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Biomedical subjects

R Hussain

Publications and source records attributed to R Hussain.

156 records · Page 9Linked to original sources
PubMedDate not supplied

Consanguinity and early mortality in the Muslim populations of India and Pakistan.

Empirical information from studies conducted in Pakistan has indicated a high level of offspring mortality that can be attributed to parental consanguinity even when non-biological variables are controlled. However, with the exception of some small and geographically restricted studies, few comparable data are available on the influence of inbreeding in child survival among the Muslim population of India, which numbers between 100 and 120 million. The present study compares deaths during the first 5 years of life among the offspring of first cousin (F = 0.0625) and non-consanguineous unions (F = 0), using data collected in the 1992-1993 Indian National Family Health Survey (NFHS) and the 1990-1991 Pakistan Demographic and Health Survey (PDHS). The focus was on determinants of mortality in live-born children to age 5 years. In both countries, bivariate analyses indicated that mortality was significantly increased in the offspring of first cousin unions during the neonatal and post-neonatal, total infant, and under-5 year periods. The findings were confirmed by multivariate regression, which incorporated control for a range of biological and demographic factors.

Case-Control Studies↗
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Detection of high titres of Toxoplasma gondii antibodies in sera of patients with leprosy in Pakistan.

Untreated and treated leprosy patients and their household contacts were screened for antibody to Toxoplasma gondii using antigen-coated latex particles. A significantly high level of seroprevalence (29.6%) was observed in the untreated leprosy patients compared to endemic controls (P < 0.01) with a mean reciprocal antibody titre of 20,007 +/- 3580 (n = 98) in seropositive patients. In treated patients seroprevalence dropped to 13.5%. Seroprevalence in a group of household contacts of leprosy patients was similar to that of control subjects from an endemic area but not exposed to leprosy (7.8% and 6.1% respectively), indicating that the increased seroprevalence in leprosy patients was not merely due to increased exposure related to socioeconomic factors. Antigenic cross-reactivity between T. gondii and Mycobacterium leprae antigens was ruled out by cross inhibition experiments carried out with soluble antigens from each of the organisms. We believe these antibodies may be induced by an increase in T. gondii load in leprosy due to a transient reactivation of latent T. gondii infections, as the antibodies in these leprosy patients were not associated with any sign of eye or lymphatic pathology related to toxoplasmosis.

Adult↗
PubMedDate not supplied

Breast cancer imaging with radiolabelled peptide from complementarity-determining region of antitumour antibody.

Specific tumour imaging with radiolabelled monoclonal antibodies has been extensively investigated. Although some success has been reported, there are many limitations due to the slow kinetics, poor extravasation, catabolism by the reticuloendothelial system, and non-specific uptake of macromolecules such as antibodies. We have tried to overcome some of the problems associated with monoclonal antibodies while retaining their specificity by using an antibody-derived synthetic peptide. A synthetic pentadecapeptide (alpha M2) derived from the third heavy-chain complementarity-determining region (CDR-3H) of a tumour-associated monoclonal antibody was produced and shown to retain its specificity against the pan-carcinoma cell-surface antigen, polymorphic epithelial mucin, detected by the parent antibody. The peptide was radiolabelled with technetium-99m and injected intravenously to image malignant lesions in 26 women with primary, recurrent, or metastatic breast cancer. Visualisation of breast tumours and their metastases was obtained shortly after administration of alpha M2, and was optimum by 3 h. Overall, 57 (77%) of 74 sites were visualised. Successful imaging was achieved in 14 of 15 primary tumour sites and all of eight local recurrences. Five of six metastases in the opposite breast, eight of 15 metastatic axillary lymph nodes, and all of six metastatic supraclavicular lymph nodes were imaged. Metastatic sites in the lungs, mediastinum, chest wall, and liver were poorly visualised because of background cardiac blood pool. alpha M2 detected small lesions ( < 2 cm) as efficiently as larger ones. The peptide was rapidly (3 h) cleared from the circulation. No acute or chronic adverse reactions due to the alpha M2 were observed. Specific tumour targeting with the radiolabelled anticancer peptide alpha M2 offers new opportunities for breast cancer imaging and possibly therapy.

Adult↗
PubMedDate not supplied

An analysis of consanguineous marriage in the Muslim population of India at regional and state levels.

Consanguineous marriage is widely favoured in a large majority of the world's Islamic populations. According to recent estimates, the resident Muslim population of India is over 100 million. However, apart from a few numerically small or geographically defined surveys, little is known about their patterns of marriage preferences since partition of the Indian Subcontinent in 1947. This study seeks to determine the prevalence and patterns of consanguineous marriages contracted among Indian Muslims at regional and state levels during the last two generations. Data from the 1992/93 Indian National Family Health Survey (NFHS) were used in the analysis. The NFHS was a nationally-representative survey of ever-married women aged 13-49 years, conducted across 25 states of India. Of the initial 9845 respondents, 8436 were included in the final weighted analysis sample. Overall, 22.0% of marriages were found to be contracted between spouses related as second cousins or closer, ranging from 15.9% in the eastern states to 32.9% in the western states of India. In all parts of the country first cousin marriages were the preferred form of consanguineous union, and in four of the five regions paternal first cousin marriages predominated. Despite predictions to the contrary, there was no evidence of a significant change in the prevalence of consanguineous unions over the course of the study period, which extended from the late 1950s to the early 1990s.

Adolescent↗
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Does inbreeding lead to decreased human fertility?

In most Western countries there is a widespread belief, fostered in part by historical prejudice and religious proscription, that inbreeding in human populations causes a reduction in fertility. Support for this belief has been claimed in HLA-based studies, with increased rates of fetal losses suggested in HLA-compatible unions. To critically assess the overall status of fertility in consanguineous unions, data on 30 populations resident in six countries were collated from a systematic review of the literature. The mean numbers of live births were then compared in four consanguinity test categories, ranging from second cousin to uncle-niece/double first cousin, and corresponding non-consanguineous reference groups. Linear regressions indicated a positive association between consanguinity and fertility at all levels of inbreeding, attaining statistical significance at first cousin level (p < 0.0001). The results were, however, subject to a number of potential limitations, in particular lack of control for important socio-demographic variables. To overcome this problem, data on first cousin marriages were abstracted from the National Family and Health Survey conducted in India during 1992-1993. Multivariate analysis showed that fertility in first cousin unions was positively influenced by a number of variables, including illiteracy, earlier age at marriage and lower contraceptive uptake, but the most important of these parameters were duration of marriage and reproductive compensation. In net terms, consanguinity was not found to be associated either with a significant positive or negative effect on fertility.

Adolescent↗
PubMedDate not supplied

The effect of religious, cultural and social identity on population genetic structure among Muslims in Pakistan.

Knowledge of historical demography and contemporary social stratification can be valuable in understanding disease patterns, including genetic disorders, especially in communities that have a high prevalence of endogamous and/or consanguineous marriages. This paper provides a background to the religious, historical and socio-cultural factors that have helped define the bounds of endogamy for Muslims in undivided India and more specifically since the creation of Pakistan. The preference for endogamous marriage is based on the clan-oriented nature of the society, which values and actively seeks similarities in social group identity based on several factors, including religious, sectarian, ethnic, and tribal/clan affiliation. Religious affiliation is itself multi-layered and includes religious considerations other than being Muslim, such as sectarian identity (e.g. Shia or Sunni, etc.) and religious orientation within the sect (Isnashari, Ismaili, Ahmedi, etc.). Both ethnic affiliation (e.g. Sindhi, Baloch, Punjabi, etc.) and membership of specific biraderis or zat/quoms are additional integral components of social identity. Within the bounds of endogamy defined by the above parameters, close consanguineous unions are preferential due to a congruence of key features of group- and individual-level background factors.

Consanguinity↗
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Parallel recognition of filarial antigens by IgE and IgG4 antibodies.

IgE responses are highly modulated in human filariasis and allergic symptoms usually associated with IgE antibodies are seldom observed in individuals with Elephantiasis and Microfilaremia. Only a minor group with tropical pulmonary eosinophilia (TPE) suffer from nocturnal asthma. One possible mechanism may be the presence of IgG blocking antibodies which can block IgE mediated histamine release in vitro. Using immunoblot analysis we have further shown that remarkably similar pattern of antigen recognition were obtained with IgE and IgG antibodies which would be a major prerequisite for the blocking activity. In the present study, we have tried to determine if a particular IgG subclass is responsible for the parallelism seen with IgE antibodies. Immunoblotting with autoradiographic analysis was used to study IgE and IgG subclasses using highly characterized radiolabeled antibodies in 24 sera representing all three groups mentioned above. The most striking observation was that in 23/24 sera, the only antibody that showed consistent and parallel binding was IgG4. No consistent pattern of response was seen with any of the other three subclasses. IgG1 and 2 when present were usually directed predominantly to the high molecular weight antigens and were detected with greater frequency in Elephantiasis group. These results suggest that IgG4 may be an ideal candidate for the blocking activity seen in these sera. Such modulation of IgE responses may have important survival value for the host in filarial infection which tend to evoke rigorous IgE responses.

Adolescent↗
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Neuro-ophthalmic features in pediatric tubercular meningoencephalitis.

PURPOSE: To examine the neuro-ophthalmic profile in childhood tubercular meningoencephalitis and assess its prognostic importance. METHODS: One hundred consecutive patients with tubercular meningoencephalitis underwent evaluation for optic nerve functions, supra- and infranuclear oculomotor involvement, and raised intracranial tension. Patients underwent follow-up for 9 months. RESULTS: In 100 patients with tubercular meningoencephalitis, 67 had neuro-ophthalmic features. Common findings were retrobulbar neuritis (32) and gaze palsy (20). Others, in decreasing prevalence, were third and sixth nerve palsy, conjugate deviation, primary optic atrophy, and complete ophthalmoplegia. Raised intracranial tension was associated with neuro-ophthalmic features in 53 of 67 patients (P<.05). Complete ophthalmoplegia was significantly associated with mortality on logistic regression analysis (relative risk, 6.35; P=.012). By 6 months, 56% of patients with retrobulbar neuritis progressed to optic atrophy. CONCLUSION: Neuro-ophthalmic features, in association with raised intracranial tension, often are a part of pediatric tubercular meningoencephalitis presentation. The type of neuro-ophthalmic features may have prognostic value. Optic nerve involvement is the most common finding in tubercular meningoencephalitis.

Child↗
PubMedDate not supplied

The role of Tc-99m HMPAO functional brain imaging in detection of cerebral radionecrosis.

BACKGROUND: Cerebral radionecrosis is a possible complication of brain radiation therapy in patients with primary or metastatic tumors. This retrospective study evaluated the role of Tc-99m hexamethyl propyleneamine oxime (HMPAO) scintigraphy in monitoring the effects of radiation on the brain. METHODS: Ninety-eight patients (41 female, 57 male) with a mean age of 51 years (range, 16-82 years) underwent 128 sets of single-photon emission computed tomography studies. TI-201 and Tc-99m HMPAO single-photon emission computed tomography studies were performed for tumor localization and evaluation of the effect of radiation on the cerebral cortex. Thirty concomitant neuropsychological tests and 96 anatomic imaging (computed tomography/magnetic resonance imaging) were performed. The average radiation dose was 52 Gy delivered as 1.8 to 2 Gy/fraction. Thirty-two patients received an average dose of 160 mCi of I-125 EGFr concomitantly. The average follow-up period was 34 months. Abnormalities away from the tumor site were interpreted as positive on HMPAO studies, neuropsychological testing, or anatomic imaging; otherwise, they were classified as negative. RESULTS: There were 10/45 (22%) and 75/83 (90%) abnormal HMPAO study results before and after radiation therapy. The HMPAO studies compared with neuropsychological testing showed 3/13 (23%) and 14/17 (82%) concordant abnormalities in addition to tumor site in patients pre- versus postradiation therapy. There was better concordance of HMPAO and anatomic imaging in 22/30 (76%) patients versus 24/67 (36%) patients before radiation therapy. HMPAO imaging after radiation therapy revealed significantly more perfusion abnormalities. There were significant differences between all of the aforementioned parameters. CONCLUSION Tc-99m HMPAO imaging is useful in the evaluation of the effects of radiation therapy on the brain and is highly concordant with neuropsychological testing. It is superior to anatomic studies in identifying radiation-induced changes.

Adolescent↗
PubMedDate not supplied

A sensitive enzyme-linked immunosorbent assay for dihydrofolate reductase.

A competitive enzyme-linked immunosorbent assay (ELISA) has been developed for the enzyme, dihydrofolate reductase. The sensitivity of the assay system approximates 3 ng of immunoreactive enzyme protein which is comparable to the sensitivity achieved in the radioimmunoassay (RIA) for this enzyme. The mean coefficient of variation for within--and between--assay precision was less than 13%. The assay appears to be specific and valid as the concentration of the enzyme is the same whether measured by ELISA or [3H]-methotrexate binding. Since this method, like the RIA, measures the mass concentration of enzyme protein, in conjunction with a [3H]-methotrexate binding assay it will be useful for quantitating functional as well as non-functional immunoreactive forms of the enzyme.

Animals↗
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Structure-function correlation and biostability of antibody CDR-derived peptides as tumour imaging agents.

Based on the CDR3 V(H) sequence of a monoclonal antibody (ASM2) raised against epithelial cancer cells, the synthetic peptide YCAREPPTRTFAYWG (EPPT1) has been found to have an appreciable affinity (Kd = 20 microM) for the deglycosylated mucin-derived peptide antigen YVTSAPDTRPAPGST (PDTRP). The technetium-radiolabelled form of this peptide has been found to be a good tumour-imaging candidate for diagnosis of breast carcinoma. Several EPPT1 peptide analogues were synthesised. A differential biostability was obtained blocking the end groups of EPPT1. The susceptibility to proteolytic degradation was significantly decreased for the C-amidated form of EPPT1 than the N-acetylated form. Using resonant mirror biosensor technique, the EPPT1 analogues were classified as active and non-active peptides according to their PDTRP-binding properties. The binding of EPPT1 to PDTRP in free solution was also determined unambiguously by CD spectroscopy. CD spectra of both active and non-active peptides showed the presence of irregular conformations in H2) and SDS above cmc. In TFE, significant degree of ordered conformations of alpha-helix or beta-turn type were induced but did not correlate well with their binding properties. In SDS below cmc a conformational difference was observed between the active and non-active peptides. The active peptides exhibited CD spectra of aggregation of beta-strand type whilst the non-active showed CD spectra similar to those in H2O and SDS above cmc, critical micelle concentration. A good correlation between the extended conformation of beta-strand type and the binding affinity of the active peptides suggests this conformation as the binding feature of the EPPT tumour-imaging peptides. These information are vital for the design of novel EPPT analogues. Any modification to improve binding affinity must retain the ability of the peptides to adopt the extended conformation of beta-strand type.

Amino Acid Sequence↗