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Biomedical subjects

J Nelson

Publications and source records attributed to J Nelson.

At least 127 records · Page 7Linked to original sources
PubMed1996

Neurological Symptoms, Not Signs, Are Common in Early HIV Infection.

UNLABELLED: Objective. To examine the cross-sectional prevalence of neurological symptoms and signs in a large cohort of human immunodeficiency virus (HIV)-seropositive men, and determine the relationship of the symptoms to disease stage, immunologic markers, and independent variables from neuropsychological (NP) testing and psychiatric interview. METHODS: One hundred-nine controls and 386 HIV-infected volunteers enrolled in the HIV Neurobehavioral Research Center (HNRC) longitudinal study. The majority, without acquired immune deficiency syndrome (AIDS), were screened for alcohol/substance abuse; previous diagnosis of HIV-associated dementia; and HIV-unrelated developmental, neurological, medical, and neurobehavioral conditions which potentially impair cognition; and underwent a structured neurological interview and examination, standardized NP testing, and psychiatric interview as part of a more extensive battery. A large subset (N = 377) underwent lumbar puncture for cerebrospinal fluid (CFS) examination. We examined the relationship of sixteen select but independent variables, using stepwise multiple regressions, from demographic/staging, immunological, NP, and psychiatric domains to neurological symptoms in an effort to identify possible predictors of subclinical nervous systems involvement. Results. All categories of neurological symptoms were significantly more prevalent among medically asymptomatic (CDC stage A) subjects than controls, with a further rise in prevalence in those with more advanced stages of infection. The most marked rise was seen in cognitive and sensorimotor complaints. In contrast, significant findings on neurological examination were evident in only the sicker (stage C) subjects. Stage of illness, serum β2-microglobulin, psychiatric indices of depressed mood or anxiety, and NP "motor" performance were the most significant independent variables associated with the presence of neurological symptoms. CSF pleocytosis was seen early (CDC stage A), and may reflect the presence of HIV in the central nervous system (CNS) at the least stages of infection. We also confirmed the value of CSF β2m and neopterin as important markers of advancing disease stage. Whether they predict subclinical CNS involvement is to be determined by longitudinal observations. Conclusion. Neurological complains are common in medically asymptomatic HIV subjects whereas signs are not. The symptoms correlate with commonly determined independent measures of depression, anxiety, NP tests of fine motor speed and strength, as well as indices of disease worsening (CDC stage, serum β2m).

AIDS Dementia Complex↗
PubMed1996

Transformation of essential thrombocythaemia to T cell acute lymphoblastic leukaemia.

Leukaemic transformation of essential thrombocythaemia is a rare event and is usually associated with previous treatment with either alkylating agents or radioactive phosphorous. We describe a patient with essential thrombocythaemia who developed an acute leukaemia of T cell phenotype following hydroxyurea therapy. The T cell phenotype of the blasts suggests the target cell for leukaemic transformation was a pluripotential stem cell.

Aged↗
PubMed1996

Antenatal phenobarbital therapy and neonatal outcome. II: Neurodevelopmental outcome at 36 months.

OBJECTIVE: To evaluate the effect of antenatal phenobarbital (PB) therapy on neurodevelopmental outcome at 36 months. DESIGN: Prospective, randomized, controlled trial. SETTING: Single-institution study. SUBJECT AND INTERVENTIONS: Children born to women who participated in the study evaluating the effect of antenatal phenobarbital (PB) on neonatal intracranial hemorrhage were prospectively followed to 3 years of age. OUTCOME MEASURES: Physical growth, neurologic examinations, and developmental testing (McCarthy Scales of Children's Abilities). Comparisons between groups were made on all children and those born to multiple gestations. RESULTS: Forty-one children born to women who received 10 mg/kg PB before delivery and 55 children in the control group were evaluated. Three children, all in the control group, had growth parameters (height, weight, and head circumference) below the fifth percentile. The McCarthy General Cognitive Index (standard, 100 +/- 16) was 93 +/- 20 in the PB group and 85 +/- 18 in the control group. The subscores tended to be higher in the PB group than in the control group, with higher quantitative scores in the PB group (44 +/- 11 vs 39 +/- 8). Neurologic deficits were noted in 2 of 41 in the PB group and in 6 of 55 in the control group. CONCLUSIONS: Infants born to women who received antenatal PB therapy had similar neurodevelopmental outcomes as infants born to women who did not receive PB. No adverse effects of PB exposure were detected.

Anticonvulsants↗
PubMed1996

Lifestyle change for coronary artery disease. What to tell patients.

Heart-healthy living is a wise choice for anyone, but it assumes even greater importance in persons who have or are at risk for coronary artery disease. Such patients need to know which measures have proved most effective in the prevention and treatment of the disease. This article reviews the data regarding risk factor reduction and offers recommendations for effective lifestyle modifications.

Alcohol Drinking↗
PubMed1996

Screening for coeliac disease as a possible maternal risk factor for neural tube defect.

Coeliac disease is an important cause of malabsorption, particularly of folic acid, in adults. We investigated the possibility that it might be a maternal risk factor for neural tube defect (NTD)-associated pregnancy by screening affected mothers using serum endomysial antibody (EmA) which has high sensitivity and specificity for coeliac disease. One (1.6%) of 60 patients was EmA positive and had a diagnosis of coeliac disease confirmed by the finding of villous atrophy on jejunal biopsy. In conclusion, the majority of NTD-associated pregnancies are not associated with maternal coeliac disease and our study is additional evidence that abnormalities of folic acid metabolism rather than absorption are the most important risk factors for NTD. Further studies are needed to determine whether the coeliac disease prevalence among women with NTD-affected pregnancy is higher than that of the general population.

Adult↗
PubMed1996

Betaseron: a breakthrough treatment for multiple sclerosis.

Multiple sclerosis (MS) is the most common cause of disability in young adults; in Canada, it affects 1 in 1,000 people. A chronic and complicated demyelinating autoimmune disorder of the central nervous system, MS has no known cure. Indeed, there has been no effective treatment until recently.

Adjuvants, Immunologic↗
PubMed1995

Delayed density-dependence in a small-rodent population.

The role of delayed density-dependent processes in the dynamics of animal populations poses a problem for ecologists; although generally assumed important in populations that show cyclic or chaotic fluctuations, little experimental evidence for such processes exist. Through manipulation of vole densities within enclosed areas it was shown that reproduction, recruitment, and body growth rate in introduced populations were negatively affected by high previous density. In addition, female movement patterns shifted, and territoriality as well as home-range size was increased after high density. The observed changes in female spacing-behaviour suggested that negative effects of previous density were partly mediated by social interactions, and agreed with the finding that smaller (less competitive) females were the ones suffering most from increased competition. Contrary to expectations from recent work, predation could be excluded as the cause of delayed density-dependence in this study. Instead, chemical analyses of a dominating food plant suggested that herbivory at high vole-density had delayed negative effects on food quality.

Animals↗
PubMed1995

Effects of pravastatin with niacin or magnesium on lipid levels and postprandial lipemia.

This study was designed to evaluate the therapeutic effectiveness of 3 different pharmacologic lipid-lowering regimens in the treatment of patients with clustered lipid risk factors. Sixty-five patients with low high-density lipoprotein (HDL) levels and hypertriglyceridemia were randomized to 1 of 3 treatment arms: pravastatin/niacin, pravastatin/magnesium, or pravastatin/placebo. After 18 weeks, patients in the pravastatin/niacin group had a -41% change in the total cholesterol/HDL ratio compared with -13% in the pravastatin/magnesium arm and -16% in the pravastatin/placebo group. The HDL2 and HDL3 subfractions, as well as the apolipoprotein A-I levels, were increased significantly only in the pravastatin/niacin arm. The levels of small dense low-density lipoprotein (LDL) cholesterol (LDL3) were decreased to a greater extent in the pravastatin/niacin arm (-43%) than in either the pravastatin/magnesium (-13%) or the pravastatin/placebo (-20%) arm. Only the pravastatin/niacin regimen significantly diminished postprandial lipemia (-32% change in the remnant particle triglyceride concentration and decreased very-low-density lipoprotein remnant levels). Thus, in this group of patients with clustered risk factors, the combination of pravastatin and niacin resulted in significant improvements in HDL and triglyceride levels, total cholesterol to HDL ratio, small dense LDL levels, and postprandial lipemia. Pravastatin alone or in combination with magnesium resulted in less significant changes that were largely limited to LDL cholesterol reduction.

Adult↗
PubMed1995

Murine epidermal growth factor (EGF) fragment (33-42) inhibits both EGF- and laminin-dependent endothelial cell motility and angiogenesis.

Laminin, murine epidermal growth factor (mEGF), and the synthetic laminin peptide Lam.B1(925-933) (a linear peptide from the B1 chain of murine laminin, CDPGY1GSR-amide) all stimulate endothelial cell motility above basal rates, whereas a synthetic mEGF fragment, mEGF33-42 (a linear peptide from the C-loop of mEGF, acetyl-C-[S-Acm]-VIGYSGDR-C-[S-Acm]-amide), inhibits motility. In both human SK HEP-1 and embryonic chick endothelial cells, mEGF33-42 blocks both EGF- and laminin-stimulated locomotion of endothelial cells. In vivo, mEGF33-42 also blocks both laminin- and mEGF-induced angiogenesis in the chick. In the human cell line. Lam.B1(925-933) has an additive effect in coincubation with either laminin or mEGF, but it blocks their effects in the chick cells. Lam.B1(925-933) alone stimulates angiogenesis in the chick but blocks laminin-induced angiogenesis. Thus, mEGF33-42 acts as a general laminin antagonist, whereas Lam.B1(925-933) acts as a laminin agonist in human cells, but in chick cells it acts as a partial antagonist. We propose that the presence of an anionic group at the eighth residue of mEGF33-42 may be the source of the antagonistic effects seen with this peptide as compared with the laminin fragment. These findings have important implications in the design of human antiangiogenic agents, and also in the use of chick models in the study of human disease.

Amino Acid Sequence↗
PubMed1995

Small patella syndrome.

We report on 2 sporadic cases of small patella syndrome (coxo-podo-patellaire syndrome) most probably representing new mutations. Both children showed retarded patellar bone age (small patellae in Patient 1 and absent patellae in Patient 2) and pelvic abnormalities. Patient 1 who was fully investigated had an unusual facies with characteristic morphological abnormalities of the forefoot and generalized bone changes. Patient 2 was not available for examination and only X-ray films of his knees, pelvis, and chest were available. These were all abnormal. He was said to have an "unusual facies" with flattened nose and prominent forehead but no further information was available. We think that small patella syndrome (coxo-podo-patellaire syndrome) is a generalized bone dysplasia with morphological and diagnostic radiographic appearances.

Adolescent↗
PubMed1995

Peripheral blood stem cell transplants for multiple myeloma: identification of favorable variables for rapid engraftment in 225 patients.

Transfusion of autologous peripheral blood stem cells (PBSCs) of good quality ensures fast hematopoietic engraftment after myeloablative therapy with a decrease in procedure-related morbidity and mortality. We have analyzed variables influencing the kinetics of engraftment, and therefore reflecting the quality of PBSC collections, in 225 patients with newly diagnosed or refractory multiple myeloma (MM) who received an autotransplant in support of high dose melphalan (200 mg/m2); 132 of these patients also completed a second transplant. All PBSCs were collected before the first transplant after high-dose cyclophosphamide (6 g/m2) and hematopoietic growth factors, mainly granulocyte-macrophage colony-stimulating factor. PBSCs were administered either alone (91 patients) or with bone marrow (134 patients). A highly significant correlation was observed between the number of CD34+ cells per kilogram infused and prompt recovery of both granulocytes (P = .0001) and platelets (P = .0001). After correction for the proportion of patients with > or = 2 x 10(6)/kg CD34 PBSCs infused and with < or = 12 months of prior therapy, no difference in engraftment kinetics was seen between patients receiving PBSCs only and those also receiving bone marrow. Exposure to chemotherapy, even to < or = 6 months of alkylating agents, significantly delayed hematopoietic recovery posttransplantation. The threshold dose of CD34 cells necessary for prompt engraftment was > or = 2.0 x 10(6)/kg for patients with < or = 24 months of chemotherapy before the first transplant, whereas greater than 5 x 10(6)/kg CD34 cells were required to assure rapid recovery also in those with longer exposure. Such quantities, easily collected in the large majority of patients with shorter exposure (91%), were obtained in only 28% of patients with more than 24 months of prior chemotherapy. Rapid platelet recovery within a narrow range of time (before day 14) was almost invariably seen (94%) when greater than 5 x 10(6)/kg CD34 cells were infused, irrespective of the duration of prior therapy, whereas the range widened progressively when less CD34 cells were infused. In the absence of CD34 measurements, fast recovery of platelets to greater than 50 x 10(9)/L within 14 days after high-dose cyclophosphamide and < or = 12 months of prior chemotherapy were the best predictors of early engraftment. Prudent use of stem cell-damaging agents, such as melphalan and nitrosoureas, is recommended in MM patients who might be candidates for autotransplantation. Alternatively, PBSCs should be collected early after diagnosis.

Adult↗
PubMed1995

Characterization of the mouse lymphotoxin-beta gene.

Lymphotoxin-beta (LT-beta) is a member of the TNF family of ligands which when expressed with lymphotoxin-alpha (LT-alpha, i.e., the original LT or TNF-beta) forms a heteromeric complex with LT-alpha on the cell surface. The mouse gene structure was determined by both cDNA cloning and analysis of a genomic DNA fragment encompassing the TNF/LT locus in the H-2 region of chromosome 17. The mouse and human genomic structures were found to be similar in terms of location in the class III region of the MHC; however, the mouse gene lacks one intron found in most members of the family. Both the cDNA and the genomic sequences revealed an altered splice donor in the conventional intron 2 position, rendering it nonfunctional. The altered gene retains an open reading frame such that an additional 66 amino acids are inserted into the stalk region connecting the transmembrane domain with the receptor binding domain encoded by exon 4 in this type II membrane protein. Northern analysis showed that this gene is expressed predominantly in lymphoid organs. The outlining of the complete mouse TNF locus will further studies of the relationship between these genes and immune function.

Amino Acid Sequence↗
PubMed1995

Carboxyfluorescein and biotin neuromedin C analogues: synthesis and applications.

Two neuromedin C (NC) analogues were constructed by Fmoc synthesis and in situ coupling of 4(5)-carboxyfluorescein or biotin to the N-terminus. Both displayed full agonism in an amylase release assay and cross-reacted fully with a NC-specific antiserum. Biotin NC functioned in a streptavidin-capture ELISA. Carboxyfluorescein NC was used to probe receptor localization in rat stomach. Specific NC binding sites, which did not interact with substance P, angiotensin I, or neurokinin A, were labeled in the antrum. Identity of NC binding sites was confirmed by microautoradiography. The specifically labeled cells were all found in the lamina propria and at least some of cells were identified as eosinophils.

Amylases↗
PubMed1995

Prospective study of adenovirus antigen detection in eye swabs by radioimmune dot-blot.

Rapid laboratory diagnosis of ocular adenovirus infection is crucial in the containment of nosocomial transmission of the virus. In a large prospective study of adenovirus assay in eye swabs, antigen detection by radioimmune dot-blot (turnaround time 72 hours) achieved a sensitivity of 67% (239/355) and a specificity of 93% (3065/3285) in comparison with virus culture (median turnaround time 14 days). When specimens weakly reactive for adenovirus antigen, or equally reactive for both adenovirus antigen and Chlamydia trachomatis antigen, were considered falsely reactive in the adenovirus test, the sensitivity of the latter was reduced and false positive reactions were only marginally less frequent. The radioimmune dot-blot provides a more rapid diagnosis of ocular adenovirus infection than virus culture, but the high risk of false negative and in particular false positive results limits its clinical utility.

Adenovirus Infections, Human↗
PubMed1995

Insensitivity to anti-müllerian hormone due to a mutation in the human anti-müllerian hormone receptor.

Anti-Müllerian hormone (AMH) and its receptor are involved in the regression of Müllerian ducts in male fetuses. We have now cloned and mapped the human AMH receptor gene and provide genetic proof that it is required for AMH signalling, by identifying a mutation in the AMH receptor in a patient with persistent Müllerian duct syndrome. The mutation destroys the invariant dinucleotide at the 5' end of the second intron, generating two abnormal mRNAs, one missing the second exon, required for ligand binding, and the other incorporating the first 12 bases of the second intron. The similar phenotypes observed in AMH-deficient and AMH receptor-deficient individuals indicate that the AMH signalling machinery is remarkably simple, consisting of one ligand and one type II receptor.

Alternative Splicing↗