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Biomedical subjects

R Hussain

Publications and source records attributed to R Hussain.

At least 73 records · Page 4Linked to original sources
PubMed1996

Evaluation of dipstrips, direct gram stain and pyuria as screening tests for the detection of bacteriuria.

Two hundred and fifty cases of clinically suspected urinary tract infection were analysed for the detection of bacteriuria. Parameters studied included direct Gram staining, pyuria on microscopic examination of uncentrifuged urine and dip strip method for the detection of blood, protein, nitrite and leucocyte esterase. Significant bacteriuria (colony count 10(5) per ml) was found in 112 cases with a positivity ranging from 65 to 83% for the presence of blood, protein, nitrite and leucocyte esterase. Highest positive predictive values were obtained with the presence of nitrite and leucocyte esterase (98%), blood, protein and nitrite (94%) as well as with blood, protein, nitrite and leucocyte esterase (98%). Both pyuria and direct Gram staining were positive in 85% cases. The combined presence of both these parameters gave 100% positive predictive value. Gram staining combined with pyuria was more effective and economical as compared to the dipstrips for the detection of bacteriuria.

Bacteriological Techniques↗
PubMed1996

Selective decrease of M. leprae-specific IgG1 and IgG3 antibodies in leprosy patients associated with ENL.

Erythema nodosum leprosum (ENL) is a serious complication of lepromatous leprosy. Because of the similarities with the Arthus-type reaction, ENL is presumed to be due to immune complex formation and their deposition in tissues. The aim of this study was to dissect the antibody response at the IgG subclass level to ascertain differences in IgG subclasses in nonreactional lepromatous/borderline lepromatous (LL/BL) patients and reactional (ENL) lepromatous patients. The ENL group showed significantly lower serum antibody levels for the four subclasses compared to the LL/BL group of patients using the Mann-Whitney U test (IgG1, p = 0.0001; IgG2, p = 0.0009; IgG3, p = 0.0001; IgG4, p = 0.03). Since the majority of ENL patients (54 of 67) had received leprosy chemotherapy for varying durations of time, LL/BL patients were also compared with 19 ENL patients who had received < or = 2 weeks of chemotherapy. In this group only IgG1 (p = 0.048) and IgG2 (p = 0.001) antibodies showed significantly lower concentrations. Immunoblotting analysis demonstrated that in ENL patients IgG1 showed a selective disappearance of several antigenic bands recognized by the LL/BL serum pool; while most of the antigens recognized by IgG3 antibodies in the LL/BL serum pool were not detected in the ENL serum pool or in the sera of pretreated individual ENL patients. These results suggest that IgG1 and IgG3 may be the most pathogenic IgG subclass antibodies during ENL, and their deposition in tissues could initiate the complement-mediated inflammatory pathway resulting in the clinical disease associated with ENL.

Antigens, Bacterial↗
PubMed1996

Alterations in serum lipids in lepromatous leprosy patients with and without ENL reactions and their relationship to acute phase proteins.

The concentrations of serum lipids were measured in patients with lepromatous (LL/BL) leprosy and erythema nodosum leprosum (ENL). The relationships between serum lipid levels and serum amyloid A (SAA) and C-reactive protein (CRP) were also examined in these patients. LL/BL patients had significantly higher serum triglyceride and lower HDL-cholesterol concentrations compared to the endemic controls. ENL patients had significantly lower total, HDL- and LDL-cholesterol levels compared to the endemic controls. The levels of all lipid metabolites also were significantly lower in ENL patients compared to LL/BL patients. The concentrations of SAA and CRP were markedly elevated in ENL patients but were not statistically different in LL/BL patients compared to control subjects. There was a significant negative correlation between SAA and HDL-cholesterol levels in both stable lepromatous and reactional (ENL) patients; there was no statistically significant correlation between CRP and HDL-cholesterol levels. SAA levels also had a significant negative correlation with total and LDL-cholesterol levels. Our results indicate that serum lipids are significantly altered in patients with lepromatous disease and ENL reaction. Our results also suggest that an increase in SAA levels may divert the metabolism of lipoproteins from hepatocytes toward macrophages, resulting in a decrease in serum lipoprotein levels.

Acute-Phase Proteins↗
PubMed1996

Microbial colonizers in leprosy skin ulcers and intensity of inflammation.

The microflora of 55 patients with leprosy skin ulcers was studied and related to a weighted inflammatory score (IS). The control group consisted of 18 ulcers with different underlying pathology. Leprosy ulcers were characterized by the exclusive presence of two types of branching gram-positive rods; a particular interesting proposal is that Mycobacterium leprae share common antigens with these unusual "leprosy ulcer associated" organisms and group G beta-hemolytic streptococci. In the leprosy group, corynebacteria and branching rods accounted for 97% of gram-positive bacilli and Bacillus species constituted only 3%. In the control group, B. species formed 50% of gram-positive rods; the rest were corynebacteria (p = 0.03). In the leprosy group, one third of the gram-positive bacteria were branching rods; none of them was acid fast. Ten of them were identified as Arcanobacterium haemolyticum, and the remaining 7 could not be identified. The IS of leprosy patients was lower than in the control group. The presence of more than two species of facultative or aerobic gram-negative rods or single species of pyogenic gram-positive cocci correlated with a high IS. The presence of two or more different pyogenic cocci resulted in a lower IS. Further studies into the nature of leprosyunique organisms as well as the inflammation inhibition factors in mixed infections are warranted. It is recommended that management of ulcers should consist of the application of local disinfection and early treatment of episodes of inflammation with a combination of fluoroquinolone and penicillin.

Actinomycetaceae↗
PubMed1996

Frequency of metabolic bone disease in haemodialysis patients.

The frequency of metabolic bone disease related to secondary hyperparathyroidism was studied in 47 haemodialysis patients, using biochemical, radiological parameters and bone biopsy (30 males, 17 females; mean age 48 years). The duration on dialysis ranged from 1-5 years. Hypocalcemia was found in 47% while 62% had raised phosphorus levels and 49% raised alkaline phosphatase. Serum parathyroid hormone was elevated in 86%, while in 13% it was markedly raised. On radiological examination there was generalized osteopenia in 49% and decreased bone density in 21%. In 30% no radiological abnormality was detected. In 40% bone biopsy revealed osteomalacia, mixed osteodystrophy 21%, osteoporosis 8.5% and in 25% no histological abnormality was observed.

Bone Diseases, Metabolic↗
PubMed1996

Pulmonary tuberculosis in a BCG vaccinated area: relationship of disease severity with immunological and hematological parameters and drug resistance patterns.

Clinical hematological and immunological parameters were studied in a group of 145 pulmonary patients with active tuberculosis, from a defined area of Karachi (Kharadar) belonging to the lower socioeconomic strata. Although clinical symptomatology could not differentiate the extent of lung involvement, a majority (69.6%) of the patients were diagnosed radiologically as having moderately advanced pulmonary disease. The peak number of patients were in their second decade of life. No differences were observed in the extent of disease based on age or gender. All hematological parameters for the group were in the normal ranges except for low levels of hemoglobin (9.58 +/- 1.55 SD; normal range 12-14 mg/dl) and a high ESR (90 +/- 31 SD; normal range 0-13 mm/hour). A negative correlation of PPD skin test induration (r = 0.21, p = 0.02), and a positive correlation of total white blood cell (r = 0.20; p = 0.015) was observed with the amount of lung tissue involved. The resistance amongst the strains for the four first line anti-tuberculosis agents was found to be: isoniazid = 27.4%; ethambutol = 14.5%; rifampicin = 11.29% and streptomycin = 12.9%. Multi-drug resistance to the most commonly prescribed combination (rifampicin and ethambutol) was 8.06%. Drug resistance patterns to individual drugs were comparable with resistance patterns observed in strains from greater Karachi at The Aga Khan Hospital during the same period. Such studies should provide improved rationale for patients diagnosis and treatment.

Adolescent↗
PubMed1995

Aortic arch dissection from patent ductus arteriosus.

An unusual case of aortic arch dissection from a patent ductus arteriosus (PDA) is described. An adult man had been diagnosed as suffering from pectus excavatum and PDA 10 years before. At that time the pectus was repaired, but he failed to return for surgery on the PDA and the sub-sternal strut for pectus repair was also never removed. Recently he was admitted in a peripheral hospital with chest infection. Patent ductus arteriosus murmur was audible on clinical examination. The chest X-ray showed a widened mediastinum and the pectus strut. On further investigations dissection of the aortic arch was discovered and arch replacement performed.

Adult↗
PubMed1995

Role of beta-adrenergic mechanisms in exercise training-induced metabolic changes in respiratory and locomotor muscle.

To test the hypothesis that beta-adrenergic stimulation is required for the normal increase in oxidative capacity of respiratory and locomotor skeletal muscle in response to exercise training, we examined the effects of beta-blockade on muscle oxidative capacity in trained and sedentary rats. Thirty-four female adult Sprague-Dawley rats were randomly divided into four experimental groups: 1) trained+propranolol (TP); 2) trained + sham injection (TS); 3) sedentary + propranolol (SP); and 4) sedentary + sham injection (SS). Training increased (p < 0.05) citrate synthase (CS) activity in the plantaris (+29%) and costal diaphragm (+12%) of TS animals compared to SS animals. In contrast, training did not (p > 0.05) increase costal diaphragm CS activity in TP animals compared to the SS group. Further, although training increased (p < 0.05) plantaris CS activity in the TP group (+18%) compared to the SP group, the training-induced increase in muscle CS activity was 11% lower (p < 0.05) than observed in TS animals. Collectively, these results suggest that beta-adrenergic mechanisms may play a role in the normal training-induced increase in oxidative capacity in both respiratory and locomotor skeletal muscles.

Adaptation, Physiological↗
PubMed1995

Selective increases in antibody isotypes and immunoglobulin G subclass responses to secreted antigens in tuberculosis patients and healthy household contacts of the patients.

Mycobacterium tuberculosis-specific antibodies (immunoglobulin M [IgM], IgE, IgG, and IgG subclasses) were determined in 164 tuberculosis patients (pulmonary involvement, n = 135; lymph node involvement, n = 29), 59 healthy household contacts (HC), and 51 healthy endemic donors (EC) by a quantitative enzyme-linked immunosorbent assay for reactivity with culture filtrate. Among the isotypes, significant differences between tuberculosis patient groups with either pulmonary or lymph node involvement and healthy control groups (HC and EC) were detected only for IgG (P < 0.001) and IgG1 (P < 0.001) antibodies. Pulmonary patients also showed a significant difference with IgM (P < 0.01) and IgE (P < 0.05) antibodies. HC showed elevation of only IgM antibodies compared with EC, indicating that IgM antibodies may be an indicator of recent infection with M. tuberculosis. These results suggest that the switching of IgM antibody response to IgG1 is a critical event in disease progression. Polyclonal IgG1, IgG3, and IgE antibodies also showed significant elevation (P < 0.05) in patients compared with EC. A strong correlation (rho = 0.254; P < 0.003) was observed between M. tuberculosis-specific IgG1 and polyclonal IgG1 in patients, suggesting that activations of antigen-specific and polyclonal antibodies are related events. No correlation was found between IgG1 antibodies and purified protein derivative skin test results. Since IgG1 antibody responses to culture filtrate are present only after disease establishment, IgG1 responses could provide a useful diagnostic marker of disease.

Antibodies, Bacterial↗
PubMed1995

Immunoglobulin G1 (IgG1) and IgG3 antibodies are markers of progressive disease in leprosy.

Mycobacterium leprae-specific and polyclonal immunoglobulin G (IgG) subclass and IgE antibodies in leprosy patients across the histopathological spectrum were determined by using a quantitative enzyme-linked immunosorbent assay. Antibody responses to M. leprae sonicates were detected only in IgG1, -2, and -3 subclasses. Even at 100-times-lower dilutions, very little IgG4 and IgE antibody activity against M. leprae was detected in any group of leprosy patients. Quantitatively, antibody responses were highest at the lepromatous pole and decreased towards the tuberculoid pole. The greatest quantitative difference in antibodies between the lepromatous and tuberculoid poles was observed with IgG1 (140-fold), this was followed by the difference with IgG3 antibodies (32-fold). Polyclonal antibodies, on the other hand, were elevated for all four IgG subclasses as well as IgE in both lepromatous and tuberculoid leprosy patients compared with healthy controls from a leprosy-endemic area. Selective elevation of M. leprae-specific antibody responses in IgG1 and IgG3 subclasses, therefore, could not be attributed to selective polyclonal activation in these particular subclasses. Furthermore, polyclonal activation for IgE was observed in both lepromatous and tuberculoid leprosy patients, with higher levels in the tuberculoid group, which does not support selective TH2 activation in lepromatous leprosy patients. IgG1 and IgG3 antibodies also showed the highest Spearman rank correlation with the bacterial index in these patients (rho = 0.748 and P < 0.001 for IgG1; rho = 0.721 and and P < 0.001 for IgG3). Thus, disease progression in leprosy showed a significant correlation with selective increases in IgG1 and IgG3 responses.

Antibodies, Bacterial↗
PubMed1995

Recognition of Mycobacterium leprae recombinant 18,000 MW epitopes by IgG subclasses in leprosy.

IgG subclasses are known to be differentially regulated by cytokines (elaborated by activated T cells), which act as growth factors and immunoglobulin switch factors on B cells. In leprosy, we have previously shown that IgG subclass antibodies to a purified recombinant antigen of Mycobacterium leprae (18,000 MW) are restricted to IgG1 and IgG3 across the disease spectrum. The only significant difference observed was that lepromatous patients with low to undetectable T-cell responses showed a strong correlation between IgG1 and IgG3 (P < 0.001) antibodies while tuberculoid patients who showed strong T-cell responses did not show such a correlation. To examine if these differences were related to T-cell-mediated class switching in tuberculoid leprosy patients, we have studied epitope recognition by IgG1 and IgG3 using a panel of synthetic peptides spanning the 18,000 MW molecule in an enzyme-linked immunosorbent assay (ELISA). In lepromatous patients there was little similarity in peptide recognition by IgG1 and IgG3, with IgG1 recognition being restricted to a single dominant carboxy-terminal peptide while the IgG3 antibodies recognized a diverse set of peptides in the N-terminal half of the 18,000 MW molecule. In tuberculoid patients both IgG1 and IgG3 antibody showed recognition of similar peptides in the N-terminal half of the 18,000 MW molecule. Our results therefore support the hypothesis that immunoglobulin class switching is occurring in tuberculoid but not in lepromatous patients.

Antibodies, Bacterial↗
PubMed1995

Clinical and histological discrepancies in diagnosis of ENL reactions classified by assessment of acute phase proteins SAA and CRP.

Sixteen out of 45 (36%) leprosy patients with clinical features of acute erythema nodosum leprosum (ENL) did not show the characteristic presence of neutrophils (polymorphs) in histology of the ENL lesion. The acute-phase reactants, serum amyloid A (SAA) and C-reactive protein (CRP) which are systemic markers of inflammation, and IgM and IgG antibody to Mycobacterium leprae were determined in these patients in order to understand the differences in histological diagnosis. Both SAA and CRP were elevated in ENL patients, irrespective of the presence of polymorph infiltrates, as compared to nonreactional lepromatous patients, patients with histologically confirmed reversal reactions and endemic controls, indicating that all clinically diagnosed ENL patients had ongoing inflammatory reactions. On the other hand, IgM and IgG antibodies were significantly lower (> 70%) in ENL patients as compared to nonreactional lepromatous patients. When the two ENL groups [ENL-PMN+ve (positive for neutrophils) and ENL-PMN-ve (negative for neutrophils)] were compared, there were no significant differences in the mean SAA, IgM or IgG antibody concentrations, but CRP was eightfold lower in ENL-PMN-ve as compared to the ENL-PMN+ve group. This may indicate that the timing or modulation of the reaction was different in the two ENL groups. Thus, measurement of the acute-phase response and the ratio of SAA/CRP in particular are helpful in the clinical diagnosis of ENL reactions in leprosy.

Adolescent↗
PubMed1995

Structure-activity relationships and physico-chemical properties of synthetic lipopeptide inhibitors of PKC.

Four synthetic lipopeptides, (K-pm 19,31), (K-pm 19,21,31), (K-pm 19,28,31) and (K-pm 19,21,28,31) with the lysine-palmitoyl (K-pm) residue as a lipophilic moiety, based on the pseudosubstrate sequence 19RFARKGALRQKNV31 (R19-V31), were found to be potent protein kinase C (PKC) inhibitors. However, the lipopeptides (K-pm 19,21,31), (K-pm 19,28,31) and (K-pm 19,21,28,31) were also found to act as protein kinase cAMP-dependent (PKA) inhibitors. Peptide (K-pm 19,31), the least water soluble, is marginally selective towards PKC, unlike the other palmitoyl derivatives studied here. Since the non-palmitoylated analogues (K 19,31), (K-ac 19,31), (K 19,21,31) and (K-ac 19,21,31) were inhibitors of PKC but not of PKA, the palmitoyl moiety must play a role in the specificity of protein kinase inhibition. In vitro, the lipophilic peptides showed greater stability to protease-mediated hydrolysis than the pseudosubstrate peptide depending upon the number of lipophilic (K-pm) residues. CD studies showed that in comparison with the peptide analogues, the remarkable resistance of the pseudosubstrate (R19-V31) to adopt an alpha-helix conformation in TFE, known to be strongly alpha-helix inducing, rules out this structure as the peptide binding conformation to PKC. By contrast, in aqueous media all the peptides show an extended conformation that correlates well with their inhibitory activity. This is in compliance with the crystallographic observation that an extended structure has been observed for the (5-24) PKI peptide inhibitor bound to PKA.

Circular Dichroism↗
PubMed1994

IgG subclass antibody to Mycobacterium leprae 18,000 MW antigen is restricted to IgG1 and IgG3 in leprosy.

IgG subclass responses to Mycobacterium leprae 18,000 MW recombinant antigen (18K) were determined in sera from untreated leprosy patients using an ELISA-based assay with specific monoclonal antibodies. Antibodies to M. leprae 18K were restricted to IgG1 and IgG3 antibodies with higher seropositivity in lepromatous patients (25.5% for IgG1 and 12.8% for IgG3) compared to patients with tuberculoid disease (11.5% for IgG1 and 5% for IgG3). No significant antibody response was detectable in IgG2 and IgG4 in patients with either lepromatous or tuberculoid leprosy. The selective production of antibodies in IgG1 and IgG3 subclasses could not be related to polyclonal activation in these subclasses as all IgG subclasses showed similar elevated levels at the polyclonal level. The major difference noted between lepromatous and tuberculoid leprosy patients with the IgG subclass antibody response was a strong linear correlation between IgG1 and IgG3 responses to M. leprae 18K in lepromatous patients (r = 0.703, P < 0.001) but not in tuberculoid leprosy patients (r = 0.007, P > 0.10) which may be related to immunoglobulin class switching of IgG3 to IgG1 rather than selective shifts in T-helper subsets. Our results therefore, do not support the hypothesis that activation of Th2 cells occurs in lepromatous leprosy; this issue needs further examination.

Antibodies, Bacterial↗
PubMed1994

A colorimetric PCR method for the detection of M. leprae in skin biopsies from leprosy patients.

A one-tube nested polymerase chain reaction (PCR) method for the diagnosis of paucibacillary leprosy was developed using the repetitive RLEP sequence as a target. Detection of the PCR products was simplified by the adaptation of a colorimetric method. The test was specific for Mycobacterium leprae, and the sensitivity of the assay was 1 fg of purified genomic M. leprae DNA (less than one genome). Complete concordance was seen between the development of color and resolution on agarose gels. The results of frozen skin sections from untreated patients showed that the assay could detect 100% of multibacillary samples [bacterial index (BI) of 2 or more] and 69% and 70% of the samples with BIs of 1 and 0, respectively. The use of one-tube nested PCR in assessing the effectiveness of multidrug therapy (MDT) in leprosy also was determined. The simplified colorimetric assay was found to be sensitive, rapid and specific, and is suitable for use in routing diagnostic laboratories.

Base Sequence↗
PubMed1994

Risk factors for intrauterine growth retardation: results of a community-based study from Karachi.

There is a serious lack of community-based information on low birthweight or intrauterine growth retardation from Pakistan. A community based prospective study was conducted in four squatter settlements of Karachi, to examine the prevalence and risk factors for adverse pregnancy outcome. This paper reports on the prevalence and risk factors for intrauterine growth retardation (<10th percentile birthweight gestational age) among 755 singleton births. The incidence of intrauterine growth retardation was 25.4% (192 intrauterine growth retarded and 563 appropriate for gestational age). Major socioeconomic risk factors identified were low maternal education (RR = 1.4, 95% CI = 1.0,2.1) and poor housing material (RR = 1.7, 95% CI = 1.0,3.0). Among the significant biologic factors, primiparity (RR = 1.9, 95% CI = 1.4,2.7), consanguinity (RR = 1.4, 95% CI = 1.4,2.7), consanguinity (RR = 1.4, 95% CI = 1.1,1.8), short birth to CI = 1.1,2.1), short stature (RR = 2.2, 95% CI = 1.6,3.0), low maternal weight (RR = 2.0, 95% CI = 1.6,2.5) and non-vegetarian diet (RR = 2.3, 95% CI = 1.3,4.2) were especially important. Investigations to assess the adverse mortality and morbidity effects of intrauterine growth retardation are ongoing.

Adult↗
PubMed1994

Once weekly subcutaneous administration of erythropoietin in haemodialysis patient.

Twenty-five anaemic patients of End Stage Renal Disease (ESRD) on maintenance haemodialysis at the Kidney Centre were studied. Recombinant human erythropoietin (EPO) 50-units/kg body weight was given once a week subcutaneously to see the response to therapy. In 21 cases haemoglobin increased significantly from 7.5 to 9.5 g/dl and haematocrit from 23 to 30.5 l/l with success rate of 84% and marked improvement in their quality to life. Once a week subcutaneous administration of erythropoietin is convenient and cost effective in reversing renal anaemia with minimal complications.

Adult↗