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Biomedical subjects

R Hussain

Publications and source records attributed to R Hussain.

At least 19 recordsLinked to original sources

The role of the gallium scan in primary extranodal lymphoma.

UNLABELLED: The purpose of this study was to examine the factors influencing gallium scan positivity for patients with primary extranodal lymphoma and to examine the role of the gallium scan in staging the disease and assessing response to initial treatment. METHODS: Ninety-two patients with extranodal lymphoma who had a gallium scan were reviewed. The influences of tumor site, size, grade and the presence of clinically detectable disease after biopsy on the rate of gallium scan positivity were analyzed. The role of the gallium scan in staging and selecting treatment was assessed. Nineteen patients had a gallium scan to assess their response to treatment, and its predictive value was reviewed. RESULTS: The overall gallium scan positivity (sensitivity) rate was 70%. This rate was low in patients whose extranodal lymphoma occurred in skin, intestine and testis, or was low grade (0%-25%). When these patients were excluded, the rate rose to 88%. Gallium scan positivity was not related to the presence of clinically detectable disease after biopsy and there was insufficient data about tumor size to determine a relationship. The gallium scan increased the disease stage in six patients (7%) and changed the initial treatment in six patients (7%). The gallium scan became negative in 15 (79%) of those patients who had a gallium scan to assess their response to treatment. All but two of these patients remain alive with a median follow-up of 3.75 yr. CONCLUSION: The gallium scan was rarely positive for patients with skin, intestinal, testicular and low-grade lymphomas, but was otherwise comparable to lymphoma arising in lymph nodes. The result affected staging or treatment in seven patients (8%). After treatment, an initially-positive gallium scan usually became negative, a conversion associated with a favorable outcome.

Citrates

Plasma cytokines in paediatric typhoidal salmonellosis: correlation with clinical course and outcome.

We evaluated the clinical profile, outcome and serial plasma interleukin 6 (IL-6) and tumor necrosis factor alpha (TNF-alpha) concentrations in 38 consecutive children (aged 6 months-14 years) admitted with culture-proven multidrug-resistant typhoid. All children received therapy for 14 days with either i.v. ceftriaxone or oral cefixime, with comparable outcome. Concentrations of IL-6 and TNF-alpha were significantly elevated in over 50% of the cases and correlated with clinical severity of illness as quantitated by the typhoid morbidity score. Sequential measurements revealed a significant decrease in IL-6 and TNF-alpha concentrations within 7 days of initiation of therapy (P<0.05). While no clear relationship was seen with time-to-defervescence, the failure rate was significantly higher in children with baseline serum IL-6 values >400 pg/ml (P<0.05). Our data suggest that plasma cytokine activity is frequently elevated in children with typhoidal salmonellosis, and IL-6 concentrations show a correlation with clinical severity and recovery from the illness.

Adolescent

Pneumonia perceptions and management: an ethnographic study in urban squatter settlements of Karachi, Pakistan.

Childhood pneumonia continues to be the second highest contributor to childhood morbidity and mortality in all ethnic groups in Pakistan. Information on community perceptions and management is largely limited to the Punjabi populace. In this study, ethno-specific illness terminologies, recognition and severity indicators and resort to treatment options for childhood pneumonia are explored among the two main ethnic groups in Sindh. Results are based on focus group discussions with 90 caretakers and 16 case history interviews. The findings indicate that pneumonia recognition is almost universal. The main recognition and severity indicator was pasli chalna (chest indrawing) followed by signs and symptoms relating to the quality of breathing and presence of high fever, lethargy and anorexia. Recognition of rapid breathing was low and mostly associated with fever. Exposure to thand (cold) through a variety of mechanisms was perceived to be the dominant causal model. The concept of contagion was virtually non-existent. Despite this, belief in efficacy of allopathic care was very high. Most caretakers reported seeking outside care within one to three days of the onset of symptoms. However, unrealistic expectations of cure often led to change in physicians and treatment regimen, if no improvement was observed by the second day. On the other hand, the quality of care provided by the physicians (both licensed and unlicensed) left much to be desired. Female autonomy and mobility did not appear to be a major constraint in seeking outside care other than for hospitalisation. Implications of these findings for the national acute respiratory infections control programme and future research are discussed

Anthropology, Cultural

Fore quarter gangrene: complication of Blalock-Taussig shunt.

A pre-term baby with complex congenital heart disease was operated upon for construction of Blalock-Taussig (B-T) Shunt. Soon after surgery the upper limb became blanched and cold. Despite conservative measures to improve circulation, limb ischaemia progressively worsened and resulted in fore quarter gangrene.

Arm

Pharmacokinetics of oral fluconazole when used for prophylaxis in bone marrow transplant recipients.

The pharmacokinetics of fluconazole was investigated in 20 bone marrow transplant patients following oral administration of 200 mg of this drug. Blood samples were collected from each patient at different time intervals within 48 h after the first dose, and fluconazole was measured in plasma by high-performance liquid chromatography with UV detection. Urine was collected from 14 of these patients and analyzed similarly. The plasma concentration-time data exhibited the characteristics of the one-compartment model with first-order absorption quite well. The means +/- standard deviations of half-lives for absorption and elimination, peak concentration, time to peak, mean residence time, apparent volumes of distribution, area under the curve, and apparent oral clearance observed in these patients were 2.84 +/- 1.34 h, 19.94 +/- 18.7 h, 4.45 +/- 1.86 microg/ml, 8.34 +/- 5.97 h, 39.57 +/- 20.5 h, 0.874 +/- 0.48 liter/kg, 156.0 +/- 60.6 microg x h/ml, and 0.0256 +/- 0.0138 liter/h x kg, respectively. The amount of fluconazole excreted in urine in 24 h was 67.1 +/- 83 mg, which represents 33.55% +/- 41.6% of the dose administered. Patients who developed hemorrhagic cystitis excreted significantly (P < or = 0.0094) more fluconazole in 24 h than did those who did not.

Administration, Oral

Mediastinitis due to Mycobacterium fortuitum infection following Fontan operation in a child.

Here we report a case of mediastinitis due to Mycobacterium fortuitum infection in a child after a Fontan operation. To our knowledge this is the first report of atypical mycobacterial mediastinal infection after congenital heart surgery. Atypical mycobacteria can be the cause of "culture negative" sternal and thoracotomy wound infections. A brief review of the literature is included in the discussion.

Child

Significantly increased IgG2 subclass antibody levels to Blastocystis hominis in patients with irritable bowel syndrome.

Blastocystis hominis is a common intestinal parasite of humans in the tropics whose pathogenic role is in dispute. Its presence has been reported in a variety of intestinal disorders resembling irritable bowel syndrome (IBS) such as diarrhea, anorexia, and flatulence. We have therefore investigated a possible link between IBS and blastocystosis by determining IgG antibody levels to B. hominis in patients with IBS. Levels of IgG antibodies were significantly elevated in patients with IBS compared with asymptomatic controls (P < 0.0001, by Student's t-test) in both B. hominis stool culture-positive and stool culture-negative IBS patients. When IgG antibodies were divided into their respective subclasses, only IgG2 levels were significantly increased in IBS patients compared with asymptomatic controls, indicating that the predominant response in these patients may be directed to carbohydrate antigens. The diagnostic usefulness of this test in IBS patients remains to be established because these data are only suggestive of a possible link between B. hominis and IBS. However, we hope that this antibody test will help in elucidating the controversy that surrounds the role of B. hominis as a pathogen at present.

Animals

Low serum HDL-cholesterol is associated with raised tumor necrosis factor-alpha during ENL reactions.

The concentrations of serum lipids and tumor necrosis factor (TNF) were measured in leprosy patients across the spectrum of the disease and in erythema nodosum leprosum (ENL) patients at the onset of the reaction and after the reaction had clinically subsided. Lepromatous/borderline lepromatous (LL/BL) patients had significantly higher serum triglyceride and lower HDL-cholesterol levels; there was no such change in the tuberculoid/borderline tuberculoid (TT/BT) patients. The household contacts (HC) of the LL/BL patients also had significantly lower serum HDL levels. ENL patients during the acute phase of the reaction had significantly lower total, LDL-, HDL-cholesterol levels compared to the stable LL/BL patients, and these changes were reversible to pre-ENL levels after the reaction had subsided. Serum TNF levels were significantly higher in household contacts and in LL/BL patients but were not statistically different in TT/BT patients. Serum TNF levels were also significantly higher during the acute phase of ENL, and declined after the clinical remission of the reaction to levels comparable with those of LL/BL patients. There was a significant negative correlation between serum TNF and HDL-cholesterol levels during and after ENL reaction. However, there was no such correlation between TNF and total or LDL-cholesterol levels in ENL patients. Our results suggest that the changes in HDL-cholesterol metabolism are a specific part of the host response to lepromatous leprosy and to the ENL reaction and may be mediated by increased TNF production.

Adolescent

Open fractures caused by high velocity missiles: the outcome of treatment of 39 fractures followed for 1-3 years.

Between 1993 and 1995, thirty-three patients having 39 fractures caused by missiles fired from a high velocity rifle were reviewed retrospectively between 1 and 3 years after injury and the outcome of treatment assessed. Majority (33 out of 39) were Grade III. Union was achieved in 35 out of 39 fractures, there was deep infection and delayed union in one case each. Non-union occurred in three fractures. The fractures were stabilized using different techniques, but highest complication rate was seen with the use of the static external fixator. This was related to the severe nature of the injury as well as the inherent limitations of the external fixator. Revision of the external fixator with internal fixation after healing of the soft tissues seems to be the direction of the future.

Adolescent

Immune response profile in patients with active tuberculosis in a BCG vaccinated area.

Tuberculosis patients with pulmonary (N = 95) or lymph node disease (N = 23) were assessed for Th1 responses (PPD skin test and lymphocyte blastogenic and interferon gamma) and Th2 responses (polyclonal and antigen specific IgE). Skin test responses to PPD and lymphocyte proliferative responses to crude mycobacterial antigens (PPD, culture filtrate and sonicate) and recall antigens (tetanus toxoid and streptolysin O) were significantly suppressed (p < 0.001) in patients with pulmonary disease compared to endemic controls. However, mitogen (phytohemagglutinin)-stimulated responses were comparable in patients and controls. Polyclonal and antigen specific (M. tuberculosis culture filtrate) IgE responses which are considered to be surrogate markers for Th2 responses were significantly higher in patients with pulmonary disease compared to healthy endemic controls (Mann Whitney analysis p < 0.01). Patients with lymph node disease showed strong Th1 responses but did not show significant responses for either polyclonal or antigen specific IgE. Thus overall suppression of T cell memory response was observed only in patients with pulmonary disease but not in patients with lymph node disease suggesting that sequestration of antigen in different compartments leads to differential activation of Th1 and Th2 responses. PPD skin test responses were highly positive in endemic controls (47% positive) and household contacts (86% positive). Furthermore, PPD positivity decreased with disease severity. Therefore PPD positivity in a BCG vaccinated TB endemic area cannot be used as a diagnostic marker for active tuberculosis particularly in advanced disease.

Antibodies, Bacterial

Cross-modulation by transforming growth factor beta in human tuberculosis: suppression of antigen-driven blastogenesis and interferon gamma production.

In tuberculosis, Mycobacterium tuberculosis (MTB)-stimulated T-cell responses are depressed transiently, whereas antibody levels are increased. Lymphoproliferative responses of peripheral blood mononuclear cells (PBMCs) from Pakistani tuberculosis (TB) patients to both mycobacterial and candidal antigens were suppressed by approximately 50% when compared to healthy purified protein derivative (PPD)-positive household contacts. Production of interferon gamma (IFN-gamma) in response to PPD also was depressed by 78%. Stimulation with PPD and the 30-kDa alpha antigen of MTB (30-kDa antigen) induced greater secretion of transforming growth factor beta (TGF-beta), but not interleukin 10 (IL-10) or tumor necrosis factor alpha (TNF-alpha), by PBMCs from TB patients compared to healthy contacts. The degree of suppression correlated with the duration of treatment; patients treated for <1 month had significantly lower T-cell blastogenesis and IFN-gamma production and higher levels of TGF-beta than did patients treated for >1 month. Neutralizing antibody to TGF-beta normalized lymphocyte proliferation in response to PPD, partially restored blastogenesis to candidal antigen, and significantly increased PPD-stimulated production of IFN-gamma in TB patients but not in contacts. Neutralizing antibody to IL-10 augmented, but did not normalize, T-cell responses to both PPD and candida in TB patients and candidal antigen in contacts. TGF-beta, produced in response to MTB antigens, therefore plays a prominent role in down-regulating potentially protective host effector mechanisms and looms as an important mediator of immunosuppression in TB.

Antigens, Bacterial

Erythema nodosum leprosum is associated with up-regulation of polyclonal IgG1 antibody synthesis.

Erythema nodosum leprosum (ENL) is a serious complication of lepromatous (L) disease in leprosy. We have previously shown that of the four IgG subclasses, IgG1 and IgG3 Mycobacterium leprae-specific antibodies are significantly lower in leprosy patients during ENL reaction compared with untreated L patients. To see if this decrease results from a down-regulation of antibody synthesis during ENL, the frequency of antibody-secreting B cells (ABSC) in the blood compartment was determined by ELISPOT and related to serum immunoglobulin concentrations (microgram/ABSC). Control groups consisted of 16 patients with stable L disease and 32 healthy endemic controls (EC). Paired samples were analysed during acute ENLS (n = 13) and after the reaction had subsided to identify changes associated with ENL. Polyclonal (PC) IgG1 was elevated in L patients compared with EC (325 micrograms versus 180 micrograms). Interestingly, patients during acute ENL showed concentrations higher than L patients (419 micrograms), which decreased after the reaction had subsided (260 micrograms), indicating the transient nature of the antibody response. IgG2 antibodies showed the reverse trend and were lower during ENL and increased after the reaction had subsided. The mean concentrations for PC IgG3 and IgG4 antibodies were similar during ENL and after the reaction had subsided. Thus, decrease in M. leprae-specific IgG1 and IgG3 antibodies is not related to down-regulation of B cell responses. Identification of factors which regulate PC IgG1 antibody synthesis may provide additional insights into determinants of ENL reactions.

Enzyme-Linked Immunosorbent Assay

Effects of clenbuterol on contractile and biochemical properties of skeletal muscle.

We investigated the effects of clenbuterol on the muscle mass, contractile properties, myosin phenotype, and bioenergetic enzyme activity in the gastrocnemius (GS)-plantaris (PL)-soleus (SO) muscle complex. Rats were sham-injected or treated with clenbuterol (2 mg.kg-1, subcutaneously) for 14 d. Clenbuterol increased (P < 0.05) body weight and muscle complex weight. Also, clenbuterol treatment resulted in an increase in total muscle force production and maximal shortening velocity (P < 0.05). No difference (P > 0.05) in relative force production (force.g-1 muscle) existed between experimental groups. However, muscle fatigue increased with clenbuterol treatment. Myosin heavy chain (MHC) composition was not altered in the GS or PL muscles, but shifted toward the fast Type II MHC in the SO. Myosin light chain (MLC) composition was not altered in any of the muscles. Clenbuterol caused a decrease in oxidative and glycolytic enzyme activity in the GS and PL, but not the SO. These data suggest that the clenbuterol-induced increase in muscle mass and maximal force generation is due to hypertrophy of both fast and slow fibers. Furthermore, these findings support the notion that beta-agonists may be beneficial in combating conditions that result in muscle wasting and dysfunction.

Adrenergic beta-Agonists

Induction of Th1 cytokine responses by mycobacterial antigens in leprosy.

Twelve mycobacterial antigens were compared for induction of gamma interferon (IFN-gamma) secretion by human blood mononuclear cells of patients with leprosy. Fractionated Mycobacterium leprae antigens containing cell wall proteins or cytosolic and membrane proteins induced good IFN-gamma responses in tuberculoid leprosy patients. Lipoarabinomannan from M. tuberculosis Erdman and M. leprae mycolylarabinogalactan peptidoglycan were the poorest IFN-gamma inducers.

Antigens, Bacterial

IgG subclass recognition pattern in leprosy: recognition of M. leprae antigens by IgG1 and IgG3 antibodies is distinct across the disease spectrum.

The recognition of Mycobacterium leprae antigens by IgG subclasses in patients with leprosy was investigated by electrophoresing M. leprae sonicate in SDS-polyacrylamide gel and immunoblotting analysis. Serum pools were used from leprosy patients with either lepromatous (LL/BL) or tuberculoid (BT/TT) disease. A serum pool from healthy controls (EC) was used to determine the baseline antibody activity. To adjust for quantitative differences in antibodies across the disease spectrum, the LL/BL serum pool was used at a 1:200 dilution; the BT/TT serum pool, at 1:20 dilution. Monoclonal antibodies specific for each of the IgG subclasses were used as probes, with anti-mouse IgG conjugated to alkaline phosphatase as the revealing probe. IgG1 antibodies bound to several discrete bands in the range of 10-70 kDa in LL/BL patients, while BT/TT patients showed a more diffuse pattern with the strongest IgG1 antibody binding in the region of 25-40 kDa. Recognition with IgG2 was restricted to a region between 25-36 kDa (which also stained strongly for carbohydrates) in both LL/BL and BT/TT patients. Binding with IgG3 antibodies was more restricted than IgG1 antibodies in LL/BL sera with strong recognition restricted to 25 and 28 kDa. BT/TT sera showed strong binding with IgG3 antibodies in the region of 25-32 as well as 5-7 kDa. IgG4 antibodies showed weak binding to a 28-kDa in lepromatous patients only. The differences in IgG subclass recognition patterns and their implications are discussed.

Antibodies, Bacterial

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

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

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