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Biomedical subjects

A Levin

Publications and source records attributed to A Levin.

At least 19 recordsLinked to original sources

[Benign meningioma following scalp irradiation in north African immigrants].

Many Jewish immigrants from North Africa in the late 1950s were treated with low-dose irradiation of the scalp for tinea capitis. In 2 such patients, a 47-year-old man and a 43-year-old woman, both with long histories of headaches and dizziness, meningiomas were found. There is a well-known correlation between low-dose irradiation of the scalp and development of meningioma. Therefore, in immigrants from North Africa with prolonged headaches and dizziness, there should be a careful history with regard to irradiation of the scalp and investigation to exclude meningioma.

Africa, Northern

Prenatal diagnosis of retinal nonattachment in the Walker-Warburg syndrome.

We report on the prenatal ultrasonographic diagnosis of Walker-Warburg syndrome based on cerebral and ocular findings. The ultrasound study done at 37 weeks gestation documented hydrocephalus and retinal nonattachment consistent with this syndrome. The ability to detect retinal nonattachment prenatally may have implications for the prenatal diagnosis of other conditions which have early retinal nonattachment as one of their findings. However, it is uncertain how early in pregnancy this defect can be detected.

Abnormalities, Multiple

Monoclonal anti-dipeptide antibodies cross-react with detyrosinated and glutamylated forms of tubulins.

Two monoclonal antibodies, GLU-1 and A1.6, raised against gamma-L-glutamyl-L-glutamic acid dipeptide (Glu-Glu) and Ca(2+)-dependent ATPase from Paramecium, respectively, recognized the dipeptide Glu-Glu sequence. Whereas the antibodies immunofluorescently stained very few, if any, cytoskeletal fibers in cultured mammalian cells, almost all interphase as well as mitotic spindle microtubules became visible after treatment of cells with carboxypeptidase A. Immunoblot analysis demonstrated intense cross-reaction of the antibodies to the alpha-tubulin subunit. alpha-Tubulin isotypes produced as fusion proteins in bacteria were labeled by both the antibodies only when the proteins did not contain a tyrosine residue at the C terminus, indicating that GLU-1 and A1.6 specifically recognize the detyrosinated form of alpha-tubulin. When microtubule protein purified from brain was probed, not only alpha-but also, to a lesser extent, beta-tubulin were revealed by the dipeptide antibodies. A synthetic tripeptide YED containing one glutamyl group linked to the second residue of the peptide via the gamma position was also recognized by the antibodies. Since this peptide sequence corresponds to the amino acid sequence of polyglutamyated class III beta isotype at amino acid position 437 to 439, it is suggested that GLU-1 and A1.6 are able to recognize the glutamylated form of beta-tubulin. These results indicate that the C-terminal Glu-Glu sequence displays strong antigenicity, and the antibodies recognize the sequence present in the C terminus of the detyrosinated form of alpha-tubulin and the glutamyl side chain of beta-tubulin. Particularly strong immunoreaction was detected with ciliary and flagellar microtubules; thus, stable axonemal microtubules appear to be rich in post-translationally modified tubulin subunits.

Animals

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

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

Crossreacting human lymphoma idiotypes.

We have examined an unselected series of 72 lymphomas of diverse histologies with a panel of mouse monoclonal antibodies specific for human B-lymphoma-derived Ig idiotypes (anti-ids) to determine the nature and extent of id/anti-id crossreactivity. The anti-id antibodies were prepared from Ig isolated from seven follicular center cell lymphomas by heterohybridoma technique. Thirty-six of 75 individual anti-ids obtained in this manner were further selected based on their reactivity with highly restricted or private idiotypic determinants. Twelve of the 72 (17%) lymphoma biopsies reacted with one or more of the 36 anti-ids that detect private determinants. A pool consisting of five individual antibodies would have detected 11 of the 12 crossreacting tumors. Staining of tumor cell populations was homogeneous in the positive cases, suggesting uniform idiotype expression. If there was a segregated staining pattern, it was generally related to the presence of CD3+ T cells in the section. These follicular center cell-derived anti-ids cross-reacted with follicular center cell tumors of all histologic grades with frequencies ranging from 13% to 50%. The structural basis for the crossreactivity of our lymphoma-derived private anti-ids is as yet not known. However, the reactivity of certain anti-ids with both kappa- and lambda-expressing tumors suggests a biased use of V gene segments in these crossreactive clones that is probably related to the VH gene. These data suggest the possibility that lymphoma may develop in a highly restricted pool of normal differentiated B cells or in B-cell subsets that express a limited repertoire of unmutated VH gene segments.

Animals

Human spumavirus antibodies in sera from African patients.

Serum samples collected from patients with a wide variety of diseases from African and other countries were tested for antibodies to the human spumaretrovirus (HSRV). A spumaviral env-specific ELISA was employed as screening test. Out of 3020 human sera screened, 106 were found to be positive (3.2%). While the majority of patients' sera from Europe (1581) were negative, 26 were positive (1.6%). Sera from healthy adult blood donors (609), from patients with multiple sclerosis (48), Graves' disease (45), and chronic fatigue syndrome (41) were negative or showed a very low prevalence for spumaviral env antibodies. A higher percentage of seropositives (6.3%) were found among 1338 African patients from Tanzania, Kenya, and Gabon. Out of 1180 patients from Tanzania, 708 suffered from tumors, 75 from AIDS, and 128 had gynecological problems; 51 of the Tanzanian patients were HSRV seropositive (4.3%). A particularly high percentage of 16.6% seropositives were identified among nasopharyngeal carcinoma patients (NPC) from Kenya and Tanzania consistent with results reported 10 years ago. However, 20 nasopharyngeal carcinoma patients from Malaysia were HSRV-seronegative. In selected cases, sera from seropositive individuals were reacted with proteins from HSRV-infected cells in vitro. HSRV env- and gag-specific antibodies were specifically detected by these sera in Western blots. The results indicate spumavirus infections in human patients with various diseases at a relatively low prevalence worldwide; in African patients, however, the prevalence of spumavirus infections is markedly higher.

Africa

T-cell lymphoma in Singapore: pathology, clinical findings and association with HTLV-1 antibodies.

Of 128 cases of malignant lymphomas studied in Singapore between 1986 and 1988, 28 were identified as peripheral T-cell lymphomas. Sera from two of the 128 cases were positive for HTLV-1 antibodies and both cases had the clinical and pathological features of adult T-cell leukaemia/lymphoma. The pathological and clinical features of the 28 cases of peripheral T-cell lymphoma are presented in detail. Survival data indicated no significant difference between the low grade and high grade histological types. Three of the patients had previous or concomitant malignancies. The percentage of T-cell lymphomas associated with HTLV-1 infection in Singapore is low compared to those areas in which HTLV-1 is endemic.

Adolescent

Studies to determine the basis for hyperkalemia in recipients of a renal transplant who are treated with cyclosporine.

Hyperkalemia is commonly encountered in patients who receive a renal transplant and the immunosuppressive drug, cyclosporine. There is also a high incidence of hypertension (which is thought to be due to expansion of the extracellular fluid volume) and hyperchloremic metabolic acidosis in this group of patients. This constellation of findings led to the suspicion of the possibility that their basis might be type II hypoaldosteronism. To test this hypothesis, 12 patients with hyperkalemia (plasma K+, 5.1 +/- 0.2 mmol/L at the time of study) while receiving cyclosporine were studied. Patients who had diabetes mellitus, those receiving drugs known to cause hyperkalemia (e.g., beta blockers, angiotensin-converting enzyme inhibitors, K(+)-sparing diuretics), or those with a serum creatinine greater than 200 mumol/L were excluded. The renal response to hyperkalemia was inappropriate because the transtubular K+ concentration gradient (TTKG) was only 4.3 +/- 0.4 compared with a TTKG of 13 +/- 1, 2 h after 50 mmol of KCl was given to normal subjects. The TTKG, after administration of 200 micrograms of fludrocortisone, was still very low (5.6 +/- 0.6) in the patients compared with that of controls (12 +/- 1). After administration of 250 to 500 mg of acetazolamide to increase the delivery of bicarbonate to the distal nephron, the TTKG rose significantly to 11 +/- 1 in patients on cyclosporine, compared with 17 +/- 1 in the controls.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetazolamide