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Biomedical subjects

J Bernstein

Publications and source records attributed to J Bernstein.

At least 55 records · Page 3Linked to original sources

Antibacterial agents that inhibit two-component signal transduction systems.

A class of antibacterials has been discovered that inhibits the growth of Gram-positive pathogenic bacteria. RWJ-49815, a representative of a family of hydrophobic tyramines, in addition to being a potent bactericidal Gram-positive antibacterial, inhibits the autophosphorylation of kinase A of the KinA::Spo0F two-component signal transduction system in vitro. Analogs of RWJ-49815 vary greatly in their ability to inhibit growth of bacteria and this ability correlates directly with their activity as kinase A inhibitors. Compared with the potent quinolone, ciprofloxacin, RWJ-49815 exhibits reduced resistance emergence in a laboratory passage experiment. Inhibition of the histidine protein kinase::response regulator two-component signal transduction pathways may present an opportunity to depress chromosomal resistance emergence by targeting multiple proteins with a single inhibitor in a single bacterium. Such inhibitors may represent a class of antibacterials that potentially may represent a breakthrough in antibacterial therapy.

Anti-Bacterial Agents↗

Diffuse renal cystic disease in children: morphologic and genetic correlations.

During a 5-year period, we evaluated seven infants and two fetuses who presented with enlarged, hyperechoic kidneys. In each, the initial clinical diagnosis was autosomal recessive polycystic kidney disease (ARPKD). Among the seven unrelated infants were three Caucasian and four African-American infants. No syndromic stigmata were evident in any of these infants. At the time of the initial evaluation, the family data were incomplete for four infants. The two fetuses were presumed to be at-risk for ARPKD based on the diagnosis in previous siblings. Renal histopathology was evaluated in all nine cases and revealed a spectrum of cystic disease ranging from ARPKD to glomerulocystic kidney disease to autosomal dominant polycystic kidney disease to diffuse cystic dysplasia. In the eight cases for whom liver histopathology was available, varying degrees of biliary dysgenesis were evident. We present a detailed analysis of the key histopathological features in each case and discuss the histopathological findings in an embryological context. In addition, we address the current role of molecular genetics in the diagnostic evaluation.

Female↗

Failure to collect oocytes in assisted reproductive technology: a retrospective.

While there is much information and discussion on pregnancy failure after assisted reproductive technologies, less emphasis is placed on the failure to collect oocytes after apparently successful ovarian stimulation. This retrospective survey reviewed 4973 treatment cycles in order to obtain information about the likelihood of this event. Overall 42 women (43 treatment cycles) failed to have oocytes collected [0.86% of treatments started and 0.92% of women given human chorionic gonadotrophin (HCG)]. However, in only six cases was this failure unexpected (0.1%) with no obvious potential clinical reason (i.e. all six cases had: HCG administered; more than two follicles >15 mm in diameter; oestradiol values >2000 pmol/l; <38 years old; normal body mass index). Indifference concerning uncommon events is fraught with peril, as although rare, the particular outcome may be devastating to the individual, both economically and psychologically. Eighteen of the 42 women did not return for on-going treatment suggesting increased contact by clinic staff may be required when oocyte retrieval is not achieved. These data suggest that the failure to collect oocytes after apparently successful ovarian stimulation is rare and random. The information has proved useful in allaying the fears of couples contemplating assisted reproductive technologies.

Adult↗

Apparent renal cell carcinomas in tuberous sclerosis are heterogeneous: the identification of malignant epithelioid angiomyolipoma.

Renal epithelial tumors (carcinoma and oncocytoma) have been reported with higher a frequency than expected in patients with the tuberous sclerosis complex. However, the recent identification of a monotypic, epithelioid variant of angiomyolipoma, closely simulating renal cell carcinoma, has cast doubt on the real frequency of carcinoma. Immunohistochemical analysis with a panel of antibodies, including melanogenesis marker HMB45, can discriminate between carcinoma and carcinoma-like angiomyolipoma. We studied five tumors previously reported as carcinoma and found that only one of them showed an immunohistochemical phenotype indicative of an epithelial tumor (Ker+, HMB45-). Three tumors exhibited a phenotype compatible with the monotypic epithelioid variant of angiomyolipoma (HMB45+, Ker-), and two of the three patients died of metastatic disease. The last patient had unusual clinical features, and the tumor was positive both for HMB45 and keratin. It is concluded that (1) renal cell carcinoma is less common in tuberous sclerosis complex than previously believed, (2) some cases called renal cell carcinoma probably represent a monotypic, epithelioid variant of angiomyolipoma, and (3) epithelioid angiomyolipoma is a potentially malignant tumor with invasion and metastases. These findings indicate that all reported renal carcinomas in tuberous sclerosis complex, therefore, must be reevaluated.

Adenoma, Oxyphilic↗

Anterior cruciate ligament injury and reconstruction among university students.

The consequences of athletic injuries extend beyond the musculoskeletal system. Depression, anger, and tension have been observed in athletes with athletic injuries. It was hypothesized that among student athletes, the psychologic impact of injury may be seen as a drop in academic performance. Thirty-eight students who had an anterior cruciate ligament injury and subsequent reconstruction were evaluated retrospectively by academic transcript and questionnaire to measure their academic performance before their injury, in the semester of their injury, and in the semester after their surgery. The patients were compared with randomly selected undergraduate control subjects. To evaluate any effect of the timing of the surgery on academic performance, the patients were separated into two groups, according to the timing of their reconstruction: those who had surgery during the academic semester, and those who elected to wait for a school break. There was a significant drop in grade point average of 0.3 grade points during the semester of injury among all injured students. Compared with those who had surgery during a break, the students who had surgery during the semester received more frequently the grade of failure (6% versus 0%) or incomplete (33% versus 9%). These students also missed more school days (10.5 days versus 1.5 days) and examinations (2.2 examinations versus 0.1 examinations). Only 47% of students who had surgery during the semester were satisfied with their decision for surgical timing, compared with 96% satisfied with the timing during an academic break. Acute anterior cruciate ligament rupture, and surgical reconstruction during an academic semester, have a significant academic effect in university students.

Achievement↗

Patients with alcohol problems in the emergency department, part 1: improving detection. SAEM Substance Abuse Task Force. Society for Academic Emergency Medicine.

Medical and social problems related to alcohol use are frequently seen in the ED. Often, the tempo of emergency medicine practice seems to preclude assessment beyond that required by the acute complaint. However, detection of ED patients with alcohol problems can occur using brief screening tools. This article was developed by members of the SAEM Substance Abuse Task Force, and describes screening tools that have been used successfully to identify at-risk and dependent drinkers. Their brevity, reproducibility, and accuracy vary somewhat, but screening can be realistically performed in the busy ED setting. The early detection of patients with alcohol problems would provide the opportunity for early intervention, and may reduce subsequent morbidity and mortality in this patient population.

Adult↗

Patients with alcohol problems in the emergency department, part 2: intervention and referral. SAEM Substance Abuse Task Force. Society for Academic Emergency Medicine.

Early intervention and appropriate referral of patients with alcohol problems have the potential to reduce alcohol-related morbidity and mortality. Part 1 of this series introduced screening tools that can be applied in the ED to allow early detection of at-risk drinkers. This article was developed by members of the SAEM Substance Abuse Task Force and describes assessment and intervention techniques once the at-risk or dependent drinkers has been identified. Appropriate aftercare and referral of patients found to have alcohol problems are also discussed.

Alcoholism↗

The adequacy of medical school education in musculoskeletal medicine.

A basic familiarity with musculoskeletal disorders is essential for all medical school graduates. The purpose of the current study was to test a group of recent medical school graduates on basic topics in musculoskeletal medicine in order to assess the adequacy of their preparation in this area. A basic-competency examination in musculoskeletal medicine was developed and validated. The examination was sent to all 157 chairpersons of orthopaedic residency programs in the United States, who were asked to rate each question for importance and to suggest a passing score. To assess the criterion validity, the examination was administered to eight chief residents in orthopaedic surgery. The study population comprised all eighty-five residents who were in their first postgraduate year at our institution; the examination was administered on their first day of residency. One hundred and twenty-four (81 per cent) of the 154 orthopaedic residency-program chairpersons who received the survey responded to it. The chairpersons rated twenty-four of the twenty-five questions as at least important. The mean passing score (and standard deviation) that they recommended for the assessment of basic competency was 73.1 +/- 6.8 per cent. The mean score for the eight orthopaedic chief residents was 98.5 +/- 1.07 per cent, and that for the eighty-five residents in their first postgraduate year was 59.6 +/- 12 per cent. Seventy (82 per cent) of the eighty-five residents failed to demonstrate basic competency on the examination according to the chairpersons' criterion. The residents who had taken an elective course in orthopaedic surgery in medical school scored higher on the examination (mean score, 68.4 per cent) than did those who had taken only a required course in orthopaedic surgery (mean score, 57.9 per cent) and those who had taken no rotation in orthopaedic surgery (mean score, 55.9 per cent) (p = 0.005 and p = 0.001, respectively). In summary, seventy (82 per cent) of eighty-five medical school graduates failed a valid musculoskeletal competency examination. We therefore believe that medical school preparation in musculoskeletal medicine is inadequate.

Clinical Competence↗

Policy implications of physician income homeostasis.

Physicians tend to protect their desired target incomes in the face of declining fees by working more. This homeostatic "volume response" in the name of income protection can have budgetary consequences opposite of those intended: overall spending will probably rise. This is seen because when the physician tries to earn one extra dollar, he or she causes many additional dollars to be spent within the health care economy. The fraction of total costs represented by the physician's fee varies among specialties and procedures. Among certain medical services that are susceptible to doctor-induced demand, the Medicare standard physician payment may represent 10 percent or less of the total cost of that service. Accordingly, even if physicians were very inefficient at finding additional work to compensate for lower fees, cutting physician payments may still lead to increased spending. For example, a 50 percent decrease in the physician payment for a single operation, total hip replacement, may trigger nearly one billion dollars in additional annual Medicare spending, even if surgeons can find only half of the additional work they would need to neutralize the effect of the fee reduction. A sophisticated health care spending policy would recognize that cutting fees induces volume increases. It would recognize that such fee decreases without controls on the volume response will lead to increases in overall costs. Finally, it would recognize that the fiscal effect of the volume response varies between specialties and procedures, and thus flexible guidelines are in order.

Arthroplasty, Replacement, Hip↗

[Attitudes of family physicians to alternative medicine].

80 Israeli family physicians (51.25% men and 48.75% women) participated in a telephone survey concerning attitudes, practices and experience with alternative medicine. 23.75% reported practicing 1 or more alternative techniques, most commonly acupuncture (28%) and hypnotherapy (24%). 55% had referred at least 1 patient to an alternative practitioner during the preceding month. Physicians who studied in Israel or Western countries referred more patients than graduates of medical schools of Eastern Europe. Specialists referred patients more often than residents. The most common reason for referral was back pain.

Acupuncture Therapy↗

PDGF2/c-sis mRNA leader contains a differentiation-linked internal ribosomal entry site (D-IRES).

It has become clear that a given cell type can qualitatively and quantitatively affect the expression of the platelet-derived growth factor B (PDGF2/c-sis) gene at multiple levels. In a previous report, we showed that PDGF2/c-sis 5'-untranslated region has a translational modulating activity during megakaryocytic differentiation of K562 cells. This study points to the mechanism used for this translational modulation. The unusual mRNA leader, which imposes a major barrier to conventional ribosomal scanning, was found to contain an internal ribosomal entry site that becomes more potent in differentiating cells and was termed differentiation-linked internal ribosomal entry site (D-IRES). The D-IRES element defines a functional role for the cumbersome 1022-nucleotide-long mRNA leader and accounts for its uncommon, evolutionary conserved architecture. The differentiation-linked enhancement of internal translation, which provides an additional step to the fine tuning of PDGF2/c-sis gene expression, might be employed by numerous critical regulatory genes with unusual mRNA leaders and might have widespread implications for cellular growth and development.

Base Sequence↗

Project ASSERT: an ED-based intervention to increase access to primary care, preventive services, and the substance abuse treatment system.

STUDY OBJECTIVE: To test the feasibility and effectiveness of Project ASSERT, an innovative program developed by us to facilitate access to the substance abuse treatment system and to primary care and preventive services for emergency department patients with drug- and alcohol-related health problems. METHOD: Multicultural health promotion advocates (HPAs) were trained by ED personnel to screen patients using a health needs history, to administer a brief negotiated interview based on readiness-to-change principles, and to use an active referral process to capture the marginal capacity of the substance abuse treatment system. Outcome measures included (1) number of referrals to the substance abuse treatment system, (2) patient self-report of satisfaction with services received from Project ASSERT and utilization of treatment resources, and (3) changes in self-reported frequency of drug and alcohol use and in Drug Abuse Screening Test scores between enrollment and follow-up at 60 to 90 days. RESULTS: Between March 1, 1995, and February 29, 1996, 7,118 adult ED patients were screened. Substance abuse was detected among 2,931 patients (41%), and 1,096 (37% of detected patients) were enrolled. A total of 8,848 referrals were made: 3,189 to primary care, 2,018 to a variety of substance abuse treatment services, 2,253 for smoking cessation, 339 for mammography, and 689 to other support services (eg, psychiatric nurse, social worker, battered women's advocate or shelter). Comparison of enrollment and follow-up scores for the 245 enrollees who kept a follow-up appointment demonstrated significant reductions, including a 45% reduction in severity of drug problem, a 56% reduction in alcohol use, and a 64% reduction in the frequency of drinking six or more drinks at one sitting. At follow-up, patients expressed satisfaction with Project ASSERT: 91% were satisfied with their referrals; 93% thought the HPAs explained things well; and 99% thought the HPAs respected them as individuals. Among the follow-up group, 50% self-reported that they had kept an appointment for treatment. CONCLUSION: Project ASSERT is an innovative approach to link ED patients with the substance abuse treatment system and with primary care and other preventive services. Its success is further demonstrated by its adoption by Boston Medical Center as a funded ED value-added service.

Adult↗

Renal cystic disease in tuberous sclerosis: role of the polycystic kidney disease 1 gene.

Tuberous sclerosis is an autosomal dominant trait characterized by the development of hamartomatous growths in many organs. Renal cysts are also a frequent manifestation. Major genes for tuberous sclerosis and autosomal dominant polycystic kidney disease, TSC2 and PKD1, respectively, lie adjacent to each other at chromosome 16p13.3, suggesting a role for PKD1 in the etiology of renal cystic disease in tuberous sclerosis. We studied 27 unrelated patients with tuberous sclerosis and renal cystic disease. Clinical histories and radiographic features were reviewed, and renal function was assessed. We sought mutations at the TSC2 and PKD1 loci, using pulsed field- and conventional-gel electrophoresis and FISH. Twenty-two patients had contiguous deletions of TSC2 and PKD1. In 17 patients with constitutional deletions, cystic disease was severe, with early renal insufficiency. One patient with deletion of TSC2 and of only the 3' UTR of PKD1 had few cysts. Four patients were somatic mosaics; the severity of their cystic disease varied considerably. Mosaicism and mild cystic disease also were demonstrated in parents of 3 of the constitutionally deleted patients. Five patients without contiguous deletions had relatively mild cystic disease, 3 of whom had gross rearrangements of TSC2 and 2 in whom no mutation was identified. Significant renal cystic disease in tuberous sclerosis usually reflects mutational involvement of the PKD1 gene, and mosaicism for large deletions of TSC2 and PKD1 is a frequent phenomenon.

Adolescent↗

Public and private workers' compensation insurance.

Utilizing unique data from the federal government's Social Security office, we analyze the costs of providing workers' compensation by public vs private insurers. Our analysis has the advantage that public and private recipients are likely to be more similar than public (Medicare, Medicaid) and private recipients of health insurance in the US or Canadian economies. We find that public firms appear to provide workers' compensation insurance more efficiently than private firms.

Canada↗