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Biomedical subjects

S Abid

Publications and source records attributed to S Abid.

At least 19 recordsLinked to original sources

Analysis of monoclonal antibody chimeric BR96-doxorubicin immunoconjugate by sodium dodecyl sulfate-capillary gel electrophoresis with ultraviolet and laser-induced fluorescence detection.

Sodium dodecyl sulfate-capillary gel electrophoresis (SDS-CAGE), the capillary version of SDS-polyacrylamide-based slab gel electrophoresis, has been utilized for the separation and analysis of monoclonal antibody chimeric BR96 and the corresponding immunoconjugate prepared between BR96 and the anticancer drug doxorubicin (BR96-DOX). SDS-CAGE was performed in a coated capillary column filled with a polymer solution-based gel network matrix. Two detection formats, a uv absorbance detector and an argon-ion laser-based fluorescence detector, were incorporated into this system, providing complementary information for the determination of conjugated species. Both monoclonal antibody and immunoconjugates were studied in their native, denatured, and denatured and reduced states, respectively. Six peaks were identified following separation of the denatured BR96-DOX. These peaks were confirmed to correspond to all the possible conjugated species as expected. Analysis of the resulting "fingerprint" maps indicated that the light, heavy, and light-heavy chain conjugates are the predominant species. SDS-CAGE offers an alternative approach to the conventional slab gel electrophoresis and other chromatographic techniques, providing rapid, efficient, sensitive, and accurate information for the analysis of antibody and bioconjugates.

Antibodies, Monoclonal

[Study of class I HLA polymorphism in the Tunisian population].

The HLA class I gene polymorphism (HLA-A, -B) was investigated in a population of 102 Tunisians. Allele and haplotype frequencies as well as linkage disequilibrium between HLA-A and HLA-B loci were calculated and compared with other populations. The most frequent alleles were A2 (23%), A30 (12.5%), A3 (10.2%), A1 (8.5%), A23 (7.4%) for the HLA-A locus and B21 (14.3%), B44 (11.4%), B35 (9.6%), B5 (8.5%) for the HLA-B locus. The most frequent haplotype was A3 B21 (2.6%) and a positive linkage disequilibrium was found for the following allelic associations: A11 B35 (X2 = 6.8), A28 B35 (X2 = 5.3), and A30 B35 (X2 = 5). In conclusion, a specific distribution of HLA class I components in terms of antigen and haplotype frequencies characterizes the Tunisian population. This specific pattern may reflect the great ethnical diversity of this community. All these informations may be helpful in the future for HLA and disease association studies.

Alleles

Cholera admissions in adults 1989-1994: a hospital based study.

In order to gain insight into the distribution of cholera over the years and proportion of monthly admissions under our adult medical services, we scrutinized our records of hospital discharges between 1989 and 1994. Only culture positive cases were included. Each year most of the cases of cholera are admitted between May and November with almost disease free interval from December to April. In 1992 admission rate was 4.24/1000 medical admissions which increased to 12.65 in 1993 and 13.73 in 1994. Though the Vibrio cholerae 01 Ogawa was the major isolate upto May, 1993, Vibrio cholerae non-01 serogroup 0139 dominated between June and August, 1993. Ogawa strain re-established itself in October, 1993. In August, 1994, non-01 strain reappeared and became the major isolate in September. Cholera has caused multiple epidemics throughout the Indian subcontinent. Since 1800, there have been seven pandemics of cholera. The seventh pandemic originated in Indonesia and continues today.

Adolescent

[HCV antibodies in hemodialyzed patients in Tunisia].

The prevalence of seropositivity to Hepatitis C and B virus and HIV infection in Haemodialysis patients was assessed in sera from 235 patients from 6 dialysis units in Tunisia. Anti-HCV antibodies were found in 106 patients (45.10%), the hepatitis B surface antigene was found in 19 patients (8%), and no case of HIV infection was found. Anti-HCV positivity was correlated with duration of dialysis (p < 0.001). There was no correlation between anti-HCV positivity and the number of transfusions.

Adult

[ABO system polymorphism in the Tunisian population].

A survey carried out on 18820 Tunisian blood donors enabled us to evaluate the distribution of ABO blood group in Tunisia. The genic frequencies in ABO system were as follows: A(0,192), B(0,122), O(0,686).

ABO Blood-Group System

Treatment of achalasia: the best of both worlds.

OBJECTIVE: To conduct a retrospective analysis of one center's experience with treating achalasia over 4 yr with skilled gastroenterologists using primarily the Rigiflex balloon dilator and with a senior surgeon performing Heller myotomies. METHODS: Newly diagnosed cases of achalasia were identified by a computer search of hospital records. Charts were reviewed for the presence/severity of dysphagia, regurgitation, heartburn, and chest pain. Weight loss was also recorded. Esophageal manometries and barium swallows were reviewed. Choice of treatment was made freely by patients. With an a priori definition of success, follow-up was conducted by telephone interviews. RESULTS: A total of 45 achalasia patients (mean age, 46 yr; 32 females, 13 males) were identified with a symptoms-frequency as follows: dysphagia, 100%; regurgitation, 78%; heartburn, 50%; and chest pain, 42%. Mean weight loss was 17.5 pounds. Primary treatment was pneumatic dilation in 36 patients and surgery in nine patients. In a total of 45 pneumatic dilations, three (6.6%) were complicated by perforation. Five (14%) patients required repeat dilation. Mean duration of follow-up for pneumatic dilation and surgery was 27 months and 20.8 months, respectively. The overall excellent-good success rates were: pneumatic dilation 88% and surgery 89%. In comparing the efficacy of pneumatic dilation versus surgery, all symptoms were improved significantly (p < 0.01) in both groups, except heartburn, which increased postmyotomy. CONCLUSIONS: If both procedures are available by skilled operators, pneumatic dilation and surgery are equally effective in the treatment of achalasia.

Adolescent

Oncostatin M is a mitogen for rabbit vascular smooth muscle cells.

The growth regulatory protein oncostatin M was initially discovered in macrophage-conditioned medium. We investigated the effects of oncostatin M on cultured rabbit aorta smooth muscle cells (SMCs) and found that the peptide stimulated an increase in the incorporation of [3H]thymidine into DNA. The magnitude of the stimulation was dependent on oncostatin M concentration and SMC confluency. In subconfluent cultures, 1-2 nM stimulated 4- to 5-fold increases in DNA synthesis after 20 hr. Other structurally related cytokines (granulocyte colony-stimulating factor, leukemia inhibitory factor, interleukin 6, ciliary neurotrophic factor) did not affect SMC DNA synthesis. After 5 or 8 days, oncostatin M caused a doubling in SMC number and also induced a transformed phenotype. The combination of oncostatin M and platelet-derived growth factor for 8 days resulted in a 4-fold increase in cell number, approximately the same increase in cell number as induced by the addition of 10% fetal calf serum. Further investigation suggested that the mitogenic effect of oncostatin M was in part due to tyrosine kinase activation. Within 1-2 min, the factor increased phosphotyrosine levels of several SMC proteins. In addition, detectable increases in diacylglycerol levels occurred within 2-5 min, reached 50% above control by 30 min, and remained elevated through 45 min of incubation with oncostatin M. SMC inositol phosphate levels were also elevated within 2 min and then returned to near control values by 20 min. Within 30 min, oncostatin M induced expression of the immediate-early gene EGR-1. These data indicate that oncostatin M may be an important, naturally occurring mitogen for vascular SMCs.

Animals

Lyme disease and pregnancy outcome: a prospective study of two thousand prenatal patients.

OBJECTIVE: The purpose of the study was to determine if prenatal exposure to Lyme disease was associated with an increased risk of adverse pregnancy outcome. STUDY DESIGN: Approximately 2000 Westchester County, New York, women completed questionnaires and had sera tested for antibody to Borrelia burgdorferi at their first prenatal visit and at delivery. Fetal death, birth weight, length of gestation at delivery, and congenital malformations were examined in relation to maternal Lyme disease exposure before and during pregnancy. RESULTS: Maternal Lyme disease or an increased risk of exposure to Lyme disease was not associated with fetal death, decreased birth weight, or length of gestation at delivery. Tick bites or Lyme disease around the time of conception was not associated with congenital malformations. Tick bites within 3 years preceding conception were significantly associated with congenital malformations, but this could have reflected reporting differences between exposed and unexposed women. CONCLUSIONS: Maternal exposure to Lyme disease before conception or during pregnancy is not associated with fetal death, prematurity, or congenital malformations taken as a whole. We have not ruled out the possibility that exposure to Lyme disease as defined by maternal history increases the risk of specific malformations or has an effect if it is not treated. We have insufficient numbers of women who were seropositive at their first prenatal visit to determine if this subgroup of exposed women are at a moderately increased risk of having a child with a congenital abnormality. The low frequency of seroconversion at delivery in this endemic area suggests that preventive measures are being taken by obstetricians and patients.

Congenital Abnormalities

Prostacyclin agonists reduce early atherosclerosis in hyperlipidemic hamsters. Octimibate and BMY 42393 suppress monocyte chemotaxis, macrophage cholesteryl ester accumulation, scavenger receptor activity, and tumor necrosis factor production.

We determined the effects of two prostacyclin agonists (octimibate and BMY 42393) on the progression of the fatty streak in vivo and on macrophage function in vitro. Hamsters were fed chow plus 0.05% cholesterol and 10% coconut oil. Control hamsters were compared with animals receiving either octimibate (10 or 30 mg/kg per day) or BMY 42393 (30 mg/kg per day). After 10 weeks of treatment, octimibate decreased plasma total cholesterol and triglycerides by 43% and 32%, respectively. Neither agonist affected blood pressure or heart rate. Lesion-prone aortic arches were stained with hematoxylin and oil red O and examined en face. Compared with controls, octimibate and BMY 42393 on average decreased mononuclear cells attached to the luminal surface by 44% and reduced subendothelial macrophage-foam cell number by 56%, foam cell size by 38%, and fatty streak area by 63%. Since octimibate is a putative inhibitor of acyl coenzyme A cholesterol acyltransferase, we studied the effect of both agents on cholesteryl ester metabolism in murine macrophages. At 10 microM, octimibate and BMY 42393 decreased cholesteryl ester accumulation in macrophages by 90% and 41%, respectively. Octimibate inhibited cholesteryl ester synthesis by 96% and increased the rate of cholesteryl ester degradation by 52%. Both prostacyclin agonists reduced macrophage scavenger receptor-mediated uptake of acetylated low density lipoprotein by 24-66% and increased cyclic adenosine monophosphate levels. Octimibate and BMY 42393 inhibited the secretion of tumor necrosis factor by 80-88% when macrophages were activated with lipopolysaccharide. At 10 microM, both agents decreased human monocyte chemotaxis to N-formyl-methionyl-leucyl-phenylalanine by 64-79%. The in vitro results with octimibate and BMY 42393 are consistent with the low number of small foam cells quantified in vivo. We suggest that octimibate and BMY 42393 suppress monocyte-macrophage atherogenic activity and cytokine production and thus inhibit the development of early atherosclerosis.

Animals

Microscopic colitis: a diagnosis to consider.

Microscopic colitis is a syndrome of chronic watery diarrhoea for which no cause can be identified other than the presence of diffuse, chronic inflammation in the lamina propria on colonic biopsy. Endoscopically and radiologically the colon appears normal. We studied case records of 215 patients presenting to our institution over a three year period with chronic diarrhoea. Nineteen patients were included in the study where two pathologists agreed on the presence of chronic inflammation on colonic biopsies. All patients had watery diarrhoea with urgency. Stool examination, laboratory indices, radiology of the large and small bowel and colonoscopy were normal in all patients. Patients did not respond to a variety of drugs. A significant improvement was noted in one patient given salazopyrin. In developing countries chronic diarrhoea is most often attributed to infection and treated with antibiotics. Microscopic colitis should be considered in the diagnosis of such patients.

Adult

Yet another cause of chronic viral hepatitis?

The clinical features, course and histology of liver in 20 patients; mostly middle aged to elderly females, closely resembling chronic Non A Non B hepatitis is presented. They presented quite late in their disease and therefore, complications such as variceal bleeds, ascites and encephalopathy were frequent. Our patients were negative for hepatitis B and C virus serology. Metabolic and immune causes of chronic liver disease were also ruled out. To the best of our knowledge, this is the first study of its kind elaborating the clinical features, course and histology of liver in chronic Non B Non C hepatitis and raises a number of questions as to the nature of the infecting virus and the epidemiology of disease.

Chronic Disease

Supervised training of practical procedures in the internal medicine residency.

In order to get feedback whether the medical residents are getting adequate supervised training to perform practical procedures, a questionnaire was distributed among the residents asking their involvement in sixteen frequently performed procedures in the medical unit of the Aga Khan University Medical Centre. Though the residents were satisfied about their training in doing lumbar punctures, pleural and peritoneal aspirations, bone marrow aspiration and trephine and chest tubes placement, they showed their concern about training in putting central lines, venous cut downs, cardiac pacing and biopsies. A better schedule training programme, organized subspecialty rotation, continuous evaluation of resident's skill, credentialing procedures and willingness on the part of faculty to teach and residents to learn may improve the training.

Internal Medicine