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Biomedical subjects

L Weiss

Publications and source records attributed to L Weiss.

At least 91 records · Page 5Linked to original sources
PubMed1998

Adult and two children with fetal methotrexate syndrome.

The folic acid antagonists, methotrexate and aminopterin, are known to be teratogenic in humans. The critical period for their teratogenecity is suspected to be between 6 to 8 weeks post-conception. Fetal exposure from 10 to 32 weeks weeks post-conception to methotrexate alone or in combination with other anti-cancer drugs has not resulted in obvious teratogenic effects. Methotrexate is often used to treat cancers but is occasionally used as an abortifacient. The long-term outcome of the fetal aminopterin syndrome has been published in only four adults. We report on a 28-year-old man with fetal methotrexate syndrome and two children with mild manifestations of the syndrome. One child was inadvertently exposed to methotrexate from 7 1/2 through 30 weeks post-conception because his mother was receiving it for treatment of breast cancer. The other was exposed from 11 weeks and 5 days through 25 weeks in an attempt to induce abortion. The 28-year-old man has craniofacial and digital anomalies, growth retardation but normal intelligence as noted in the previously reported cases. These cases remind us of the teratogenicity of methotrexate and should serve as a warning that if methotrexate is used as an abortifaciant and an abortion does not ensue, there is a teratogenic risk.

Abnormalities, Drug-Induced↗
PubMed1998

The sequential occurrence of pol 215 and pol 41 zidovudine resistance mutations is associated in an additive fashion with low CD4 cell counts and high plasma and cellular HIV viral load.

We report on a cross-sectional study of virological and immunological surrogate markers of HIV infection in 115 patients for whom a determination of the pol 215 and pol 41 zidovudine (ZDV) resistance mutations had been described between January 1995 and February 1996. The patients received ZDV alone or a combination of ZDV and zalcitabine or didanosine. A total of 55, 15 and 45 patients exhibited a wild (W), a mixed (MIX) or a mutant (M) genotype at codon pol 215, respectively; 85, 10 and 20 patients exhibited a W, a MIX or a M genotype at codon pol 41, respectively. Patients exhibiting the pol 215 M genotype had lower CD4 cells, higher plasma viral load and higher proviral burden than patients exhibiting the pol 215 W genotype. Patients who had variants exhibiting both pol 215 M and pol 41 M or MIX genotypes had significantly worsened surrogate marker values than patients having variants only carrying the pol 215 M genotype. These observations demonstrate that the two mutations additively associate with pejorative surrogate markers.

Adult↗
PubMed1998

Persistent expansion, in a human immunodeficiency virus-infected person, of V beta-restricted CD4+CD8+ T lymphocytes that express cytotoxicity-associated molecules and are committed to produce interferon-gamma and tumor necrosis factor-alpha.

The present study describes the persistent expansion of a subpopulation of circulating double-positive CD4+CD8+ T cells in a human immunodeficiency virus (HIV)-infected person over 8 years. The percentage of double-positive cells was remarkably stable with time and was not related to HIV plasma virus load. CD4+CD8+ cells exhibited phenotypic characteristics of activated memory T lymphocytes. Analysis of V beta usage by the T cell receptors of these cells indicated restricted expression to the V beta 14 and V beta 17 families. Most CD4+CD8+ cells constitutively expressed cytotoxicity-associated molecules (C1.7 and perforin) and were selectively committed to produce interferon-gamma and tumor necrosis factor-alpha, cytokines involved in cytotoxic function. The kinetics of changes in the relative proportion of single-positive CD4+ and double-positive CD4+CD8+ T cell subsets and a similar bias in V beta usage by these subsets suggest that CD4+CD8+ lymphocytes originate from peripheral expansion of mature CD4+ T cells.

CD4 Antigens↗
PubMed1998

Confirmation of nosocomial transmission of hepatitis C virus by phylogenetic analysis of the NS5-B region.

Four hepatitis C virus transmission chains at three dialysis units were disclosed by limited sequencing; three of these were disclosed by analysis of the NS5-B region of the genome. Dialysis on the same shift as that during which infected patients were dialyzed was the common factor for seven patients in two chains. Two nurses exposed to needle sticks and their sources of infection constituted two other chains. The strains of three chains belonged to subtype 1a and formed clusters with an intrachain variability of 0 to 6 nucleotides compared to 8 to 37 nucleotides for unrelated strains within this subtype. The clusters were supported by bootstrap values ranging from 89 to 100%.

Cross Infection↗
PubMed1998

Constitutional and mosaic large NF1 gene deletions in neurofibromatosis type 1.

A set of neurofibromatosis type 1 (NF1) patients was screened for large NF1 gene deletions by comparing patient and parent genotypes at 10 intragenic polymorphic loci. Of 67 patient/parent sets (47 new mutation patients and 20 familial cases), five (7.5%) showed loss of heterozygosity (LOH), indicative of NF1 gene deletion. These five patients did not have severe NF1 manifestations, mental retardation, or dysmorphic features, in contrast to previous reports of large NF1 deletions. All five deletions were de novo and occurred on the maternal chromosome. However, two patients showed partial LOH, consistent with somatic mosaicism for the deletion, suggesting that mosaicism may be more frequent in NF1 than previously recognised (and may have bearing on clinical severity). We suggest that large NF1 deletions (1) are not always associated with unusual clinical features, (2) tend to occur more frequently on maternal alleles, and (3) are an important mechanism for constitutional and somatic mutations in NF1 patients.

Adult↗
PubMed1998

Hypertensive vascular disease as a cause of death in blacks versus whites: autopsy findings in 587 adults.

Cardiovascular disease is the major cause of excess mortality among urban US blacks, but autopsy data comparing black-white differences in underlying pathological causes of cardiovascular death are lacking. We reviewed all 720 adult cases autopsied in 1991 in the New York City Medical Examiner's Office in which the coded cause of death was cardiovascular disease (International Classification of Diseases, 9th Revision, codes 391, 393 to 398, 401 to 404, 410, 411, 414 to 417, 420 to 438, and 440 to 444). After exclusion of 133 cases because race was missing or coded as other than black or white, gender was not coded, or there was an unusual circumstances of death or extreme obesity, 587 cases were available for analysis. There were 314 black and 273 white subjects. Black women were younger than white women at time of death (mean age, 54.7 versus 61.5 years; P<.001), whereas black and white men did not differ in mean age at death. Hypertensive vascular disease was the autopsy cause of death in 42% of blacks compared with 23% of whites (P<.001). Conversely, atherosclerotic heart disease was the autopsy cause of death in 64% of white subjects but only 38% of blacks. These patterns were consistent in both sexes and after adjustment for age. Hypertensive vascular disease was far more common than atherosclerotic heart disease as the cause of death at autopsy among blacks compared with whites in New York City, whereas atherosclerotic heart disease was more common in whites. These findings suggest that ineffective control of hypertension is a major factor contributing to excess cardiovascular mortality among urban blacks.

Adult↗
PubMed1998

Amelioration of diabetes in nonobese diabetic mice with advanced disease by linomide-induced immunoregulation combined with Reg protein treatment.

Oral linomide, (quinoline-3-carboxamide), has been shown to prevent autoimmune insulitis, islet destruction, and diabetes in NOD mice treated at an early stage of the disease, but confers only partial protection in animals with advanced disease. Reg protein, the gene product of a complementary DNA isolated from a regenerating rat islet library, has been previously shown to induce expansion of beta-cell mass in pancreatectomized rats. To determine the effect of treatment combining immunomodulation and Reg protein on advanced autoimmune diabetes, we treated female NOD mice with oral linomide and i.p. Reg protein injections. In 14-week-old animals with less severe disease (glucose tolerant), treatment with each agent alone resulted in amelioration of diabetes, as did treatment with Reg alone in 5-week-old prediabetic mice. In 14-week-old animals with more severe disease (glucose intolerant), only treatment with the combination of both agents, but not that with each separately, resulted in amelioration of diabetes. Our study suggests that treatment aimed at abrogation of autoimmunity combined with expansion of beta-cell mass constitutes a potential therapeutic approach for treatment of insulin-dependent diabetes mellitus.

Adjuvants, Immunologic↗
PubMed1998

Human complement factor H deficiency associated with hemolytic uremic syndrome.

This study reports on six cases of deficiency in the human complement regulatory protein Factor H (FH) in the context of an acute renal disease. Five of the cases were observed in children presenting with idiopathic hemolytic uremic syndrome (HUS). Two of the children exhibited a homozygous deficiency characterized by the absence of the 150-kD form of Factor H and the presence, upon immunoblotting, of the 42-kD Factor H-like protein 1 (FHL-1) and other FH-related protein (FHR) bands. Southern blot and PCR analysis of DNA of one patient with homozygous deficiency ruled out the presence of a large deletion of the FH gene as the underlying defect for the deficiency. The other four children presented with heterozygous deficiency and exhibited a normal immunoblotting pattern of proteins of the FH family. Factor H deficiency is the only complement deficiency associated with HUS. These observations suggest a role for FH and/or FH receptors in the pathogenesis of idiopathic HUS.

Acute Disease↗
PubMed1998

Complex apolipoprotein B-containing lipoprotein particles are associated with a higher rate of progression of human chronic renal insufficiency.

Chronic renal failure is characterized by specific alterations of the lipoprotein metabolism. It has been suggested that renal dyslipoproteinemia contributes to the progression of renal dysfunction. The objective of this study was to investigate the impact of different apoB-containing lipoprotein families on the progressive decline of renal function in patients with moderately advanced chronic renal failure. As part of a larger prospective study, 44 adult nondiabetic patients with primary chronic renal disease were followed with repeated GFR measurements for an average of 2.4 (SD 1.0) yr. Patients' characteristic variables, including plasma levels of lipids, apolipoproteins (apo), and apoA- and apoB-containing lipoprotein families (LP), were determined at the beginning of the observation period. The baseline variables were prospectively related, using linear regression, to the rate of progression (deltaGFR). The patient study group had a mean GFR at baseline of 40.3 (SD 16.7) ml/min per 1.73 m2 body surface area. The average rate of progression was a yearly decline in GFR of -3.2 (SD 5.1) ml/min per 1.73 m2 body surface area. A strong association was observed between the plasma concentration of complex, triglyceride-rich apoB-containing lipoproteins (LP-Bc) and the rate of progression (r=0.43, P < 0.01), whereas there was no association between the cholesterol-rich apoB-containing lipoproteins (LP-B) and deltaGFR. The association between the levels of LP-Bc and the rate of progression was not dependent on the baseline values of GFR, BP, and the degree of proteinuria. The results of this study extend earlier observations regarding the importance of renal dyslipoproteinemia for progressive renal insufficiency. In particular, elevated levels of intact or partially metabolized triglyceride-rich apoB-containing lipoproteins of intermediate- and low-density ranges seem to promote the progression of human renal insufficiency.

Adult↗
PubMed1997

[Quality control in the therapy of chronic pain. Results obtained by a task force of the German Section of the International Association for the Study of Pain on psychological assessment of chronic pain. XI. Assessment and multiaxial classification of pain].

This paper reviews instruments in German language for the psychological assessment and classification of pain. Usually chronic pain syndromes are classified within the International Classification of Diseases (ICD). Instead of the psychiatric chapter of the ICD, it is possible to use the Diagnostic and Statistical Manual of Mental Disorders (DSM). The proposed classification system of the International Association of the Study of Pain (IASP) is based on a multiaxial solution. The numerous ways to classify chronic pain include many problems and limits, especially in the case of an interdisciplinary assessment. They provide no specific system for classifying pain syndromes. They are impractical to handle and restrict classifying pain as either somatogenic or psychogenic. It is not possible to describe both sides in one diagnosis without loss of information. As a result of this situation, a task force of the German Chapter of the International Association for the Study of Pain developed a Multiaxial Classification of Pain (Multiaxiale Schmerzklassifikation; MASK) as an advanced system of pain assessment and an alternative to the common classification systems. MASK embraces a somatic (MASK-S) and a psychological (MASK-P) part. Both parts constitute an 'interdisciplinary diagnosis'. MASK-S enables classifying a pain syndrome using hierarchical levels, with progredient specific degrees of differentiation. In addition there are 6 axes to describe pain syndromes qualitatively and quantitatively (e.g. localization, quality). The psychosocial part (MASK-P) embraces 5 main levels (1. behavioral, 2. emotional, 3. cognitive, 4. stress-related, 5. habitual personal factors) and 2 additional levels (6. functional coherence, 7. ICD/DSM-diagnosis additional). The MASK-P part of the diagnosis is composed of graduation on these levels. Differential axis of the pain syndromes are described phenomenologically and specifically. MASK provides the possibility of establishing an integrative, interdisciplinary diagnosis.

English Abstract↗
PubMed1997

[Quality assurance in chronic pain therapy. Results obtained by a task force of the German Chapter of the International Association for the Study of Pain on psychological Assessment of chronic Pain. Psychological instruments for the assessment of pediatric pain].

The present paper is one in a series of publications reviewing German instruments for the psychological assessment of pain. Part X deals with pain measurement of acute and chronic pain in infants and children. German assessment instruments of pediatric pain together with frequently used instruments of American origin are examined and described. The survey contains self-report and behavioral pain measures. Multidimensional pain interviews for both children and parents, diaries and rating scales, as well as observation measures especially for infants, are examined. Since the selection of pain-assessment instruments is dependent on the age and cognitive level of the children, for each instrument a minimum age limit is given. In cases in which quantitative indices of reliability, validity and objectivity are still needed, the evaluation is based on qualitative quotations.

English Abstract↗
PubMed1997

Flow-cytometric assessment of in vivo cytokine-producing monocytes in HIV-infected patients.

We have used two-color flow cytometry to study in vivo monocytic cytokine production at the single-cell level in HIV-infected patients. We demonstrated the presence of intracellular IL-1 alpha, IL-1 beta, IL-1ra, and TNF alpha in circulating CD14+ monocytes from HIV-infected patients. The specificity of intracellular staining with anti-cytokine antibodies was demonstrated by the suppression of the fluorescent signal when staining was performed in the presence of recombinant cytokines. We did not detect any specific intracellular staining when anti-IL-4 antibodies were used since monocytes do not produce IL-4. In vivo intracellular cytokine production of IL-1 alpha, IL-1 beta, IL-1ra, and TNF alpha was higher in monocytes from HIV-infected individuals compared to monocytes from healthy controls; however, only the data concerning IL-1 alpha reached statistical significance. Monocytic cytokines are involved in the regulation of HIV gene expression and may participate in the modulation of the Th1/Th2 balance. The ability to follow the production of a wide range of cytokines by circulating monocytes of HIV-infected patients should allow one to better analyze the role of monocytic cytokines in the pathogenesis of HIV disease.

Cytokines↗
PubMed1997

Deletions in Xq26.3-q27.3 including FMR1 result in a severe phenotype in a male and variable phenotypes in females depending upon the X inactivation pattern.

High resolution cytogenetics, microsatellite marker analyses, and fluorescence in situ hybridization were used to define Xq deletions encompassing the fragile X gene, FMR1, detected in individuals from two unrelated families. In Family 1, a 19-year-old male had facial features consistent with fragile X syndrome; however, his profound mental and growth retardation, small testes, and lover limb skeletal defects and contractures demonstrated a more severe phenotype, suggestive of a contiguous gene syndrome. A cytogenetic deletion including Xq26.3-q27.3 was observed in the proband, his phenotypically normal mother, and his learning-disabled non-dysmorphic sister. Methylation analyses at the FMR1 and androgen receptor loci indicated that the deleted X was inactive in > 95% of his mother's white blood cells and 80-85% of the sister's leukocytes. The proximal breakpoint for the deletion was approximately 10 Mb centromeric to FMR1, and the distal breakpoint mapped 1 Mb distal to FMR1. This deletion, encompassing approximately 13 Mb of DNA, is the largest deletion including FMR1 reported to date. In the second family, a slightly smaller deletion was detected. A female with moderate to severe mental retardation, seizures, and hypothyroidism, had a de novo cytogenetic deletion extending from Xq26.3 to q27.3, which removed approximately 12 Mb of DNA around the FMR1 gene. Cytogenetic, and molecular data revealed that approximately 50% of her white blood cells contained an active deleted X. These findings indicate that males with deletions including Xq26.3-q27.3 may exhibit a more severe phenotype than typical fragile X males, and females with similar deletions may have an abnormal phenotype if the deleted X remains active in a significant proportion of the cells. Thus, important genes for intellectual and neurological development, in addition to FMR1, may reside in Xq26.3-q27.3. One candidate gene in this region, SOX3, is thought to be involved in neuronal development and its loss may partly explain the more severe phenotypes of our patients.

Adult↗