JPMA. The Journal of the Pakistan Medical Association, 2007
OBJECTIVE To find the relationship between human leukocyte antigens (HLA) and cryoglobulin positi... more OBJECTIVE To find the relationship between human leukocyte antigens (HLA) and cryoglobulin positivity in hepatitis C virus (HCV) infected individuals. METHODS Eligible individuals selected from pre and post renal transplant settings were divided into three groups. Group A (n = 301) consisted of normal controls, while group B (n = 200) comprised of pathological controls that were HCV antibody (anti-HCV) positive but negative for cryoglobulins. Group C comprised of 56 anti-HCV positive, cryoglobulin positive patients. HLA-A, -B and -DRB1 loci were typed by polymerase chain reaction (PCR) method and relationship between HLA antigens, anti-HCV status and cryoglobulinaemia was analyzed. RESULTS HLA-A*02, -B*57 and -DRB1*03 were more frequently found among group C members as compared to groups A and B. Only HLA-B* 57 occurrence reached statistical significance (14.3% versus 6% and 4%, corrected P-value = 0.045 and 0.012 and OR = 2.6 and 4 respectively) No differences in the distribution o...
I am writing to you with reference to a recent article published in the April 2002 issue of the J... more I am writing to you with reference to a recent article published in the April 2002 issue of the Journal.1 Following the release of this article, a misperception has been formed amongst some medical practitioners and lay press in India that batches of Lupin’s rifampicin products were withdrawn from the South African market as a direct result of failing in bio studies. This is a wrong perception and I would like to take this opportunity to set out the facts surrounding this issue. Further, the title of the article suggests that only Lupin’s formulation had inferior bioavailability. This, we submit, requires reconsideration in the context of the internationally accepted Rifampicin Cmax cut-off at 8.0 g/ml for bio considerations. (Even the referred article accepts and mentions this reference standard.) The above-mentioned study (which was carried out purely for ‘academic reasons’, as we learn from Dr McIlleron) clearly highlights the need for undertaking bioavailability studies even wit...
OBJECTIVE To investigate the association of cryoglobulinaemia and autoimmune markers with hepatit... more OBJECTIVE To investigate the association of cryoglobulinaemia and autoimmune markers with hepatitis C virus (HCV) infection in patients on maintenance haemodialysis (HD) and post renal transplantation. METHODS Serum samples of 103 HCV-antibody (anti-HCV) positive and 105 anti-HCV negative patients were investigated for cryoglobulins. These comprised 136 patients on HD and 72 renal transplant recipients. Serum creatinine and liver function tests were obtained on all patients. Rheumatoid factor (RF), anti nuclear antibodies (ANA), anti smooth muscle antibodies (ASMA), liver kidney microsomal antibodies (LKM), immunoglobulins (Igs) and complement levels were performed on all cryoglobulin positive (cryopositive) samples. HCV RNA and genotyping detection tests were done for cryopositive patients. RESULTS The prevalence of cryoglobulins in patients on HD or after renal transplantation was found to be higher (57.6%) among anti-HCV positive patients compared to the anti-HCV negative patient...
Background: Disordered immune system is responsible for the pathogenesis in most of the glomerulo... more Background: Disordered immune system is responsible for the pathogenesis in most of the glomerulonephritis (GN) including FSGS. Elucidation of involvement of immune cells is important to avoid invasive procedures for monitoring of disease progression. Methods: We analyzed the frequencies of CD25, CD122 and CD5 on CD4 + , CD8 + and CD19 + T and B cells in blood and urine samples of 50 individuals including FSGS, other GN, pathological controls (PC)) and healthy controls (HC)). Data was analyzed using spss software. Results: The ratio of CD4 + 25 + to CD4 + 122 + was found significantly low in blood of FSGS patients compared to HC and PC (37.6 ± 44.1% vs. 100% in HC and PC, P = 0.000). The ratio of CD19 + 25 + to CD19 + 122 + cells were also significantly low in FSGS compared to HC (21.6 ± 20.6% vs.9.4 ± 7.7%, P =0.021). Overall, the percentages CD4 + 25 + 122 + , CD8 + 25 + 122 + and CD19 + 25 + 122 + cells were more in the urine of FSGS patients compared to controls. CD19 + 5 + B cells were significantly high in blood and urine of FSGS compared to controls. These cells were also significantly more in the blood of steroid dependent and resistant FSGS patients compared to steroid responsive and in urine of patients with renal dysfunction compared to normal renal functions. Conclusions: Our results show that T and B cells have a definite role in the pathogenesis of FSGS. A low expression of CD25 found on T and B cells in FSGS found in this study indicate down regulation of Treg and Breg cells in these patients. A high expression of CD5 + B in blood and urine of FSGS may be responsible for disease severity. The results of this study are important as it may help in avoiding unnecessary invasive procedure for patient monitoring. However there is a need to do further studies to validate these results.
Background BKVN remains an important cause of graft dysfunction in renal transplant setting. Earl... more Background BKVN remains an important cause of graft dysfunction in renal transplant setting. Early detection of BKVN and reduction of immunosuppression is recommended for preventing BKVN. Methods This is a retrospective study where all live related renal transplants were included performed from 2000 to 2015. There were 3962 transplants during the study period. Laboratory investigations and immunosuppression were retrieved and the data was entered in SPSS. Results Out of 3962 patients, 78 (2%) developed BK Viremia. Subsequently they underwent graft biopsy. Out of these 11 patients developed BKVN. Clearance of BK Viremia was achieved in 64 patients after reducing the immunosuppression from more potent to less potent immunosuppression. But subsequent BPAR occurred in 3 patients. Majority of them had preserved graft function. Conclusion We conclude that repeated testing of BKV replication and reduction of immunosuppression is an effective strategy to preserve graft function.
Applied Clinical Research, Clinical Trials and Regulatory Affairs
Background: Glomerulonephritis (GN) mostly occurs as a result of dysregulated immune system. In G... more Background: Glomerulonephritis (GN) mostly occurs as a result of dysregulated immune system. In GN patients the impairment of the immune mechanisms can be primary or secondary to an underlying autoimmune disease (AID). Antinuclear antibodies (ANA) are hallmark of AID. ANA may be found nonspecifically in certain infections, malignancies and also in 5%-10% healthy individuals at low titers. In AID ANA are usually found at high titer (≥ 1: 160). A positive ANA test with high titer is followed by anti-double stranded deoxyribonucleic acid (anti-dsDNA) and anti-extractable nuclear antigens (anti-ENA) tests for characterization of underlying AID. Heavy proteinuria can affect ANA results, however available data based on this information is scarce. Our aim was to determine the impact of heavy proteinuria on ANA titer, anti-dsDNA and anti-ENA in GN patients. Methods: Over all 150 GN patients were enrolled in this study with a positive ANA test. Serum samples of these patients were further te...
Objective: To evaluate the utility of serum CD30 (sCD30) levels as predictor of early acute graft... more Objective: To evaluate the utility of serum CD30 (sCD30) levels as predictor of early acute graft rejection in live related renal transplant programme. Methods: This prospective study included 50 consecutive renal transplant recipients who received their first live related renal allograft at the Sindh Institute of Urology and Transplantation (SIUT) between October 2006 and March 2007. Blood samples were obtained one day before transplantation and on the third and fourteenth posttransplant days. Blood samples were also obtained from 50, age and sex matched healthy control individuals. Levels of serum sCD30 were measured by Enzyme Linked Immunosorbent Assay (ELISA). Result: Donor-recipient blood group matching was identical in all patients. Pre-transplant lymphocyte crossmatch for T and B cells was negative, and panel reactive antibodies (PRA) were 0% for all recipients. The mean age of recipients was 31.6± 10.23 years (range 5 to 55 years), while mean donor age was 32.74± 8.48 years (range 21-50 years). Eleven (22%) recipients and donors were HLA identical while remaining (78%) were one haplotype match. Average serum sCD30 pre-transplant levels (37.8±4.97U/ml) were significantly higher than those of healthy individual's mean value of 8.48± 4.97 U/ml, (P = 0.001). Eight (16%) patients developed acute rejection episode during this follow up period. Rejections were described and classified according to BANFF 97 classification. Conclusion: In this small single center study the serum levels of sCD30 did not show any significant difference between rejection and non rejection group in our transplant population (JPMA 59:212; 2009).
Acute rejections (ARs) with plasma cell-rich infiltrates (PCARs) are associated with poor outcome... more Acute rejections (ARs) with plasma cell-rich infiltrates (PCARs) are associated with poor outcomes. Between February 2012 and December 2013, 1630 dysfunctional renal graft biopsies were performed. Of these, 50 (3%) showed PCAR. ARs with >10% plasma cells were defined as PCAR. Human leukocyte antigen (HLA) antibodies were tested in historic sera and at the time of PCAR. Treatment for PCAR comprised methylprednisolone, antithymocyte globulin, plasmapheresis, and anti-CD20 antibody. Of the 1630 dysfunctional biopsies, 50 (3%) had PCAR which occurred 3.1 ± 2.55 yr after transplant. The percentage of plasma cells was 28.8 ± 11.7, and CD138, 29.0 ± 12.4. Donor-specific antibodies (DSAs) were found in 32 (64%) overall, Class I in 15% and Class II in 65%. Post-treatment serum creatinine improved from 3.80 ± 2.59 to 2.66 ± 1.59 mg/dL in DSA positive (p < 0.003) and from 2.59 ± 1.09 to 2.08 ± 0.86 mg/dL in DSA negative (p < 0.008). One- and two-yr graft survival after PCAR was 72%, 42% in the DSA-positive vs. 89%, 82% in the DSA-negative group, respectively (p = 0.071). Our results show that PCAR occurs late after transplant and in many cases is associated with DSAs. Graft outcome was poor when PCAR was associated with DSAs.
JPMA. The Journal of the Pakistan Medical Association, 2009
To determine the morphological pattern in renal biopsies from nephrotic patients and their correl... more To determine the morphological pattern in renal biopsies from nephrotic patients and their correlation with immunoglobulin and complement deposition as detected by immunofluorescence microscopy (IMF) and serology to arrive at correct diagnosis of glomerulonephritis (GN). The study was carried out at the departments of Immunology and Histopathology, Sindh Institute of Urology and Transplantation (SIUT) from April 2007 to March 2008. A total of 200 patients, including children and adults were included. All patients presented with nephrotic syndrome (NS). Clinical and laboratory investigations including serology were noted, renal biopsies performed and studied by light and immunofluorescence microscopy (IMF). Of 200 patients, 74 (37%) were children (< or = 18 years) and 126 (63%) adults (> or = 19 years). Mean age of children was 11.34 +/- 4.85 years (range 3-18 years) and that of adults was 35.44 +/- 11.4 years (range: 19-70 years). The total percent change in L/M diagnosis afte...
The international journal of tuberculosis and lung disease : the official journal of the International Union against Tuberculosis and Lung Disease, 2002
Sputum samples were collected from suspected tuberculosis patients attending out-patient clinics ... more Sputum samples were collected from suspected tuberculosis patients attending out-patient clinics at the Ojha Institute of Chest Diseases, Karachi, Pakistan. To evaluate the performance of the FASTPlaqueTB assay for rapid diagnosis of pulmonary tuberculosis. A comparative study of 584 sputum samples using acid-fast smear microscopy, Lowenstein-Jensen culture and FASTPlaqueTB. A total of 514 samples yielded complete results. Seventy specimens were lost to analysis due to the overgrowth of contaminants. The addition of antimicrobials inhibited growth of gram-positive contaminants, and reduced the overall contamination rate from 18.2% to 7.2%. Mycobacterium tuberculosis was isolated from 175 smear-positive and 70 smear-negative specimens. FASTPlaqueTB detected M. tuberculosis in 81.6% of specimens, with a specificity of 97.7%. The sensitivity and specificity of the assay for smear-positive specimens were respectively 87.4% and 88.2%. For smear-negative specimens, the sensitivity of the ...
Journal of immunology (Baltimore, Md. : 1950), Jan 15, 1994
Nerve growth factor (NGF) is a neurotrophic protein essential for the maintenance and growth of p... more Nerve growth factor (NGF) is a neurotrophic protein essential for the maintenance and growth of peripheral sympathetic neurons and basal forebrain cholinergic neurons. Recently, NGF has also been shown to have effects on cells of the immune system. In a search for extra neural sources of NGF, we detected NGF-specific mRNA in mouse T lymphocytes of both the CD4+ and CD8+ phenotypes with the use of an RNase protection assay, PCR, and DNA sequence analysis. In CD4+ cells, NGF was present in both Th1 and Th2 Ag-specific clones, but an increase of NGF-specific message was detected after antigenic stimulation only in Th2 clones. NGF mRNA was also detected in splenic B lymphocytes and in a cell line derived from a murine follicular center cell lymphoma. Translation into protein and secretion of NGF were demonstrated by Western blot analysis. The secreted NGF is in an active form capable of inducing differentiation of PC12 cells into sympathetic-like neurons. Furthermore, conditioned medium...
JPMA. The Journal of the Pakistan Medical Association, 2007
To investigate the association of cryoglobulinaemia and autoimmune markers with hepatitis C virus... more To investigate the association of cryoglobulinaemia and autoimmune markers with hepatitis C virus (HCV) infection in patients on maintenance haemodialysis (HD) and post renal transplantation. Serum samples of 103 HCV-antibody (anti-HCV) positive and 105 anti-HCV negative patients were investigated for cryoglobulins. These comprised 136 patients on HD and 72 renal transplant recipients. Serum creatinine and liver function tests were obtained on all patients. Rheumatoid factor (RF), anti nuclear antibodies (ANA), anti smooth muscle antibodies (ASMA), liver kidney microsomal antibodies (LKM), immunoglobulins (Igs) and complement levels were performed on all cryoglobulin positive (cryopositive) samples. HCV RNA and genotyping detection tests were done for cryopositive patients. The prevalence of cryoglobulins in patients on HD or after renal transplantation was found to be higher (57.6%) among anti-HCV positive patients compared to the anti-HCV negative patients (42.4%) (P=0.000). RF, A...
JPMA. The Journal of the Pakistan Medical Association, 2009
To estimate size of injection drug users (IDU), determine their high risk behaviours and assess t... more To estimate size of injection drug users (IDU), determine their high risk behaviours and assess the prevalence of HIV. As part of second generation surveillance (SGS), we investigated specific demographic and behavioural characteristics of IDUs in Hyderabad and Sukkur in 2005. It was a cross sectional study. The survey was preceded by geographic mapping to determine size estimation and to define sampling procedures prior to integrated behavioural and biological survey (IBBS). A sample size of at least 400 was calculated for each city. Besides calculating frequencies, chi square was used for comparing variables among HIV positive and negative IDUs like time elapsed as IDU, number of injections, sharing needles and self perception of acquiring HIV infection. A total of 800 (Hyderabad 398; Sukkur 402) questionnaires and DBS samples were collected. The estimated number of IDUs in both cities was 3,225 (Hyderabad 975 and Sukkur 2250 respectively). Average age of IDUs in Hyderabad was 36....
Hepatitis B virus (HBV) genotypes have distinct geographic distribution. Moreover, much genetic v... more Hepatitis B virus (HBV) genotypes have distinct geographic distribution. Moreover, much genetic variability has been described in the precore (PC) and basal core promoter (BCP) regions of the HBV genome. The local prevalence of HBV genotypes and mutations has not been well studied. The aim of the present study is to determine the prevalence of HBV genotypes and mutations in the PC and BCP region in HBV strains in Karachi. A total of 109 chronic hepatitis B patients with detectable HBV DNA by a PCR assay were enrolled in the study. Sera were tested for HBeAg, anti-HBe antibody and liver profile. HBV genotypes and mutations in the PC and BCP regions were detected by INNO-LiPA line-probe assays. Of the 109 patients investigated, 38 (35%) were HBeAg positive while 71 (65%) were HBeAg negative. Genotype D was present in 100% of the patients. Two patients had co-infection with genotype A. There was no significant difference in the baseline characteristics, mean ALT levels, and presence of...
Journal of the College of Physicians and Surgeons--Pakistan : JCPSP, 2007
To document the prevalence of Helicobacter pylori (H. pylori), Hepatitis A virus (HAV), Hepatitis... more To document the prevalence of Helicobacter pylori (H. pylori), Hepatitis A virus (HAV), Hepatitis C virus (HCV), Hepatitis E virus (HEV) antibodies and Hepatitis B virus surface antigen (HBsAg), in the pediatric age group of low socioeconomic urban communities of Karachi and to identify risk factors associated with these infections. Cross-sectional survey. Three selected squatter settlements of Karachi during April 2002 to December 2004. Three hundred and eighty children, ages 5 months to 15 years were investigated. Venous blood samples were collected and questionnaire filled on sociodemographic characteristics (family income, number of dependents in the family, area of living, number of people per room per house, and number of children sharing bed with parents and siblings). Gastrointestinal symptoms were recorded. Anti-HAV IgG (Hepatitis A virus IgG antibody), anti-HCV (Hepatitis C virus antibody), anti-HEV (Hepatitis E antibodies) and HBsAg, were analyzed by enzyme immunoassays (...
JPMA. The Journal of the Pakistan Medical Association, 2007
To find the relationship between human leukocyte antigens (HLA) and cryoglobulin positivity in he... more To find the relationship between human leukocyte antigens (HLA) and cryoglobulin positivity in hepatitis C virus (HCV) infected individuals. Eligible individuals selected from pre and post renal transplant settings were divided into three groups. Group A (n = 301) consisted of normal controls, while group B (n = 200) comprised of pathological controls that were HCV antibody (anti-HCV) positive but negative for cryoglobulins. Group C comprised of 56 anti-HCV positive, cryoglobulin positive patients. HLA-A, -B and -DRB1 loci were typed by polymerase chain reaction (PCR) method and relationship between HLA antigens, anti-HCV status and cryoglobulinaemia was analyzed. HLA-A*02, -B*57 and -DRB1*03 were more frequently found among group C members as compared to groups A and B. Only HLA-B* 57 occurrence reached statistical significance (14.3% versus 6% and 4%, corrected P-value = 0.045 and 0.012 and OR = 2.6 and 4 respectively) No differences in the distribution of HLA antigens were seen a...
Antiphospholipid antibodies (aPL) are autoantibodies that are associated with a clinical state of... more Antiphospholipid antibodies (aPL) are autoantibodies that are associated with a clinical state of hypercoagulability and diverse clinical manifestations collectively known as antiphospholipid syndrome (APS). To investigate the prevalence of anti-beta2glycoproteinI-antibodies (anti-β2GPI) and their isotypes in patients with renal diseases and clinical suspicion of antiphospholipid syndrome (APS). This is a retrospective study in which we have analyzed the prevalence of anti-β2GPI and its isotypes in 170 patients on initial testing and in 29 patients repeated after 12 weeks for confirmation of APS. The clinical information was provided by the treating physicians or retrieved from the clinical records. The tests for anti-β2GPI screening and its isotypes (IgG, IgM and IgA) detection were assessed. On initial samples, anti-β2GPI was positive in 118patients. IgA-β2GPI positivity (93; 79%) was significantly higher than IgM and IgG isotypes. Out of anti-β2GPI positive patients, clinical ...
The distinct pattern of transcriptional responses of cells to different extracellular signals req... more The distinct pattern of transcriptional responses of cells to different extracellular signals requires a signal transduction pathway that provides rapid, accurate, and faithful transmission of information from the cell surface to the nucleus. One mechanism exploited by many cytokines, exemplified by interferons (IFN) but also used by many interleukins and growth factors, uses a family of cytoplasmic transcription factors that are activated by tyrosine phosphorylation. Once phosphorylated by receptor-associated tyrosine kinases, these proteins assemble into multimeric transcription factors, translocate to the nucleus, and bind specific DNA sequence elements in the promoters of target genes.
JPMA. The Journal of the Pakistan Medical Association, 2007
OBJECTIVE To find the relationship between human leukocyte antigens (HLA) and cryoglobulin positi... more OBJECTIVE To find the relationship between human leukocyte antigens (HLA) and cryoglobulin positivity in hepatitis C virus (HCV) infected individuals. METHODS Eligible individuals selected from pre and post renal transplant settings were divided into three groups. Group A (n = 301) consisted of normal controls, while group B (n = 200) comprised of pathological controls that were HCV antibody (anti-HCV) positive but negative for cryoglobulins. Group C comprised of 56 anti-HCV positive, cryoglobulin positive patients. HLA-A, -B and -DRB1 loci were typed by polymerase chain reaction (PCR) method and relationship between HLA antigens, anti-HCV status and cryoglobulinaemia was analyzed. RESULTS HLA-A*02, -B*57 and -DRB1*03 were more frequently found among group C members as compared to groups A and B. Only HLA-B* 57 occurrence reached statistical significance (14.3% versus 6% and 4%, corrected P-value = 0.045 and 0.012 and OR = 2.6 and 4 respectively) No differences in the distribution o...
I am writing to you with reference to a recent article published in the April 2002 issue of the J... more I am writing to you with reference to a recent article published in the April 2002 issue of the Journal.1 Following the release of this article, a misperception has been formed amongst some medical practitioners and lay press in India that batches of Lupin’s rifampicin products were withdrawn from the South African market as a direct result of failing in bio studies. This is a wrong perception and I would like to take this opportunity to set out the facts surrounding this issue. Further, the title of the article suggests that only Lupin’s formulation had inferior bioavailability. This, we submit, requires reconsideration in the context of the internationally accepted Rifampicin Cmax cut-off at 8.0 g/ml for bio considerations. (Even the referred article accepts and mentions this reference standard.) The above-mentioned study (which was carried out purely for ‘academic reasons’, as we learn from Dr McIlleron) clearly highlights the need for undertaking bioavailability studies even wit...
OBJECTIVE To investigate the association of cryoglobulinaemia and autoimmune markers with hepatit... more OBJECTIVE To investigate the association of cryoglobulinaemia and autoimmune markers with hepatitis C virus (HCV) infection in patients on maintenance haemodialysis (HD) and post renal transplantation. METHODS Serum samples of 103 HCV-antibody (anti-HCV) positive and 105 anti-HCV negative patients were investigated for cryoglobulins. These comprised 136 patients on HD and 72 renal transplant recipients. Serum creatinine and liver function tests were obtained on all patients. Rheumatoid factor (RF), anti nuclear antibodies (ANA), anti smooth muscle antibodies (ASMA), liver kidney microsomal antibodies (LKM), immunoglobulins (Igs) and complement levels were performed on all cryoglobulin positive (cryopositive) samples. HCV RNA and genotyping detection tests were done for cryopositive patients. RESULTS The prevalence of cryoglobulins in patients on HD or after renal transplantation was found to be higher (57.6%) among anti-HCV positive patients compared to the anti-HCV negative patient...
Background: Disordered immune system is responsible for the pathogenesis in most of the glomerulo... more Background: Disordered immune system is responsible for the pathogenesis in most of the glomerulonephritis (GN) including FSGS. Elucidation of involvement of immune cells is important to avoid invasive procedures for monitoring of disease progression. Methods: We analyzed the frequencies of CD25, CD122 and CD5 on CD4 + , CD8 + and CD19 + T and B cells in blood and urine samples of 50 individuals including FSGS, other GN, pathological controls (PC)) and healthy controls (HC)). Data was analyzed using spss software. Results: The ratio of CD4 + 25 + to CD4 + 122 + was found significantly low in blood of FSGS patients compared to HC and PC (37.6 ± 44.1% vs. 100% in HC and PC, P = 0.000). The ratio of CD19 + 25 + to CD19 + 122 + cells were also significantly low in FSGS compared to HC (21.6 ± 20.6% vs.9.4 ± 7.7%, P =0.021). Overall, the percentages CD4 + 25 + 122 + , CD8 + 25 + 122 + and CD19 + 25 + 122 + cells were more in the urine of FSGS patients compared to controls. CD19 + 5 + B cells were significantly high in blood and urine of FSGS compared to controls. These cells were also significantly more in the blood of steroid dependent and resistant FSGS patients compared to steroid responsive and in urine of patients with renal dysfunction compared to normal renal functions. Conclusions: Our results show that T and B cells have a definite role in the pathogenesis of FSGS. A low expression of CD25 found on T and B cells in FSGS found in this study indicate down regulation of Treg and Breg cells in these patients. A high expression of CD5 + B in blood and urine of FSGS may be responsible for disease severity. The results of this study are important as it may help in avoiding unnecessary invasive procedure for patient monitoring. However there is a need to do further studies to validate these results.
Background BKVN remains an important cause of graft dysfunction in renal transplant setting. Earl... more Background BKVN remains an important cause of graft dysfunction in renal transplant setting. Early detection of BKVN and reduction of immunosuppression is recommended for preventing BKVN. Methods This is a retrospective study where all live related renal transplants were included performed from 2000 to 2015. There were 3962 transplants during the study period. Laboratory investigations and immunosuppression were retrieved and the data was entered in SPSS. Results Out of 3962 patients, 78 (2%) developed BK Viremia. Subsequently they underwent graft biopsy. Out of these 11 patients developed BKVN. Clearance of BK Viremia was achieved in 64 patients after reducing the immunosuppression from more potent to less potent immunosuppression. But subsequent BPAR occurred in 3 patients. Majority of them had preserved graft function. Conclusion We conclude that repeated testing of BKV replication and reduction of immunosuppression is an effective strategy to preserve graft function.
Applied Clinical Research, Clinical Trials and Regulatory Affairs
Background: Glomerulonephritis (GN) mostly occurs as a result of dysregulated immune system. In G... more Background: Glomerulonephritis (GN) mostly occurs as a result of dysregulated immune system. In GN patients the impairment of the immune mechanisms can be primary or secondary to an underlying autoimmune disease (AID). Antinuclear antibodies (ANA) are hallmark of AID. ANA may be found nonspecifically in certain infections, malignancies and also in 5%-10% healthy individuals at low titers. In AID ANA are usually found at high titer (≥ 1: 160). A positive ANA test with high titer is followed by anti-double stranded deoxyribonucleic acid (anti-dsDNA) and anti-extractable nuclear antigens (anti-ENA) tests for characterization of underlying AID. Heavy proteinuria can affect ANA results, however available data based on this information is scarce. Our aim was to determine the impact of heavy proteinuria on ANA titer, anti-dsDNA and anti-ENA in GN patients. Methods: Over all 150 GN patients were enrolled in this study with a positive ANA test. Serum samples of these patients were further te...
Objective: To evaluate the utility of serum CD30 (sCD30) levels as predictor of early acute graft... more Objective: To evaluate the utility of serum CD30 (sCD30) levels as predictor of early acute graft rejection in live related renal transplant programme. Methods: This prospective study included 50 consecutive renal transplant recipients who received their first live related renal allograft at the Sindh Institute of Urology and Transplantation (SIUT) between October 2006 and March 2007. Blood samples were obtained one day before transplantation and on the third and fourteenth posttransplant days. Blood samples were also obtained from 50, age and sex matched healthy control individuals. Levels of serum sCD30 were measured by Enzyme Linked Immunosorbent Assay (ELISA). Result: Donor-recipient blood group matching was identical in all patients. Pre-transplant lymphocyte crossmatch for T and B cells was negative, and panel reactive antibodies (PRA) were 0% for all recipients. The mean age of recipients was 31.6± 10.23 years (range 5 to 55 years), while mean donor age was 32.74± 8.48 years (range 21-50 years). Eleven (22%) recipients and donors were HLA identical while remaining (78%) were one haplotype match. Average serum sCD30 pre-transplant levels (37.8±4.97U/ml) were significantly higher than those of healthy individual's mean value of 8.48± 4.97 U/ml, (P = 0.001). Eight (16%) patients developed acute rejection episode during this follow up period. Rejections were described and classified according to BANFF 97 classification. Conclusion: In this small single center study the serum levels of sCD30 did not show any significant difference between rejection and non rejection group in our transplant population (JPMA 59:212; 2009).
Acute rejections (ARs) with plasma cell-rich infiltrates (PCARs) are associated with poor outcome... more Acute rejections (ARs) with plasma cell-rich infiltrates (PCARs) are associated with poor outcomes. Between February 2012 and December 2013, 1630 dysfunctional renal graft biopsies were performed. Of these, 50 (3%) showed PCAR. ARs with &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt;10% plasma cells were defined as PCAR. Human leukocyte antigen (HLA) antibodies were tested in historic sera and at the time of PCAR. Treatment for PCAR comprised methylprednisolone, antithymocyte globulin, plasmapheresis, and anti-CD20 antibody. Of the 1630 dysfunctional biopsies, 50 (3%) had PCAR which occurred 3.1 ± 2.55 yr after transplant. The percentage of plasma cells was 28.8 ± 11.7, and CD138, 29.0 ± 12.4. Donor-specific antibodies (DSAs) were found in 32 (64%) overall, Class I in 15% and Class II in 65%. Post-treatment serum creatinine improved from 3.80 ± 2.59 to 2.66 ± 1.59 mg/dL in DSA positive (p &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.003) and from 2.59 ± 1.09 to 2.08 ± 0.86 mg/dL in DSA negative (p &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.008). One- and two-yr graft survival after PCAR was 72%, 42% in the DSA-positive vs. 89%, 82% in the DSA-negative group, respectively (p = 0.071). Our results show that PCAR occurs late after transplant and in many cases is associated with DSAs. Graft outcome was poor when PCAR was associated with DSAs.
JPMA. The Journal of the Pakistan Medical Association, 2009
To determine the morphological pattern in renal biopsies from nephrotic patients and their correl... more To determine the morphological pattern in renal biopsies from nephrotic patients and their correlation with immunoglobulin and complement deposition as detected by immunofluorescence microscopy (IMF) and serology to arrive at correct diagnosis of glomerulonephritis (GN). The study was carried out at the departments of Immunology and Histopathology, Sindh Institute of Urology and Transplantation (SIUT) from April 2007 to March 2008. A total of 200 patients, including children and adults were included. All patients presented with nephrotic syndrome (NS). Clinical and laboratory investigations including serology were noted, renal biopsies performed and studied by light and immunofluorescence microscopy (IMF). Of 200 patients, 74 (37%) were children (< or = 18 years) and 126 (63%) adults (> or = 19 years). Mean age of children was 11.34 +/- 4.85 years (range 3-18 years) and that of adults was 35.44 +/- 11.4 years (range: 19-70 years). The total percent change in L/M diagnosis afte...
The international journal of tuberculosis and lung disease : the official journal of the International Union against Tuberculosis and Lung Disease, 2002
Sputum samples were collected from suspected tuberculosis patients attending out-patient clinics ... more Sputum samples were collected from suspected tuberculosis patients attending out-patient clinics at the Ojha Institute of Chest Diseases, Karachi, Pakistan. To evaluate the performance of the FASTPlaqueTB assay for rapid diagnosis of pulmonary tuberculosis. A comparative study of 584 sputum samples using acid-fast smear microscopy, Lowenstein-Jensen culture and FASTPlaqueTB. A total of 514 samples yielded complete results. Seventy specimens were lost to analysis due to the overgrowth of contaminants. The addition of antimicrobials inhibited growth of gram-positive contaminants, and reduced the overall contamination rate from 18.2% to 7.2%. Mycobacterium tuberculosis was isolated from 175 smear-positive and 70 smear-negative specimens. FASTPlaqueTB detected M. tuberculosis in 81.6% of specimens, with a specificity of 97.7%. The sensitivity and specificity of the assay for smear-positive specimens were respectively 87.4% and 88.2%. For smear-negative specimens, the sensitivity of the ...
Journal of immunology (Baltimore, Md. : 1950), Jan 15, 1994
Nerve growth factor (NGF) is a neurotrophic protein essential for the maintenance and growth of p... more Nerve growth factor (NGF) is a neurotrophic protein essential for the maintenance and growth of peripheral sympathetic neurons and basal forebrain cholinergic neurons. Recently, NGF has also been shown to have effects on cells of the immune system. In a search for extra neural sources of NGF, we detected NGF-specific mRNA in mouse T lymphocytes of both the CD4+ and CD8+ phenotypes with the use of an RNase protection assay, PCR, and DNA sequence analysis. In CD4+ cells, NGF was present in both Th1 and Th2 Ag-specific clones, but an increase of NGF-specific message was detected after antigenic stimulation only in Th2 clones. NGF mRNA was also detected in splenic B lymphocytes and in a cell line derived from a murine follicular center cell lymphoma. Translation into protein and secretion of NGF were demonstrated by Western blot analysis. The secreted NGF is in an active form capable of inducing differentiation of PC12 cells into sympathetic-like neurons. Furthermore, conditioned medium...
JPMA. The Journal of the Pakistan Medical Association, 2007
To investigate the association of cryoglobulinaemia and autoimmune markers with hepatitis C virus... more To investigate the association of cryoglobulinaemia and autoimmune markers with hepatitis C virus (HCV) infection in patients on maintenance haemodialysis (HD) and post renal transplantation. Serum samples of 103 HCV-antibody (anti-HCV) positive and 105 anti-HCV negative patients were investigated for cryoglobulins. These comprised 136 patients on HD and 72 renal transplant recipients. Serum creatinine and liver function tests were obtained on all patients. Rheumatoid factor (RF), anti nuclear antibodies (ANA), anti smooth muscle antibodies (ASMA), liver kidney microsomal antibodies (LKM), immunoglobulins (Igs) and complement levels were performed on all cryoglobulin positive (cryopositive) samples. HCV RNA and genotyping detection tests were done for cryopositive patients. The prevalence of cryoglobulins in patients on HD or after renal transplantation was found to be higher (57.6%) among anti-HCV positive patients compared to the anti-HCV negative patients (42.4%) (P=0.000). RF, A...
JPMA. The Journal of the Pakistan Medical Association, 2009
To estimate size of injection drug users (IDU), determine their high risk behaviours and assess t... more To estimate size of injection drug users (IDU), determine their high risk behaviours and assess the prevalence of HIV. As part of second generation surveillance (SGS), we investigated specific demographic and behavioural characteristics of IDUs in Hyderabad and Sukkur in 2005. It was a cross sectional study. The survey was preceded by geographic mapping to determine size estimation and to define sampling procedures prior to integrated behavioural and biological survey (IBBS). A sample size of at least 400 was calculated for each city. Besides calculating frequencies, chi square was used for comparing variables among HIV positive and negative IDUs like time elapsed as IDU, number of injections, sharing needles and self perception of acquiring HIV infection. A total of 800 (Hyderabad 398; Sukkur 402) questionnaires and DBS samples were collected. The estimated number of IDUs in both cities was 3,225 (Hyderabad 975 and Sukkur 2250 respectively). Average age of IDUs in Hyderabad was 36....
Hepatitis B virus (HBV) genotypes have distinct geographic distribution. Moreover, much genetic v... more Hepatitis B virus (HBV) genotypes have distinct geographic distribution. Moreover, much genetic variability has been described in the precore (PC) and basal core promoter (BCP) regions of the HBV genome. The local prevalence of HBV genotypes and mutations has not been well studied. The aim of the present study is to determine the prevalence of HBV genotypes and mutations in the PC and BCP region in HBV strains in Karachi. A total of 109 chronic hepatitis B patients with detectable HBV DNA by a PCR assay were enrolled in the study. Sera were tested for HBeAg, anti-HBe antibody and liver profile. HBV genotypes and mutations in the PC and BCP regions were detected by INNO-LiPA line-probe assays. Of the 109 patients investigated, 38 (35%) were HBeAg positive while 71 (65%) were HBeAg negative. Genotype D was present in 100% of the patients. Two patients had co-infection with genotype A. There was no significant difference in the baseline characteristics, mean ALT levels, and presence of...
Journal of the College of Physicians and Surgeons--Pakistan : JCPSP, 2007
To document the prevalence of Helicobacter pylori (H. pylori), Hepatitis A virus (HAV), Hepatitis... more To document the prevalence of Helicobacter pylori (H. pylori), Hepatitis A virus (HAV), Hepatitis C virus (HCV), Hepatitis E virus (HEV) antibodies and Hepatitis B virus surface antigen (HBsAg), in the pediatric age group of low socioeconomic urban communities of Karachi and to identify risk factors associated with these infections. Cross-sectional survey. Three selected squatter settlements of Karachi during April 2002 to December 2004. Three hundred and eighty children, ages 5 months to 15 years were investigated. Venous blood samples were collected and questionnaire filled on sociodemographic characteristics (family income, number of dependents in the family, area of living, number of people per room per house, and number of children sharing bed with parents and siblings). Gastrointestinal symptoms were recorded. Anti-HAV IgG (Hepatitis A virus IgG antibody), anti-HCV (Hepatitis C virus antibody), anti-HEV (Hepatitis E antibodies) and HBsAg, were analyzed by enzyme immunoassays (...
JPMA. The Journal of the Pakistan Medical Association, 2007
To find the relationship between human leukocyte antigens (HLA) and cryoglobulin positivity in he... more To find the relationship between human leukocyte antigens (HLA) and cryoglobulin positivity in hepatitis C virus (HCV) infected individuals. Eligible individuals selected from pre and post renal transplant settings were divided into three groups. Group A (n = 301) consisted of normal controls, while group B (n = 200) comprised of pathological controls that were HCV antibody (anti-HCV) positive but negative for cryoglobulins. Group C comprised of 56 anti-HCV positive, cryoglobulin positive patients. HLA-A, -B and -DRB1 loci were typed by polymerase chain reaction (PCR) method and relationship between HLA antigens, anti-HCV status and cryoglobulinaemia was analyzed. HLA-A*02, -B*57 and -DRB1*03 were more frequently found among group C members as compared to groups A and B. Only HLA-B* 57 occurrence reached statistical significance (14.3% versus 6% and 4%, corrected P-value = 0.045 and 0.012 and OR = 2.6 and 4 respectively) No differences in the distribution of HLA antigens were seen a...
Antiphospholipid antibodies (aPL) are autoantibodies that are associated with a clinical state of... more Antiphospholipid antibodies (aPL) are autoantibodies that are associated with a clinical state of hypercoagulability and diverse clinical manifestations collectively known as antiphospholipid syndrome (APS). To investigate the prevalence of anti-beta2glycoproteinI-antibodies (anti-β2GPI) and their isotypes in patients with renal diseases and clinical suspicion of antiphospholipid syndrome (APS). This is a retrospective study in which we have analyzed the prevalence of anti-β2GPI and its isotypes in 170 patients on initial testing and in 29 patients repeated after 12 weeks for confirmation of APS. The clinical information was provided by the treating physicians or retrieved from the clinical records. The tests for anti-β2GPI screening and its isotypes (IgG, IgM and IgA) detection were assessed. On initial samples, anti-β2GPI was positive in 118patients. IgA-β2GPI positivity (93; 79%) was significantly higher than IgM and IgG isotypes. Out of anti-β2GPI positive patients, clinical ...
The distinct pattern of transcriptional responses of cells to different extracellular signals req... more The distinct pattern of transcriptional responses of cells to different extracellular signals requires a signal transduction pathway that provides rapid, accurate, and faithful transmission of information from the cell surface to the nucleus. One mechanism exploited by many cytokines, exemplified by interferons (IFN) but also used by many interleukins and growth factors, uses a family of cytoplasmic transcription factors that are activated by tyrosine phosphorylation. Once phosphorylated by receptor-associated tyrosine kinases, these proteins assemble into multimeric transcription factors, translocate to the nucleus, and bind specific DNA sequence elements in the promoters of target genes.
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Papers by Rana Muzaffar