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R Hussain

Publications and source records attributed to R Hussain.

At least 37 records · Page 2Linked to original sources
PubMed2001

Tropical pulmonary eosinophilia and filariasis in Pakistan.

Filariasis is a major health problem in South Asia, particularly India, Sri Lanka and Bangladesh. Pakistan was presumed to be not affected. We report for the first time confirmed cases of tropical pulmonary eosinophilia (TPE) in indigenous patients as a result of infection with Wuchereria bancrofti. Following clinical examination, total leukocyte and eosinophil counts were recorded. Parasitological examinations included blood for microfilariae and stool and urine for eggs of intestinal parasites. Total immunoglobulin (Ig) E and specific antifilarial IgG were measured. Suspected cases of TPE were treated with diethylcarbamazine, 6 mg/kg for four weeks and were followed up to 2 and 4 weeks after treatment. Four persons fulfilled the criteria for TPE. Their response to treatment was marked with clinical improvement, reduction in eosinophil count and reduced titers of specific antifilarial antibodies. Two persons had W. bancrofti antigen in their sera confirmed by filariasis antigen detection test. Tropical pulmonary eosinophilia due to Wuchereria. bancrofti, although rare, is present in Pakistan.

Adolescent↗
PubMed2001

Pericardial effusion as a cause of morbidity in patients on maintenance hemodialysis: is it preventable?

OBJECTIVE: Cardiovascular diseases are the cause for 45% mortality and 20% morbidity in hemodialysis (HD) patients. Pericardial effusion (PE) accounts for 03-04% of all deaths in HD patients as a result of tamponade, arrhythmias or heart failure. This study aims to find out the prevailance and precipitating factors for PE in hemodialysis patients. PATIENTS AND METHODS: Fifty-five patients were identified for echo-cardiographic assessment on the basis of signs and symptoms suggestive of PE i.e., hypotension during dialysis, dyspnea, globular heart in chest x-ray, raised JVP, soft heart sounds and low voltage ECG. A matched controlled group of 55 patients for age, sex, dialysis schedule, cause of ESRD and dialysis bath, was also studied echocardiographically. RESULTS: Pericardial Effusion was detected in 12 patients (10.9%), 10 (83.3%) were on 2/week and only two on 3/week dialysis. Of these 75% were non-compliant in fluid intake and 58.3% were irregular in treatment. The morbidity of PE in study group (18.2%) is significantly higher as compared to controls (3.6%) (P = < 0.05). No correlation was found between development of PE and high iPTH and low albumin levels. Ten patients with mild PE responded to vigorous dialysis. Two patients developed cardiac tamponade needing pericardiocentesis. CONCLUSION: We have identified 2/week dialysis (inadequate dialysis dose), acetate bath and fluid and dialysis non-compliance as factors contributing to development of PE in HD patients.

Adult↗
PubMed2000

Oligomerization of beta-amyloid of the Alzheimer's and the Dutch-cerebral-haemorrhage types.

A novel ELISA has been developed which detects oligomerization of beta-amyloid (A beta). Oligomerization, fibrillization and neurotoxicity of native A beta associated with Alzheimer's disease (AD) type has been compared with E22Q A beta (amyloid beta-protein containing residues 1--40 with the native Glu at residue 22 changed to Gln) implicated in Dutch cerebral haemorrhage disease. Solutions of A beta rapidly yield soluble oligomers in a concentration-dependent manner, which are detected by the ELISA, and by size-exclusion gel chromatography. Conformational changes from disordered to beta-sheet occur more slowly than oligomerization, and fibrils are produced after prolonged incubation. The E22Q A beta oligomerizes, changes conformation and fibrillizes more rapidly than the native form and produces shorter stubbier fibrils. Aged fibrillar preparations of E22Q A beta are more potent than aged fibrils of native A beta in inducing apoptotic changes and toxic responses in human neuroblastoma cell lines, whereas low-molecular-mass oligomers in briefly incubated solutions are much less potent. The differences in the rates of oligomerization of the two A beta forms, their conformational behaviour over a range of pH values, and NMR data reported elsewhere, are consistent with a molecular model of oligomerization in which strands of A beta monomers initially overcome charge repulsion to form dimers in parallel beta-sheet arrangement, stabilized by intramolecular hydrophobic interactions, with amino acids of adjacent chains in register.

Alzheimer Disease↗
PubMed2000

Direct amplification of Entamoeba histolytica DNA from amoebic liver abscess pus using polymerase chain reaction.

An important and serious complication of intestinal infection with Entamoeba histolytica is the involvement of the liver (hepatic amoebiasis). Hepatic amoebiasis is usually diagnosed by the clinical picture (pain in the right upper quadrant and fever), ultrasound examination and positive serology. However, none of these tests are definitive and the picture overlaps with pyogenic liver abscess caused by bacteria. It is for this reason that the feasibility of using polymerase chain reaction (PCR) for the detection of E. histolytica DNA in liver abscess pus was investigated. A comparative study was done to verify the sensitivity of ten pairs of primers specific for detecting E. histolytica in stools. Samples of liver abscess pus from 22 serology-positive patients were collected under ultrasound guidance; and these were used directly in PCR assays without any prior pre-treatment of the samples. Of the ten pairs of previously published primers tested, two pairs of primers (PI + P2 and P11 + P12) were found to give 100% sensitivity. Based on these results, we recommend that PCR assay can be successfully used to confirm the diagnosis of amoebic liver abscess with the primers identified.

Animals↗
PubMed2000

Sociodemographic correlates of consanguineous marriage in the Muslim population of India.

Using data derived from the 1992-1993 National Family Health Survey, the sociodemographic characteristics of consanguineous marriage were determined in the Muslim population of India. In this nationally representative sample of 8436 women, consanguineous marriages accounted for 22.0% of the total. No differences between the consanguineous and non-consanguineous groups were observed in terms of mean age at marriage or mean age at cohabitation. The study confirmed the negative association between consanguineous marriage and maternal education but also indicated that women in consanguineous unions were more likely to be employed, albeit mainly in agricultural work on behalf of the family. Consanguineous couples more frequently lived in smaller towns and in an extended family environment. Somewhat conflicting results were obtained with indicators of socioeconomic status, but the overall picture suggested that consanguineous households had greater access to consumer goods because of their larger number of co-resident persons.

Adolescent↗
PubMed2000

PPD-specific IgG1 antibody subclass upregulate tumour necrosis factor expression in PPD-stimulated monocytes: possible link with disease pathogenesis in tuberculosis.

Cachexia is a prominent feature of advanced tuberculosis, in association with increased expression of the monokine tumour necrosis factor (TNF)-alpha. Monocytes, have high affinity receptors (mannose, complement and Fc gamma1 and gamma111) which mediate antigen uptake and subsequent cytokine activation. Several mycobacterial proteins, including PPD, can stimulate TNF-alpha secretion from monocytes. However, the role of various receptors in stimulating or regulating TNF-alpha secretion is still unclear. We have previously shown selective augmentation of opsonic antibodies (IgG1 and IgG3) in tuberculosis patients with advanced pulmonary disease. We now analyse the role of opsonizing antibodies in modulating TNF-alpha expression in antigen stimulated monocytes. PPD was used as the prototypic mycobacterial antigen to stimulate monocytes from PPD skin test negative donors (n = 7) in the presence of plasma from tuberculosis patients (n = 8), containing known amounts of IgG1 and IgG3 anti-PPD antibodies. TNF-alpha secretion was enhanced in the presence of TB plasma (4/8) but not in the presence of control plasma. Using Spearman Rank analysis (two-tailed Fisher exact test), a significant correlation (rho = 0.762; P = 0. 04) was observed between IgG1 antibodies and enhancement of TNF-alpha secretion. No significant association was observed with IgG2 (rho = 0.310; P = 0.41), IgG3 (rho = 0.089; P = 0.81) or IgG4 (rho = - 0.357; P = 0.347) subclass antibodies. Absorption of IgG1 with protein 'A' removed the enhancement of TNF-alpha secretion activity from the plasma samples. Our results therefore indicate that IgG1 antibodies may enhance the chronic release of TNF-alpha in TB patients with progressive disease and, for the first time, show a direct link between disease pathogenesis and raised antibody levels.

Cells, Cultured↗
PubMed2000

A postgenomic approach to identification of Mycobacterium leprae-specific peptides as T-cell reagents.

To identify Mycobacterium leprae-specific human T-cell epitopes, which could be used to distinguish exposure to M. leprae from exposure to Mycobacterium tuberculosis or to environmental mycobacteria or from immune responses following Mycobacterium bovis BCG vaccination, 15-mer synthetic peptides were synthesized based on data from the M. leprae genome, each peptide containing three or more predicted HLA-DR binding motifs. Eighty-one peptides from 33 genes were tested for their ability to induce T-cell responses, using peripheral blood mononuclear cells (PBMC) from tuberculoid leprosy patients (n = 59) and healthy leprosy contacts (n = 53) from Brazil, Ethiopia, Nepal, and Pakistan and 20 United Kingdom blood bank donors. Gamma interferon (IFN-gamma) secretion proved more sensitive for detection of PBMC responses to peptides than did lymphocyte proliferation. Many of the peptides giving the strongest responses in leprosy donors compared to subjects from the United Kingdom, where leprosy is not endemic, have identical, or almost identical, sequences in M. leprae and M. tuberculosis and would not be suitable as diagnostic tools. Most of the peptides recognized by United Kingdom donors showed promiscuous recognition by subjects expressing differing HLA-DR types. The majority of the novel T-cell epitopes identified came from proteins not previously recognized as immune targets, many of which are cytosolic enzymes. Fifteen of the tested peptides had > or =5 of 15 amino acid mismatches between the equivalent M. leprae and M. tuberculosis sequences; of these, eight gave specificities of > or =90% (percentage of United Kingdom donors who were nonresponders for IFN-gamma secretion), with sensitivities (percentage of responders) ranging from 19 to 47% for tuberculoid leprosy patients and 21 to 64% for healthy leprosy contacts. A pool of such peptides, formulated as a skin test reagent, could be used to monitor exposure to leprosy or as an aid to early diagnosis.

Amino Acid Sequence↗
PubMed2000

Diagnostic assays for leprosy based on T-cell epitopes.

To date, only a limited number of antigens have been described as specific for Mycobacterium leprae, and in many cases, homologues have subsequently been shown to exist in mycobacteria such as M. avium and M. intracellulare. A Leprosy Synthetic Peptide Skin Test Initiative was established by the Steering Committee on the Immunology of Mycobacteria of the UNDP/World Bank/WHO Special Programme for Research and Training in Tropical Diseases, to investigate the potential of synthetic peptides that encode T-cell epitopes as diagnostic tools, which could be used to develop a skin-test reagent specific for leprosy. Such M. leprae-specific peptides should have unique amino acid sequences, or significant sequence-dissimilarity from those in other mycobacteria. Synthetic peptides, 15 amino acids long, were synthesised from 33 genes or open reading frames within the M. leprae genome. Tuberculoid leprosy patients from four leprosy-endemic countries, Brazil, Ethiopia, Nepal and Pakistan, were tested as subjects known to have been infected with M. leprae, and to make good T-cell responses to antigens of M. leprae; UK blood donors were used as non-exposed or non-infected subjects. Peptides inducing potentially specific responses in leprosy patients and not in UK controls, and those inducing cross-reaction responses, present in both leprosy patients and non-exposed, non-infected controls, were identified. A difference from the equivalent M. tuberculosis sequence of five or more amino acid residues did not, by itself, identify peptides that were M. leprae-specific, suggesting that many of these peptides may have homologues in environmental mycobacteria. To date, this approach has identified a number of peptides with greater than 90% specificity and 19-47% sensitivity, which are undergoing further specificity-testing. Such peptides would have great potential as T-cell reagents with which to monitor exposure to M. leprae within communities, formulated either as skin-test reagents, or as antigens for tests in vitro.

Epitopes, T-Lymphocyte↗
PubMed2000

The role of son preference in reproductive behaviour in Pakistan.

The sex of surviving children is an important determinant of reproductive behaviour in South Asia in general and Pakistan in particular. This cohort study evaluates the role of the sex of children on reproductive intentions and subsequent behaviour of women in urban slums of Karachi, Pakistan. The analysis is based on two rounds of surveys conducted in 1990-91 and 1995 of a cohort of married women aged 15-49 years. The results show that pregnancies became increasingly unwanted as the number of surviving sons increased. The sex of surviving children was strongly correlated with subsequent fertility and contraceptive behaviour. However, rather than an exclusive son preference, couples strove for one or more sons and at least one surviving daughter. The policy implications of the link between overt son preference and low status of women are discussed.

Adolescent↗
PubMed1999

Consanguineous marriage and differentials in age at marriage, contraceptive use and fertility in Pakistan.

Fertility rates in Pakistan have remained consistently high over the past three decades. While numerous studies have examined sociodemographic determinants, the role of biological factors, and particularly consanguinity, has received little attention, even though marriage between close biological relatives continues to be the norm in Pakistan. Reproductive behaviour among women in consanguineous (first cousin) and non-consanguineous unions was compared, using data from a 1995 study of multi-ethnic communities in Karachi and the 1990-91 Pakistan Demographic & Health Survey (PDHS). The results show that, although female age at first marriage has been gradually rising in both study samples, women in consanguineous unions married at younger ages and were less likely to use modern contraceptive methods. In the Karachi sample, women in first cousin unions experienced a higher mean number of pregnancies and also reported a higher mean number of children ever born (CEB). However, their mean number of surviving children did not differ from those born to women in non-consanguineous unions, implying higher prenatal and/or postnatal losses in couples related as first cousins. On the other hand, the PDHS showed both lower CEB values for women in consanguineous marriages and a lower number of surviving children. Given the continuing popularity of consanguineous marriage, these findings have important implications for future fertility reduction in Pakistan.

Adolescent↗
PubMed1999

Community perceptions of reasons for preference for consanguineous marriages in Pakistan.

Although the recent Pakistan Demographic and Health Survey (DHS) show that two-thirds of marriages in Pakistan are consanguineous, the sociocultural determinants of such marriages remain largely unexplored. This paper examines the relative importance of the three commonly perceived reasons for such marriages: religious, economic and cultural. The analysis is based on qualitative data collected in 1995 from multi-ethnic and multi-religious communities in Karachi, the largest city of Pakistan. Results show that consanguineous marriages are preferred across all ethnic and religious groups to a varying degree, and that parents continue to be the prime decision-makers for marriages of both sons and daughters. The major reasons for a preference for consanguineous marriages are sociocultural rather than any perceived economic benefits, either in the form of consolidation of family property or smaller and less expensive dowries. Among Muslims, following religious traditions is the least commonly cited reason for such marriages. Despite the reported sociocultural advantages of consanguineous marriages, such unions are perceived to be exploitative as they perpetuate the existing power structures within the family.

Adolescent↗
PubMed1999

Dominant recognition of a cross-reactive B-cell epitope in Mycobacterium leprae 10 K antigen by immunoglobulin G1 antibodies across the disease spectrum in leprosy.

Mycobacterium leprae-specific immunoglobulin G1 (IgG1) antibodies in patients with leprosy show a direct correlation with bacterial load (rho=0.748; P<0002) suggesting that IgG1 B-cell responses may be surrogate markers of disease progression. To investigate if this upregulation was a general feature of IgG1 responses to all M. leprae (ML) antigens, we analysed responses to several recombinant purified ML heat-shock proteins (HSP). Three recombinant HSPs (ML10 K, ML 18 K and ML 65 K) were tested for their ability to induce various IgG subclasses in patients with either the lepromatous (LL/BL, n=26) or tuberculoid form (BT/TT, n=39) of the disease as well as in healthy households (HC, n=14) and endemic controls (EC=19). Our major findings were: (1) selective augmentation of IgG1 antibody responses to ML10 K; (2) recognition of a restricted number of epitopes across the disease spectrum and healthy controls by IgG1 antibodies; (3) dominant recognition of cross-reactive epitopes which were common to both ML and MT 10 K. This response was not related to contamination with endotoxin. Epitope mapping using 15-mer overlapping peptides spanning the ML 10 000 MW revealed an immunodominant IgG1 binding peptide (aa41-55) in patients as well as healthy controls. This peptide is a shared epitope with M. tuberculosis 10 K suggesting that postswitched IgG1 B cells recognizing this epitope rather than naive B cells are being expanded.

Antibodies, Bacterial↗
PubMed1999

Selective correlation of interferon-gamma, tumour necrosis factor-alpha and granulocyte-macrophage colony-stimulating factor with immunoglobulin G1 and immunoglobulin G3 subclass antibody in leprosy.

Dysregulation of both B- and T-cell responses is observed in leprosy. Immunoglobulin G1 (IgG1) and IgG3 antibody subclasses are selectively elevated towards the lepromatous or disseminated form of the disease accompanied by a depression of T-cell responses. T-cell and macrophage cytokines influence antibody class switching, differentiation and proliferation of B cells. To understand the dynamic nature of the immune response in leprosy, we examined the relationship between circulating Mycobacterium leprae-specific antibodies and secreted cytokines [interferon-gamma (IFN-gamma), interleukin-2 (IL-2), IL-5, IL-10, IL-6, tumour necrosis factor-alpha (TNF-alpha) and granulocyte-macrophage colony-stimulating factor (GM-CSF)] in leprosy patients (19 lepromatous patients; 25 tuberculoid patients) and their exposed household contacts (HC=14) in response to M. leprae antigens. Paired comparison revealed a highly significant negative correlation between IFN-gamma and IgG (P=0.016), IgG1 (P<0.001) and IgG3 (P=0. 007) antibodies. No significant relationship was observed with other T-cell cytokines (IL-2, IL-5 and IL-10). These results strongly suggest that IFN-gamma may play a role in down-regulating antigen-specific IgG1 and IgG3 antibodies. Among the macrophage cytokines, TNF-alpha and GM-CSF which have not been shown to play a role in B-cell activation were positively associated with IgG1 (TNF-alpha, P=0.0005; GM-CSF, P=0.001) and IgG3 (TNF-alpha, P=0.001; GM-CSF, P=0.021) antibodies. Since macrophages have high-affinity Fc receptors for IgG1 and IgG3, it is possible that antigen uptake via these receptors may influence cytokine expression of TNF-alpha, a key modulator of disease pathogenesis in mycobacterial diseases. We are currently investigating the role of Fc receptors on activated macrophages, in expression of pro-inflammatory cytokines in mycobacterial diseases.

Antibodies, Bacterial↗
PubMed1998

Abnormal astrocyte development and neuronal death in mice lacking the epidermal growth factor receptor.

Stimulation of the epidermal growth factor receptor (EGF-R) produces numerous effects on central nervous system (CNS) cells in vitro including neuronal survival and differentiation, astrocyte proliferation and the proliferation of multipotent progenitors. However, the in vivo role of EGF-R is less well understood. In the present study, we demonstrate that EGF-R null mice generated on a 129Sv/J Swiss Black background undergo focal but massive degeneration the olfactory bulb, piriform cortex, neocortex, and thalamus between postnatal days 5 and 8 which is due, at least in part, to apoptosis. Some of the neuronal populations that degenerate do not normally express EGF-R, indicating an indirect mechanism of neuronal death. There were also delays in GFAP expression within the glia limitans and within structures outside the germinal zones in early postnatal ages. At or just prior to the onset of the degeneration, however, there was an increase in GFAP expression in these areas. The brains of EGF-R (-/-) animals were smaller but cytoarchitecturally normal at birth and neuronal populations appeared to be intact, including striatal GABAergic and midbrain dopaminergic neurons which have previously been shown to express EGF-R. Multipotent progenitors and astrocytes derived from EGF-R (-/-) mice were capable of proliferating in response to FGF-2. These data demonstrate that EGF-R expression is critical for the maintenance of large portions of the postnatal mouse forebrain as well as the normal development of astrocytes.

Animals↗
PubMed1998

Determinants of 30-day mortality of spontaneous intracerebral hemorrhage in Pakistan.

BACKGROUND: The present study was undertaken to evaluate the determinants of acute (30-day) mortality after spontaneous intracerebral hemorrhage (ICH) in a developing country setting, and to compare these findings with those available from studies conducted in the West. METHODS: Medical records of 146 patients admitted to a major tertiary hospital in Karachi, Pakistan between 1990 and 1991 with a diagnosis of spontaneous ICH were reviewed. The level and intensity of care provided to these patients was similar to that available at modern neurosurgical centers. The salient prognostic indicators that were studied included hypertension, pulse pressure, GCS score, neurologic deficits, and CT-scan predictors including site, size, and intraventricular spread of hemorrhage. These data were used to determine independent predictors of 30-day mortality by univariate and multivariate analysis. Additionally, 30-day survival probabilities for these outcome predictors were also computed. RESULTS: The 30-day mortality after spontaneous ICH was 39.7%. Two-thirds of the patients had a history of hypertension. The important clinical predictors at the multivariate level included GCS score < or =8 and progressive increase in pulse pressure. The CT scan predictors included intraventricular spread of hemorrhage, ventricular enlargement, and size of the bleed. Location of the lesion did not appear to significantly influence mortality. Survival analysis showed a large clustering of deaths within the first 72 hours of hospitalization. CONCLUSIONS: The 30-day mortality rate and prognostic predictors for spontaneous intracerebral hemorrhage were found to be similar to those reported in the Western hemisphere. However, the correlation of incremental increase in pulse pressure with deteriorating prognosis was a new and significant finding.

Adult↗
PubMed1998

The prevalence and demographic characteristics of consanguineous marriages in Pakistan.

Consanguineous marriages are strongly preferred in much of West and South Asia. This paper examines the prevalence and sociodemographic correlates of consanguineous unions in Pakistan using local and national data. Information from 1011 ever-married women living in four multi-ethnic and multi-lingual squatter settlements of Karachi, the main commercial centre of the country, are compared with data from the national 1990/91 Pakistan Demographic and Health Survey (PDHS), based on information provided by 6611 women. Both sets of results indicate that approximately 60% of marriages were consanguineous, over 80% of which were between first cousins. The mean coefficients of inbreeding (F) in the present generation were 0.0316 and 0.0331 for the Karachi and PDHS data respectively. In both surveys the prevalence of consanguineous unions appeared to be unchanged over the past three to four decades. Consanguineous unions were more common among women who were illiterate or had only primary level education, were first or second generation migrants from rural areas of Pakistan or, in the PDHS, lived in rural areas, and whose parents were also consanguineously married.

Adolescent↗
PubMed1998

Leprosy patients with lepromatous disease recognize cross-reactive T cell epitopes in the Mycobacterium leprae 10-kD antigen.

T cell responses play a critical role in determining protective responses to leprosy. Patients with self-limiting tuberculoid leprosy show high T cell reactivity, while patients with disseminated lepromatous form of the disease show absent to low levels of T cell reactivity. Since the T cell reactivity of lepromatous patients to purified protein derivative (PPD), a highly cross-reactive antigen, is similar to that of tuberculoid patients, we queried if lepromatous patients could recognize cross-reactive epitopes in Mycobacterium leprae antigens as well. T cell responses were analysed to a recombinant antigen 10-kD (a heat shock cognate protein) which is available from both M. tuberculosis (MT) and M. leprae (ML) and displays 90% identity in its amino acid sequence. Lymphoproliferative responses were assessed to ML and MT 10 kD in newly diagnosed leprosy patients (lepromatous, n = 23; tuberculoid, n = 65). Lepromatous patients showed similar, but low, lymphoproliferative responses to ML and MT 10 kD, while tuberculoid patients showed much higher responses to ML 10 kD. This suggests that the tuberculoid patients may be recognizing both species-specific and cross-reactive epitopes in ML 10 kD, while lepromatous patients may be recognizing only cross-reactive epitopes. This was further supported by linear regression analysis. Lepromatous patients showed a high concordance in T cell responses between ML and MT 10 kD (r=0.658; P<0.0006) not observed in tuberculoid patients (r=0.203; P>0.1). Identification of cross-reactive T cell epitopes in M. leprae which could induce protective responses should prove valuable in designing second generation peptide-based vaccines.

Antigens, Bacterial↗