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Biomedical subjects

R Cohn

Publications and source records attributed to R Cohn.

At least 19 recordsLinked to original sources
PubMed2001

Autosomal dominant distal myopathy: further evidence of a chromosome 14 locus.

In 1995 Laing et al. (Am J Hum Genet 56(1995)422) described a single family with nine members affected by an autosomal dominant infantile onset distal myopathy. This family generated a LOD score of 2.6 for a locus on chromosome 14. We describe two families with an infantile onset distal myopathy: a new family with four affected members and the family previously described by Scoppetta et al. (Acta Neurol Scand 92(1955)122) in both of which haplotype segregation was compatible with linkage to the same chromosome 14 locus, generating LOD scores of 0.9 at a penetrance of 100% for the markers D14S283 and D14S64 (theta=0) in both families. The loci for autosomal recessive hereditary inclusion body myopathy and Nonaka myopathy on chromosome 9 and for autosomal dominant distal myopathy of Markesberry-Griggs and Udd on chromosome 2q31-33 were excluded by linkage analysis. The disease followed a uniform course with selective wasting of the anterior tibial muscles, starting in infancy and recognizable by a characteristic clinical sign of the 'hanging big toe'. This was followed by slow progression, with involvement of the finger and wrist extensor muscles in the third decade and proximal limb muscles in the fourth decade. Interestingly, we also found evidence of an accompanying mild peripheral neuropathy in the oldest individual with hypomyelination of numerous large myelinated fibres. In addition, this patient's muscle biopsy also showed autophagic vacuoles and numerous intranuclear tubulo-filamentous inclusions of 15-20 nm diameter. Given that all three families with infantile onset distal myopathy are compatible with linkage to the same locus on chromosome 14, this study supports evidence for, and enlarges the clinical and neuropathological spectrum of the distal myopathy on chromosome 14.

Adolescent↗
PubMed2000

Congenital muscular dystrophy with rigid spine syndrome: a clinical, pathological, radiological, and genetic study.

Rigid spine syndrome is a term first proposed by Dubowitz to describe a subset of patients affected by myopathy with early spinal contractures as a prominent feature. While spinal rigidity is a nonspecific feature, found in Emery-Dreifuss muscular dystrophy and in some congenital myopathies, it is also a prominent feature in a group of patients with merosin-positive congenital muscular dystrophy, where it is generally associated with stable or only slowly progressive weakness and early respiratory insufficiency. Recently, the first locus for congenital muscular dystrophy in association with rigid spine syndrome was mapped to chromosome 1p35-p36 in consanguineous Moroccan, Turkish, and Iranian families. We present here a detailed phenotypic description of the familial syndrome linked to this locus, describing 4 siblings (3 boys and 1 girl) of Northern European-American heritage who are the offspring of a nonconsanguineous marriage. All 4 siblings were affected by hypotonia and prominent neck weakness in infancy, early spinal rigidity, and early scoliosis. After initial improvement, muscle strength stabilizes or slowly declines, and skeletal deformities and respiratory insufficiency supervene. Muscle biopsy in an affected child at age 9 months revealed minimal, nonspecific myopathic changes, leading to a diagnosis of "minimal change myopathy." Muscle biopsy in his sibling, at the age of 14 years, revealed chronic and severe myopathic (dystrophic) changes, with normal staining for laminin-2 and for proteins of the dystrophin-glycoprotein complex. A possible explanation for these biopsy findings is that magnetic resonance imaging of the thighs reveals stereotyped selective muscle involvement, with the selectivity more pronounced early in the disease course followed by widespread muscular signal abnormalities in the late stages of the disease. In this family, linkage to the chromosome 1p rigid spine syndrome locus (RSMD1) is supported by maximum LOD scores for several markers of 1.81 at theta = 0, representing the maximum statistical power possible for this family. In combination with the previous report, this syndrome is linked to the RSMD1 locus with a summated maximum LOD score of 6.29, and analysis of recombination events in our family narrows the previously reported RSMD1 locus to 3 centiMorgans.

Adolescent↗
PubMed2000

[Oral granisetron solution as prophylaxis for chemotherapy-induced emesis in children: double-blind study of 2 doses].

This multicentric double-blind, dose-ranging study was to compare efficacy and safety of two oral doses of granisetron solution in the prevention of chemotherapy-induced emesis in children with malignant diseases : 294 children, aged 1 to 16, treated with a moderately or highly emetogenic chemotherapy were randomly assigned to receive oral granisetron either 20 microg/kg (n = 143) or 40 microg/kg (n = 151) before and 6 to 12 hours after the start of chemotherapy. Fifty-one percent of patients treated with 20 microg/kg bd of oral granisetron solution achieved a complete response (no vomiting, no worse than mild nausea, no rescue therapy and no withdrawal during the specified period) and 59% achieved a major response (no more than one episode of vomiting, no worse than mild nausea, no rescue therapy and no withdrawal during the specified period). There was no difference between the two oral doses of granisetron. Treatment was rated as good or very good by investigators in 70% of cases. In conclusion, oral granisetron suspension either at 20 microg/kg bd or at 40 microg/kg bd showed good efficacy and safety in the prevention of chemotherapy-induced emesis in children with malignant diseases. Oral granisetron solution can be used as prophylaxis of emesis in children receiving moderately or highly emetogenic chemotherapy.

Administration, Oral↗
PubMed1998

Assessment of the impact of a CD4+ T-cell testing laboratory improvement program.

OBJECTIVE: To evaluate the effectiveness of the Centers for Disease Control and Prevention's CD4+ T-cell laboratory testing improvement program and the influence of other laboratory improvement programs on CD4+ T-cell testing practices. DESIGN: Surveys asking for practice changes and factors that influenced the changes, a survey of clinicians' perceptions of laboratory quality in CD4 testing, and analysis of data from the Model Performance Evaluation Program. INTERVENTIONS: Centers for Disease Control and Prevention interventions included a series of 3-day workshops on flow cytometry, CD4+ T-cell testing guidelines published in the Morbidity and Mortality Weekly Report, the Clinical Laboratory Improvement Amendments of 1988, and the Model Performance Evaluation Program. PARTICIPANTS: All known laboratories in the United States that perform clinical CD4+ T-cell testing, workshop participants, and a sample of clinicians that treat patients infected with the human immunodeficiency virus. MAIN OUTCOME MEASURES: Changes in practices, factors most influential in effecting change, and performance on samples mailed to laboratories by the Model Performance Evaluation Program; knowledge before and after presentation of material in workshops; and practicing clinicians' observations of any effects of changes in laboratory practices. RESULTS: Many existing laboratories changed practices as a result of both governmental and nongovernmental CD4+ T-cell testing improvement programs. Sources of influence varied with each testing practice. Perceptions that test results were more reproducible seemed to offset presumed increases in the time and cost of testing. Clinicians who had ordered CD4+ T-cell testing for more than 10 years noted some improvements in results reported. CONCLUSIONS: As new complex testing methodologies are introduced into clinical and public health laboratories, the users seem to seek guidance in appropriate application of preanalytic, analytic, and postanalytic phases of the testing process. Testing improvement programs from a variety of sources were credited with changing practices and should continue to provide this guidance.

CD4 Lymphocyte Count↗
PubMed1993

Plasma triglyceride level and mortality from coronary heart disease.

BACKGROUND: Whether the plasma triglyceride level is a risk factor for coronary heart disease has been controversial, and evaluation of the triglyceride level as a risk factor is fraught with methodologic difficulties. METHODS: We studied the association between plasma triglyceride levels and the 12-year incidence of death from coronary heart disease in 10 North American populations participating in the Lipid Research Clinics Follow-up Study, while adjusting for the potential confounding effects of other risk factors for cardiovascular disease, including the level of high-density lipoprotein (HDL) cholesterol. All analyses were sex-specific, and separate analyses were performed in high and low strata of HDL cholesterol, low-density lipoprotein (LDL) cholesterol, fasting plasma glucose, and age. RESULTS: The rates of coronary death in both men and women increased with the triglyceride level. In Cox proportional-hazards models adjusted for age, in which the natural log of the triglyceride levels was used to give a normal distribution, the relative risk per natural-log unit of triglyceride (e.g., a triglyceride level of 150 mg per deciliter vs. a level of 55 mg per deciliter) was 1.54 (95 percent confidence interval, 1.19 to 1.98; P < 0.001) in men and 1.88 (95 percent confidence interval, 1.19 to 2.98; P < 0.007) in women. After an adjustment for potential covariates, however, these relative risks were not statistically significant. Analyses based on lipoprotein cholesterol levels revealed a positive association between the triglyceride level and coronary mortality in the lower stratum of both HDL and LDL cholesterol, but not in the higher stratum. Conversely, the HDL cholesterol level was unrelated to coronary mortality in the lower stratum of LDL cholesterol, but was strongly inversely associated with coronary death in the higher stratum of LDL cholesterol. The relative risk of coronary death associated with triglyceride level was higher at younger ages. The associations between the triglyceride level and coronary mortality in the lower HDL cholesterol, LDL cholesterol, and age strata were small and were further reduced by an adjustment for the fasting plasma glucose level. CONCLUSIONS: Overall, the plasma triglyceride level showed no independent association with coronary mortality. However, in subgroups of subjects with lower HDL and LDL cholesterol levels and in younger subjects, defined a priori, an association between the triglyceride level and coronary mortality was observed, although this association was small and was not statistically significant after an adjustment for the plasma glucose level.

Adult↗
PubMed1992

CD10 antigen density in childhood common acute lymphoblastic leukaemia: comparisons of race and sex.

During the 25 month period from July 1989 until August 1991, 58 children with FAB defined acute lymphoblastic leukaemia (ALL) were referred for immunophenotypic analysis. Of these, 42 children with a common/pre-B phenotype (CD19/CD10-positive) were studied specifically to assess CD10 antigen density. A pattern of segregation was found between males and females and between black and white children. Black males, who are the worst prognostic group, had the lowest CD10 density, while white females, known to constitute the best prognostic group, had significantly higher CD10 antigen density than the other groups. Black females and white males occupied intermediate positions with respect to CD10 antigen density. A two way analysis of variance showed that although sex had contributed significantly to this variation (p = 0.0038), the contribution of race was marginal (p = 0.0530). It is hypothesized that low CD10 antigen density patterns in males and in Blacks could be causally related to poor prognosis.

Black People↗
PubMed1992

Reduced latency of the visual evoked cortical response following cryogenic injury to the cerebral cortex--a neuroexcitatory phenomenon.

Changes in the latency of visual cortical evoked responses (VER) were studied in rats subjected to cryogenic injury of the cerebral cortex. Four hours after cold injury the animals revealed a significant reduction of VER latency, which lasted approximately one week, with maximal reduction in latency occurring after 3 days. A potential role of excitotoxic amino acids in this phenomenon was tested by direct application of glutamate to the exposed cerebral cortex of the control rat and by administration of MK-801, antagonist of the NMDA receptor, in rats subjected previously to cryogenic injury and displaying a significant reduction in the VER latency. The direct application of glutamate to the cortex resulted in a decrease of the VER latency similar in magnitude to that observed after cold injury and this effect could repeatedly be demonstrated after washing out the initial application of the glutamate. The administration of MK-801 in animals subjected previously to cryogenic injury produced, within 5 minutes, reversion of reduced VER latencies. The maximal prolongation of latency occurred 30 min after MK-801 administration and reached in some cases latency values greater than in controls. Reduced latencies, corresponding to those observed originally, reappeared within 2 to 4 hours. Our studies suggest that the described reductions in the VER latencies are related to cortical areas of hyperexcitation due to excessive release of neuroexcitatory transmitters.

Animals↗
PubMed1992

Decreased visual evoked cortical response latency associated with cerebral ischaemia in the gerbil.

The observation of Xu et al. concerning reduction in latency of the visual evoked responses (VER) following cortical cryogenic injury, prompted us to ascertain whether similar VER changes could be demonstrable after ischaemic brain injury, especially, since both conditions have in common involvement of neuroexcitatory mechanisms. In our study, the Mongolian gerbils, which were subjected to 10 min bilateral carotid occlusion ischaemia, revealed decreased latency of the VER, with the peak of latency reduction between 4 and 7 h. An almost immediate decrease in VER latency was observed when glutamate was directly applied to the pial surface of the brain. These observations indicate that the reduction of VER latency may be related to neuroexcitation induced by release of excitatory amino acids, the latter constituting a widespread phenomenon, concomitant with brain injuries of various aetiologies.

Animals↗
PubMed1991

Neuropsychological deficit in haemophiliacs with human immunodeficiency virus.

Neuropsychological impairment is widely accepted as being common in acquired immunodeficiency syndrome (AIDS) but infrequent in asymptomatic human immunodeficiency virus (HIV)-infected individuals. The neuropsychological function of a homogenous sample of HIV-infected haemophiliacs was investigated. Neuropsychological impairment, the nature of which is compatible with that described in the existing literature, was found in one of four AIDS cases. Eleven AIDS related complex (ARC) and 12 asymptomatic HIV-infected individuals were free of neuropsychological deficit.

AIDS Dementia Complex↗
PubMed1990

Characterization of beta-amyloid precursor proteins with or without the protease-inhibitor domain using anti-peptide antibodies.

Alternative splicing of the transcript encoding the beta-amyloid precursor protein (BAPP) of Alzheimer's disease produces multiple mRNA species. Translation of these mRNAs predicts protein products of 770, 751, and 695 amino acids. The difference arises from the inclusion in BAPP-770/751 of a 56-residue insert region which is homologous to Kunitz-type protease inhibitors. We have prepared and affinity-purified anti-peptide antibodies that react specifically with either BAPP-770/751 (insert-specific) or BAPP-695 (junction-specific). A detectable level of the mRNA corresponding to the BAPP-770/751 protein was found in all cell lines tested. Immunoprecipitation of 35S-labeled proteins from these cell lines showed them to contain one or two Mr 105,000 bands reactive with the insert-specific serum, i-291. In contrast, only cos-7 cells and the human neuroblastoma cell line, IMR-32, contained mRNA species that encode the BAPP-695 protein, as shown by Northern analysis with a junction-spanning oligonucleotide probe. A band of Mr 95,000 was immunoprecipitated specifically from these two cell lines using the junction-specific serum, J-284. Indirect immunofluorescence labeling of cells corroborated these findings. All cells reacted with the insert-specific antibodies, i-291 and i-324. Only cos-7 and IMR-32 cells reacted with the junction-specific antibody, J-284. These results demonstrate the usefulness of anti-peptide antibodies for the differential detection of the BAPP-695 and BAPP-770/751 proteins.

Alzheimer Disease↗
PubMed1989

Biochemical characterisation of the haemophilias on the Witwatersrand.

Blood samples obtained from patients on the Witwatersrand with haemophilia A, haemophilia B and von Willebrand disease were analysed. Factor activities were assayed by conventional methods. Immunoradiometric assay using labelled monoclonal anti-VIIIC:Ag was developed to assay factor VIIIC:Ag in haemophilia A. Factor IX:Ag levels were determined by a commercial ELISA kit. Multimer pattern analysis of von Willebrand factor was performed by agarose gel electrophoresis and Western blotting. In 43 patients haemophilia A was severe, in 8 it was moderate and in 2 it was mild. Factor VIIIC:Ag was undetected in 36 haemophiliacs (CRM-) while VIIIC:Ag was detected in levels exceeding or correlating with those of VIII:C in 17 cases (CRM+). Four severe, CRM- haemophiliacs were found to have inhibitors. An assay of IX:Ag in 6 severely and 2 moderately affected patients with haemophilia B revealed 6 to be CRM- while 2 were CRM+. Multimer pattern analysis was performed on 11 von Willebrand disease patients, of which 5 were type I, 5 were type II and 1 was type III. More informative techniques for the diagnosis and classification of haemophilia are now available. In addition, these results will assist in further molecular studies of these disorders.

Electrophoresis, Agar Gel↗
PubMed1989

Compliance with chemotherapy in childhood leukaemia in Africa.

Compliance with chemotherapy in childhood leukaemia is usually good because of parental fear of the disease. However, poor compliance and refusal of treatment have been reported from both the USA and the UK. Little is known about African concepts of leukaemia, attitudes to treatment or compliance. A study was undertaken to investigate factors which might affect compliance in 15 black and 30 white families of leukaemic children in Johannesburg. The socio-economic and educational status of the black families was lower than that of the white. Only 53% of black children attended hospital on the appointed day compared with 90% of white children. Less than 50% of black parents understood the nature of their child's illness. Both black and white families had unused medication at home. White parents more frequently reported toxic effects related to chemotherapy and more white children than black children exhibited lymphopenia during maintenance therapy. Assessment of drug compliance should be included as an independent variable when evaluating factors affecting response to chemotherapy in communities of diverse ethnic, socio-economic and cultural backgrounds.

Black or African American↗
PubMed1989

Comparisons of cause of death verification methods and costs in the lipid research clinics program mortality follow-up study.

Classification of causes of death by a nosologist is standardized and relatively inexpensive, although the quality of the data recorded on death certificates has been subjected to criticism and the level of detail may not allow examination of specific circumstances of the death. A costly alternative is classification by a panel of physicians reviewing additional clinical information. The costs associated with both methods of classification as utilized by the Lipid Research Clinics Program Mortality Follow-up Study are presented along with their advantages and disadvantages. For deaths among the elderly (65 years or older), determination of the underlying cause of death may be difficult, especially as regards cardiovascular disease causes of death using only the death certificate, and impossible for classifying sudden death. Both classification methods are compared for 268 deaths among the elderly and 155 deaths among the nonelderly males and females participating in the study. The kappa statistics for observer agreement indicate moderate agreement (k = 0.58) and were not significantly different between the two age-groups (p greater than 0.10). Thus, the agreement between the methods was not affected significantly by the age of the deaths being classified. However, examination of the agreement chart showed a preference by the nosological classification for cardiovascular classification in the elderly population. The effect of the different classifications upon the analysis of the predictive value of high-density lipoprotein cholesterol on coronary heart disease mortality showed little difference between both methods of classification.

Adult↗
PubMed1987

Long duration Jakob-Creutzfeldt disease.

The first patient was a woman hospitalized at the age of 43 years; she received the diagnosis of presenile dementia because of a progressive deterioration of her intellectual functions over an interval of 3 years. On admission there were no localizing neurological findings. During the ensuing years she became unable to speak and was no longer able to respond to commands. Death occurred at the age of 46 years from bronchopneumonia. The brain showed marked atrophy of the frontal lobes, moderate in the temporal lobes. The anterior horns of the lateral ventricles were greatly dilated. Microscopically cortical atrophy was severe, with marked depletion of neurons in involved regions. Lamination and polarity were not preserved. There was considerable increase of astrocytes and microglia, and focal sponginess was prominent. The hippocampus showed atrophy of Sommer's sector and subiculum. There were no neurofibrillary tangles and no argyrophilic plaques. The occipital sections showed little neuronal loss and no increased astrocytes or sponginess. The insulae showed neuronal loss and gliosis. There was bilateral atrophy of the caudate nuclei and globus pallidus adjacent to the dystrophic anterior limbs of the internal capsule. In the brain stem the frontopontine tracts were partially demyelinated and showed reactive gliosis. Ventral horns were atrophic with moderate glial reaction. In the second patient the microscopic changes were quite similar to those in Case 1, but there was more severe degeneration of the corticospinal tracts and the ventral horns of the spinal cord which showed considerable loss of neurons and degenerative changes in the remaining nerve cells and nerve fibers. There were many instances of axonal degeneration.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1987

Lipoproteins as mediators for the effects of alcohol consumption and cigarette smoking on cardiovascular mortality: results form the Lipid Research Clinics Follow-up Study.

Because alcohol consumption is associated with increased high density lipoprotein (HDL) cholesterol and decreased low density lipoprotein (LDL) cholesterol, and cigarette smoking is associated with lower HDL cholesterol and higher LDL cholesterol, there has been speculation that the protective effect of moderate alcohol consumption and/or the noxious effect of cigarette smoking for cardiovascular disease might be mediated in large part by a lipoprotein mechanism. The authors examined this question in a prospective study of 7,461 men and women in 10 North American populations initially seen in 1972-1976 and followed for an average of 8.5 years. Moderate alcohol consumption was weakly protective for cardiovascular disease, while cigarette smoking was strongly and significantly associated with cardiovascular disease mortality. As expected, LDL cholesterol was positively related and HDL cholesterol was inversely related to cardiovascular disease mortality. However, multivariable analysis of cardiovascular disease mortality alternately excluding and including HDL cholesterol and LDL cholesterol as covariates indicated that the effect of alcohol consumption on cardiovascular disease mortality was independent of an LDL cholesterol pathway and only partially mediated by an HDL cholesterol pathway, while the effect of cigarette smoking was independent of both the HDL cholesterol and LDL cholesterol pathways, suggesting alternative biologic mechanisms of action for both alcohol consumption and cigarette smoking on cardiovascular disease.

Adult↗
PubMed1986

Acute childhood leukemia in Johannesburg. Ethnic differences in incidence, cell type, and survival.

Acute childhood leukemia was found to be less common in black children than in white children in the Johannesburg area of South Africa. Of 195 consecutive patients, 78 were black and 117 white. The annual incidence was 0.8/100,000 black children and 3.3/100,000 white. The low incidence in black children was due to the very low incidence of acute lymphoblastic leukemia (ALL), which was 0.41/100,000 black children compared with 2.73/100,000 white children. The incidence of acute nonlymphoblastic leukemia (ANLL) was approximately the same for both ethnic groups; 0.38/100,000 black children and 0.57/100,000 white children. Remission rates for black children with ALL were lower than for white children and the cumulative proportion of black patients surviving at 60 months was only 32% compared with 72% of white patients (p = 0.0001). The most significant poor prognostic factors in ALL were ethnic group and age (p = 0.0006), CNS disease at onset (p = 0.006), FAB L2 and L3 morphology (p = 0.05), and irregular clinic attendance during maintenance therapy (p = 0.05). In ANLL, remission and survival rates were less favorable than in ALL but there were no significant differences between black and white patients. Black patients exhibited certain clinical features rarely seen in white patients, including chloromata, oropharyngeal lesions, and CNS involvement at onset. Karyotypic abnormalities were common. The most significant poor prognostic factors in ANLL were CNS disease at onset (p = 0.03), generalized lymphadenopathy (p = 0.0001), and FAB morphology classification M3-M6 (p = 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Disease↗