projection method. PMID- 10034312 TI - Lattice instability and high-Tc superconductivity in La2-xBaxCuO4. PMID- 10034313 TI - Electronic band properties and superconductivity in La2-yXyCuO4. PMID- 10034314 TI - Mechanism of sputtering of large biomolecular ions by impact of highly ionizing particles. PMID- 10034315 TI - Electronically driven instabilities and superconductivity in the layered La2 xBaxCuO4 perovskites. PMID- 10034316 TI - Why the Brazil nuts are on top: Size segregation of particulate matter by shaking. PMID- 10034317 TI - Electromagnetic radiation from superconducting cosmic strings. PMID- 10034318 TI - Comment on "Chaotic Rabi oscillations under quasiperiodic perturbation" PMID- 10034319 TI - Analytic fractal dimension of cantori. PMID- 10034321 TI - Masiero, Nanopoulos, and Sanda respond. PMID- 10034320 TI - Comment on a recent claim of calculable neutrino masses in superstring-inspired model. PMID- 10034322 TI - Comment on: Adsorbate-induced Rayleigh-phonon gap of p(22) O/Pt(111). PMID- 10034324 TI - Comment on "Limits of the fractal dimension for irreversible kinetic aggregation of gold colloids" PMID- 10034323 TI - Kern et al. respond. PMID- 10034325 TI - Weitz, Lin, Lindsay, and Huang respond. PMID- 10034328 TI - Scaling behavior in the supercritical sine circle map. PMID- 10034327 TI - Distinguishable quantum states generated via nonlinear birefringence. PMID- 10034329 TI - New test of general relativity: Measurement of de Sitter geodetic precession rate for lunar perigee. PMID- 10034330 TI - Search for a substance-dependent force with a new differential accelerometer. PMID- 10034332 TI - What is the most general Abelian gauge theory in two spatial dimensions? PMID- 10034333 TI - Mass dequantization. PMID- 10034331 TI - Search for an intermediate-range interaction. PMID- 10034335 TI - First measurement of the real part of a pp double-spin-flip amplitude. PMID- 10034334 TI - Observation of charge asymmetry in hadron jets from e+e- annihilation at sqrt s =29 GeV. PMID- 10034337 TI - Evidence for prolate deformation in highly excited neutron-deficient Pb isotopes. PMID- 10034336 TI - Evidence for partial occupancy of the 3s1/2 proton orbit in 208Pb. PMID- 10034338 TI - Two-dimensional polymer melts. PMID- 10034340 TI - Polarization solitons. PMID- 10034339 TI - Levy dynamics of enhanced diffusion: Application to turbulence. PMID- 10034341 TI - Complex quasiperiodic and chaotic states observed in thermally induced oscillations of gas columns. PMID- 10034342 TI - Experimental test of the quasilinear theory of the interaction between a weak warm electron beam and a spectrum of waves. PMID- 10034343 TI - Local ordering in fluid deuterium. PMID- 10034344 TI - Surface first-order phase transitions in fcc Ising ferromagnets. PMID- 10034345 TI - Thermodynamic instability of ultrathin semiconductor superlattices: The (001) (GaAs)1(AlAs)1 structure. PMID- 10034346 TI - Linearity (commutativity and transitivity) of valence-band discontinuity in heterojunctions with Te-based II-VI semiconductors: CdTe, HgTe, and ZnTe. PMID- 10034347 TI - Microstructure, dimensionality, and depression of the transition temperature in disordered superconducting films. PMID- 10034348 TI - Two-photon photoemission from adsorbate-induced states: Atomic oxygen on Cu(111). PMID- 10034349 TI - Farey-fraction frequency modulation in the neuronlike output of silicon p-i-n diodes at 4.2 K. PMID- 10034350 TI - Flux trapping and superconductive glass state in La2CuO4-y:Ba. PMID- 10034351 TI - Superconducting Tc enhancement due to excitonic negative-U centers: A Monte Carlo study. PMID- 10034352 TI - Tuning of the valence-band structure of GaAs quantum wells by uniaxial stress. PMID- 10034353 TI - Comment on "Growth of fractally rough colloids" PMID- 10034354 TI - Keefer and Schaefer respond. PMID- 10034355 TI - Energetics of single dangling and floating bonds in amorphous Si. PMID- 10034356 TI - Comment on the theory of helical magnetic structures in diluted alloys. PMID- 10034359 TI - Test for relativistic gravitational effects on charged particlesp. PMID- 10034358 TI - Phase organization. PMID- 10034360 TI - Phase transitions in the thermodynamic formalism of multifractals. PMID- 10034362 TI - N dependence of coherent radiation from crystals. PMID- 10034361 TI - Constraints on anomalous scattering of neutrinos from crystals. PMID- 10034364 TI - Superdeformed band in 152Dy as evidence for the centrifugal solidification of a rotating nucleus. PMID- 10034363 TI - Quark and Higgs-boson mass predictions in the nonperturbative grand-unification framework. PMID- 10034365 TI - Spontaneous fragmentation of multiply charged metal clusters. PMID- 10034366 TI - Atom-selective imaging of the GaAs(110) surface. PMID- 10034367 TI - Study of e+ PMID- 10034368 TI - Experimental observation of two-stage melting in a classical two-dimensional screened Coulomb system. PMID- 10034369 TI - Disclinations in quasicrystals. PMID- 10034370 TI - Translational energy transfer from molecules and atoms to adsorbed organic monolayers of long-chain amphiphiles. PMID- 10034372 TI - Lamb waves in unsupported thin films: A Brillouin-scattering study. PMID- 10034371 TI - Time-resolved observation of electron-phonon relaxation in copper. PMID- 10034373 TI - Critical wetting in three dimensions: A Ginzburg criterion. PMID- 10034374 TI - Ultrasonic determination of different phases in superconducting UPt3. PMID- 10034375 TI - Martensitic phase transformation of single-crystal lithium from bcc to a 9R related structure. PMID- 10034376 TI - Heavy-fermion behavior and the single-ion Kondo model. PMID- 10034378 TI - Resistance fluctuations in thin Bi wires and films. PMID- 10034377 TI - Low-temperature behavior of Kondo impurities and check of the Fermi-liquid model. PMID- 10034379 TI - Ferromagnetic moments in metastable magnetic films by spin-polarized-neutron reflection. PMID- 10034380 TI - First-principles determination of giant adsorption-induced surface relaxation in p(11) O/Fe(001). PMID- 10034381 TI - Off-diagonal long-range order, oblique confinement, and the fractional quantum Hall effect. PMID- 10034383 TI - Role of virtual gap states and defects in metal-semiconductor contacts. PMID- 10034382 TI - Observation of intrinsic bistability in resonant tunneling structures. PMID- 10034384 TI - Optical properties of strained-layer superlattices with growth axis along PMID- 10034385 TI - Path-integral approach to Ising spin-glass dynamics. PMID- 10034386 TI - Energy spectrum and conductance of a two-dimensional quasicrystal. PMID- 10034387 TI - Transverse fluctuations in an Ising spin-glass: Fe0.4Mg0.6Cl2. PMID- 10034388 TI - Comment on "Local structure of S impurities in GaAs" PMID- 10034389 TI - Sette et al. respond. PMID- 10034390 TI - Interchain photogeneration of charged solitons in trans-(CH)x. PMID- 10034393 TI - epsilon expansions for crumpled manifolds. PMID- 10034392 TI - Localization and anomalous diffusion of a damped quantum particle. PMID- 10034394 TI - New value for the Rydberg constant from the hydrogen Balmer- beta transition. PMID- 10034395 TI - Properties of random superpositions of plane waves. PMID- 10034396 TI - Perturbative stability of smooth strings. PMID- 10034397 TI - Noncommutative geometry model for closed bosonic strings. PMID- 10034398 TI - Testing nucleon distribution amplitudes: Relations between neutron and N- Delta form factors. PMID- 10034399 TI - Single and correlated spin alignments for resonances in 24Mg + 24Mg inelastic scattering. PMID- 10034400 TI - Optically enhanced electron attachment. PMID- 10034401 TI - Enhanced and inhibited visible spontaneous emission by atoms in a confocal resonator. PMID- 10034402 TI - Resonant-collision spectroscopy of Rydberg atoms. PMID- 10034403 TI - New precision measurement of the orthopositronium decay rate: A discrepancy with theory. PMID- 10034404 TI - Vortex-front propagation in Rayleigh-Benard convection. PMID- 10034405 TI - Electric field spectra beyond the strong turbulence regime of relativistic beam plasma interactions. PMID- 10034406 TI - High-resolution thermal-conductivity measurements near the lambda point of helium. PMID- 10034407 TI - Mechanisms for peculiar low-temperature phenomena in hydrogenated amorphous silicon. PMID- 10034408 TI - Ab initio determination of the structure of a grain boundary by simulated quenching. PMID- 10034409 TI - Magnetic probing depth in spin-polarized secondary electron spectroscopy. PMID- 10034410 TI - Interaction of magnetoexcitons in two-dimensional structures. PMID- 10034411 TI - Paramagnetic enhancement in the magnetic susceptibility of ultrafine magnesium particles. PMID- 10034412 TI - Transient phase-space filling by resonantly excited exciton interactions in CuCl. PMID- 10034413 TI - Role of electron-hole interactions in the optical spectra of metals. PMID- 10034414 TI - Electron-phonon interaction in the new superconductors La2-x(Ba,Sr)xCuO4. PMID- 10034415 TI - Observation of ionospheric cavitons. PMID- 10034417 TI - Comment on "New model of b-quark interactions: A superstring alternative" PMID- 10034416 TI - New tool for quantum many-body theory. PMID- 10034418 TI - Ma responds. PMID- 10034419 TI - Comment on "Structure of Au(100)" PMID- 10034420 TI - Comment on "f-wave effects in superfluid 3He-A" PMID- 10034421 TI - Origin of the Mooij correlation. PMID- 10034422 TI - How to ascertain the values of sigmax, sigma y, and sigma z of a spin-1/2 particle. PMID- 10034423 TI - Maslov indices of resonant tori. PMID- 10034425 TI - Lattice Virasoro algebra and corner transfer matrices in the Baxter eight-vertex model. PMID- 10034424 TI - Four-dimensional eikonal theory of linear mode conversion. PMID- 10034426 TI - What are the low-transverse-energy jets? PMID- 10034427 TI - Searches for supermassive X- particles in iron. PMID- 10034428 TI - Kinetics of muonic helium in muon-catalyzed d-d and d-t fusion. PMID- 10034430 TI - Spatial chaos in the polarization for a birefringent optical fiber with periodic coupling. PMID- 10034429 TI - Magnetic resonance as a probe of permeability in porous media. PMID- 10034431 TI - Lagrangian/Hamiltonian formalism for description of Navier-Stokes fluids. PMID- 10034432 TI - Collisional enhancement of low-frequency density fluctuations in a weakly collisional electron-ion plasma. PMID- 10034433 TI - Cross-field electron thermal conductivity in an electron-beam-plasma system. PMID- 10034434 TI - Stochastic particle acceleration in an electrostatic wave. PMID- 10034435 TI - Capillary-wave and intrinsic thicknesses of the surface of a simple liquid. PMID- 10034436 TI - A new phase transition at Ge(111) surface observed by low-energy-electron diffraction. PMID- 10034438 TI - Visualization and characterization of colloidal growth from ramified to faceted structures. PMID- 10034437 TI - Structure of Al-Li-Cu icosahedral crystals and Penrose tiling. PMID- 10034439 TI - Selective generation of oriented defects in glasses: Application to SiO2. PMID- 10034440 TI - Surface-phonon instabilities of W(001). PMID- 10034441 TI - Mechanisms of defect pairing in semiconductors: A study for chalcogens in silicon. PMID- 10034442 TI - Simple x-ray standing-wave technique and its application to the investigation of the Cu(111) ( sqrt 3 sqrt 3 )R30 degrees -Cl structure. PMID- 10034443 TI - Critical behavior of random spin systems at the percolation threshold. PMID- 10034445 TI - Cyclotron resonance of polarons in the silver halides: AgBr and AgCl. PMID- 10034444 TI - Magnetic excitations and ordering in the heavy-electron superconductor URu2Si2. PMID- 10034446 TI - Exciton self-trapping in ZnSe-ZnTe alloys. PMID- 10034448 TI - Superconductivity in high magnetic fields. PMID- 10034447 TI - Magnetoresistance of hydrogen-doped Zr2Ni metallic glass. PMID- 10034449 TI - Optically detected magnetic-resonance observation of the isolated zinc interstitial in irradiated ZnSe. PMID- 10034450 TI - Observation of a neutrino burst from the supernova SN1987A. PMID- 10034451 TI - Observation of a neutrino burst in coincidence with supernova 1987A in the Large Magellanic Cloud. PMID- 10034453 TI - Diffraction-free beams. PMID- 10034454 TI - Transfer-matrix inverison identities for exactly solvable lattice-spin models. PMID- 10034455 TI - Kahler manifolds with vanishing chiral potential. PMID- 10034456 TI - Pion-reabsorption effect on pion spectra in high-energy heavy-ion collisions. PMID- 10034457 TI - Resonant fluctuations in heavy-ion reaction cross sections: 16O(16O, alpha )28Si. PMID- 10034458 TI - Sudden change in the nuclear charge distribution of very light gold isotopes. PMID- 10034460 TI - Production of Pb+ ions following 5d core photoionization of tetramethyl lead as revealed by a coincidence experiment. PMID- 10034459 TI - Anomalous behavior of the proton-induced fission cross sections of 235U and 238U at extreme sub-barrier energies. PMID- 10034461 TI - Charge-transfer effects in graphite intercalates: Ab initio calculations and neutron-diffraction experiment. PMID- 10034462 TI - Neutron-scattering evidence of polymer persistence-length enhancement caused by physical gelation. PMID- 10034463 TI - Direct observation of atomic structures and reconstructions of silicon surfaces: A field-ion-microscope study. PMID- 10034464 TI - Flexoelectric electro-optics of a cholesteric liquid crystal. PMID- 10034465 TI - Dendritic crystallization: Numerical study of the one-sided model. PMID- 10034466 TI - Mean-field and Ising critical behavior of a polymer blend. PMID- 10034468 TI - Many-body calculation of surface states: As on Ge(111). PMID- 10034467 TI - Bond-centered hydrogen or muonium in diamond: The explanation for anomalous muonium and an example of metastability. PMID- 10034469 TI - Surface and bulk core-level shifts of the Si(111) sqrt 3 sqrt 3 -Ag surface: Evidence for a charged sqrt 3 sqrt 3 layer. PMID- 10034470 TI - Excess electrons in liquid water: First evidence of a prehydrated state with femtosecond lifetime. PMID- 10034471 TI - Non-Ohmic transport in the field-induced spin-density-wave state in tetramethyltetraselenafulvalinium chlorate, (TMTSF)2ClO4. PMID- 10034472 TI - New method to study the electron-phonon interaction in metals. PMID- 10034473 TI - Evidence for a Peierls distortion in La2CuO PMID- 10034474 TI - Superconductivity and magnetism in the high-Tc superconductor YBaCuO. PMID- 10034476 TI - Reexamination of evidence for a radiatively decaying neutrino. PMID- 10034475 TI - Statistical mechanics of cosmic strings. PMID- 10034477 TI - Comment on "Weak mixing angles from semileptonic decays in the quark model" PMID- 10034478 TI - Comment on "Entrance- and exit-channel effects and the suppression of neutron emission from 64Ni+92Zr-->156Er" PMID- 10034480 TI - Comment on "Anisotropic heat conduction in diacetylenes" PMID- 10034479 TI - Love et al. respond. PMID- 10034481 TI - Morelli and Heremans respond. PMID- 10034483 TI - Connection between long-range correlations in quantum spectra and classical periodic orbits. PMID- 10034482 TI - Comment on "Critical and noncritical roughening of surfaces" PMID- 10034484 TI - Phase change during a cyclic quantum evolution. PMID- 10034485 TI - Duality in statistical mechanics and string theory. PMID- 10034486 TI - Small and calculable Dirac neutrino mass. PMID- 10034487 TI - Lower bound on the neutron electric dipole moment in models with spontaneous CP nonconservation in scalar exchanges. PMID- 10034488 TI - Implications of a heavy top quark and a fourth generation on the decays B-->Kl+l , K nu nu -bar. PMID- 10034489 TI - Geometric interpretation of hadron-proton total cross sections and a determination of hadronic radii. PMID- 10034490 TI - Precision measurement of parity nonconservation in proton-proton scattering at 45 MeV. PMID- 10034492 TI - Ar valence-electron double-excitation satellites studied by high-energy photoelectron spectroscopy. PMID- 10034491 TI - High-resolution measurements of the 3s satellite spectrum of argon between 77 and 120 eV photon energy. PMID- 10034493 TI - Recursive calculation of dimensional expansions for two-electron atoms. PMID- 10034495 TI - Numerical simulation of interacting vortex tubes. PMID- 10034494 TI - Numerical study of vortex reconnection. PMID- 10034496 TI - Observation of deterministic chaos in a phase-conjugate mirror. PMID- 10034498 TI - Calculation of exchange frequencies in bcc 3He with the path-integral Monte Carlo method. PMID- 10034497 TI - Observation of laser-induced anisotropy in ion acoustic waves in a plasma. PMID- 10034499 TI - Development of side branching in dendritic crystal growth. PMID- 10034501 TI - Nonconvex interactions and the occurrence of modulated phases. PMID- 10034500 TI - Mesoscopic approach to the glass transformation. PMID- 10034502 TI - Spatial dependence of the order parameter of superfluid 3He at the A-B phase boundary. PMID- 10034504 TI - Pressure-induced phase transformations in ice. PMID- 10034503 TI - Local state density and long-range screening of adsorbed oxygen atoms on the GaAs(110) surface. PMID- 10034505 TI - Bulk superconductivity at 91 K in single-phase oxygen-deficient perovskite Ba2YCu PMID- 10034506 TI - Femtosecond studies of nonequilibrium electronic processes in metals. PMID- 10034507 TI - First measurement of gas adsorption to free ultrafine particles: O2 on Ag. PMID- 10034508 TI - Direct lifetime measurements and interactions of charged defect states in submicron Josephson junctions. PMID- 10034509 TI - Real-time study of oxygen reaction on Si(100). PMID- 10034510 TI - Energetic (>1 GeV) neutrinos as a probe of acceleration in the new supernova. PMID- 10034512 TI - Power spectra of strange attractors near homoclinic orbits. PMID- 10034513 TI - Zero-temperature scaling and combinatorial optimization. PMID- 10034514 TI - Magnetic monopoles from superstring models. PMID- 10034515 TI - New results on single-photon production at sqrt s = 29 GeV. PMID- 10034516 TI - Limits on xi (2.2) formation in p-barp-->K+K- PMID- 10034517 TI - Low-energy antikaon-nucleon interaction. PMID- 10034518 TI - Measurements of deuteron magnetic form factor high momentum transfer. PMID- 10034519 TI - Nuclear-density dependence of the electron-proton coupling. PMID- 10034520 TI - Effect of closed classical orbits on quantum spectra: Ionization of atoms in a magnetic field. PMID- 10034521 TI - Separated resonances in simultaneous capture and excitation of S15+ in H2 observed by K-x-ray-K-x-ray coincidences. PMID- 10034523 TI - Saffman-Taylor finger width at low interfacial tension. PMID- 10034522 TI - Asymmetric line shapes for weak transitions in strong standing-wave fields. PMID- 10034524 TI - Unified theory of ripple transport in stellarators. PMID- 10034526 TI - Investigation of thin helium films with surface-bound electrons. PMID- 10034525 TI - Observation of dynamical precursors of the isotropic-nematic transition by computer simulation. PMID- 10034527 TI - Evidence for complexes of hydrogen with deep-level defects in bulk III-V materials. PMID- 10034528 TI - Diffusion on two-dimensional random walks. PMID- 10034529 TI - Raman scattering in Fibonacci superlattices. PMID- 10034530 TI - Ab initio molecular dynamics on the Ge(100) surface. PMID- 10034531 TI - Phonon-phonon coupling and the stability of the high-temperature bcc phase of Zr. PMID- 10034532 TI - Heavy-ion-induced shock electrons from sputter-cleaned solid surfaces. PMID- 10034533 TI - Measurement of the damping dispersion of exciton polaritons in CdS. PMID- 10034534 TI - Determination of the electronic structure of anomalous muonium in GaAs from nuclear hyperfine interactions. PMID- 10034536 TI - Quantitative theory for hysteretic phenomena in CoNi magnetic thin films. PMID- 10034535 TI - Evidence for the high-spin to low-spin state transition in ordered Fe3Pt Invar. PMID- 10034537 TI - Multistable quantum systems: Information processing at microscopic levels. PMID- 10034541 TI - Two applications of axion electrodynamics. PMID- 10034538 TI - Extreme swelling of lamellar phases. PMID- 10034542 TI - Glueball masses as a test of the 1/N expansion. PMID- 10034543 TI - Particle-physics model for Voloshin-Vysotsky-Okun solution to the solar-neutrino problem. PMID- 10034544 TI - Search for heavy-neutrino production in e+e- annihilation at 29 GeV. PMID- 10034545 TI - Branching ratios of B mesons to K+,K-, and K0/K-bar0. PMID- 10034546 TI - Measurement of the Ds+ lifetime. PMID- 10034547 TI - Bounds on right-handed currents from nuclear beta decay. PMID- 10034548 TI - Separation of strangeness from antistrangeness in the phase transition from quark to hadron matter: Possible formation of strange quark matter in heavy-ion collisions. PMID- 10034550 TI - Measurements of the 23S1-2(3)PJ (J=0,1,2) fine-structure splittings in positronium. PMID- 10034551 TI - Electron-loss cross sections in symmetric multicharged-ion collisions. PMID- 10034549 TI - Isotopic-yield ratios of complex fragments from intermediate-energy heavy-ion reactions. PMID- 10034552 TI - Squeezing of quantum solitons. PMID- 10034553 TI - New cellular automaton model for magnetohydrodynamics. PMID- 10034554 TI - Electromagnetic beam modes driven by anisotropic electron streams. PMID- 10034555 TI - Experimental observation of the hot-electron equilibrium in a minimum-B mirror plasma. PMID- 10034556 TI - Three-body exchange interaction in dense helium. PMID- 10034558 TI - Random-field transition of a binary liquid in a porous medium. PMID- 10034557 TI - Green's-function approach to linear response in solids. PMID- 10034559 TI - Picosecond Raman studies of the Frohlich interaction in semiconductor alloys. PMID- 10034560 TI - Experimental evidence for the long-time decay of the velocity-autocorrelation in liquid sodium. PMID- 10034562 TI - Low temperature expansions around the multiphase point of an hcp Ising model with competing interactions. PMID- 10034561 TI - Reconstructive phase transitions and effective adsorbate-adsorbate interactions: H/Mo(100) and H/W(100). PMID- 10034563 TI - Superconductivity near 90 K in the Lu-Ba-Cu-O system. PMID- 10034564 TI - New superconducting cuprate perovskites. PMID- 10034565 TI - Superconductivity above 90 K in the square-planar compound system ABa2Cu3O6+x with A=Y, La, Nd, Sm, Eu, Gd, Ho, Er and Lu. PMID- 10034567 TI - Missing bond-charge repulsion in the extended Hubbard model: Effects in polyacetylene. PMID- 10034566 TI - Measurement of spin-correlation lengths in Eu0.54Sr0.46S by elastic light scattering. PMID- 10034568 TI - Oscillatory instability in the dynamics of incommensurate structures. PMID- 10034569 TI - Neutrino mass limits from SN1987A. PMID- 10034570 TI - Dynamics of superconducting cosmic strings. PMID- 10034571 TI - Spontaneous generation of string tension and quark potential. PMID- 10034572 TI - Momentum-scale-dependent bounds on masses in two models with more than one Higgs multiplet. PMID- 10034573 TI - Search for the charge-symmetry-breaking reaction d+d-->4He PMID- 10034574 TI - Importance of momentum-dependent interactions for the extraction of the nuclear equation of state from high-energy heavy-ion collisions. PMID- 10034575 TI - Exotic nucleus helium 9 and its excited states. PMID- 10034576 TI - Population inversion in optical adiabatic rapid passage with phase relaxation. PMID- 10034577 TI - Finite-size effects and shear viscosity in superfluid 3He-B. PMID- 10034578 TI - Observation of a soft surface-phonon mode in the reconstruction of clean W(100). PMID- 10034579 TI - Specific heat of an icosahedral superconductor, Mg3Zn3Al2. PMID- 10034580 TI - Healing length of superfluid 3He. PMID- 10034581 TI - Direct measurement of the interaction potential between discommensurations in Rb2ZnCl4. PMID- 10034582 TI - Structure of icosahedral Al-Cu-Li. PMID- 10034583 TI - Growth of hard-sphere models with two different sizes: Can a quasicrystal result? PMID- 10034584 TI - Kondo maximum of magnetic scattering. PMID- 10034586 TI - Observation of the reverse ac Josephson effect in Y-Ba-Cu-O at 240 K. PMID- 10034585 TI - Resonant Kondo scattering of weakly localized electrons. PMID- 10034587 TI - Anomalous structural behavior of the superconducting compound La1.85Ba0.15CuO4. PMID- 10034589 TI - Metallization of silicon upon potassium adsorption. PMID- 10034588 TI - Josephson effects in the Ba-Y-Cu-O compounds. PMID- 10034590 TI - Inherent spin-density-wave instability in heavy-fermion superconductivity. PMID- 10034591 TI - Theory of the chemical shift at relaxed (110) surfaces of III-V semiconductor compounds. PMID- 10034592 TI - Light-induced mobility transition in silicon. PMID- 10034593 TI - Second-order light scattering and local anisotropy of diffusion-limited aggregates and bond-percolation clusters. PMID- 10034594 TI - Comment on "Massive, unitary, renormalizable Yang-Mills theory without Higgs bosons" PMID- 10034595 TI - Comment on "Massive, unitary, renormalizable Yang-Mills theory without Higgs boson" PMID- 10034596 TI - Comment on determinations of the parameters of the A1. PMID- 10034598 TI - Connected moments expansion: A new tool for quantum many-body theory. PMID- 10034599 TI - Nonuniversal critical dynamics in Monte Carlo simulations. PMID- 10034601 TI - Static potential for smooth strings. PMID- 10034600 TI - Modular invariance and one-loop finiteness of heterotic-string amplitudes. PMID- 10034603 TI - Quark-gluon-plasma diagnostics: Measuring pi 0/ gamma ratio with dileptons. PMID- 10034602 TI - Observation of scaling of the photon structure function F2 gamma at low Q2. PMID- 10034604 TI - 12,13C(ppol, pi +/-) reactions and quasifree NpolN-->NN pi expectations. PMID- 10034605 TI - Theory of double excitation and ionization by a strong pulsed laser: Application to atomic carbon. PMID- 10034606 TI - Transition to turbulence via spatio-temporal intermittency. PMID- 10034607 TI - Observation of z-dependent impurity accumulation in the PBX tokamak. PMID- 10034608 TI - Correlation of magnetic fluctuations and edge transport in the Doublet III tokamak. PMID- 10034610 TI - Brillouin-scattering measurements of phonon-fracton crossover in silica aerogels. PMID- 10034609 TI - Observation of a high-confinement regime in a tokamak plasma with ion cyclotron resonance heating. PMID- 10034612 TI - Competition between shear melting and Taylor instabilities in colloidal crystals. PMID- 10034611 TI - Scattering of fractons, the Ioffe-Regel criterion, and the (4/3) conjecture. PMID- 10034613 TI - One-to-one correspondence between slowly decaying interfacial profiles and reflectivity. PMID- 10034614 TI - Fluctuation pressure of a stack of membranes. PMID- 10034615 TI - Structure determination of an adsorbate-induced multilayer reconstruction: (1 x 2)-H/Ni(110). PMID- 10034616 TI - Hole transport in polyvinylcarbazole: The vital importance of excitation-light intensity. PMID- 10034618 TI - Gap solitons and the nonlinear optical response of superlattices. PMID- 10034617 TI - Coulomb-induced anomalies in highly disordered superconductors: Application to tunneling. PMID- 10034619 TI - Mean-field theory of spin-glasses with finite coordination number. PMID- 10034621 TI - Luminous axion clusters. PMID- 10034620 TI - Few-dimensional Heisenberg ferromagnets at low temperature. PMID- 10034622 TI - Comment on "Fractional statistics of the vortex in two-dimensional superfluids" PMID- 10034624 TI - Exact decimation-type functional renormalization group for critical wetting in 1+1 dimensions. PMID- 10034623 TI - Chiao et al. respond. PMID- 10034626 TI - Crossover effect in the f( alpha ) spectrum for quasiperiodic trajectories at the onset of chaos. PMID- 10034628 TI - Minijets, QCD, and unitarity. PMID- 10034627 TI - Monte Carlo calculation of lattice QCD with exact treatment of dynamical quark loops. PMID- 10034630 TI - Limit on nu -bare mass from free-molecular-tritium beta decay. PMID- 10034629 TI - Neutrino mass from the beta spectrum in the decay of tritium. PMID- 10034631 TI - Observation of eta -meson production in the reaction pi -+3He--> eta PMID- 10034633 TI - Experimental evidence of disorder effects in hydrodynamic dispersion. PMID- 10034632 TI - Measurement of hyperfine structure in the infrared rotation-vibration spectrum of NH- PMID- 10034634 TI - Polarization dependence of gain in stimulated Raman scattering. PMID- 10034635 TI - Optical transmission in disordered media. PMID- 10034636 TI - Dressed neutrons. PMID- 10034637 TI - Self-propulsion at low Reynolds number. PMID- 10034638 TI - Oscillatory traveling-wave convection in a finite container. PMID- 10034639 TI - Inhibited spontaneous emission in solid-state physics and electronics. PMID- 10034640 TI - Nonlinear oscillations in a warm plasma. PMID- 10034641 TI - Amplification of magnetic modes in laser-created plasmas. PMID- 10034642 TI - Stochastic electron acceleration in obliquely propagating, electromagnetic waves. PMID- 10034643 TI - Factorization of the triplet direct correlation function in dense fluids. PMID- 10034644 TI - Anisotropic features in the dynamics of nematic-nematic phase separation. PMID- 10034645 TI - From cascade to spike-a fractal-geometry approach. PMID- 10034647 TI - Dynamics of the structural glass transition and the p-spin-interaction spin-glass model. PMID- 10034646 TI - Scaling of directed polymers in random media. PMID- 10034648 TI - Beware of 46-fold symmetry: The classification of two-dimensional quasicrystallographic lattices. PMID- 10034649 TI - Hydrodynamic screening and diffusion in entangled polymer solutions. PMID- 10034650 TI - Localization in a nondegenerate two-dimensional electron gas. PMID- 10034651 TI - Quantum conductance in networks. PMID- 10034652 TI - Long-range order and segregation in semiconductor superlattices. PMID- 10034653 TI - Critical behavior of the surface magnetization of an isotropic Heisenberg ferromagnet: EuS(111) on Si(111). PMID- 10034654 TI - Soliton-to-band optical absorption in a quasi-one-dimensional PtII-PtIV mixed valence complex under hydrostatic pressure. PMID- 10034655 TI - Magnetism of epitaxial fcc: Iron films on Cu(001) investigated by spin-polarized photoelectron emission. PMID- 10034656 TI - Observation of a many-body edge singularity in quantum well luminescence spectra. PMID- 10034658 TI - Reversible H2O adsorption on Pt(111)+K: Work function changes and molecular orientation. PMID- 10034657 TI - Charge versus fermion fractionalization in the quarter-filled Hubbard-Peierls model. PMID- 10034659 TI - Evidence for the thermal nature of laser-induced polymer ablation. PMID- 10034660 TI - Can supernovae exclude neutrinos more massive than 30 eV? PMID- 10034661 TI - Resistance in metallic rings. PMID- 10034662 TI - Lenstra and van Haeringen respond. PMID- 10034663 TI - Comment on strange stars. PMID- 10034667 TI - Potentials which cause the same scattering at all energies in one dimension. PMID- 10034666 TI - Coherence, chaos, and broken symmetry in classical, many-body dynamical systems. PMID- 10034668 TI - Diffeomorphism groups and quantized vortex filaments. PMID- 10034669 TI - Universality of deconfining phase transition in finite-temperature lattice gauge theories. PMID- 10034670 TI - Unifiable chiral color with natural Glashow-Iliopoulos-Maiani mechanism. PMID- 10034671 TI - Observation of e+e- --> DsDs at sqrt s =4.14 GeV. PMID- 10034672 TI - Light-meson distribution amplitude: Simple relativistic model. PMID- 10034673 TI - Large-N baryons: From quarks to solitons. PMID- 10034674 TI - Superdeformed band in 135Nd. PMID- 10034675 TI - Three-photon correlations in rotational nuclei. PMID- 10034677 TI - Continuous stopping and trapping of neutral atoms. PMID- 10034676 TI - Comparison of the microscopic potential with the optical potential in the alpha +16O system. PMID- 10034678 TI - Spin-orbit and exchange effects in elastic scattering of spin-polarized electrons from spin-polarized Na atoms. PMID- 10034679 TI - rf-induced quantum interference between low-field Stark levels in Rydberg states of sodium. PMID- 10034680 TI - Laser dynamics with competing instabilities. PMID- 10034681 TI - Spatial dissipative structures in passive optical systems. PMID- 10034682 TI - Unusual time-dependent phenomena in Taylor-Couette flow at moderately low Reynolds numbers. PMID- 10034683 TI - rf stabilization of ballooning modes in tokamaks. PMID- 10034684 TI - Selective electron-cyclotron heating at down-shifted frequency in the lower hybrid current driven plasma on the JFT-2M tokamak. PMID- 10034685 TI - Ordering in lipid monolayers studied by synchrotron x-ray diffraction and fluorescence microscopy. PMID- 10034686 TI - X-ray diffraction studies of organic monolayers on the surface of water. PMID- 10034687 TI - Excitations in biphenyl's incommensurate phase III. PMID- 10034688 TI - Origin of reflection high-energy electron-diffraction intensity oscillations during molecular-beam epitaxy: A computational modeling approach. PMID- 10034689 TI - Behavior of the bend elastic constant near the nematic-smectic-A-smectic-C multicritical point. PMID- 10034690 TI - Continuum percolation of disks and the random lattice. PMID- 10034691 TI - Long-range order and short-range order in Pd3V: Breakdown of the mean-field theory. PMID- 10034693 TI - Quantum-scattering determination of magnetoconductance for two-dimensional systems. PMID- 10034692 TI - Far-infrared conductivity of the high-Tc superconductor YBa2Cu3O7. PMID- 10034694 TI - Localized-state interactions in metal-oxide-semiconductor tunnel diodes. PMID- 10034696 TI - Photon-drag effect in intersubband absorption by a two-dimensional electron gas. PMID- 10034695 TI - Effects of high magnetic fields on cationic exciton lines in BiI3. PMID- 10034697 TI - Anomalous electrical conduction in quasicrystals and Fibonacci lattices. PMID- 10034698 TI - Boundary resistance of the ferromagnetic-nonferromagnetic metal interface. PMID- 10034699 TI - Comment on "Longitudinal coherence in neutron interferometry" PMID- 10034700 TI - Comment on "Observation of negative s-wave proximity effect in superconducting UBe13" PMID- 10034701 TI - Wolf, Millis, and Han respond. PMID- 10034704 TI - Adiabatic rotational splittings and Berry's phase in nuclear quadrupole resonance. PMID- 10034706 TI - Evidence of Q2Q-bar2 mesons in p-barn annihilations and gamma gamma reactions. PMID- 10034705 TI - Mass gap in non-Abelian sigma models and gauge theories. PMID- 10034707 TI - K+ and K- slope parameters as a signature for deconfinement at finite baryon density. PMID- 10034708 TI - Magnetic form factors of 205Tl and 207Pb: Establishing the limits of mean-field theory. PMID- 10034710 TI - X-ray diffraction study of phason strain field in oriented icosahedral Al-Mn. PMID- 10034709 TI - Independent determinations of temperature and ionization balance in a laser produced plasma by use of L-shell x-ray spectra. PMID- 10034711 TI - Exchange and spectral density in two-dimensional helium-3: A T1 study. PMID- 10034712 TI - Phase transition in a system of hard disks by Monte Carlo simulation. PMID- 10034713 TI - Experimental determination of the energy stored by a vacancy-interstitial pair in GaAs. PMID- 10034714 TI - Instabilities of a moving nematic-isotropic interface. PMID- 10034716 TI - Exact determination of the percolation hull exponent in two dimensions. PMID- 10034715 TI - Energetics of icosahedral phase stability in metallic alloys. PMID- 10034717 TI - X-ray scattering from sodium-doped polyacetylene: Incommensurate-commensurate and order-disorder transformations. PMID- 10034718 TI - Isotope effect in the high-Tc superconductors Ba2YCu3O7 and Ba2EuCu3O7. PMID- 10034719 TI - Search for isotope effect in superconducting Y-Ba-Cu-O. PMID- 10034720 TI - Single-crystal micro-Raman spectroscopy of phases in the Y-Ba-Cu-O superconductor. PMID- 10034721 TI - Length-independent voltage fluctuations in small devices. PMID- 10034722 TI - Nonlocal potential measurements of quantum conductors. PMID- 10034723 TI - Electron-spin-resonance study of the high-field phase of the spin-Peierls system tetrathiafulvalene-Au-bis-dithiolene. PMID- 10034724 TI - Direct subpicosecond measurement of carrier mobility of photoexcited electrons in gallium arsenide. PMID- 10034725 TI - Nuclear Bragg scattering of synchrotron radiation pulses in a single-reflection geometry. PMID- 10034726 TI - Evidence for quasi two-dimensional positronium formation in potassium intercalated graphite. PMID- 10034728 TI - Dynamic instability in the magnetic susceptibility of Dy(OH)3. PMID- 10034727 TI - Transition-metal impurities in semiconductors-their connection with band lineups and Schottky barriers. PMID- 10034729 TI - Critical divergence of the transient response of the charge-density wave near the depinning threshold in K0.3MoO3. PMID- 10034731 TI - Comment on "Compression modulus of nuclear matter and charge-distribution differences" PMID- 10034730 TI - Defect microchemistry at the SiO2/Si interface. PMID- 10034732 TI - Co' and Speth respond. PMID- 10034733 TI - Comment on "Molecular description of two-electron atoms" PMID- 10034735 TI - Exploring chaotic motion through periodic orbits. PMID- 10034736 TI - Dynamical gauge boson in the SU(N,1)-type sigma model. PMID- 10034738 TI - Electric and magnetic properties of hot gluons. PMID- 10034737 TI - Overrelaxed heat-bath and Metropolis algorithms for accelerating pure gauge Monte Carlo calculations. PMID- 10034739 TI - Symmetries and quantum chaos: Time-reversal invariance in the nucleon-nucleon interaction. PMID- 10034740 TI - Enhancement of the relative ( Delta S=1)/( Delta S=0) response of 40Ca at high excitation energies. PMID- 10034741 TI - Subthreshold pion production with associated multiplicity selection in the reaction 139La+ 139La--> pi +X. PMID- 10034742 TI - Observation of motional-field-induced ripples in the photodetachment cross section of H- PMID- 10034743 TI - Are there pi bonds in benzene? PMID- 10034744 TI - Laser-induced photoassociation of ultracold sodium atoms. PMID- 10034745 TI - Femtosecond dynamics of multielectron dissociative ionization by use of a picosecond laser. PMID- 10034748 TI - Localization of optics: Quasiperiodic media. PMID- 10034746 TI - Self-trapping and anomalous dispersion of DNA in electrophoresis. PMID- 10034747 TI - Instabilities and chaos in the polarizations of counterpropagating light fields. PMID- 10034749 TI - Relativistic klystron two-beam accelerator. PMID- 10034750 TI - Velocity distribution function of a streaming gas via nonequilibrium molecular dynamics. PMID- 10034753 TI - Measurements of melting temperatures of quasicrystalline Al-Mn phases. PMID- 10034751 TI - Imaging of acoustic phonon stop bands in superlattices. PMID- 10034752 TI - Anomalous reduction of stage-I recovery in nickel irradiated with heavy ions in the energy range 100-120 MeV. PMID- 10034754 TI - Magnetization of solid helium-3 from 0.2 to 11 T. PMID- 10034755 TI - Collective relaxation of star polymers-A neutron spin-echo study. PMID- 10034756 TI - Exact critical behavior of a random bond two-dimensional Ising model. PMID- 10034757 TI - Theory of glass dynamics: The low-lying modes of anharmonic materials. PMID- 10034758 TI - Magnetic excitons in space-charge layers in GaAs. PMID- 10034759 TI - Coexistence of intermediate-valence and antiferromagnetic ordering in europium metal. PMID- 10034760 TI - Evidence for superconductivity in La2CuO PMID- 10034761 TI - Strong localization of photons in certain disordered dielectric superlattices. PMID- 10034762 TI - Loss structure in the electron-energy-loss excitation continuum of a semimetal. PMID- 10034763 TI - Ionization energies of valence levels in physisorbed rare-gas multilayers. PMID- 10034765 TI - Diffusion limited aggregation and viscous fingering. PMID- 10034764 TI - Detection of solar neutrinos in superfluid helium. PMID- 10034767 TI - Comment on "Structure and electronic states in disordered systems" PMID- 10034766 TI - Murat and Aharony respond. PMID- 10034768 TI - Bar-Yam, Adler, and Joannopoulos respond. PMID- 10034771 TI - SU(2) spectroscopy in intermediate volumes. PMID- 10034770 TI - Correspondence of Z2-orbifold string and torus string. PMID- 10034772 TI - Numerical evidence for a first-order chiral phase transition in lattice QCD with two light flavors. PMID- 10034773 TI - Metastabilities in three-flavor QCD at low quark masses. PMID- 10034774 TI - J/ psi longitudinal polarization from pi N interactions. PMID- 10034775 TI - Source properties of intermediate-mass fragments emitted in the reaction 14N PMID- 10034776 TI - Localization of Floquet states in the rf excitation of Rydberg atoms. PMID- 10034777 TI - Observation of a magnetic-field-dependent g-factor ratio. PMID- 10034778 TI - Resonance fluorescence from an atom in a squeezed vacuum. PMID- 10034779 TI - Stability of modulated Couette flow. PMID- 10034780 TI - Nonlinear coupling of stimulated Raman and Brillouin scattering in laser-plasma interactions. PMID- 10034781 TI - Existence of superdiffusion of hydrogen in vanadium. PMID- 10034782 TI - Commensurate and incommensurate phase transitions of the (001) InAs surface under changes of bulk lattice constant, As chemical potential, and temperature. PMID- 10034783 TI - Novel type of phase transition to incommensurate structure in quartz and in berlinite. PMID- 10034784 TI - Surface phase separation of vicinal Si(111). PMID- 10034785 TI - Atomic ordering in Ga0.47In0.53As and GaxIn1-xAsyP1-y alloy semiconductors. PMID- 10034786 TI - Dynamical velocity selection: Marginal stability. PMID- 10034787 TI - Surface modifications induced by adsorbates at low coverage: A scanning tunneling microscopy study of the Ni/Si(111) sqrt 19 surface. PMID- 10034788 TI - Superconductivity at 155 K. PMID- 10034789 TI - Bloch transport of electrons and holes in superlattice minibands: Direct measurement by subpicosecond luminescence spectroscopy. PMID- 10034790 TI - Intersubband resonance in quasi one-dimensional inversion channels. PMID- 10034792 TI - Determination of a natural valence-band offset: The case of HgTe-CdTe. PMID- 10034791 TI - Valley fluctuations in degenerately doped semiconductors. PMID- 10034793 TI - Theory of magnetoexcitons in quantum wells. PMID- 10034794 TI - Infrared-induced single-phonon desorption of HD from LiF (100). PMID- 10034795 TI - Numerical simulation studies of peripheral roughening in a monolayer. PMID- 10034796 TI - Kol PMID- 10034799 TI - Metamorphosis and duality between quantum systems. PMID- 10034800 TI - Logarithmic approximations to polynomial Lagrangians. PMID- 10034802 TI - SU(5)L PMID- 10034801 TI - Scaling of the string tension in a new class of regularized string theories. PMID- 10034803 TI - Production of strange baryons in e+e- annihilations at 29 GeV. PMID- 10034804 TI - Laser spectroscopy of core-excited levels of neutral rubidium. PMID- 10034805 TI - Theory for the electron affinity of small clusters of polar molecules (NH3)n. PMID- 10034806 TI - Observation of autoionizing resonances in core electron shakeup spectra. PMID- 10034807 TI - Rotational rainbows in electron-molecule scattering. PMID- 10034808 TI - Red shifts and blue shifts of spectral lines emitted by two correlated sources. PMID- 10034809 TI - Observation of frequency shifts of spectral lines due to source correlations. PMID- 10034810 TI - Local oscillations, traveling waves, and chaos in Rayleigh-Benard convection. PMID- 10034811 TI - Can the channel capacity of a light-wave communication system be increased by the use of photon-number-squeezed light? PMID- 10034813 TI - Coupled model of wave damping, quasilinear heating, and radial transport applied to bumpy tori. PMID- 10034812 TI - Light-induced drift velocities in Na-noble-gas mixtures. PMID- 10034814 TI - Current balance at the surface of a cold cathode. PMID- 10034815 TI - Rayleigh-Taylor instability growth rates in targets accelerated with a laser beam smoothed by induced spatial incoherence. PMID- 10034817 TI - Low-temperature tunneling of 4He atoms into graphite. PMID- 10034816 TI - Rigidity and ergodicity of randomly cross-linked macromolecules. PMID- 10034818 TI - Critical-current measurements in epitaxial films of YBa2Cu PMID- 10034819 TI - Direct observation of electronic anisotropy in single-crystal Y1Ba2Cu3O7-x. PMID- 10034820 TI - Why is Tc of the oxide superconductors so low? PMID- 10034821 TI - Ferromagnetism in molecular decamethylferrocenium tetracyanoethenide (DMeFc TCNE). PMID- 10034823 TI - Bound-magnon dominance of the magnetic susceptibility of the one-dimensional Heisenberg S=1/2 ferromagnet cyclohexylammonium trichlorocuprate (II). PMID- 10034822 TI - New approach to the study of nuclear Bragg scattering of synchrotron radiation. PMID- 10034824 TI - Electronic polaron effects in heavy-electron materials. PMID- 10034826 TI - Surface magnetization of Gd at the bulk Curie temperature. PMID- 10034825 TI - Carrier photogeneration and mobility in polydiacetylene: Fast transient photoconductivity. PMID- 10034827 TI - Scattering properties of a model bicontinuous structure with a well defined length scale. PMID- 10034828 TI - Analysis of neutrino burst from the supernova 1987A in the Large Magellanic Cloud. PMID- 10034829 TI - Crossover from linear to nonlinear resistance near percolation. PMID- 10034830 TI - Gefen et al. respond. PMID- 10034831 TI - Comment on "Effective magnetic moments of heavy fermions and the Wilson ratio for Kondo lattice" PMID- 10034832 TI - Wilson ratio for Kondo lattices. PMID- 10034833 TI - Comment on "Effective magnetic moments of heavy fermions and the Wilson ratio for Kondo lattices" PMID- 10034834 TI - Anderson and Zou respond. PMID- 10034837 TI - Supersymmetry between deep and shallow nucleus-nucleus potentials. PMID- 10034836 TI - Nonuniversality in crumpled manifolds. PMID- 10034838 TI - Structural classification of polyatomic molecules based on valence electron orbital radii: AB3 and A2B2 compounds. PMID- 10034839 TI - Vibrational wave function of a radiatively dissociating level of H2 obtained from the kinetic-energy distribution of the H fragments. PMID- 10034841 TI - Time evolution of universal optical fluctuations. PMID- 10034840 TI - Nonlinear optical response of excitons confined to one dimension. PMID- 10034842 TI - Measurement of the rotational transform at the axis of a tokamak. PMID- 10034844 TI - Rebonding effects in separation and surface-diffusion barrier energies of an adatom pair. PMID- 10034843 TI - Double-sine-Gordon solitons: A model for misfit dislocations on the Au(111) reconstructed surface. PMID- 10034845 TI - Neutron diffraction by surface acoustic waves. PMID- 10034846 TI - Crumpling transition in polymerized membranes. PMID- 10034847 TI - Electron-hole-pair dephasing of adsorbate vibrations. PMID- 10034848 TI - Crystallization instability at the amorphous-silicon/liquid-silicon interface. PMID- 10034849 TI - Scaling group formulation of multifractals. PMID- 10034850 TI - Resonating-valence-bond theory of phase transitions and superconductivity in La2CuO4-based compounds. PMID- 10034851 TI - Theory of high-Tc superconductivity in oxides. PMID- 10034852 TI - Experimental evidence for granular superconductivity in Y-Ba-Cu-O at 100 to 160 K. PMID- 10034853 TI - Antiferromagnetism in La2CuO PMID- 10034854 TI - Nonequilibrium superconductivity: New crystallographic and magnetic field effects. PMID- 10034856 TI - Observation of the Aharonov-Bohm effect for omega c tau >1. PMID- 10034855 TI - High-temperature collapse of the Kondo resonance in CeSi2 observed by photoemission. PMID- 10034857 TI - Fractal distribution of galaxies modeled by a cellular-automaton-type stochastic process. PMID- 10034858 TI - Comment on "Second condensed phase of electron-hole plasma in Si" PMID- 10034859 TI - Smith and Wolfe respond. PMID- 10034861 TI - Pantelides responds. PMID- 10034860 TI - Comment on "Defects in amorphous silicon: A new perspective" PMID- 10034863 TI - Applications of the Kakutani metric to real-space renormalization. PMID- 10034864 TI - Limits on B0B-bar0 mixing and & PMID- 10034865 TI - Bounds on the electron electric dipole moment in a wide class of models. PMID- 10034866 TI - Direct observation of multiple-scattering processes in pion absorption. PMID- 10034868 TI - Emission spectra of helium hydride at 4.2 K. PMID- 10034867 TI - Measurement of charge-density differences in the interior of Pb isotopes. PMID- 10034869 TI - Nonclassical radiation of a single stored ion. PMID- 10034871 TI - Density and deceleration limits in tapered free electron lasers. PMID- 10034870 TI - Auger-electron ion coincidence studies of soft-x-ray-induced fragmentation of N2. PMID- 10034872 TI - Dynamics of laser-driven shock waves in fused silica. PMID- 10034873 TI - Field correlations within a fluctuating homogeneous medium. PMID- 10034875 TI - Observability of acoustical and optical localization. PMID- 10034874 TI - Dynamics of line defects in nematic liquid crystals. PMID- 10034876 TI - "Martensitic" instability of an icosahedral quasicrystal. PMID- 10034877 TI - Effects of segregation on grain-boundary cohesion: A density-functional cluster model of boron and sulfur in nickel. PMID- 10034878 TI - Pulsed-laser-induced reactive quenching at liquid-solid interface: Aqueous oxidation of iron. PMID- 10034880 TI - Integral-equation theory of the structure of polymer melts. PMID- 10034879 TI - Vibrational properties of the reconstructed W(100) surface. PMID- 10034881 TI - Desorption by electronically stimulated adsorbate rotation. PMID- 10034882 TI - Abnormal sound damping in the smectic-C phase of terephthal-bis-p-p'-butylaniline (TBBA): Evidence for anharmonic effects. PMID- 10034883 TI - Soliton diffusion in trans-polyacetylene. PMID- 10034884 TI - Nonlinear electrical transport effects in tetrathiafulvalene tetracyanoquinodimethane as driven through charge-density-wave commensurability. PMID- 10034885 TI - d -wave superconductivity in the large-degeneracy limit of the Anderson lattice. PMID- 10034886 TI - Quantized Hall effect in the field-induced density-wave phases of low dimensionality conductors. PMID- 10034887 TI - Universal kinetics in reaction-limited aggregation. PMID- 10034888 TI - Dynamics of three dimensional ionospheric plasma clouds. PMID- 10034889 TI - Comment on "Submicrocrystallites and orientational proximity effect" PMID- 10034890 TI - Ourmazd, Bean, and Phillips respond. PMID- 10034891 TI - Are leached porous glasses fractal? PMID- 10034892 TI - Even et al. respond. PMID- 10034895 TI - Steady-state chemical kinetics on fractals: Segregation of reactants. PMID- 10034897 TI - Unique effective action in five-dimensional Kaluza-Klein theory. PMID- 10034896 TI - Quantum effects in a macroscopic system. PMID- 10034898 TI - Numerical analysis of accelerated stochastic algorithms near a critical temperature. PMID- 10034899 TI - QCD and rising cross sections. PMID- 10034900 TI - Study of pi + pi - transitions from the Upsilon (3S). PMID- 10034902 TI - Signature of g boson in the interacting-boson model from g-factor variations. PMID- 10034901 TI - Measurement of the D+ and D0 lifetimes. PMID- 10034903 TI - Subbarrier nucleon transfer: Doorway to heavy-ion fusion. PMID- 10034904 TI - Nuclear shapes from alpha-gamma-ray angular correlations. PMID- 10034905 TI - Nuclear rotational damping: Finite-system analogue to motional narrowing in nuclear magnetic resonances. PMID- 10034906 TI - Muon-catalyzed D-T fusion at low temperature. PMID- 10034907 TI - Observation of resolved Zeeman thresholds in photodetachment in a magnetic field. PMID- 10034908 TI - Anomalous population of deep capture states of fast ions emerging from solid foils. PMID- 10034909 TI - Large resonance effect in K-shell ionization probability in elastic proton backscattering on 138Ba. PMID- 10034910 TI - Raman magnetic resonance. PMID- 10034911 TI - Scattering of electrons by intense coherent light. PMID- 10034912 TI - Observation of quantum collapse and revival in a one-atom maser. PMID- 10034913 TI - Four-mode squeezing. PMID- 10034915 TI - So-called icosahedral and decagonal quasicrystals are twins of an 820-atom cubic crystal. PMID- 10034914 TI - Observation of weak localization of light in a finite slab: Anisotropy effects and light path classification. PMID- 10034916 TI - Structure of the Ag/Si(111) surface by scanning tunneling microscopy. PMID- 10034918 TI - Singularity in the Kapitza resistance between gold and superfluid 4He near T lambda. PMID- 10034917 TI - Local electron states and surface geometry of Si(111)- sqrt 3 sqrt 3 Ag. PMID- 10034919 TI - Molar volume dependence of the nuclear magnetism of bcc solid 3He. PMID- 10034920 TI - Kohlrausch thermal relaxation in a random magnet. PMID- 10034921 TI - Model of interfacial melting. PMID- 10034922 TI - Giant dielectric response and hairpins in polymeric nematics. PMID- 10034924 TI - Evidence for anomalous thermal expansion at a crystal surface. PMID- 10034923 TI - Multifractal nature of truly kinetic random walks. PMID- 10034925 TI - Evidence for superconductivity above 40 K in the La-Ba-Cu-O compound system. PMID- 10034926 TI - Bulk superconductivity at 36 K in La1.8Sr0.2CuO4. PMID- 10034927 TI - Ground-state properties of the periodic Anderson model. PMID- 10034928 TI - Resistance noise in nonlinear resistor networks. PMID- 10034929 TI - Dimensionality dependence of the band-gap renormalization in two- and three dimensional electron-hole plasmas in GaAs. PMID- 10034930 TI - Comment on "Transverse electromagnetic waves with E||B" PMID- 10034931 TI - Chu and Ohkawa respond. PMID- 10034932 TI - Anomalous positron peaks and the Dirac equation. PMID- 10034933 TI - Wong responds. PMID- 10034934 TI - Comment on: "Pair interaction from structural data for dense classical liquids" PMID- 10034935 TI - Comment on "Heat capacity of a condensed electron system in the dilute metal n Hg0.8Cd0.2Te" PMID- 10034937 TI - Nature of spatial chaos. PMID- 10034938 TI - Nonuniversal power laws and crossover from critical to classical behavior. PMID- 10034939 TI - Origin of asymptotic freedom in non-Abelian field theories. PMID- 10034940 TI - Hadron production near threshold in photon-photon collisions. PMID- 10034942 TI - Searching for CP nonconservation in jet physics. PMID- 10034941 TI - Spin transfer in hyperon production. PMID- 10034943 TI - Quasielastic transfer of a neutron between 58Ni and 208Pb at bombarding energies of 598 and 1011 MeV. PMID- 10034944 TI - Dynamical symmetries of the interacting-boson model from a non-U(6) viewpoint. PMID- 10034945 TI - Pion production in high-energy nucleus-nucleus collisions. PMID- 10034946 TI - Mean-lifetime measurements within the superdeformed second minimum in 132Ce. PMID- 10034947 TI - Proton recoil and radiative level shifts. PMID- 10034949 TI - Chemical dissolution of a porous medium by a reactive fluid. PMID- 10034948 TI - Chaos and dynamics on 0.5-300 ps time scales in vibrationally excited acetylene: Fourier transform of stimulated-emission pumping spectrum. PMID- 10034950 TI - Observation of electron trapping and phase-area displacement in the interaction between an electron beam and two counter-propagating laser beams. PMID- 10034951 TI - Anomalous transport and the coupling of plasma diffusion and heat flow. PMID- 10034952 TI - Temporal behavior of the plasma current distribution in the ASDEX tokamak during lower-hybrid current drive. PMID- 10034953 TI - Ponderomotive stabilization of flute modes in mirrors: Feedback control and numerical results. PMID- 10034954 TI - Superfluid turbulence in convecting dilute solutions of 3He in superfluid 4He. PMID- 10034955 TI - Direct experimental determination of the crossover frequency between phonon and fracton regimes and its scaling behavior in superionic silver borate glasses. PMID- 10034957 TI - Ferromagnetic order and the critical exponent gamma for a Gd monolayer: An electron-spin-resonance study. PMID- 10034956 TI - New correlation effects observed for inner-shell excitations in titanium and vanadium. PMID- 10034958 TI - Strong-magnetic-field states of the pure electron plasma. PMID- 10034960 TI - Comment on "Observation of Berry's topological phase by use of an optical fiber" PMID- 10034959 TI - Surface structure of thermionic-emission cathodes. PMID- 10034961 TI - Comment on "Stretched-exponential dielectric relaxation in a charge-density-wave system" PMID- 10034962 TI - Kriza and Mihaly respond. PMID- 10034964 TI - Scaling in stochastic Hamiltonian systems: A renormalization approach. PMID- 10034965 TI - Massless bosonic free fields. PMID- 10034966 TI - String theory as the Kahler geometry of loop space. PMID- 10034967 TI - Induced gauge fields in a nongauged quantum system. PMID- 10034968 TI - Double ionization of helium by protons and antiprotons in the energy range 0.30 to 40 MeV. PMID- 10034969 TI - Analysis of subgrid-scale eddy viscosity with use of results from direct numerical simulations. PMID- 10034970 TI - Laser-based foilless diode. PMID- 10034972 TI - Field-induced vibrational frequency shifts of CO and CN chemisorbed on Cu(100). PMID- 10034971 TI - Nonlinear plasma dynamics in the plasma wake-field accelerator. PMID- 10034973 TI - Quantum simulation of hydrogen in metals. PMID- 10034974 TI - Origin of anomalous photoinduced transformations in amorphous Ge-based chalcogenide thin films. PMID- 10034975 TI - Neutron spin echo study of dynamic correlations near the liquid-glass transition. PMID- 10034976 TI - Metallization and structural transformation of iodine under pressure: A microscopic view. PMID- 10034978 TI - Triple-point wetting and surface melting of oxygen films adsorbed on graphite. PMID- 10034977 TI - Coordination determination of In on Si(100) from synchrotron photoemission studies. PMID- 10034979 TI - New reentrant wetting phenomena and critical behavior near bulk critical points. PMID- 10034981 TI - Glancing angle scattering and neutralization of a positron beam at metal surfaces. PMID- 10034980 TI - Microscopic metal clusters and Schottky barrier formation. PMID- 10034982 TI - Elementary pinning force for a superconducting vortex. PMID- 10034983 TI - Theory of one-dimensional hopping motion of a heavy particle interacting with phonons by different couplings. PMID- 10034984 TI - Mixed valency versus covalency in rare-earth core-electron spectroscopy. PMID- 10034985 TI - Evidence for an intrinsic intergap surface state on GaSb(110) by high-resolution angle-resolved photoemission. PMID- 10034987 TI - Quenched decay into multiple continua. PMID- 10034986 TI - Electronic structure of alkali-intercalated graphite studied by soft-x-ray emission spectroscopy. PMID- 10034988 TI - Experimental evidence for multifractality. PMID- 10034989 TI - Comment on "Origin of nonuniversality in micellar solutions" PMID- 10034990 TI - Shnidman responds. PMID- 10034992 TI - Universal strange attractor underlying Hamiltonian stochasticity. PMID- 10034993 TI - Deconfinement in the CPN-1 model by massless fermions. PMID- 10034994 TI - Closed strings in open-string field theory. PMID- 10034995 TI - Constraints on technicolor theories from delta rho. PMID- 10034996 TI - Measurement of the weak-neutral-current coupling constants of the electron and limits on the electromagnetic properties of the muon neutrino. PMID- 10034997 TI - Determination of the lifetime of bottom hadrons. PMID- 10034998 TI - Observation of Xi - production in e+e- annihilation at 29 GeV. PMID- 10035000 TI - Quantum-mechanical treatment of the Skyrme Lagrangean, and a new mass term. PMID- 10034999 TI - Determination of the real part of the isospin-even forward-scattering amplitude of pion-nucleon scattering at 55 MeV as a test of low-energy quantum chromodynamics. PMID- 10035001 TI - Algebraic description of the skyrmion and its quantization for finite N. PMID- 10035002 TI - Valence p-n interactions and the development of collectivity in heavy nuclei. PMID- 10035003 TI - Structure of the very neutron-deficient Ge region: 64Ge and 65Ge. PMID- 10035005 TI - Stationary configurations of point vortices and other logarithmic objects in two dimensions. PMID- 10035004 TI - Suppression of spontaneous decay at optical frequencies: Test of vacuum-field anisotropy in confined space. PMID- 10035006 TI - Late-stage phase separation and hydrodynamic flow in a binary liquid mixture. PMID- 10035007 TI - Surface spin waves in 3He-A, a probe for vortex phenomena in narrow gaps. PMID- 10035009 TI - Direct energy transfer in restricted geometries as a probe of the pore morphology of silica. PMID- 10035010 TI - Novel melting transition in a two-dimensional stripe-domain system. PMID- 10035008 TI - Ion-channeling studies of the structural phase transition in (GaSb)1-x(Ge2)x alloys. PMID- 10035011 TI - Adsorbate-induced surface-phonon softening on Pt(111). PMID- 10035012 TI - Disorder at the bilayer interface in the pseudohexagonal rotator phase of solid n alkanes. PMID- 10035013 TI - High-energy ion-scattering studies of anisotropic surface-atom vibrations on W(110). PMID- 10035014 TI - Quasicrystal equilibrium state. PMID- 10035015 TI - Hydrodynamic behavior of fractal aggregates. PMID- 10035016 TI - Nonclassical origin of the rocksalt-cesium chloride structural transition. PMID- 10035017 TI - Aharonov-Bohm effect in semiconductor microstructures. PMID- 10035018 TI - Quantum size effect in optical spectra of thin metallic films. PMID- 10035019 TI - Berry's geometrical phase and the sequence of states in the Jahn-Teller effect. PMID- 10035020 TI - Structurally induced optical transitions in Ge-Si superlattices. PMID- 10035021 TI - New observation of the valence-band satellite in Ni(110). PMID- 10035022 TI - Absorption of circularly polarized x rays in iron. PMID- 10035024 TI - Femtosecond time-resolved observation of coherent molecular vibrational motion. PMID- 10035023 TI - Statistical mechanics and invariant perception. PMID- 10035026 TI - Nonexistence of small-amplitude breather solutions in phi4 theory. PMID- 10035027 TI - Return of the finite-temperature phase transition in the chiral limit of lattice QCD. PMID- 10035028 TI - Virasoro algebra in 2+1 dimensions and angular momentum fractionalization. PMID- 10035029 TI - gamma rays from peripheral and central collisions in the reaction 40Ar+158Gd at 44 MeV/nucleon. PMID- 10035030 TI - Sideband control in a millimeter-wave free-electron laser. PMID- 10035031 TI - Viscous flow in supercooled liquids analyzed in terms of transport theory for random media with energetic disorder. PMID- 10035033 TI - hcp to fcc transition in silicon at 78 GPa and studies to 100 GPa. PMID- 10035032 TI - Conformal invariance and the spectrum of the XXZ chain. PMID- 10035034 TI - Electrolytic conduction in porous media with charges. PMID- 10035035 TI - Phase transitions in AlAs/GaAs superlattices under high pressure. PMID- 10035036 TI - Crossover in the Anderson transition: Acoustic localization with a flow. PMID- 10035037 TI - Phonons in rare-gas solids close to melting. PMID- 10035038 TI - Master-equation appoach to the glass transition. PMID- 10035039 TI - Pressure-induced face-centered-cubic phase of monatomic metallic iodine. PMID- 10035040 TI - Hydrodynamic boundary conditions and cooling in superfluid 3He. PMID- 10035041 TI - Suppression of superfluidity of 3He in cylindrical channels. PMID- 10035042 TI - Development of antiferromagnetic correlations in the heavy-fermion system UPt3. PMID- 10035043 TI - Low-temperature magnetic spectroscopy of a dilute magnetic semiconductor. PMID- 10035044 TI - Electron interference effects in quantum wells: Observation of bound and resonant states. PMID- 10035045 TI - Novel magnetoacoustic effects in heavy-Fermion systems in high magnetic fields. PMID- 10035046 TI - Superlattice magnetoroton bands. PMID- 10035047 TI - Experiment versus the classical model of deformable charge-density waves: Interference phenomena and mode locking. PMID- 10035048 TI - Excitonic coupling in GaAs/GaAlAs quantum wells in an electric field. PMID- 10035050 TI - Comment on "Pion absorption on the diproton" PMID- 10035049 TI - Computationally efficient modeling of ordering of quenched phases. PMID- 10035051 TI - Moinester et al. respond. PMID- 10035053 TI - Nonperturbative length scale in high-temperature QCD. PMID- 10035052 TI - Study of two magnetic impurities in a Fermi gas. PMID- 10035054 TI - Towards a resolution of certain dilemmas in preon dynamics through local supersymmetry. PMID- 10035055 TI - Polarization and magnetic moment of the Sigma + hyperon. PMID- 10035056 TI - Evidence for a new meson: A quasinuclear NN-bar bound state? PMID- 10035057 TI - Fluctuations and clustering in heavy-ion collisions. PMID- 10035058 TI - Vibrational interference in the decay of core-excited nitric oxide. PMID- 10035059 TI - Optical bistability by surface resonance modes. PMID- 10035060 TI - Fluctuating hydrodynamics in a dilute gas. PMID- 10035061 TI - Generation and control of high transient electrical potentials within a mirror confined plasma. PMID- 10035062 TI - Transmission of order in some unusual dilute systems. PMID- 10035063 TI - Inelastic neutron scattering in the amorphous and the crystalline state: The phonon-fracton density of states. PMID- 10035064 TI - Simple method for the evaluation of bond length from data. PMID- 10035065 TI - "Shattering" transition in fragmentation. PMID- 10035066 TI - Nematic-smectic-C phase transition in the polymeric liquid crystal C-6 polysiloxane: A high resolution x-ray study. PMID- 10035067 TI - Amorphization processes in electron and/or ion-irradiated silicon. PMID- 10035068 TI - Two different vortex states in rotating 3He-A observed by use of negative ions. PMID- 10035069 TI - Superconductivity at 93 K in a new mixed-phase Yb-Ba-Cu-O compound system at ambient pressure. PMID- 10035071 TI - Number of stable points for spin-glasses and neural networks of higher orders. PMID- 10035070 TI - High-pressure study of the new Yb-Ba-Cu-O superconducting compound system. PMID- 10035072 TI - Spin fluctuations in the antiferromagnetic heavy-fermion system U2Zn17. PMID- 10035073 TI - Angle-resolved positronium emission spectroscopy. PMID- 10035074 TI - Impurity bands in n-type Si/SiO2 metal-oxide semiconductors. PMID- 10035075 TI - Spatial correlations around a Kondo impurity. PMID- 10035076 TI - Ferromagnetism of thin epitaxial fcc cobalt films on Cu(001) obesrved by spin polarized photoemission. PMID- 10035078 TI - Picosecond recombination dynamics of electrons in ionic liquids. PMID- 10035077 TI - Polarons and bipolarons in a model tetrahedrally bonded homopolymer. PMID- 10035079 TI - Searching for photon localization in the time domain. PMID- 10035081 TI - Nuclear magnetic resonance study of the bonding and diffusion of CO chemisorbed on Pd. PMID- 10035080 TI - Learning of correlated patterns in spin-glass networks by local learning rules. PMID- 10035082 TI - Comment on "Evidence for correlated double-electron capture in low-energy collisions of O6+ with He" PMID- 10035084 TI - Comment on "Calculated photoemission spectra of Na" PMID- 10035083 TI - Stolterfoht et al. respond. PMID- 10035085 TI - Shung and Mahan respond. PMID- 10035087 TI - Novel decomposition of the multichannel scattering matrix at resonances. PMID- 10035088 TI - Modulation-induced negative differential resistance in bistable systems. PMID- 10035089 TI - Resolution of Loschmidt's paradox: The origin of irreversible behavior in reversible atomistic dynamics. PMID- 10035090 TI - Chiral-symmetry-breaking phase transition in lattice gauge-Higgs theories with fermions. PMID- 10035091 TI - Measurement of the lifetime of KS0 mesons in the momentum range 100 to 350 GeV/c. PMID- 10035092 TI - Evidence for charmed baryons in B-meson decay. PMID- 10035093 TI - New high-precision comparison of electron and positron g factors. PMID- 10035094 TI - Role of the omega meson in topological chiral solitons. PMID- 10035095 TI - Observation of a bound Tz=-3 nucleus: 22Si. PMID- 10035096 TI - Saddle-point electrons in ionizing ion-atom collisions. PMID- 10035097 TI - Observation of continuous-wave self-oscillation due to pressure-induced two-wave mixing in sodium. PMID- 10035098 TI - Parametric oscillation in sodium vapor. PMID- 10035099 TI - Observation of a high-density ion mode in tokamak microturbulence. PMID- 10035100 TI - Not-so-resonant, resonant absorption. PMID- 10035101 TI - Dynamics of high-Z plasmas produced by a short-wavelength laser. PMID- 10035102 TI - Nonlinear absorption of intense microwave pulses. PMID- 10035103 TI - Phases of helium adsorbed on graphite: A Feynman path-integral Monte Carlo study. PMID- 10035104 TI - Theoretical nuclear magnetic resonance spectrum of quasicrystalline ordering in cholesteric blue phase III. PMID- 10035105 TI - Beyond steady-state lamellar eutectic growth. PMID- 10035106 TI - Chemically bonded diamondlike carbon films from ion-beam deposition. PMID- 10035108 TI - Is blue phase II fcc? PMID- 10035107 TI - Incommensurate to high-order commensurate phase transition of Kr on Pt(111). PMID- 10035109 TI - Scaling properties for the unscreened surfaces of fractal patterns. PMID- 10035111 TI - Magnetostatic modes in highly polarized solid helium-three. PMID- 10035112 TI - Molecular-dynamics simulation of wetting and drying at solid-fluid interfaces. PMID- 10035110 TI - Interrelations between planes affecting adsorption kinetics on polycrystalline surfaces: Oxygen adsorption on copper. PMID- 10035113 TI - Low-energy modes in quasicrystalline and glassy Pd58.8Si20.6U20.6: A comparative study by neutron inelastic scattering. PMID- 10035115 TI - Observation of single-electron charging effects in small tunnel junctions. PMID- 10035114 TI - Observation of spin diffusion in zero-field magnetic resonance. PMID- 10035116 TI - Electronic fluctuation and cohesion in metals. PMID- 10035117 TI - Vortex signatures in dynamic structure factors for two-dimensional easy-plane ferromagnets. PMID- 10035118 TI - Ground-state properties of correlated fermions: Exact analytic results for the Gutzwiller wave function. PMID- 10035119 TI - Resonant tunneling through amorphous silicon-silicon nitride double-barrier structures. PMID- 10035120 TI - Evidence for a phase transition in the spin glass Eu0.4Sr0.6S from dynamic susceptibility measurements. PMID- 10035121 TI - Interfacial anisotropy in magnetic superlattices. PMID- 10035122 TI - Ion-molecule surface reactions induced by slow (5-20 eV) electrons. PMID- 10035123 TI - Are antiferromagnetic spin chains representations of the higher Wess-Zumino Witten models? PMID- 10035124 TI - Role of d orbitals in valence-band offsets of common-anion semiconductors. PMID- 10035126 TI - Comment on "Supersymmetric treatment of random disorder in the continuum model of polyacetylene" PMID- 10035125 TI - Monte Carlo modeling of ionospheric oxygen acceleration by cyclotron resonance with broad-band electromagnetic turbulence. PMID- 10035127 TI - Xu and Trullinger reply. PMID- 10035128 TI - Wall-induced order of a liquid crystal. PMID- 10035131 TI - Photon splitting in a plane-wave field. PMID- 10035132 TI - Wilson-loop instantons. PMID- 10035133 TI - Implications of large Bd0-B-bard0 mixing. PMID- 10035134 TI - Pion double charge exchange and the nuclear shell model. PMID- 10035135 TI - Measurement of the 16O PMID- 10035136 TI - Relativistic Vlasov equation for heavy-ion collisions. PMID- 10035137 TI - Laser-induced change in nuclear reaction rate: 6Li PMID- 10035138 TI - Above-threshold ionization with subpicosecond laser pulses. PMID- 10035139 TI - Field ionization of high-lying states of H2. PMID- 10035140 TI - Computation of the dimension of two-dimensional turbulence. PMID- 10035141 TI - Curvature instability of relativistic particle beams. PMID- 10035142 TI - Interatomic potentials in condensed matter via the maximum-entropy principle. PMID- 10035143 TI - Electron-diffraction study of free-standing liquid-crystal films. PMID- 10035144 TI - Faceting in bond-oriented glasses and quasicrystals. PMID- 10035146 TI - Experimental verification of critical exponents in the two-dimensional four-state Potts universality class: Oxygen on Ru(0001). PMID- 10035145 TI - Vibrational spectroscopy of H2 in porous Vycor glass: First evidence for the bilayer structure. PMID- 10035147 TI - Diffusion in supercooled water to 300 MPa. PMID- 10035149 TI - Nonlocal pseudopotentials in molecular-dynamical density-functional theory: Application to SiO2. PMID- 10035148 TI - Pressure-induced disproportionation of cesium iodide. PMID- 10035150 TI - Electronic structure of ultrasmall quantum-well boxes. PMID- 10035152 TI - Long-lived Coulomb gap in a compensated semiconductor-the electron glass. PMID- 10035151 TI - Picosecond optical time-of-flight studies of carrier transport in a-Si:H-a-SiNx:H multilayers. PMID- 10035153 TI - Ferromagnetic order in a Fe(110) monolayer on W(110) by Mossbauer spectroscopy. PMID- 10035155 TI - Anisotropic nature of high-temperature superconductivity in single-crystal Y1Ba PMID- 10035154 TI - Microwave-enhanced phase-relaxation observed in weak-localization experiments. PMID- 10035156 TI - Long-range interactions in adsorbed layers of virus particles. PMID- 10035158 TI - Avenel and Varoquaux reply. PMID- 10035157 TI - Temperature dependence of discrete dissipative events in superfluid 4He. PMID- 10035160 TI - Jaric-acute and Mohanty reply. PMID- 10035159 TI - Elastic constants of hard-sphere crystals. PMID- 10035162 TI - Ergodic adiabatic invariants of chaotic systems. PMID- 10035163 TI - Wave profile modification (optical guiding) induced by free-electron laser interaction. PMID- 10035164 TI - Enhancement of efficiency and gain in cyclotron autoresonance masers. PMID- 10035165 TI - Soft x-ray lasing in neonlike germanium and copper plasmas. PMID- 10035166 TI - Transition from superfluorescence to amplified spontaneous emission. PMID- 10035168 TI - Cause of the lower-hybrid current-drive density limit. PMID- 10035167 TI - Brillouin scattering measurements from plasmas irradiated with spatially and temporally incoherent laser light. PMID- 10035169 TI - Study of directly launched ion Bernstein waves in a tokamak. PMID- 10035171 TI - Smectic-Ad-smectic-A2 critical point. PMID- 10035170 TI - Simple microscopic model of a microemulsion. PMID- 10035172 TI - Density of states in fractal silica smoke-particle aggregates. PMID- 10035173 TI - Direct measurement of crystallographic phase by electron diffraction. PMID- 10035175 TI - Critical behavior of hydrogen in Nb/Ta superlattices. PMID- 10035174 TI - Time-resolved x-ray scattering study of ordering kinetics in SbCl5-intercalated graphite. PMID- 10035176 TI - Density-functional theory of the solid-liquid interface. PMID- 10035177 TI - Absence of superconductivity in metallic granular aluminum. PMID- 10035178 TI - Observation of an oxygen isotope effect in YBa2Cu PMID- 10035179 TI - Quadrupolar Kondo effect in uranium heavy-electron materials? PMID- 10035181 TI - Order-parameter-conserving anitferromagnets. PMID- 10035180 TI - Observation of a local magnetic 4d moment and its spin dynamics. PMID- 10035183 TI - Dynamics of pulsed-field electrophoresis. PMID- 10035182 TI - Dynamics of twin boundaries in martensites. PMID- 10035184 TI - Orientation of CHF3 desorbed and scattered from Ag(111): Measurements using electrostatic focusing. PMID- 10035185 TI - Metal-insulator transition in a double-donor system, Si:P,As. PMID- 10035187 TI - Hypergravitational field equations. PMID- 10035188 TI - Medium-modified form factors, relativistic dynamics, and the (e,e'p) reaction. PMID- 10035189 TI - Gamma radiation from the N=Z nucleus 4080Zr PMID- 10035190 TI - Laser resonance photoionization spectroscopy of Rydberg levels in Fr. PMID- 10035192 TI - Spontaneous spin polarization and bistability in atomic vapors by optical pumping with unpolarized light. PMID- 10035191 TI - Photoemission of pairs of electrons from rare-gas solids. PMID- 10035194 TI - Cooperative quantum jumps with two atoms. PMID- 10035193 TI - Energies of atoms with nonspherical charge densities calculated with nonlocal density-functional theory. PMID- 10035195 TI - Highly resolved spectra of local modes of benzene. PMID- 10035196 TI - Quantum-defect theory of double-minimum states in H2. PMID- 10035197 TI - Space-potential and density fluctuations in the ISX-B tokamak. PMID- 10035198 TI - Tunneling and nonuniversal conductivity in composite materials. PMID- 10035199 TI - Proof of the Peierls instability in one dimension. PMID- 10035200 TI - Observation of phonon modes through resonant mixing with electronic states in the secondary-emission spectra of a GaAs/Al0.32Ga0.68As single quantum well. PMID- 10035201 TI - Glassy thermal anomalies due to dipolar reorientations? Specific heat of N2-Ar-CO alloys. PMID- 10035203 TI - Model for smectic-A ordering of parallel hard rods. PMID- 10035202 TI - Orientation of arachidate chains in Langmuir-Blodgett monolayers on Si(111). PMID- 10035204 TI - Soft-phonon behavior and transport in single-crystal La2CuO PMID- 10035205 TI - Electronic structure and excitonic-enhanced superconducting mechanism in YBa2Cu PMID- 10035206 TI - Resistivity of La1.825Sr0.175CuO4 and YBa2Cu3O7 to 1100 K: Absence of saturation and its implications. PMID- 10035207 TI - Quantum oscillations in the thermal conductance of GaAs/AlGaAs heterostructures. PMID- 10035208 TI - Intersubband relaxation in GaAs-AlxGa PMID- 10035209 TI - Effect of repulsive and attractive scattering centers on the magnetotransport properties of a two-dimensional electron gas. PMID- 10035211 TI - Absorption spectroscopy of the continuous transition from low to high electron density in a single modulation-doped InGaAs quantum well. PMID- 10035210 TI - Evidence for edge currents in the integral quantum Hall effect. PMID- 10035212 TI - Lattice-induced double peak in the dielectric response of Be metal. PMID- 10035214 TI - Gravitational particle production in the formation of cosmic strings. PMID- 10035213 TI - Pseudopotentials and quasicrystals. PMID- 10035215 TI - Comment on "Dynamical symmetries of the interacting-boson model from a non-U(6) viewpoint" PMID- 10035217 TI - Comment on "Nuclear-density dependence of the electron-proton coupling" PMID- 10035216 TI - Geyer, Hahne, and Scholtz reply. PMID- 10035218 TI - van der Steenhoven et al. reply. PMID- 10035219 TI - Organization of chaos. PMID- 10035220 TI - Colored noise and bistable Fokker-Planck equations. PMID- 10035221 TI - Search for an intermediate-range composition-dependent force. PMID- 10035222 TI - Charge neutrality of atoms and magnetic monopoles. PMID- 10035223 TI - Classification and JPG selection rules for weak currents. PMID- 10035224 TI - Search for neutral heavy leptons from nu - N scattering. PMID- 10035225 TI - Isovector couplings for nucleon charge-exchange reactions at intermediate energies. PMID- 10035226 TI - Abundance and systematics of nuclear superdeformed states; relation to the pseudospin and pseudo-SU(3) symmetries. PMID- 10035227 TI - Limits of collective motion in hot nuclear matter. PMID- 10035228 TI - Circularly polarized He radiation for electron polarimetry. PMID- 10035229 TI - Observation of dressed-atom effects in three-level free-induction decay. PMID- 10035230 TI - Weak localization of photons: Termination of coherent random walks by absorption and confined geometry. PMID- 10035231 TI - Simple multifractal cascade model for fully developed turbulence. PMID- 10035232 TI - Ion microinstability at the outer sloshing-ion turning point of the tandem mirror experiment upgrade (TMX-U). PMID- 10035233 TI - Observation of an improved energy-confinement regime in neutral-beam-heated divertor discharges in the DIII-D tokamak. PMID- 10035234 TI - Observation of fast stochastic ion heating by drift waves. PMID- 10035235 TI - Crystal x-ray accelerator. PMID- 10035236 TI - Observation of a new toroidally localized kink mode and its role in reverse-field pinch plasmas. PMID- 10035237 TI - Anomalous electron heat transport driven by low frequency electromagnetic turbulence. PMID- 10035238 TI - Adsorbate-induced reconstruction in the Ni(110)-H system. PMID- 10035239 TI - Absence of large compressive stress on Si(111). PMID- 10035240 TI - Theory of thermal relaxation of electrons in metals. PMID- 10035242 TI - Improved high-Tc superconductors. PMID- 10035241 TI - Polaron lattice in highly conducting polyaniline: Theoretical and optical studies. PMID- 10035243 TI - Correlation functions for Hubbard-type models: The exact results for the Gutzwiller wave function in one dimension. PMID- 10035244 TI - Electronic structure of a quasiperiodic superlattice. PMID- 10035245 TI - Coherent nuclear-spin interactions of adsorbed 131Xe gas with surfaces. PMID- 10035246 TI - Electronically excited photodissociation and desorption of adsorbates: CH2I2 on Al2O3 and Ag surfaces. PMID- 10035249 TI - Realism and quantum flux tunneling. PMID- 10035247 TI - Electronic promotion of silicon nitridation by alkali metals. PMID- 10035251 TI - Arnol'd diffusion in 1(1/2 dimensions. PMID- 10035250 TI - Additional properties of random matrices and their relation to Hamiltonian systems. PMID- 10035252 TI - Domain walls of finite thickness in general relativity. PMID- 10035254 TI - Possible nonconservation of electric charge. PMID- 10035253 TI - Frozen solitons in a two-dimensional ferromagnet. PMID- 10035255 TI - Estimating the chiral-symmetry-restoration temperature in two-flavor QCD. PMID- 10035257 TI - Charmless decays of bottom mesons and a fourth generation. PMID- 10035256 TI - Probing a superlight gravitino in photon-photon collisions. PMID- 10035258 TI - Consequences of the large real-to-imaginary ratio at sqrt s =546 GeV. PMID- 10035260 TI - Production of the charmed strange baryon Xi c+ by neutrons. PMID- 10035259 TI - Measurement of the decay tau --> rho nu. PMID- 10035261 TI - Measurement with a free neutron beam of absolute neutron-proton forward elastic scattering differential cross section at intermediate energies. PMID- 10035263 TI - Equivalence between gamma instability and rigid triaxiality in finite boson systems. PMID- 10035262 TI - Isoscalar and isovector form factors of 3H and 3He for Q below 2.9 fm-1 from electron-scattering measurements. PMID- 10035264 TI - Dynamical symmetries of the perturbed hydrogen atom: The van der Waals interaction. PMID- 10035265 TI - New variational techniques for the 1snd states of helium. PMID- 10035266 TI - Non-Franck-Condon distribution of final states in photoionization of H2(C1 Pi u). PMID- 10035267 TI - Inelastic x-ray scattering from copper K-shell electrons at intermediate momentum transfers. PMID- 10035268 TI - Formation of Rydberg states in fast ions penetrating thin carbon-foil and gas targets. PMID- 10035269 TI - Transfer ionization in H++H PMID- 10035271 TI - Fast dynamo action in unsteady flows and maps in three dimensions. PMID- 10035270 TI - Ab initio approach for many-electron systems without invoking orbitals: An integral formulation of density-functional theory. PMID- 10035272 TI - Initial stages of pattern formation in Rayleigh-Benard convection. PMID- 10035273 TI - Self-organization of electrostatic turbulence in a cylindrical plasma. PMID- 10035274 TI - Suppression of stimulated Raman scattering by the seeding of stimulated Brillouin scattering in a laser-produced plasma. PMID- 10035275 TI - Melting and misalignment of solid crystalline krypton inclusions in aluminum. PMID- 10035276 TI - Adatom vibrations on Si(111) reconstructed surfaces. PMID- 10035278 TI - alpha relaxation of a simple molten salt near the glass transition. PMID- 10035277 TI - Sum-frequency vibrational spectroscopy of a Langmuir film: Study of molecular orientation of a two-dimensional system. PMID- 10035279 TI - Intrinsic optical damage in KBr at 532 nm. PMID- 10035280 TI - Observation of the magnetic field dependence of the cyclotron mass in the Kondo lattice CeB6. PMID- 10035282 TI - Slow-motion scattering and coalescence of maximally charged black holes. PMID- 10035281 TI - Two-dimensional antiferromagnetic quantum spin-fluid state in La2CuO PMID- 10035283 TI - Comment on "Realism and quantum flux tunneling" PMID- 10035284 TI - Comment on "Observation of intrinsic bistability in resonant-tunneling structures" PMID- 10035285 TI - Goldman, Tsui, and Cunningham reply. PMID- 10035286 TI - Comment on "Photon-drag effect in intersubband absorption in a two-dimensional electron gas" PMID- 10035287 TI - Graph bipartitioning problem. PMID- 10035288 TI - Coexistence of order and disorder and reentrance in an exactly solvable model. PMID- 10035290 TI - Non-Abelian anomaly and lattice-fermionic regularizations. PMID- 10035289 TI - Deviations from universality in the transition from quasiperiodicity to chaos. PMID- 10035291 TI - Theoretical limit on iota --> rho gamma and constraints on glueball-qq-bar-meson couplings with the pion and the isovector photon. PMID- 10035292 TI - Measurement of CLL PMID- 10035293 TI - Limit on neutrinoless double-beta decay with majoron emission in 82Se. PMID- 10035294 TI - Equation of state of dense asymmetric nuclear matter. PMID- 10035295 TI - Tensorial derivation of new oscillator-strength sum rules. PMID- 10035296 TI - Channeling atoms in a laser standing wave. PMID- 10035298 TI - Diffraction as tunneling. PMID- 10035297 TI - Electromagnetic shock waves from transmission lines. PMID- 10035299 TI - Drying as an immiscible displacement process with fluid counterflow. PMID- 10035300 TI - Observation of an induced-scattering instability driven by static field asymmetries in a pure electron plasma. PMID- 10035301 TI - Interface roughening in two-dimensional quasicrystals. PMID- 10035302 TI - Faceting and roughening in quasicrystals. PMID- 10035303 TI - Optical reflectance and electron diffraction studies of molecular-beam-epitaxy growth transients on GaAs(001). PMID- 10035304 TI - Stabilities of single-layer and bilayer steps on Si(001) surfaces. PMID- 10035305 TI - Synchrotron-radiation study of the five-dimensional modulated phase of tetrathiafulvalene-tetracyanoquinodimethane (TTF-TCNQ) at 15 K. PMID- 10035306 TI - Density-functional theory for the freezing of water. PMID- 10035307 TI - Oxygen incorporation in thermal-donor centers in silicon. PMID- 10035308 TI - Melting of monolayer xenon on silver: The hexatic phase in the weak-substrate limit. PMID- 10035309 TI - Cubic-lattice simulation of the dynamics of a collapsed polymer chain. PMID- 10035310 TI - Mixture of ordered domains in the NiAl(111) surface. PMID- 10035311 TI - Structural alterations in the amorphous-to-crystalline transformation of lead pyrophosphate. PMID- 10035313 TI - Equilibrium states of diffusion-limited reactions. PMID- 10035312 TI - Nature of exotic negative carriers in superfluid 4He. PMID- 10035314 TI - Information dimension in random-walk processes. PMID- 10035316 TI - First-principles study of hydrogen adsorption on Ru(0001): Possible occupation of subsurface sites. PMID- 10035315 TI - Dimensional-crossover studies of magnetic susceptibility in diluted-magnetic semiconductor superlattices. PMID- 10035317 TI - Hyperfine interactions of the Pb center at the SiO2/Si(111) interface. PMID- 10035318 TI - Origin of superconductive glassy state and extrinsic critical currents in high-Tc oxides. PMID- 10035319 TI - Optical quantum-confined Stark effect in GaAs quantum wells. PMID- 10035320 TI - Zener transitions and energy dissipation in small driven systems. PMID- 10035321 TI - Ferromagnetic-resonance study of ultrathin bcc Fe(100) films grown epitaxially on fcc Ag(100) substrates. PMID- 10035322 TI - Microwave response of confined soliton pairs (bipolarons) in (N methylphenazinium)x - (phenazine)1-x (tetracyanoquinodimethanide). PMID- 10035323 TI - Nuclear double resonance of Tb:160Tb oriented at low temperatures. PMID- 10035325 TI - Spectrum of universal conductance fluctuations. PMID- 10035324 TI - Measurement of anisotropic resistivity and Hall constant for single-crystal YBa2Cu3O7-x. PMID- 10035326 TI - Observation of an even-denominator quantum number in the fractional quantum Hall effect. PMID- 10035327 TI - Observation of acoustic umklapp-phonons in water-stabilized DNA by neutron scattering. PMID- 10035328 TI - Test of spatial isotropy using a cryogenic torsion pendulum. PMID- 10035329 TI - Comment on "Observation of Berry's topological phase by use of an optical fiber" PMID- 10035330 TI - Tomita and Chiao reply. PMID- 10035333 TI - Suppression of nonrenormalizable terms in the effective superpotential for (blown up) orbifold compactification. PMID- 10035332 TI - Normal-metal Aharonov-Bohm effect in the presence of a transverse electric field. PMID- 10035334 TI - String theories and Hirota's bilinear difference equation. PMID- 10035335 TI - Two-loop chiral anomalies in open superstrings. PMID- 10035336 TI - Collective dipole oscillations in small sodium clusters. PMID- 10035338 TI - Observation of sequential decay series in metastable Ar clusters: Arn+*-->Arn-1+* ->Arn-2* PMID- 10035337 TI - Scars of symmetries in quantum chaos. PMID- 10035339 TI - Differential form of the collision integral for a relativistic plasma. PMID- 10035340 TI - Warm electron-driven whistler instability in an electron-cyclotron-resonance heated, mirror-confined plasma. PMID- 10035341 TI - Emission of an upper-hybrid-wave soliton from an ion wave in a beam-plasma system. PMID- 10035342 TI - Lower critical dimension for the random-field Ising model. PMID- 10035344 TI - Is the ground-state structure of (KCl)0.25(KCN)0.75 a noncubic orientational glass? PMID- 10035343 TI - Stability of the missing-row reconstruction on fcc (110) transition-metal surfaces. PMID- 10035345 TI - Anisotropy of optical phonons in GaAs-AlAs superlattices. PMID- 10035346 TI - Theory of inelastic electron vibrational spectroscopy of W(001) at finite temperature. PMID- 10035347 TI - Temporal coherence in the sliding charge-density-wave condensate. PMID- 10035348 TI - Weak localization in two and three dimensions: Dephasing by zero-point motion. PMID- 10035349 TI - Giant defect-enhanced electron-phonon interactions in ternary copper oxide superconductors. PMID- 10035351 TI - Neutrino burst from SN1987A and the solar-neutrino puzzle. PMID- 10035350 TI - Evidence for two pairing energies from nuclear spin-lattice relaxation in superconducting Ba2YCu3O7- delta. PMID- 10035352 TI - Comment on "Can supernovae exclude neutrinos more massive than 30 eV?" PMID- 10035353 TI - Comment on Polarization and tilt-angle measurements near the smectic-A-chiral smectic-C transition of DOBAMBC. PMID- 10035356 TI - Self-dual fields as charge-density solitons. PMID- 10035357 TI - Adler's overrelaxation algorithm for Goldstone bosons. PMID- 10035358 TI - Hadronic screening lengths in the high-temperature plasma. PMID- 10035359 TI - 180 degrees -correlated equal-energy photons from 5.9-MeV/nucleon U + Th collisions. PMID- 10035361 TI - Spin-spin dependence of total cross sections as an effect of static nuclear deformation. PMID- 10035360 TI - Measurement of total reaction cross sections of exotic neutron-rich nuclei. PMID- 10035362 TI - Surface-melting transitions and phase coexistence in argon solvent clusters. PMID- 10035363 TI - Realization of a two-photon maser oscillator. PMID- 10035364 TI - Observation of nonclassical effects in the interference of two photons. PMID- 10035365 TI - Exciton fusion in molecular clusters. PMID- 10035366 TI - Macroscopic quantum-mechanical contributions to radiative polarization in electron storage rings. PMID- 10035367 TI - Absolute instabilities and self-sustained oscillations in the wake of circular cylinders. PMID- 10035368 TI - Wave localization characteristics in the time domain. PMID- 10035369 TI - Application of Kraichnan's decimated-amplitude scheme to the Betchov model of turbulence. PMID- 10035370 TI - Vortex-ring model of the superfluid lambda transition. PMID- 10035371 TI - Role of thermal spikes in energetic displacement cascades. PMID- 10035372 TI - Nonequilibrium phase diagram of Ising model with competing dynamics. PMID- 10035373 TI - Absence of photodarkening in bulk, glassy As2S PMID- 10035374 TI - Atomic-scale friction of a tungsten tip on a graphite surface. PMID- 10035375 TI - Discretized model of entangled-polymer dynamics. PMID- 10035376 TI - Concentration dependence of the octahedral Ti4+ center in LiNbO3: Its effect on refractive indices. PMID- 10035377 TI - Two-component order-parameter model for pure and thorium-doped superconducting UBe13. PMID- 10035379 TI - Femtosecond electronic heat-transport dynamics in thin gold films. PMID- 10035378 TI - Superconducting energy gap and normal-state reflectivity of single crystal Y-Ba Cu-O. PMID- 10035380 TI - Magnetoserpentine effect in single-crystal potassium. PMID- 10035382 TI - Edge states, transmission matrices, and the Hall resistance. PMID- 10035381 TI - Glassy relaxation without freezing in a random dipolar-coupled Ising magnet. PMID- 10035383 TI - Symmetries and learning in neural network models. PMID- 10035384 TI - Comment on "Diffusion in a random potential: Hopping as a dynamical consequence of localization" PMID- 10035385 TI - Zhang replies. PMID- 10035387 TI - Hagen replies. PMID- 10035386 TI - Comment on "What is the most general Abelian gauge theory in two spatial dimensions?" PMID- 10035389 TI - Thermodynamic behavior of two-dimensional vesicles. PMID- 10035390 TI - Production of eta and omega mesons in tau decay and a search for second-class currents. PMID- 10035392 TI - Model of jet energy flow with application to W searches. PMID- 10035391 TI - Simple predictive model for flavor production in hadronization. PMID- 10035393 TI - Model for the Stech mass matrix for quarks. PMID- 10035394 TI - Complex moments of parton distributions and new sum rules. PMID- 10035395 TI - Observation of spin-1 f1(1285) in the reaction gamma gamma *--> eta 0 pi + pi - PMID- 10035397 TI - Direct evidence for two-neutrino double-beta decay in 82Se. PMID- 10035396 TI - Evidence for a spin-1 resonance in the reaction gamma gamma *-->K0K+/- pi +/- PMID- 10035398 TI - Observation of superdeformation in the doubly closed-shell nucleus 146Gd. PMID- 10035400 TI - Geometrical interpretation of SO(7): A critical dynamical symmetry. PMID- 10035399 TI - Multipole strength distributions and form factors for E1, E2/E0, and E3 from 238U(e,e'f) coincidence experiments. PMID- 10035401 TI - Coincidence spectroscopy of highly charged xenon ions by electron impact. PMID- 10035402 TI - Three-step excitation of highly excited autoionizing states in atomic sodium by use of laser beams and synchrotron radiation. PMID- 10035404 TI - Optical guiding in a free-electron-laser oscillator. PMID- 10035403 TI - Measurement of subpicosecond time intervals between two photons by interference. PMID- 10035405 TI - Photopumping of a C III ultraviolet laser by Mn VI line radiation. PMID- 10035407 TI - Turbulent drag reduction by polymers: A quantitative theory. PMID- 10035406 TI - Observation of the infrared spectrum of the helium molecular ion (3He 4He)+ PMID- 10035408 TI - Integrable ponderomotive system: Cavitons are solitons. PMID- 10035409 TI - Some consequences of an equation of motion for diffusive growth. PMID- 10035410 TI - Imaging chemical-bond formation with the scanning tunneling microscope: NH3 dissociation on Si(001). PMID- 10035412 TI - Two-level systems observed in the mechanical properties of single-crystal silicon at low temperatures. PMID- 10035411 TI - X-ray scattering study of the thermal roughening of Ag(110). PMID- 10035413 TI - Observation of a glass transition in suspensions of spherical colloidal particles. PMID- 10035415 TI - Comparison of dipole layers, band offsets, and formation enthalpies of GaAs AlAs(110) and (001) interfaces. PMID- 10035414 TI - Passivation of shallow acceptors by H in Si: A microscopic study by perturbed angular correlations. PMID- 10035416 TI - Equivalence of the resonating-valence-bond and fractional quantum Hall states. PMID- 10035417 TI - Spin polarization of ion-excited secondary electrons from ferromagnets and its application for magnetic sputter depth profiling. PMID- 10035418 TI - Exciton kinetics in ultrathin molecular wires and pores. PMID- 10035419 TI - Exciton-mediated photovoltaic effect in Cu2O/Cu. PMID- 10035420 TI - Quantum fluctuations of the superconducting cosmic string. PMID- 10035421 TI - Comment on "Interstitial hydrogen and neutralization of shallow-donor impurities in single-crystal silicon" PMID- 10035422 TI - Johnson, Herring, and Chadi reply. PMID- 10035423 TI - Comment on "Generation of superfluid turbulence deduced from simple dynamical rules" PMID- 10035424 TI - Schwarz replies. PMID- 10035425 TI - Comment on "So-called icosahedral and decagonal quasicrystals are twins of an 820 atom cubic crystal" PMID- 10035426 TI - Pauling replies. PMID- 10035427 TI - Comment on "Hydrodynamic behavior of fractal aggregates" PMID- 10035429 TI - Wiltzius and van Saarloos reply. PMID- 10035428 TI - Comment on "Hydrodynamic behavior of fractal aggregates" PMID- 10035431 TI - Ground state instability of a random system. PMID- 10035433 TI - Optical analog of a kicked quantum oscillator. PMID- 10035432 TI - Bistability driven by weakly colored Gaussian noise: The Fokker-Planck boundary layer and mean first-passage times. PMID- 10035434 TI - Naked singularities in self-similar spherical gravitational collapse. PMID- 10035435 TI - Intrinsic quadrupole moment of the superdeformed band in 152Dy. PMID- 10035436 TI - Nonlinear nonreciprocity and directional bistability in a ring resonator with a quadratic nonlinear medium. PMID- 10035437 TI - Transient spectra of strong-field resonance fluorescence. PMID- 10035438 TI - Squeezed-light-enhanced polarization interferometer. PMID- 10035439 TI - Demonstration of soft x-ray amplification in nickel-like ions. PMID- 10035440 TI - Laser amplification at 18.2 nm in recombining plasma from a laser-irradiated carbon fiber. PMID- 10035442 TI - Tunneling images of biatomic steps on Si(001). PMID- 10035441 TI - Steady-state tokamak discharge via dc helicity injection. PMID- 10035443 TI - Reconstruction of steps on the Si(111)2 x 1 surface. PMID- 10035445 TI - Location of atoms in the first monolayer of GaAs on Si. PMID- 10035444 TI - Direct imaging of surface reconstructions on CdTe by high-resolution electron microscopy. PMID- 10035446 TI - Finite-density Onsager-type theory for the isotropic-nematic transition of hard ellipsoids. PMID- 10035447 TI - Commensurability effects and modulated structures in polyanilines. PMID- 10035448 TI - Grazing incidence x-ray study of the structures and phase transitions of hydrogen on tungsten (100). PMID- 10035449 TI - Recursive computation of many-phonon densities of states. PMID- 10035450 TI - Distribution of barrier heights in amorphous organic materials. PMID- 10035451 TI - Explosive crystallization starting from an amorphous-silicon surface region during long pulsed-laser irradiation. PMID- 10035452 TI - Lattice theory of crystal surface melting. PMID- 10035454 TI - Mechanism of ion desorption by electronic transitions: A density-functional study. PMID- 10035453 TI - Cubic anharmonicity and strong sidebands: An experimental test for vibrational phase relaxation at surfaces? PMID- 10035455 TI - Optical measurements on oriented thin YBa2Cu3O7- delta films: Lack of evidence for excitonic superconductivity. PMID- 10035456 TI - Determination of intervalley scattering rates in GaAs by subpicosecond luminescence spectroscopy. PMID- 10035458 TI - Generalization of back-propagation to recurrent neural networks. PMID- 10035457 TI - New method to study the proximity effect at the normal-metal-superconductor interface. PMID- 10035459 TI - Comments on skyrmion mass calculation in the gauged chiral model. PMID- 10035460 TI - Zahed replies. PMID- 10035461 TI - Lacombe et al. reply. PMID- 10035463 TI - Clarke and Merlin reply. PMID- 10035462 TI - Comment on "Synchrotron x-ray study of a Fibonacci superlattice" PMID- 10035464 TI - Comment on "Ionization energies of valence levels in physisorbed rare-gas multilayers" PMID- 10035466 TI - Scaling structure of attractors at the transition from quasiperiodicity to chaos in electronic transport in Ge. PMID- 10035467 TI - Molecular Kramers degeneracy and non-Abelian adiabatic phase factors. PMID- 10035468 TI - Interpretation of the energy of the vacuum as the sum over zero-point energies. PMID- 10035469 TI - Lorentzian algebra for the superstring. PMID- 10035470 TI - Surface terms in the cubic action. PMID- 10035472 TI - QCD enhancement of radiative B decays. PMID- 10035471 TI - Cancellation of dilaton tadpoles and two-loop finiteness in SO(32) type-I superstring theory. PMID- 10035473 TI - Prediction of B-->K gamma as a test of the standard model. PMID- 10035475 TI - Stable (Na19)2 as a giant alkali-metal-atom dimer. PMID- 10035476 TI - Self-induced spatial disorder in a nonlinear optical system. PMID- 10035474 TI - Study of the KK-bar pi final state in J/ psi hadronic decays. PMID- 10035477 TI - Squeezed-state generation by the normal modes of a coupled system. PMID- 10035478 TI - Radiation focusing and guiding with application to the free electron laser. PMID- 10035479 TI - Effect of variable eigenmode excitation on rf stabilization of a mirror plasma. PMID- 10035480 TI - Reverse anisotropy of the diffusion coefficients in a polymeric nematic medium. PMID- 10035481 TI - Si--> PMID- 10035483 TI - Explanation of peak shapes observed in diffraction from icosahedral quasicrystals. PMID- 10035482 TI - Pressure dependence of elementary excitations in normal liquid helium-3. PMID- 10035484 TI - Influence of valence, electronegativity, atomic radii, and crest-trough interaction with phonons on the high-temperature copper oxide superconductors. PMID- 10035485 TI - Antiferromagnetism, localization, and pairing in a two-dimensional model for CuO2. PMID- 10035486 TI - Mass renormalizations and superconductivity in heavy-fermion UPt3. PMID- 10035487 TI - Image charge effects in electron stimulated desorption: O- from O2 condensed on Ar films grown on Pt. PMID- 10035488 TI - Electronic structure of the neutral manganese acceptor in gallium arsenide. PMID- 10035489 TI - Proposed decorated lattice-gas model of H/Pd(100). PMID- 10035490 TI - Comment on "Gelation of colloidal silica" PMID- 10035491 TI - Dietler Iet al.P reply. PMID- 10035493 TI - Dynamical superalgebra and supersymmetry for a many-fermion system. PMID- 10035494 TI - Quark-number susceptibility of high-temperature QCD. PMID- 10035496 TI - Determination of the pp pi 0 coupling constant and breaking of charge independence. PMID- 10035495 TI - Consequences of the Kawarabayashi-Suzuki-Riazuddin-Fayyazuddin relation in the strongly interacting Higgs model. PMID- 10035498 TI - Ground states of Ca- and Sc- from two theoretical points of view. PMID- 10035497 TI - Missing-energy dependence of the separated response functions for the 12C(e,e'p) reaction. PMID- 10035499 TI - Evidence for a stable negative ion of calcium. PMID- 10035500 TI - Observation of radiative electron capture into K,L,M shells of 25-MeV/u Xe53+ ions channeled in silicon. PMID- 10035501 TI - New constraints on time-reversal asymmetry from a search for a permanent electric dipole moment of 199Hg. PMID- 10035502 TI - New oscillatory structure in electron energy spectra from autoionizing quasi molecules: Subthermal collisions of He(2(3)S) atoms with He(2(1)S,2(3)S) atoms. PMID- 10035504 TI - First-principles examination of hydrogen bonds: Polymeric hydrogen fluoride. PMID- 10035503 TI - Dynamics of collisional excitation x-ray lasers. PMID- 10035505 TI - Photodetachment threshold shift in a strong laser field. PMID- 10035506 TI - Impedance characteristics of applied-B ion diodes. PMID- 10035507 TI - Large-Larmor-radius interchange instability. PMID- 10035509 TI - Missing-row surface reconstruction of Ag(110) induced by potassium adsorption. PMID- 10035508 TI - Persistent density perturbations at rational-q surfaces following pellet injection in the Joint European Torus. PMID- 10035510 TI - Dimensionality crossover in superconducting wire networks. PMID- 10035512 TI - Size dependence of the gradual transition to metallic properties in isolated mercury clusters. PMID- 10035511 TI - Stability of the dense radial morphology in diffusive pattern formation. PMID- 10035513 TI - Thermodynamic perturbation scheme for the ground-state energy of Lennard-Jones bosons. PMID- 10035514 TI - Dynamics of spreading phenomena in two-dimensional Ising models. PMID- 10035515 TI - Registration and nucleation of the Ag/Si(111)( sqrt 3 x sqrt 3)R30 degrees structure by scanning tunneling microscopy. PMID- 10035516 TI - Role of spin exchange in elastic electron scattering from magnetic surfaces. PMID- 10035517 TI - Linewidth dependence of radiative exciton lifetimes in quantum wells. PMID- 10035518 TI - Resonant electron scattering due to the central cells of impurities observed in AlGaAs under hydrostatic pressure. PMID- 10035519 TI - Experimental evidence for a nontrivial number of scattering channels in a dilute alloy. PMID- 10035520 TI - Measurement of the sliding charge-density-wave phase velocity in Rb0.3MoO3. PMID- 10035522 TI - Tunneling escape rate of electrons from quantum well in double-barrier heterostructures. PMID- 10035521 TI - f-sum rule and effective masses in superlattices. PMID- 10035523 TI - Density-functional theory in strong magnetic fields. PMID- 10035525 TI - Constraints on the lifetime of massive neutrinos from SN1987A. PMID- 10035524 TI - Mixed phase of spin-glass ordering and antiferromagnetism in an Ising system, FexMn1-xTiO3. PMID- 10035526 TI - Galaxy and structure formation with hot dark matter and cosmic strings. PMID- 10035527 TI - Natural quantum state of matter fields in quantum cosmology. PMID- 10035528 TI - Comment on "Spinning cosmic strings and quantization of energy" PMID- 10035530 TI - Comment on "Possible manifestation of quark-gluon plasma in multiplicity distributions from high-energy reactions" PMID- 10035529 TI - Mazur replies. PMID- 10035531 TI - Fowler et al. reply. PMID- 10035532 TI - Neutrinoless double- beta decay and pion double charge exchange. PMID- 10035533 TI - Fazely and Liu reply. PMID- 10035535 TI - Comment on "Ultrasound as a sensitive probe of f-wave pairing fluctuations in 3He A" PMID- 10035534 TI - Triplet and higher-order direct correlation functions in dense fluids. PMID- 10035536 TI - Wojtanowski and Wolfle reply. PMID- 10035539 TI - World-sheet action for the three-dimensional Ising model. PMID- 10035538 TI - Parametrization of the space of solutions of Einstein's equations. PMID- 10035541 TI - Charge-nonconserving decays. PMID- 10035540 TI - Lattice fermions. PMID- 10035542 TI - Unitarity bound on the scale of fermion mass generation. PMID- 10035543 TI - Understanding electroweak couplings of the pion as a qq-bar composite. PMID- 10035544 TI - Observation of Omega - production in e+e- annihilation at 29 GeV. PMID- 10035545 TI - Population and decay of the superdeformed rotational band of 152Dy. PMID- 10035546 TI - Relativistic mean-field theory and nuclear deformation. PMID- 10035547 TI - Measurement of nuclear time-delay effects in delta -electron emission. PMID- 10035548 TI - Observation of asymmetric Stark profiles from plasmas created by a picosecond KrF laser. PMID- 10035549 TI - External modulation of Rayleigh-Benard convection. PMID- 10035550 TI - Direct evidence of a stretched C-C distance for C2H2 and C2H4 on Cu(100) at 60 K. PMID- 10035551 TI - Renormalization-group treatment of the beta -incommensurate transition in quartz and berlinite. PMID- 10035552 TI - Observation of substitutional site preference in a quasicrystal and implication on local structure. PMID- 10035554 TI - New approach to calculation of total energies of solids with defects: Surface energy anisotropies. PMID- 10035553 TI - Roughening transition of a stepped Cu(113) surface: A synchrotron x-ray scattering study. PMID- 10035555 TI - Critical stresses for SixGe PMID- 10035556 TI - Photoexcited coherent tunneling in a double-barrier superlattice. PMID- 10035557 TI - Direct evidence for perpendicular spin orientations and enhanced hyperfine fields in ultrathin Fe(100) films on Ag(100). PMID- 10035558 TI - Generalized cooperative-ring-exchange theory of the fractional quantum Hall effect. PMID- 10035559 TI - Electronic properties of antimony chalcogenides. PMID- 10035560 TI - Random-matrix theory and universal statistics for disordered quantum conductors. PMID- 10035561 TI - Electronic structure of disordered CuPd alloys: A two-dimensional positron annihilation study. PMID- 10035562 TI - Magnetism of epitaxial bcc iron on Ag(001) observed by spin-polarized photoemission. PMID- 10035563 TI - Instability and deformation of a spherical vesicle by pressure. PMID- 10035564 TI - Early-Universe thermal production of not-so-invisible axions. PMID- 10035565 TI - Variational study of ordinary and superconducting cosmic strings. PMID- 10035566 TI - Comment on "Two-dimensional antiferromagnetic quantum spin-fluid state in La2CuO PMID- 10035568 TI - Reversible cellular automata and statistical mechanics. PMID- 10035569 TI - Generic 1/f noise in chaotic Hamiltonian dynamics. PMID- 10035571 TI - Heterotic-string Lagrangean in the bosonic formulation. PMID- 10035570 TI - Local quantum field theory of possible violation of the Pauli principle. PMID- 10035572 TI - Light-neutrino masses and the strong CP problem. PMID- 10035573 TI - Measurement of the tau -lepton lifetime. PMID- 10035575 TI - Minijet production in high-energy nucleus-nucleus collisions. PMID- 10035574 TI - Search for highly ionizing particles at the Fermilab proton-antiproton collider. PMID- 10035576 TI - Search for quark-gluon plasma in nucleus-nucleus collisions at 3.2 TeV. PMID- 10035577 TI - Charges and angular distributions of fast fragments produced in 3.2-TeV 16O collisions with Pb. PMID- 10035578 TI - Unitary symmetry and the stability of Sigma hypernuclei. PMID- 10035579 TI - Forward- and backward-angle differential cross section for 2H PMID- 10035580 TI - Spontaneous emission of radiation in the presence of a phase-conjugate mirror. PMID- 10035581 TI - Observation of the transition state HD2++ in collisions, H PMID- 10035583 TI - Resonant multiphoton ionization of krypton by intense uv laser radiation. PMID- 10035582 TI - Observation of quantum noise reduction on twin laser beams. PMID- 10035584 TI - Stability of doubly charged transition-metal dimers. PMID- 10035586 TI - Perfect wave-number selection and drifting patterns in ramped Taylor vortex flow. PMID- 10035585 TI - Pulsed squeezed light. PMID- 10035587 TI - Structural transition on cooling of plastic adamantane: A molecular-dynamics study. PMID- 10035589 TI - Defect core structure in nematic liquid crystals. PMID- 10035588 TI - Preroughening transitions in surfaces. PMID- 10035590 TI - Evidence for anomalous diffusion in a conducting polymer. PMID- 10035591 TI - Femtosecond studies of coherent transients in semiconductors. PMID- 10035593 TI - Finite-size effects in a CuMn spin-glass. PMID- 10035592 TI - Observation of hexagonally correlated flux quanta in YBa2Cu PMID- 10035594 TI - Study of dynamics of microemulsion droplets by neutron spin-echo spectroscopy. PMID- 10035595 TI - Search for high-energy neutrinos from SN1987A: First six months. PMID- 10035596 TI - Anthropic bound on the cosmological constant. PMID- 10035597 TI - Comment on "Diffraction-free beams" PMID- 10035598 TI - Durnin, Miceli, and Eberly reply. PMID- 10035599 TI - Comment on "Coulomb energy in pseudobinary alloys" PMID- 10035600 TI - van Schilfgaarde, Chen, and Sher reply. PMID- 10035601 TI - Comment on "Bulk superconductivity at 91 K in single-phase oxygen-deficient perovskite YBa2Cu3O9- delta " PMID- 10035602 TI - Batlogg et al. reply. PMID- 10035603 TI - Pairing in fermion systems. PMID- 10035604 TI - Hirsch replies. PMID- 10035606 TI - Vacuum radiative level shift and spontaneous-emission linewidth of an atom in an optical resonator. PMID- 10035605 TI - Torsion constraints and super Riemann surfaces. PMID- 10035607 TI - Time-dependent density-functional theory in the linear-response regime. PMID- 10035608 TI - Trapping of neutral sodium atoms with radiation pressure. PMID- 10035610 TI - Evolution of polarization in localized nonlinear Alfven waves. PMID- 10035609 TI - Study of fuel-pusher mixing in laser-driven implosions, using secondary nuclear fusion reactions. PMID- 10035611 TI - Neoclassical diffusion of heavy impurities in a rotating tokamak plasma. PMID- 10035612 TI - Nonlinear state of m=1 instability in tokamaks with nonmonotonic q profiles. PMID- 10035613 TI - Nonlinear evolution of the internal kink in tokamaks. PMID- 10035614 TI - Theory of the stripe phase in bend-Freedericksz-geometry nematic films. PMID- 10035615 TI - "Chevron" local layer structure in surface-stabilized ferroelectric smectic-C cells. PMID- 10035616 TI - Elastic constants of crystals from linear-response theory. PMID- 10035617 TI - Application of the embedded-atom method to covalent materials: A semiempirical potential for silicon. PMID- 10035618 TI - Pressure-induced structural phase transitions in solid xenon. PMID- 10035619 TI - New view of entanglements in dense polymer systems. PMID- 10035620 TI - Crystal-face dependence of surface melting. PMID- 10035621 TI - Light-scattering study of bond orientational order in a tilted hexatic liquid crystal film. PMID- 10035622 TI - Study of solid-liquid interfaces during solidification, using ultrasonic waves. PMID- 10035623 TI - Many-body effects in a modulation-doped semiconductor quantum well. PMID- 10035624 TI - Barrier-bound resonances in semiconductor superlattices in strong magnetic fields. PMID- 10035626 TI - Ferroelectric transition in Pb1-xGexTe: Extended x-ray-absorption fine-structure investigation of the Ge and Pb sites. PMID- 10035625 TI - Apparent destruction of superconductivity in the disordered one-dimensional limit. PMID- 10035627 TI - Statistical fine structure of inhomogeneously broadened absorption lines. PMID- 10035628 TI - Extension of "Four-dimensional eikonal theory of linear mode conversion" to parametrically unstable media. PMID- 10035629 TI - Measurements of the Sigma 0c- Lambda c+ and Sigma c++- Lambda c+ mass differences. PMID- 10035630 TI - Search for spontaneous conversion of muonium to antimuonium. PMID- 10035631 TI - Fragment flow in nuclear collisions. PMID- 10035632 TI - Effect of surface fluctuations on the nuclear density. PMID- 10035634 TI - Radiative decay rates in Hg+ from observations of quantum jumps in a single ion. PMID- 10035633 TI - Nonthermal intramolecular vibrational energy distribution in infrared-multiphoton excited CF2Cl PMID- 10035635 TI - Strong correlation and alignment near the Be 1s photoionization threshold. PMID- 10035637 TI - Observaton of envelope solitons in solids. PMID- 10035636 TI - Bifurcation of quasiperiodic and nonstationary patterns under external forcing. PMID- 10035638 TI - Enhanced velocity diffusion along electron-cyclotron-resonance heating characteristics observed in hot electron energy spectra in the plasma loss cone. PMID- 10035640 TI - Order-disorder transition of Au and Pt(110) surfaces: The significance of relaxations and vibrations. PMID- 10035639 TI - Nonlinear interaction between a warm electron beam and a single wave. PMID- 10035641 TI - Defect-induced crystal-to-amorphous transition in an atomistic simulation model. PMID- 10035642 TI - Theory of adsorbate-induced surface relaxations: Hydrogen on Cu(110). PMID- 10035643 TI - Effect of translational energy on the chemisorption of N2 on Fe(111): Activated dissociation via a precursor state. PMID- 10035644 TI - Orthorhombic distortion at the superconducting transition in YBa2Cu3O7: Evidence for anisotropic pairing. PMID- 10035645 TI - Ordering and decomposition in the high-temperature superconducting compound YBa2Cu3Ox. PMID- 10035646 TI - Bond asymmetry and high-Tc superconductivity. PMID- 10035647 TI - Fractional quantum Hall effect at half-filled Landau level in a multiple-layer electron system. PMID- 10035648 TI - CrO2-a new half-metallic ferromagnet? PMID- 10035649 TI - Observation of direct multiquantum vibrational excitation in gas-surface scattering: NH3 on Au(111). PMID- 10035650 TI - Production of free charge carriers during fracture of single-crystal silicon. PMID- 10035651 TI - Catastrophe model for micromagnetics. PMID- 10035652 TI - Capacitance oscillations in one-dimensional electron systems. PMID- 10035654 TI - Persistent photoconductivity in Si-doped AlxGa PMID- 10035653 TI - Observation of magnetoquantized interface states by electron tunneling in single barrier n-(InGa)As-InP-n+(InGa)As heterostructures. PMID- 10035655 TI - Statistical treatment of fluctuations in the gravitational focusing of light due to stellar masses within a gravitational lens. PMID- 10035656 TI - Pole structures in nuclear and particle physics. PMID- 10035657 TI - Hale, Brown, and Jarmie reply. PMID- 10035658 TI - Comment on "Modification of the electron-phonon interactions in GaAs-GaAlAs heterojunctions" PMID- 10035659 TI - Brummell et al. reply. PMID- 10035660 TI - Optical mode in tilted hexatics. PMID- 10035661 TI - Comment on "Phase change during a cyclic quantum evolution" PMID- 10035663 TI - Davey-Stewartson I system: A quantum (2+1)-dimensional inte- grable system. PMID- 10035664 TI - Exact construction of (0,2) Calabi-Yau manifolds. PMID- 10035665 TI - Search for short-lived neutral particles emitted in K+ decay. PMID- 10035666 TI - Dynamics of skyrmion collisions in 3+1 dimensions. PMID- 10035667 TI - Cross section and T20 in 0 degrees deuteron breakup at 2.1 GeV. PMID- 10035668 TI - Correlated fragment production in 18O-induced reactions at E/A=84 MeV. PMID- 10035669 TI - Causes for nuclear collective flow revealed by its mass dependence. PMID- 10035670 TI - Strong energy dependence of the optical potential for 32S PMID- 10035671 TI - Asymmetric fission of 56Ni. PMID- 10035672 TI - Giant dipole resonance in highly excited thorium: Evidence for strong fission hindrance. PMID- 10035673 TI - Determination of muonic helium x-ray yields after muon-catalyzed pd, dd, and dt fusion. PMID- 10035675 TI - Half width of neutron spectra. PMID- 10035674 TI - Origin of chaotic relaxation oscillations in an optically pumped molecular laser. PMID- 10035676 TI - Metastable state of EL2 in GaAs. PMID- 10035677 TI - Observation of atomic corrugation on Au(111) by scanning tunneling microscopy. PMID- 10035678 TI - Structural change induced by electronic excitation on GaP surfaces. PMID- 10035679 TI - Atomic structure of symmetric tilt grain boundaries in NiO. PMID- 10035680 TI - Chaotic transients and multiple attractors in spin-wave experiments. PMID- 10035681 TI - Spatiotemporal observation of the soliton-antisoliton collision in a Josephson transmission line. PMID- 10035682 TI - Discovery of polyexcitons. PMID- 10035683 TI - Effect of entanglements on polymer reaction rates. PMID- 10035684 TI - Optical observation of angular momentum alignment in a heat-conducting gas. PMID- 10035685 TI - Exact Lyapunov dimension of the universal attractor for the complex Ginzburg Landau equation. PMID- 10035687 TI - Out-of-plane measurement of the D(e,e'p) coincidence cross section. PMID- 10035686 TI - Search for sequential heavy leptons in e+e- collisions at the energy sqrt s =52 GeV. PMID- 10035688 TI - Measurement of the anomalous neutron orbital g factor in 190mOs. PMID- 10035689 TI - Localization of diffusive excitation in the two-dimensional hydrogen atom in a monochromatic field. PMID- 10035690 TI - Observation of a phase transition of stored laser-cooled ions. PMID- 10035691 TI - Atomic ion Coulomb clusters in an ion trap. PMID- 10035693 TI - Model of an H2-precursor state on metal surfaces. PMID- 10035692 TI - Influence of coherence on associative ionization in Na(3p)+Na PMID- 10035694 TI - Spectroscopy of Rydberg atoms at n PMID- 10035695 TI - Asymmetry of the polarized-laser-induced photofragmentation of oriented CH3I molecules. PMID- 10035696 TI - Anomalous spontaneous emission time in a microscopic optical cavity. PMID- 10035697 TI - Oscillator strengths for the alkaline-earth atoms using rotor-vibrator and configuration-interaction wave functions. PMID- 10035698 TI - Resonant vacuum-ultraviolet photoelectron spectra of aligned Li atoms. PMID- 10035699 TI - Dynamic capillary pressure in porous media: Origin of the viscous-fingering length scale. PMID- 10035700 TI - Theory and simulation of the Rayleigh-Taylor instability in the large Larmor radius. PMID- 10035701 TI - Measurement of the anisotropic temperature relaxation rate in a pure electron plasma. PMID- 10035702 TI - Nonlinear wave propagation in Fermi liquids with resonant excitations across an energy gap: Application to superfluid 3He. PMID- 10035703 TI - Finite-size scaling and critical nucleation. PMID- 10035704 TI - Solid-state amorphization of Zr3Al: Evidence of an elastic instability and first order phase transformation. PMID- 10035705 TI - Onset of magnetic correlations in CeAl3 below 2 K. PMID- 10035707 TI - Dynamical properties of quantum many-body systems at zero temperature. PMID- 10035706 TI - Time-resolved continuum-edge-shift measurements in laser-shocked solids. PMID- 10035708 TI - Discrete valence-electron states in thin metal overlayers on a metal. PMID- 10035709 TI - Local density of states at Fermi energy for Li atoms adsorbed on metal surfaces. PMID- 10035712 TI - Manifestation of Berry's topological phase in neutron spin rotation. PMID- 10035710 TI - Quenching of the Hall effect in a one-dimensional wire. PMID- 10035713 TI - Classical resonance overlapping and quantum avoided crossings. PMID- 10035714 TI - Excitation spectrum of the spin-(1/2 Heisenberg chain and conformal invariance. PMID- 10035715 TI - Decay width and the shift of a quasistationary state. PMID- 10035716 TI - Observation of Bhabha scattering in the center-of-mass kinetic-energy range 342 to 845 keV. PMID- 10035718 TI - Above-threshold ionization with elliptically polarized light. PMID- 10035717 TI - Superdeformed bands at high spin in Z=66 and 68 isotopes. PMID- 10035719 TI - Precision measurement beyond the shot-noise limit. PMID- 10035720 TI - Forced phase diffusion in a convection experiment. PMID- 10035721 TI - Intensity correlation functions and fluctuations in light scattered from a random medium. PMID- 10035722 TI - Gigawatt-level microwave bursts from a new type of virtual cathode oscillator. PMID- 10035723 TI - Observation of steepening in electron plasma waves driven by stimulated Raman backscattering. PMID- 10035724 TI - Formation of a metastable ordered surface phase due to competitive diffusion and adsorption kinetics: Oxygen on Pd(100). PMID- 10035725 TI - Hierarchical random surfaces. PMID- 10035726 TI - Thermal roughening of the copper (110) surface: An x-ray diffraction experiment. PMID- 10035727 TI - Ion channeling and catastrophe theory. PMID- 10035728 TI - Are surface-atom vibrational amplitudes along the normal always larger than in the plane? PMID- 10035730 TI - X-ray emission from core excitons. PMID- 10035729 TI - Scaling in the ordering kinetics of a chemisorbed overlayer: W(110)-p(21)O. PMID- 10035731 TI - Fermi-liquid theory of interacting disordered systems and the scaling theory of the metal-insulator transition. PMID- 10035732 TI - Observations of bistability effects in electron paramagnetic resonance experiments. PMID- 10035733 TI - Determination of xenon valence and conduction bands by spin-polarized photoemission. PMID- 10035734 TI - Magnetoelastic properties of single-S, single-Q chromium. PMID- 10035735 TI - Inelastic electron tunneling from a metal tip: The contribution from resonant processes. PMID- 10035736 TI - Novel ferroelectric fluids. PMID- 10035737 TI - Pressure-induced suppression of the proton-glass phase and isotope effects in Rb1 x(NH4)xH2PO4. PMID- 10035738 TI - Temperature-induced magnetism in FeSi. PMID- 10035739 TI - Nuclear Bragg scattering of synchrotron radiation with strong speedup of coherent decay, measured on antiferromagnetic 57FeBO PMID- 10035740 TI - Exact solution of a layered neural network model. PMID- 10035742 TI - Physical implications of the Kamioka observation of neutrinos from supernova 1987A. PMID- 10035741 TI - Cluster-size evolution in a coagulation-fragmentation system. PMID- 10035743 TI - Field-theoretical approach to the dynamical many-polaron system in one spatial dimension. PMID- 10035744 TI - Marino replies. PMID- 10035745 TI - Intractable computations without local minima. PMID- 10035746 TI - Comment on "Intractable computations without local minima" PMID- 10035747 TI - Baum replies. PMID- 10035748 TI - Comment on "Electron-electron scattering in nondegenerate semiconductors" PMID- 10035749 TI - Wingreen, Stanton, and Wilkins reply. PMID- 10035750 TI - Energy comparison of SU(2) vortex solution in two different Ansatze. PMID- 10035751 TI - de Vega and Schaposnik reply. PMID- 10035752 TI - Comment on"Realistic calculation of the indirect-exchange interaction in metals" PMID- 10035754 TI - Self-organized criticality: An explanation of the 1/f noise. PMID- 10035755 TI - Nonlinear realization of heavy fermions and effective Lagrangean. PMID- 10035757 TI - Universal seesaw mechanism? PMID- 10035756 TI - Discriminating technicolor theories through flavor-changing neutral currents: Slowly varying or fixed coupling constants? PMID- 10035759 TI - Hadronic spectrum of the quark plasma. PMID- 10035758 TI - Axion production by electromagnetic fields. PMID- 10035760 TI - Is there Koba-Nielsen-Olesen scaling at Fermilab Tevatron collider energies (1600 2000 GeV)? PMID- 10035761 TI - Gamma (b-->ul nu )/ Gamma (b-->cl nu ) from the end point of the lepton momentum spectrum in semileptonic B decay. PMID- 10035762 TI - Study of tau decay modes with multiple neutral mesons in the final states. PMID- 10035764 TI - Limits on neutrinoless beta beta decay, including that with majoron emission. PMID- 10035765 TI - Nucleon compositeness and relativistic phenomena in nuclear physics. PMID- 10035763 TI - Precise measurement of the lifetime of the tau lepton. PMID- 10035766 TI - y scaling in electron-nucleus scattering. PMID- 10035767 TI - Giant M1 resonance in 90Zr. PMID- 10035768 TI - New test of the reduced-width-amplitude distribution. PMID- 10035769 TI - Gamow-Teller strength deduced from 54Fe(n,p) 54Mn cross sections at 298 MeV. PMID- 10035770 TI - Finite-PT contribution to relativistic Coulomb excitation: A possible explanation for the clean-fission puzzle. PMID- 10035771 TI - Observation of surface light-induced drift. PMID- 10035772 TI - Regime of improved confinement in neutral-beam-heated limiter discharges of a tokamak. PMID- 10035773 TI - Surface fractals in irreversible aggregation. PMID- 10035774 TI - Photovoltaic effect on fast mixed conductor LiAl. PMID- 10035775 TI - Ultrasonic spectroscopy of the J=1(-) collective mode in superfluid 3He-B. PMID- 10035777 TI - Theory of hopping motion of a heavy particle interacting with a degenerate electron gas. PMID- 10035776 TI - Momentum transfer between 3He quasiparticles and surfaces: The effective viscosity of dilute solutions of 3He in 4He. PMID- 10035778 TI - Electrical properties of semimetallic silicon III and semiconductive silicon IV at ambient pressure. PMID- 10035779 TI - Thermal conductivity in disordered interacting-electron systems. PMID- 10035781 TI - Effective mass and lifetime of electrons in a layered electron gas. PMID- 10035782 TI - Charging energy and phase delocalization in single very small Josephson tunnel junctions. PMID- 10035780 TI - Magnetostatic soliton propagation at microwave frequency in magnetic garnet films. PMID- 10035784 TI - Exact electron-gas response functions at high density. PMID- 10035783 TI - Spectral evidence for the importance of single-site effects in heavy-fermion uranium materials. PMID- 10035785 TI - Band-edge hydrostatic deformation potentials in III-V semiconductors. PMID- 10035786 TI - Electron-stimulated desorption enhanced by coherent scattering. PMID- 10035788 TI - Long-period structures in alloys. PMID- 10035787 TI - Soliton pinning in polyacetylene revealed by multiple-quantum spin coherences. PMID- 10035789 TI - Bruinsma and Zangwill reply. PMID- 10035790 TI - Are TiH2 aggregates fractal? PMID- 10035791 TI - Mangin, Rodmacq, and Chamberod reply: PMID- 10035793 TI - Comment on "Resonant microwave absorption by dissolved DNA" PMID- 10035792 TI - Comment on "Novel magnetoacoustic effects in heavy-fermion systems in high magnetic fields" PMID- 10035795 TI - Space-time as a causal set. PMID- 10035797 TI - Simple discrete symmetries in phenomenologically viable E6 superstring models. PMID- 10035796 TI - Relativistic, many-particle Lagrangean for electromagnetic interactions. PMID- 10035798 TI - Operator regularization of Green's functions. PMID- 10035799 TI - First observation of a near-harmonic vibrational nucleus. PMID- 10035800 TI - Exact tricritical exponents for polymers at the FTHETA point in two dimensions. PMID- 10035801 TI - Squeezing of spontaneous emission in a laser. PMID- 10035802 TI - Single-mode operation of a high-power, step-tunable gyrotron. PMID- 10035803 TI - Chaotic behavior and period doubling in plasmas. PMID- 10035804 TI - Wetting phenomena of binary liquid mixtures on chemically altered substrates. PMID- 10035805 TI - Role of multiple scattering in x-ray photoelectron spectroscopy and Auger electron diffraction in crystals. PMID- 10035806 TI - An inference of high atom densities in solid tritium for nuclear magnetic resonance measurements. PMID- 10035807 TI - Phonon ringing and anharmonicity effects in core spectra. PMID- 10035808 TI - Ab initio determination of a structural phase transition temperature. PMID- 10035809 TI - Mode anharmonicity in molecular crystals studied by piezomodulated Raman spectrosocpy. PMID- 10035810 TI - Spin localization in Si:P-direct evidence from 31P NMR. PMID- 10035811 TI - Two-dimensional open-orbit edge states: A new type of quantum oscillation. PMID- 10035813 TI - New configuration-coordinate model for the ground, excited, and metastable states of EL2 in GaAs. PMID- 10035812 TI - Nature of the Griffiths phase. PMID- 10035814 TI - Test for low-Q, "infrared" spin-fluctuation effects in heavy fermions and 3He. PMID- 10035816 TI - Comment on "Excitonic coupling in GaAs/GaAlAs quantum wells in an electric field" PMID- 10035815 TI - Optical pair interactions in the four-wave mixing spectrum of Nd3+-doped beta " Na-alumina. PMID- 10035817 TI - Vin PMID- 10035818 TI - Raman scattering from fractal structures. PMID- 10035819 TI - Boukenter Iet al.P reply. PMID- 10035820 TI - Comment on "Signature of g boson in the interacting-boson model from g-factor variations" PMID- 10035822 TI - Necessity of three or more generations for calculable Dirac neutrino masses in E6 superstring models. PMID- 10035821 TI - Comment on "Large intensity fluctuations for wave propagation in random media" PMID- 10035825 TI - Observation of deterministic chaos in electrical discharges in gases. PMID- 10035824 TI - Galilean test for the fifth force. PMID- 10035826 TI - First-order phase transition in compact lattice QED with light fermions. PMID- 10035827 TI - Exclusive charmonium decays: The J/ psi ( psi ')--> rho pi, KK-bar puzzle. PMID- 10035828 TI - E2/M1 ratio of gamma N--> Delta (1232) transitions in a relativistic three-quark model. PMID- 10035829 TI - Strangeness -3 dibaryons. PMID- 10035831 TI - Reconstructing the nuclear profile in gauge space. PMID- 10035830 TI - Change of collective-flow mechanism indicated by scaling analysis of transverse flow. PMID- 10035832 TI - Dissociative attachment from condensed O2: Violation of the selection rule Sigma Sigma + PMID- 10035834 TI - Opening of new decay channels for core-excited resonances. PMID- 10035833 TI - Low-energy scattering of electrons on positronium atoms. PMID- 10035835 TI - Mechanism for rapid sawtooth crashes in tokamaks. PMID- 10035837 TI - Renormalized acoustic branch in the vibrational spectrum of the pi -bonded-chain model of Si(111)21. PMID- 10035836 TI - Observation of high-energy electrons accelerated by electrostatic waves propagating obliquely to a magnetic field. PMID- 10035838 TI - Structure of liquid As: A Peierls distortion in a liquid. PMID- 10035839 TI - Strain in ultrathin epitaxial films of Ge/Si(100) measured by ion scattering and channeling. PMID- 10035840 TI - Kinetics of phase separation in Mn0.67Cu PMID- 10035841 TI - Magnetic trapping of spin-polarized atomic hydrogen. PMID- 10035843 TI - Spinodal decomposition for Langevin equations. PMID- 10035842 TI - Spin-polarized deuterium in magnetic traps. PMID- 10035844 TI - Quasielastic light-scattering study of the movement of particles in gels. PMID- 10035846 TI - Direct determination of the probability distribution function of concentration in polymer mixtures undergoing phase separation. PMID- 10035845 TI - Band tails, entropy, and equilibrium defects in hydrogenated amorphous silicon. PMID- 10035847 TI - Time-resolved Raman scattering in GaAs quantum wells. PMID- 10035848 TI - Resonant Raman scattering by phonons in a strong magnetic field: GaAs. PMID- 10035850 TI - Experimental evidence for spin-energy coupling in CsNiF3. PMID- 10035849 TI - Comparative study of superconducting energy gaps in oriented films and polycrystalline bulk samples of Y-Ba-Cu-O. PMID- 10035851 TI - Magnetic excitations in commensurable periodic structures. PMID- 10035852 TI - Nonequilibrium longitudinal-optical phonon effects in GaAs-AlGaAs quantum wells. PMID- 10035853 TI - Positron-annihilation study of the electronic structure of Cu91Ge PMID- 10035854 TI - Coherent double-plasmon excitation in aluminum. PMID- 10035855 TI - Discontinuous metal-insulator transitions and Fermi-liquid behavior of correlated electrons. PMID- 10035857 TI - Type II supernovae from prompt explosions. PMID- 10035856 TI - Quantum transport in an electron-wave guide. PMID- 10035858 TI - Gravitational stability of local strings. PMID- 10035860 TI - Observations of fractal patterns induced in thin solid films by ion irradiation. PMID- 10035861 TI - Semiclassical quantization of classically chaotic systems. PMID- 10035862 TI - Experimental limit on the decay tau ---> nu tau K-K0. PMID- 10035864 TI - Proposed experiment to produce and detect light pseudoscalars. PMID- 10035863 TI - Search for short-lived axions in an electron-beam-dump experiment. PMID- 10035865 TI - Pole structure of the J pi =3/2(+) resonance in 5He. PMID- 10035866 TI - Observation of a quasifree three-nucleon-absorption mode of pions in 4He. PMID- 10035867 TI - Direct measurement of nuclear magnetic moments of radium isotopes. PMID- 10035868 TI - Dynamical suppression of spontaneous emission. PMID- 10035869 TI - Decay induced narrow resonances in backward nearly degenerate four-wave mixing spectroscopy. PMID- 10035870 TI - Histograms of helicity and strain in numerical turbulence. PMID- 10035871 TI - H- formation process in a multicusp ion source. PMID- 10035872 TI - Direct detection of neutral atoms photodesorbed from monolayers and multilayers of rare gases on a metal surface by excitonic and ionic primary processes. PMID- 10035873 TI - Nature of surface-phonon anomalies in noble metals. PMID- 10035874 TI - Rigorous results on valence-bond ground states in antiferromagnets. PMID- 10035876 TI - Observation of the incremental charging of Ag particles by single electrons. PMID- 10035875 TI - Accurate estimate of nu for the three-dimensional Ising model from a numerical measurement of its partition function. PMID- 10035877 TI - Surface states of excess electrons on water clusters. PMID- 10035878 TI - Investigation of the DX center in heavily doped n-GaAs. PMID- 10035879 TI - Theory of quasiparticle energies in alkali metals. PMID- 10035880 TI - Localization, hopping, and diffusion of electrons in molten salts. PMID- 10035881 TI - Quantum saturation of a Bose gas: Excitons in Cu2O. PMID- 10035883 TI - Observation of resonant electron transmission through a Ni/Cu/Ni(100) sandwich structure. PMID- 10035882 TI - Electron correlation and bond alternation in polymers. PMID- 10035884 TI - Limits on the abundance and coupling of cosmic axions at 4.5