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Biomedical subjects

A Levin

Publications and source records attributed to A Levin.

At least 37 records · Page 2Linked to original sources

DNA-based carrier detection and prenatal diagnosis of tyrosinase-negative oculocutaneous albinism (OCA1A).

We describe molecular prenatal diagnosis and carrier detection of tyrosinase-negative oculocutaneous albinism (OCA1A) in two families. In one family, we carried out DNA-based prenatal diagnosis of OCA1A. In the other family, mutation analysis and carrier detection obviated the need for prenatal diagnosis. Molecular analysis is safer and probably more accurate than fetoscopy and fetal scalp biopsy, and should become the method of first choice for prenatal diagnosis of OCA1.

Albinism, Oculocutaneous

Mutations in the coding region of c-myc occur independently of mutations in the regulatory regions and are predominantly associated with myc/Ig translocation.

Constitutive expression of c-myc resulting from a chromosomal translocation, which juxtaposes c-myc to an immunoglobulin gene, is a pivotal lesion in Burkitt's lymphomas. This deregulated expression of c-myc is associated with mutations in the regulatory regions, i.e. the first exon and the first intron of c-myc in tumors where the chromosomal breakpoint is not itself within the regulatory region. Until recently it was widely believed that the c-myc protein in these tumors is wild type. We have demonstrated that in a fraction of Burkitt's lymphomas from Africa and from the continental USA, and in mouse plasmacytomas, the c-myc gene carries mutations in the coding region. We now show that, occasionally, such mutations are also present in multiple myelomas--tumors which do not carry translocations or amplifications of c-myc. We also show that the frequency of the c-myc coding region mutations in BL is independent of the frequency of mutations in the regulatory region. These results suggest that the mechanisms that induce missense mutations involving the coding region of c-myc may be different from those that lead to mutations in the regulatory regions.

Burkitt Lymphoma

BK virus and a new type of JC virus excreted by HIV-1 positive patients in rural Tanzania.

HIV-1 positive patients from Tanzanian villages near Shirati were examined for urinary excretion of the human polyomaviruses JC and BK using the polymerase chain reaction (PCR). BK virus (BKV) was detected in 11 of 23 individuals tested. The BKV DNA sequences were all closely related to prototype Gardner strain and BKV (DUN). In contrast, a new type of JCV, termed Type 3 [or JCV (Shi)], was identified in seven of these same 23 individuals by comparison with Type 1 and Type 2 sequences of the VP1/intergenic/T antigen region of U.S., European and Asian strains. This suggests that JCV and BKV, although closely related, have different evolutionary histories within the African population. The six BKV regulatory regions amplified all showed the archetypal configuration. However, two of the seven JCV regulatory regions showed rearrangements: a small deletion and an inverted repeat. JCV causes a fatal demyelinating disease, progressive multifocal leukoencephalopathy (PML), in about 5% of AIDS patients in Europe and the U.S.A., but only one case has been reported in Africa. Our results suggest that this rarity of PML is not due to the absence of JCV in the African population.

Adolescent

Evidence-based recommendations for the clinical use of recombinant human erythropoietin.

In an era of increasing scrutiny regarding use of health care resources, it is critical that physicians have rational, evidence-based guidelines for treatment decisions. This review of more than 200 published papers constitutes a comprehensive approach to evaluating the current evidence regarding the clinical use of recombinant human erythropoietin therapy in renal failure patients. After this review, specific recommendations are provided regarding who should receive r-HuEPO; what the target hemoglobin should be; the best route of administration of r-HuEPO; how iron status should be evaluated and managed; and monitoring and follow-up of patients taking r-HuEPO. Throughout the article, areas for important future research are also identified.

Anemia

Use of patient-controlled analgesia with alfentanil for extracorporeal shock wave lithotripsy.

STUDY OBJECTIVE: To compare the efficacy of patient-controlled analgesia (PCA) to physician-controlled analgesia in patients undergoing extracorporeal shock wave lithotripsy (ESWL). DESIGN: Prospective, randomized trial. SETTING: New Jersey Kidney Stone Treatment Center at Robert Wood Johnson University Hospital, New Brunswick, NJ. PATIENTS: 62 ASA I, II, and III patients undergoing ESWL. INTERVENTIONS: The control group (n = 29) received physician-controlled analgesia with continuous infusions (0.75 mcg/kg/min) and intermittent boluses (5 mcg/kg) of alfentanil. PCA patients (n = 33) initially received alfentanil 0.5 mcg/kg followed by a continuous background infusion (0.2 to 0.5 mcg/kg/min) and self-administered alfentanil (3 to 5 mcg/kg) with a 5-minute lockout period. Bolus doses and infusion rates were determined by patient comfort and cardiorespiratory response to alfentanil. MEASUREMENTS AND MAIN RESULTS: Prior to the procedure, the patients completed two questionnaires (State-Trait Anxiety Inventory and Multidimensional Health Locus of Control Scales). During ESWL, blood pressure, heart rate, respiratory rate, oxygen saturation, end-tidal CO2, and pain and sedation levels were measured at 0, 800, 1,600, 2,400, and 3,000 shock waves. The total doses of alfentanil administered were calculated. PCA patients received 31% less alfentanil than control group patients (p < 0.0001). Patients with more preoperative anxiety required larger doses of alfentanil (p < 0.05). The pain level was slightly higher in the patients receiving PCA (p > 0.05) but most patients reported either no or only mild pain. Side effects from the therapy, such as nausea and vomiting, were either not present or were mild in both groups, with one patient (3% to 4%) in each group reporting mild nausea. Both patients and urologists were very satisfied with the pain management in both groups. CONCLUSIONS: PCA is a useful alternative to physician-controlled analgesia during ESWL since it provides equivalent pain control while using less alfentanil.

Adult

Halothane and isoflurane alter the Ca2+ binding properties of calmodulin.

BACKGROUND: Ca2+ plays an important role in signal transduction and anesthetic mechanisms. To date, no one has observed a direct effect of volatile anesthetics on a Ca(2+)-binding protein. We therefore examined the effects of halothane and isoflurane on the Ca(2+)-binding properties of bovine brain calmodulin. METHODS: The fluorescence emission of calmodulin was obtained over a range of Ca2+ concentrations (10(-7)-10(-4)M) in the presence and absence of halothane and isoflurane. The intrinsic tyrosine fluorescence of calmodulin was measured at an excitation wavelength of 280 nm and an emission wavelength of 320 nm. Fluorescence measurements were carried out in 50 mM hydroxyethylpiperazineethane sulfonic acid, 100 mM KC1, and 2 mM ethyleneglycol-bis-(beta-aminoethyl ether) tetraacetic acid at pH 7.0 and 37 degrees C. Experiments were performed in polytetrafluorethylene-sealed cuvettes so that the volatile anesthetic concentrations remained constant. The titration data were analyzed in two ways. The data were fit to the Hill equation by using nonlinear regression analysis to derive the Hill coefficient and the dissociation constant. The data were also analyzed by two-way analysis of variance with multiple comparisons to determine statistically significant effects. Volatile anesthetic concentrations were measured by gas chromatography. RESULTS: The presence of volatile anesthetics altered the Ca(2+)-binding affinity of calmodulin in a dose-dependent fashion. At 0.57% (0.25 mM) halothane and 1.7% (0.66 mM) isoflurane, the affinity of calmodulin for Ca2+ relative to control was decreased. However, at higher concentrations of both anesthetics, the affinity for Ca2+ was increased. When the volatile anesthetics were allowed to evaporate from the experimental solutions, the observed rightward shift of the calmodulin-Ca2+ binding curve for Ca2+ at low concentrations of the anesthetics returned to the control position. The leftward shift seen at high concentrations of the anesthetics was irreversible after evaporation of 8.7% (3.3 mM) isoflurane and 5.7% (2.5 mM) halothane. CONCLUSIONS: These data demonstrate a complex interaction of two hydrophobic volatile anesthetics with calmodulin. A biphasic effect was observed both for halothane and for isoflurane. Calmodulin, an EF-hand Ca(2+)-binding protein, undergoes a conformational shift when binding Ca2+, exposing several hydrophobic residues. These residues may be sites at which the anesthetics act.

Animals

Use of the Brief Symptom Inventory to assess psychological distress in three immigrant groups.

This paper examined the internal consistency reliability of two newly developed alternate language versions of the Brief Symptom Inventory (BSI) (This is not the Bradford Somatic Inventory, which is also known as the BSI) when used with Polish and Filipino immigrants and the original versions of the BSI and its parent instrument, the Symptom Checklist 90 (SCL-90) when used with Irish immigrants; and, the theoretical and criterion related validity of the Psychoticism subscale of the BSI for Polish, Filipino, and Irish immigrants. Internal consistency estimates and triangulation of individual BSI global and subscale scores with verbal self-reports and clinical assessments demonstrated that the BSI is a relatively reliable and valid cross-cultural measure of psychological distress. However, problems with the Psychoticism subscale occurred across all three immigrant groups, which suggested that this subscale should be interpreted with caution when used with immigrants.

Acculturation

Challenging consults: application of principles of physiology and biochemistry to the bedside. Osmotic diuresis: the importance of counting the number of osmoles excreted.

Polyuria is usually the result of a water diuresis or an osmotic diuresis. Traditionally, the assessment of the extracellular fluid (ECF) volume and the concentration of Na+ in plasma is sufficient to differentiate between the two. We present a case and our approach, which is based on calculations and quantitation of osmoles, to demonstrate the utility of this approach. A patient with diabetes mellitus, human T-cell lymphocyte virus, type 1 (HTLV-1) associated lymphoma, and hypercalcemia presented with marked ECF volume contraction and polyuria. A spot urine osmolality was 567 mOsm/kg H2O in the face of urine output of approximately 6 L/d. The initial diagnosis was an osmotic diuresis. However, a quantitative analysis revealed the enormous number of osmoles could not be accounted for physiologically. Hence, we postulated a water diuresis to be the cause of the polyuria. To confirm this hypothesis, we found that at different times during his hospitalization, the urine specific gravity ranged from 1.005 to 1.022, and urine output varied markedly over 8-h periods. Despite a plasma sodium of 147 mmol/L, the patient did not complain of thirst. Taken together, this suggested the presence of a hypothalamic lesion which caused central diabetes insipidus with variable output of antidiuretic hormone together with a blunted thirst response. Illustration of the utility of a quantitative approach to polyuria is the focus of the discussion.

Chlorides

Stereotactic radiosurgery for glioblastoma multiforme: report of a prospective study evaluating prognostic factors and analyzing long-term survival advantage.

PURPOSE: Prospective evaluation of the toxicity and efficacy of radiosurgery with external beam radiotherapy in the management of newly diagnosed glioblastoma. METHODS AND MATERIALS: From 5/89 to 12/92, 31 out of 51 patients with glioblastoma multiforme underwent radiosurgery, in addition to 54 Gy in 1.8 Gy/fraction following biopsy (n = 12) or resection (n = 19). Eligibility required supratentorial glioblastoma, tumor not > 4 cm in > 1 axis, age > 18 years, and location > 1 cm from optic chiasm. Patient characteristics were: age 20-78 years (median = 57); 22 male, 9 female; Karnofsky score 20-90 (m = 70), and volume of 2.3-59.7 c.c. (m = 17.4). Eighteen patients were treated with 1 collimator, 5 with 2, 7 with 3, and 1 with 4; peripheral isodoses were 40-90% (m = 72.5) and minimum and maximum tumor dose ranges were 10-20 (m = 12) and 15-35 Gy (m = 18.75). Patients were followed clinically and radiographically every 8-12 weeks to analyze survival, quality of life, and toxicity. RESULTS: With a follow-up of 12-171 weeks, 8 out of 31 (26%) patients are alive. Median survival is 42 weeks. Twelve and 24-month actuarial survival are 38 and 28%. Comparison of the 2-year survival with previous Radiation Therapy Oncology Group patients was carried out using a nonparametric recursive partitioning technique and the observed vs. expected values are 28 vs. 9.7% (p < 0.05). Extent of resection and performance status were associated with improved survival in a multivariate analysis. No significant acute toxicity was encountered. Four patients (13%) developed clinically significant necrosis verified by biopsy or positron emission tomography scan at 9-59 weeks after radiosurgery. CONCLUSION: The improvement in median survival in broadly selected glioblastoma patients treated with radiosurgery is difficult to determine, but the 2-year survival may be superior. Future randomized trials of radiosurgery are recommended, and ad hoc use of this modality should be discouraged.

Adult

Sexual behaviour survey in a rural area of northwest Tanzania.

OBJECTIVE: Little is known about variations in patterns of sexual behaviour in different countries, cultures, and subpopulations that determine the spread of HIV-1. Quantitative studies are required to improve understanding. METHODS: To assess reported patterns of sexual behaviour, we administered a standardized questionnaire to 416 men and 498 women aged 15-49 years from a rural population in northwest Tanzania. RESULTS: Reported levels of sexual activity were highest in men and among younger age groups. The number of sexual partners and number of sex acts per unit of time were strongly correlated: men reported 10 times as many lifetime partners than women. Frequency of sexual partner exchange plateaued earlier in women (by age 25 years) than in men (by age 35 years). For the great majority, age of first intercourse was 15 years or younger; older subjects were older at first intercourse and had fewer lifetime partners than younger subjects. CONCLUSIONS: This age-related pattern suggests that more recent birth cohorts have behaviour patterns that increase the risk of sexually transmitted infectious agents such as HIV. Preventive education programmes should be targeted at young adults, who adopt higher risk profiles of frequent partner exchange linked with first intercourse at an early age.

Adolescent

The Mother-Infant unit at Tallinn Children's Hospital, Estonia: a truly baby-friendly unit.

A mother-infant neonatal unit was established in 1979 at Tallinn Children's Hospital in Estonia to provide medical and nursing care to newborn and premature babies and their mothers. Its leading principles are 24-hour care by the mother, minimal use of technology, and little contact between the baby and medical and nursing staff. The unit was based on a conceptual model of the "psychological and biological umbilicus," which proposes that this connection binds the mother and infant together during the early weeks of life. Separation of mother and baby disrupts this important tie and may have adverse consequences for both. This paper presents data comparing weight gain during the first 30 days of life for a group of 159 preterm and full-term infants who were admitted to the unit between 1988 and 1989. Eighty-seven infants were cared for by their mothers, and 72 by nurses because their mothers were unwilling or unable to stay with the infants in the hospital. The holistic, humanistic approach used in the unit represents a truly baby-friendly hospital.

Adult

Prevalence of Chlamydia pneumoniae antibodies in patients with acute respiratory infections in Israel.

AIMS: To evaluate the prevalence of antibodies to Chlamydia pneumoniae (TWAR) in relation to other aetiological agents of acute respiratory infections in Israeli patients. METHOD: Serum samples from 604 patients (183 children and 421 adults) were collected over three years. Antibodies to C pneumoniae, C trachomatis, and Legionella sp were evaluated using the microimmunofluorescence (MIF) assay. Antibodies to Mycoplasma pneumoniae were detected using the Serodia Myco II test. RESULTS: Antibodies to TWAR were detected in 319 (51.3%) sera. Twenty one patients had MIF results indicative of recent infection. TWAR prevalence and antibody titres in children (aged 1-10 years) were low, gradually increased in teenagers (11-18 years), and were highest in adults and elderly patients. In contrast to the consistently noted TWAR antibody prevalence and serological evidence of recent infection during the study period, a significant decrease in those variables was recorded for C trachomatis. Six patients had serological evidence of recent infection with both C pneumoniae and C trachomatis. The presence of antibodies to Mycoplasma pneumoniae and Legionella sp was tested in 473 of the patients; 29 had antibodies to M pneumoniae and 23 to Legionella sp. Six patients (including five children) had serological evidence of recent infection with M pneumoniae and four with Legionella sp. CONCLUSION: C pneumoniae should be considered in patients with acute respiratory diseases. MIF is the preferred method for monitoring the presence of antibodies to this organism.

Acute Disease

Population-based study of HIV-1 infection in 4,086 subjects in northwest Tanzania.

A population-based HIV-1 seroprevalence survey of 4,086 individuals, aged 15-49 years, in the North Mara district of Tanzania from rural, periurban, and urban areas, including high-risk (prostitutes, and co-workers) individuals, was performed in 1989 and 1990. The overall seroprevalence was 7.3% (95% confidence interval, 6.5-8.1), with a gradient of seropositivity from high-risk 13.0% (9.1, 16.8), urban 8.8% (7.6, 10.0), periurban 6.5% (4.7, 8.4), to rural 2.6% (1.6, 3.7) subjects. Adjusted for population group, HIV-1 seroprevalence was significantly elevated for men over age 24 and for women 20-34 years old, while age-specific prevalence rates were similar for men and women in the rural area. Recent treponemal infection, measured by the rapid plasma reagin test, was not associated with HIV-1 seropositivity in men or women. These data suggest a growing HIV-1 epidemic paralleling rising rates in other rural areas of Africa distant from areas that have been previously recognized as having high prevalence.

Adolescent

Treatment of arteriovenous malformations with stereotactic radiosurgery employing both magnetic resonance angiography and standard angiography as a database.

Twenty-one arteriovenous malformations were prospectively evaluated using magnetic resonance angiography and compared with stereotactic angiography. The goals were to establish the feasibility of magnetic resonance angiography, compare it to stereotactic angiography, employ magnetic resonance angiography in follow-up, and semiquantify flow. A correlative evaluation between flow and response to stereotactic radiosurgery was carried out. Phase contrast angiograms were obtained at flow velocities of 400, 200, 100, 60, and 20 cm/sec. The fractionated velocities provided images that selectively demonstrated the arterial and venous components of the arteriovenous malformations. Qualitative assessment of the velocity within the arteriovenous malformations and the presence of fistulae were also determined by multiple velocity images. In addition, 3-dimensional time-of-flight magnetic resonance angiograms were obtained to define the exact size and shape of the nidus. This technique also permitted evaluation of the nidus and feeding arteries for the presence of low flow aneurysms. Correlation between the two imaging modalities was carried out by subjective and semiquantitative estimation of flow velocity and estimation of nidus size. The following velocity parameters were employed: fast, intermediate, slow, and none (arteriovenous malformation obliterated). In 19 of 21 (90.5%) arteriovenous malformations, magnetic resonance angiography was equal or superior to stereotactic angiography for flow quantification and visualization of the nidus. Only 2 of 21 arteriovenous malformations were better demonstrated by stereotactic angiography than by magnetic resonance angiography (failure rate of 9.5%). The nidus size in one case was clearly underestimated by stereotactic angiography and would have resulted in a geographic miss without magnetic resonance angiography. Seven post-radiosurgery arteriovenous malformations were evaluated for follow-up with both magnetic resonance angiography and stereotactic angiography. In 6 of 7 arteriovenous malformations, magnetic resonance angiography response matched stereotactic angiography response. Correlation of flow with outcome was carried out for 14 arteriovenous malformations using magnetic resonance angiography only. Interestingly, all nine arteriovenous malformations with intermediate or slow flow demonstrated partial or complete obliteration; whereas only 3 of 5 fast flow arteriovenous malformations achieved a response with a median follow-up of 10 months. This early analysis suggests that slower flowing arteriovenous malformations may obliterate faster after stereotactic radiosurgery and flow parameters could be employed to predict response. In conclusion, magnetic resonance angiography permits semiquantitative flow velocity assessment and may therefore be superior to stereotactic angiography. An additional advantage of magnetic resonance angiography is the generation of serial transverse images which can replace the conventional CT scan employed for stereotactic radiosurgery treatment planning.(ABSTRACT TRUNCATED AT 400 WORDS)

Cerebral Angiography

Neuropsychiatric impairment in impulsive personality disorders.

It has been suggested that impulsivity and aggression are associated with neuropsychiatric impairment. Neurological soft signs may be a useful marker of nonspecific brain damage, and may therefore be increased in impulsive and aggressive patients compared with normal control subjects. A structured examination was used to evaluate neurological soft signs in 28 patients with personality disorders characterized by impulsivity and 28 healthy control subjects. All of the patients met DSM-III-R criteria for borderline personality disorder, and 10 also met criteria for antisocial personality disorder. All patients were questioned about past history of physical aggression, and a subset of 18 patients underwent neuropsychological testing with a select battery. Left-sided neurological soft signs were significantly increased in patients compared with normal control subjects. Patients with a history of aggression, however, had significantly more right-sided neurological soft signs than those without a history of aggression. Increased neurological soft signs were associated with impairment on the Wisconsin Card Sort, a test of frontal lobe executive function. Specific neuropsychiatric abnormalities, such as lateralized neurological soft signs and associated impairment on select neuropsychological tests, may be present in patients with personality disorders characterized by impulsivity.

Adult

Mathematical formulation to help identify the patient at risk of ischemic tissue necrosis--a potentially lethal complication of chronic renal failure.

Ischemic tissue necrosis (ITN) has been described as a complication of hyperparathyroidism (HPT) in patients with end-stage renal disease (ESRD) and is associated with a mortality rate of up to 80%. Early recognition of ITN is important but difficult. Optimal treatment is controversial. Based on an analysis of the English literature and a recent clinical experience, a mathematical expression to aid in the identification of high-risk patients (2 x [CaPO(4) - 5] x alkaline phosphatase x PTH ratio) was developed. The values for this expression were calculated in 3 recently reported cases and our case (n = 4). The values were compared with those of a group of 54 hyperparathyroid chronic hemodialysis patients (controls); the mean values were significantly different (p < 0.001). The expression, consisting of 4 easily measured laboratory values, appears to differentiate patients with this complication of ITN from patients with only severe HPT. Ten new additional cases were evaluated using the equation; the sensitivity of the equation was 80% and the specificity 92%, positive predictive value was 66% and the negative predictive value 96%. Long-term validation of this equation is required but it appears to be discriminatory and, thus, promising, given the potentially lethal consequences of ITN.

Adult