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Biomedical subjects

S Sood

Publications and source records attributed to S Sood.

At least 91 records · Page 5Linked to original sources

Cutaneous necrosis associated with recombinant interferon injection. Report of three cases with interferon beta-1b and review of the literature.

Interferons are cytokines produced by cells in response to stimulation by certain antigens and infectious agents. In recent years, recombinant interferons have been developed, which have antiviral, antiproliferative, and immunomodulatory functions. Several cutaneous reactions have been reported, including cutaneous ulceration at injection sites. We now report three cases of cutaneous ulceration caused by interferon beta-1b injections. In addition, we review all of the previously reported cases of cutaneous ulceration caused by recombinant interferons and discuss the different mechanisms by which these substances may produce this effect.

Adjuvants, Immunologic↗

Visual evoked responses in megaloblastic anemia.

Pattern shift visual evoked responses (PSVER) were studied in thirty patients suffering from severe megaloblastic anemia (mean Hb level was 4.25 +/- 1.22 g/dL) of nutritional origin. All patients lacked clinical stigmata of visual and neurologic impairment. Mean P100 latency in thirty age and sex matched controls was 96.35 +/- 6.75 ms (range 86-108 ms) and mean amplitude was 10.37 +/- 3.88 microV (range 4.8-20.8 microV). Mean P100 latency in megaloblastic anemia was 114.77 +/- 11.68 (range 91-142) ms, P < 001 vs. control) and mean amplitude was 8.85 +/- 2.8 microV (range 5.1-16.2 microV). Seventy percent cases had prolonged latency of P 100. After correction of anemia with therapeutic doses of vitamin B12 and folic acid in three months (mean Hb level was 12.08 +/- 1.86 g/dL), the mean P100 latency was 105.13 +/- 9.30 ms (range 92-121 ms P < 0.001 vs. controls) and mean amplitude was 10.72 +/- 4.13 microV (range 5.1-21.4 microV). There was significant improvement in P100 latency after correction of anemia (P < 0.01). There was a negative correlation between P100 latency and hemoglobin levels, though it was statistically not significant.

Adolescent↗

Mutation in fibrillin-1 and the Marfanoid-craniosynostosis (Shprintzen-Goldberg) syndrome.

Recent reports have described a distinct and recurrent pattern of systemic malformation that associates craniosynostosis and neurodevelopmental abnormalities with many clinical features of the Marfan syndrome (MFS), an autosomal dominant disorder of the extracellular microfibril caused by defects in the gene encoding fibrillin-1, FBN1 (ref. 8). Additional common findings include other craniofacial anomalies, hypotonia, obstructive apnea, foot deformity, and congenital weakness of the abdominal wall. So far, only 11 cases have been reported precluding the assignment of definitive diagnostic criteria. While it remains unclear whether these cases represent a discrete clinical entity with a single aetiology, they have been pragmatically grouped under the rubric Marfanoid-craniosynostosis or Shprintzen-Goldberg syndrome (SGS). Because of the significant clinical overlap between MFS and SGS, we proposed that they may be caused by allelic mutations. We now report two SGS patients who harbour mutations in FBN1. While it remains unclear whether these mutations are sufficient for the clinical expression of the entire SGS phenotype, these data suggest a role for fibrillin-1 in early craniofacial and central nervous system development. Our recent observation that FBN1 transcript is expressed as early as the 8-cell stage of human embryogenesis is consistent with this hypothesis.

Abnormalities, Multiple↗

Recommendation to include OspA and OspB in the new immunoblotting criteria for serodiagnosis of Lyme disease.

In October 1994, the Second National Conference on the Serologic Diagnosis of Lyme Disease recommended a two-step approach to serological testing. The first step was the performance of an enzyme-linked immunosorbent assay (ELISA); the second step was a confirmatory immunoblot. New criteria for the interpretation of a positive immunoblot were also recommended. The committee decided to omit the 31- and 34-kDa bands (OspA and OspB, respectively) from the choice of bands considered diagnostic for a positive immunoblot. Since we had previously included these in our diagnostic criteria for Lyme disease-positive immunoblots, we reviewed data for all patients attending a Lyme disease center with positive ELISAs and immunoblot assays for Lyme disease from 1 September 1992 to 31 December 1993. The criteria for a positive Western blot (immunoblot) were the presence of 5 or 12 bands, including the 10 recommended by the conference, and the presence of the 31- and 34-kDa protein bands. Of the 136 patients evaluated, 50 were considered to have Lyme disease. Of these 50, 4 (8%) would not have met immunoblot criteria for the diagnosis if the new recommendations were used. Had the 31- and 34-kDa bands been included as part of the diagnostic requirements for immunoblot, these patients would have been included. Although overdiagnosis of Lyme disease appears to be the more frequent problem, our concern is that the exclusion of the 31- and 34-kDa protein bands from the diagnostic criteria may result in the underdiagnosis of Lyme disease by those who would rely too heavily on serological confirmation. The addition of the 31- and 34-kDa bands to those recommended for confirmatory immunoblot should be reconsidered.

Adult↗

Correction of the spontaneous and DEB-induced chromosomal aberrations in Fanconi anemia cells of the FA(C) complementation group by the FACC gene.

Fanconi anemia (FA) cells are hypersensitive to the cytotoxic and clastogenic effects of DNA cross-linking agents. Four complementation groups have been identified to date. The gene (FACC) that corrects the hypersensitivity of one of them, FA(C), has been cloned. In the present study, both the increased spontaneous and diepoxybutane (DEB)-induced chromosomal instability in FA(C) lymphoblastoid cells were corrected by transfection of FACC.

Cell Cycle Proteins↗

Social and living skills of new long-stay hospital patients and new long-term community patients.

OBJECTIVE: The study assessed differences in social behavior skills and everyday living skills in two groups of psychiatric patients: hospital inpatients with stays of between six months and five years (new long-stay patients) and discharged patients who had resided in the community for a similar length of time (new long-term patients). METHODS: In a cross-sectional study based on a point prevalence survey in an outer London psychiatric hospital, 23 new long-stay and 23 new long-term patients were rated using the Social Behaviour Scale (SBS) and Basic Everyday Living Skills (BELS). RESULTS: Mean scores on both scales indicated significantly poorer functioning in the new long-stay group. Ratings on the BELS self-care and domestic skills subscales also indicated poorer functioning in that group. No significant differences between groups were found for the subscales measuring community and social relations skills. Significant gender differences emerged in ratings of domestic skills; men's scores indicated more impairment in the new long-stay group than in the new long-term group, while women's scores were comparable between the groups. CONCLUSIONS: Developing, enhancing, and maintaining skills among new long-stay patients, especially self-care and domestic skills, may facilitate their discharge into supported community settings.

Activities of Daily Living↗

Mean electrical axis of heart in chronic severe anemia.

The mean electrical axis (MEA) of heart was evaluated in 38 patients suffering from chronic severe anemia. It was found that despite cardiomegaly the MEA of heart remains unaffected in chronic severe anemia as compared to age and sex matched control subjects.

Adult↗

Preservation of pulmonary function in the ventilated neonatal piglet with normal lungs.

Little attention has been focused on the progressive pulmonary deterioration which occurs in mechanically ventilated infants with normal or mildly abnormal lungs. We hypothesized that lung function would deteriorate over a 24-hr period in anesthetized neonatal piglets with normal lungs mechanically ventilated at 2 cm H2O PEEP (2PEEP group). We further hypothesized that an intermittent lung inflation procedure consisting of 15 out of 60 min of increasing lung distention (4, 8, 12 cm H2O PEEP), with the remaining 45 min at 2 cm H2O PEEP (Inflation group) would prevent this deterioration in lung function, similar to piglets mechanically ventilated continuously at 6 cm H2O PEEP (6PEEP). Results indicate that 2PEEP piglets experienced progressive deterioration in lung function, including dynamic lung compliance (-42%) and lung resistance (+55%). In contrast, inflation piglets and 6PEEP piglets had no deterioration in lung function. Hemodynamics were similar between groups, although they were the most stable in the 6PEEP group. Histopathological changes were not significantly different. We conclude that (1) prolonged mechanical ventilation at 2 cm H2O PEEP in neonatal piglets resulted in progressive deterioration in pulmonary function, (2) intermittent lung inflation or continuous 6 cm H2O PEEP prevented deterioration, and (3) functional changes occurred without changes in histopathology. Lung inflation strategies other than PEEP can be used to prevent deterioration in lung function which accompanies prolonged mechanical ventilation in anesthetized nonspontaneously breathing piglets with normal lungs.

Analysis of Variance↗

The V-region repertoire of Haemophilus influenzae type b polysaccharide antibodies induced by immunization of infants.

Haemophilus influenzae type b (Hib) is a significant pathogen for young children, and three Hib vaccines (named PRP-OMPC, HbOC, and PRP-T) are currently available for young children. Extensive studies of anti-Hib polysaccharide (PS) antibodies (Abs) have shown that the V regions of Abs against the Hib PS comprise a VH gene in the VH3 gene family and a VL gene from various K kappa and V lambda subgroups. To study immunogenic properties of the three vaccines in young children, we determined the VL subgroups and avidities of anti-Hib-PS Abs induced by the three clinically available conjugate vaccines. Ab avidity was measured by determining the concentration of a Hib-PS oligomer that abrogates half of the binding of immunoglobulin G anti-Hib-PS Abs to microwells. The PRP-OMPC vaccine induced lower-avidity Abs than the prelicensure HbOC vaccine (P = 0.05). When we compared anti-Hib-PS Abs expressing V kappa Ia, V kappa II, and V lambda subgroups, a greater Ab response was induced by the prelicensure HbOC vaccine than other vaccines (P < 0.05). When anti-Hib-PS Abs with the V kappa III subgroup were compared, however, both PRP-T and prelicensure HbOC vaccines induced a comparable response, which in turn was greater than those induced by the PRP-OMPC or the postlicensure HbOC vaccine (P < 0.001). The VL repertoire of Abs induced with the prelicensure HbOC or PRP-T vaccine in young children is dominated (about 80%) by anti-Hib-PS Abs using subgroup V kappa II. However, anti-Hib-PS using V kappa II VL accounts for only about 40% of the total anti-Hib-PS Abs induced with the PRP-OMPC vaccine or the postlicensure HbOC. Our data suggest that immunogenic properties of Hib vaccines in young children vary depending on the vaccine preparations as well as the vaccine types.

Antibodies, Bacterial↗

Effect of vitamin D repletion on testicular function in vitamin D-deficient rats.

Freshly weaned 30-day-old male Wistar rats were fed a vitamin D-deficient diet adequate in calcium and phosphorus for 3 months. On the 120th day of age three different doses of vitamin D were injected intramuscularly into three groups of rats and maintained for another month with water and a normal diet ad libitum. One group was continued with a vitamin D-deficient diet up to the 150th day. One group of animals was killed by decapitation on the 120th day and testicular functions like sperm count in testis and epididymis, testicular glutamyl transpeptidase activity and Leydig cell count as well as body weight were noted. On the 150th day animals of all groups were killed and testicular function was studied. Body weight and testicular function decreased significantly on the 120th and 150th day of age in vitamin D-deficient rats as compared to age-matched normal control rats. Injection of lower doses of vitamin D on the 120th day of age improved testicular function after 1 month whereas administration of a high dose of vitamin D caused a deterioration of the testicular function. The result suggests that retardation of spermatogenesis due to disturbances in Sertoli and Leydig cell function in vitamin D deficiency is reversible and can be corrected by supplementing an optimal dose of vitamin D.

Aging↗

Pulse wave velocity and lipid profile in varicose vein patients.

In 20 varicose vein patients, aged twenty-five to forty-five years, and suffering the disease for more than two years, pulse wave velocity (PWV) of the femoral-dorsalis pedis artery of the lower limbs was measured and compared with that of 20 age-matched normal subjects. Blood pressure and fasting serum total cholesterol level, triglycerides, high density lipoprotein (HDL), low density lipoprotein (LDL), very low density lipoprotein (VLDL) were also estimated for these subjects. PWV showed a significant increase (P < 0.001) in varicose vein patients as compared with control subjects. There was no significant difference either in the blood pressure or lipid profile. It appears that neither hypertension nor atherosclerosis is responsible for the increase in PWV in varicosities. On the basis of the present study, it may be suggested that arteries are also involved in the pathogenesis of varicose veins. The involvement of the arterial tree in the pathogenesis of varicose veins, if given due consideration, may add a new dimension to the understanding of many ill-defined facets of this disease.

Adult↗

Continuous negative extrathoracic pressure and positive end-expiratory pressure. A comparative study in Escherichia coli endotoxin-treated neonatal piglets.

Recent clinical studies have suggested that improvement in pulmonary gas exchange with the use of continuous negative extrathoracic pressure (CNEP) in conjunction with intermittent mandatory ventilation (IMV) may be due to increased pulmonary blood flow. Accordingly, we investigated the effects of CNEP vs positive end-expiratory pressure (PEEP) in ventilated neonatal piglets after Escherichia coli endotoxin was administered to induce pulmonary hypertension. Two experimental groups of piglets with six in each, were subjected to three 30-min alternating periods--6 cm H2O CNEP with 6 cm H2O PEEP, beginning 2 h after endotoxin infusion. End-expiratory lung volume (EELV) increased similarly from baseline (13 +/- 2 mL/kg) with both CNEP (28 +/- 2 mL/kg) and PEEP (29 +/- 2 mL/kg). In addition, the increase in PaO2 from baseline with CNEP (106 +/- 9 to 135 +/- 7 mm Hg) was similar to that with PEEP (114 +/- 11 to 132 +/- 6 mm Hg). Further, no differences were found in dynamic lung compliance, EELV, lung resistance, blood gas indexes, or hemodynamics, including transmural pulmonary artery pressure and pulmonary vascular resistance between CNEP and PEEP. With transpulmonary pressure and transrespiratory pressure equal, CNEP in tandem with IMV is physiologically equivalent to PEEP and IMV.

Animals↗

Fifteen novel FBN1 mutations causing Marfan syndrome detected by heteroduplex analysis of genomic amplicons.

Mutations in the gene encoding fibrillin-1 (FBN1), a component of the extracellular microfibril, cause the Marfan syndrome (MFS). This statement is supported by the observations that the classic Marfan phenotype cosegregates with intragenic and/or flanking marker alleles in all families tested and that a significant number of FBN1 mutations have been identified in affected individuals. We have now devised a method to screen the entire coding sequence and flanking splice junctions of FBN1. On completion for a panel of nine probands with classic MFS, six new mutations were identified that accounted for disease in seven (78%) of nine patients. Nine additional new mutations have been characterized in the early stages of a larger screening project. These 15 mutations were equally distributed throughout the gene and, with one exception, were specific to single families. One-third of mutations created premature termination codons, and 6 of 15 substituted residues with putative significance for calcium binding to epidermal growth factor (EGF)-like domains. Mutations causing severe and rapidly progressive disease that presents in the neonatal period can occur in a larger region of the gene than previously demonstrated, and the nature of the mutation is as important a determinant as its location, in predisposing to this phenotype.

Base Sequence↗