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Biomedical subjects

K V Johny

Publications and source records attributed to K V Johny.

At least 19 recordsLinked to original sources

Safety of caspofungin for treating invasive nasal sinus aspergillosis in a kidney transplant recipient.

INTRODUCTION: Invasive fungal sinusitis is a rare but often fatal infection in immunocompromised patients. Aggressive antifungal treatment is mandatory, but is not without risk. Caspofungin, an antifungal agent that is a member of the echinocandin family, an inhibitor of glucan synthesis in the fungal wall, is active against Aspergillus and Candidae infections. Although it works on the fungal wall, it does not affect mammalian cells; hence, its toxicity is minimal. CASE SUMMARY: This report describes a case of invasive Aspergillus sinusitis in a kidney transplant recipient with diabetes mellitus. The infection involved the apex of the right orbit causing optic nerve compression. The patient was treated with transnasal endoscopic decompression of the optic nerve and intravenous AmBisome (liposomal amphotericin B) for 2 weeks without clinical improvement. The combination of caspofungin and AmBisome administered for another 2 weeks yielded partial improvement. The AmBisome had to be discontinued due to deterioration of renal and hepatic function, but the patient completed a further 7-week course of caspofungin alone. Retro-orbital biopsy confirmed a complete response to treatment; the patient's renal and hepatic function returned to normal. CONCLUSION: This case indicates that caspofungin is effective to treat invasive Aspergillus sinusitis in kidney transplant recipients. This agent is well tolerated and safe with respect to renal and hepatic function.

Antifungal Agents↗

Early acute rejection episodes in renal transplantation in relation to immunosuppression protocols: an audit of 100 cases.

INTRODUCTION: Early acute rejection episodes (ARE) have deleterious effects on graft outcomes. The incidence of ARE in the first 3 months has been reported to be <20%. In a recent audit of ARE among 100 renal transplants, we observed the rates to be high (30%). We retrospectively collected details of donor type, induction therapy, immunosuppression medications, drug levels, HLA mismatches, acute tubular necrosis (ATN), and delayed graft function (DGF) to correlate with ARE and response to therapy. RESULTS: Thirty rejection episodes occurred after a mean period of 14.3 days after transplantation. Ninety-one patients had induction treatment with either antithymocyte globulin (ATG) or interleukin 2 receptor antibodies (IL2 Rab). The drugs included cyclosporine, mycophenolate, sirolimus, azathioprine, and prednisolone in these patients. There was no significant difference in ARE among the different drug protocols (30.7%-35.2%). Subjects with 4 or more HLA mismatches displayed more ARE (40.3%) compared with those with 3 or less (23%). Subjects with ATN or DGF immediately posttransplantation had a higher incidence of ARE (39.2%) than those without them (26.3%). Deceased donor recipients had a higher episode of ARE (45.1%) compared with live related donor recipients (25%). On stratifying the known risk factors for ARE, subjects with no risk factors had the least (22.2%) ARE compared with those with one (32.5%) or two (47.6%) risk factors. Subjects who failed to achieve adequate cyclosporine (C2) levels showed significantly higher rates of ARE (86.9%) than those with adequate or higher levels (8.6%). CONCLUSION: Higher HLA mismatches, DGF, deceased donor, and failure to achieve adequate cyclosporine levels were observed to be major risk factors for the development of ARE.

Acute Disease↗

Single daily dose administration of cyclosporine in renal transplant recipients: a preliminary report.

INTRODUCTION: Cyclosporine microemulsion has been the mainstay immunosuppressive agent in renal transplantation for years. Since single daily dosing of cyclosporine is rarely used, the objective of this investigation was to evaluate the efficacy of a single daily dose versus twice daily dosing of cyclosporine in renal transplant recipients. METHODS: Retrospective evaluation of single-dose cyclosporine use was conducted for 15 renal transplant recipients for 12 months (study group). Equal numbers of matched renal transplant recipients were selected for age, sex, human leukocyte antigen mismatch, donor type, and immunosuppressive regimen (control group). Cyclosporine trough level and peak cyclosporine blood levels, 12-hour cyclosporine profile, and the area under the concentration-time curve were measured. RESULTS: There was a significant difference in cyclosporine peak blood level and calculated area under the curve after shifting to single-dose cyclosporine (P = .001). In the study group, the mean area under the curve was significantly below the average therapeutic range before (3154 ng/mL/ho) versus 5532 ng/mL/h after shifting to the single-dose regimen (which was therapeutic). This value was 5749 ng/mL/h in the control group. Total daily cyclosporine dose was lower in the study group when compared with the control group at 6 and 12 months (P = .01). There were significantly fewer adverse effects in patients in the study group than in patients in the control group. CONCLUSION: We conclude that although cyclosporine dose should be individualized in renal transplant recipients, a single dose of cyclosporine has the added advantage of decreasing dosages and cyclosporine-related adverse effects while maintaining optimal graft function.

Adult↗

The area under the concentration-time curve versus trough and peak blood level monitoring in renal transplant recipients on cyclosporine.

OBJECTIVE: The area under the concentration-time curve of cyclosporine microemulsion is the best measure of the absorption and beneficial effects in renal transplant recipients. We sought to determine the best method of monitoring cyclosporine levels in these patients. METHODS: Prospective evaluation of peak cyclosporine blood levels and area under the curve monitoring were performed for 1 year in 65 renal transplant recipients (study group). Cyclosporine trough levels and peak cyclosporine blood levels were correlated with the calculated area under the curve. Cyclosporine trough levels were monitored in equal numbers of matched controls. RESULTS: There were no significant differences in the incidence of acute rejection, cyclosporine nephrotoxicity, proteinuria, serum creatinine levels, or graft and patient outcomes between the groups (P = .1). Peak cyclosporine blood levels guided by calculating the area under the curve were found to be 27% to 32% lower than previously reported. The correlation coefficient was <70% for cyclosporine trough levels (P < .02) and >90% for peak cyclosporine blood levels (P < .001) when related to the calculated area under the curve. The calculated area under the curve was approximately 6000 ng/mL/h following transplantation, gradually decreasing to approximately 3000 ng/mL/h at 1 year. Both appeared to the acceptable therapeutic values. CONCLUSION: Calculating the area under the curve using trough and peak blood levels versus using isolated readings for either of these levels alone is the most effective method of monitoring cyclosporine in recipients undergoing renal transplant.

Adolescent↗

BK virus nephropathy in renal transplant recipients in Kuwait: a preliminary report.

INTRODUCTION: BK virus nephropathy (BKVN) is a significant cause of graft loss among renal transplant recipients. The treatment outcomes of BKVN have been variably reported in the literature. PATIENTS AND METHODS: We prospectively investigated BKV infection and BKVN among a population of renal transplant recipients with suspected BKV infection. The 42 subjects who all had acute allograft dysfunction, were categorized in three groups: those with clinical, laboratory, and histological findings that did not suggest acute rejection, drug toxicity, or obstruction (group 1, n = 24); those with findings that suggested probable acute cellular rejection but did not respond to antirejection treatment (group 2, n = 10); and those whose renal histology suggested BKVN (group 3, n = 8). Polymerase chain reaction analysis was done to detect BKV DNA in urine and blood samples from each subject. BKV DNA was detected in 19 (45%) urine samples with 11 of these subjects (26.1% of total) having BK viremia as well. RESULTS: No evidence of BKVN was detected histologically in seven subjects with isolated BK viruria, while the others proved to be JC virus infections. Among the 11 subjects with BK viremia, eight had BKVN based on renal histology at the time of diagnosis with BKV infection, while the other three subsequently developed histological features of BKVN. BKVN developed after 5.3 +/- 2.5 (2 to 44) months after transplantation. The serum creatinine at time of BKVN diagnosis was 158.9 +/- 58 (87 to 285) micromol/L. All subjects were initially treated with a 50% reduction in immunosuppressive drug doses. Further decreases in immunosuppression were performed in all patients with close monitoring of renal function. All subjects were followed up for a of 18.2 +/- 5 (12 to 26) months. Two grafts were lost not due to BKVN, and one patient was lost to follow-up during this period. The latest serum creatinine in eight recipients is 113 + 20 (81 to 138) micromol/L, which is better than the renal function at diagnosis. CONCLUSION: The prevalence of BKVN in suspected BKV infection was 26%. Although the study period was short (30 months), BK viremia strongly correlated with BKVN, which seemed to be successfully treated with reduction in immunosuppression.

Adult↗

Results in 158 consecutive cadaveric renal transplantations.

OBJECTIVES: We investigated the outcome of deceased donor kidney transplantations performed in a single center in a developing country. MATERIALS AND METHODS: A total of 158 patients (69 male and 89 female patients, including 32 children) received kidney grafts obtained from deceased donors between March 1996 and October 2004. Cadaveric renal grafts were transplanted after a cold ischemia time of 4 to 24 hours (mean, 12.5 hours). Retransplantation was performed in 19 recipients. Induction immunosuppression was achieved with antithymocyte globulin. The diagnosis of acute graft rejection was based on histopathological findings. RESULTS: Primary graft function was observed in 77% of cases. Posttransplantation complications were: surgical (n = 60; 38%), systemic bacterial and viral infections (n = 33; 21%), acute rejection (n = 47; 30%), and malignancy (n = 2; 1.3%). Seventeen recipients died with a functioning graft, and 23 more grafts were lost. The 7-year actuarial survival rates were 89% and 75% for recipients and grafts, respectively. CONCLUSIONS: The kidney transplantation program in Kuwait is steadily growing. Kidney grafts obtained from deceased donors contributed 28% of the transplantation activity and were associated with a high rate of primary function. Overall actuarial recipient and graft survival rates were comparable to those reported by larger centers.

Adolescent↗

Vascular calcification in dialysis patients.

UNLABELLED: The risk factors for vascular calcification (VC) in dialysis patients include duration of dialysis, diabetes mellitus, aging, hyperphosphatemia, hyperparathyroidism, and calcium or vitamin D supplementation. This study was performed to evaluate the prevalence of and risk factors for VC in our dialysis population. METHODS: One hundred twenty-nine chronic dialysis patients underwent plain x-rays of the hands for VC. Patients were grouped as either positive (PVC) or negative (NVC) for VC. Age, gender, duration of dialysis, presence of non-insulin-dependent diabetes mellitus (NIDDM), oral calcium, and 1alpha-hydroxyvitamin D3 supplement, serum levels of calcium (Ca), phosphorus (P), calcium phosphorus product (CaxP), alkaline phosphates (ALP) and intact parathyroid hormone (iPTH) were compared between the two groups. RESULTS: Thirty-four patients (26.35%) showed VC. There were no differences between PVC and NVC patients for duration of dialysis (38.4 +/- 27.7 for PVC and 34.6 +/- 31.2 months for NVC, P = .80), levels of serum Ca (P = .26), P (P = .19), CaxP (P = .33), ALP (P = .89), or iPTH (P = .24). Similarly, oral calcium and 1alpha-hydroxyvitamin D3 intake were not different between the two groups (P = .971 and P = .3710 respectively). Compared to NVC patients, PVC patients were older (56.3 +/- 10.4 versus 47.5 +/- 16.1 years, P = .008) and had a greater incidence of NIDDM (17/34 PVC and diabetic versus 20/95 NVC, P = .001). In conclusion, for patients with a medium length of dialysis, the duration of dialysis as well as the doses of calcium salts and of 1alpha-hydroxyvitamin D3 were not significantly associated with vascular calcifications, but it was not possible to exclude a role for these and other factors in patients with longer dialysis.

Alkaline Phosphatase↗

Cutaneous cryptococcosis in a diabetic renal transplant recipient.

A diabetic renal transplant recipient with cellulitis caused by Cryptococcus neoformans, serotype A, is described. The diagnosis was based on the demonstration of capsulated, budding yeast cells in the aspirated material and tissue from the cellulitic lesion and isolation of the aetiological agent in culture. The isolate formed well-developed capsules in the brain tissue of experimentally infected mice and produced cherry-brown colonies on niger seed medium. The patient's serum was positive for cryptococcal antigen (titre 1 : 4) with no other evidence of systemic infection. He was successfully treated with AmBisome, followed by fluconazole, resulting in the complete resolution of cellulitis and disappearance of the cryptococcal antigen. This report underscores the fact that patients with cutaneous cryptococcosis should be thoroughly evaluated, as it may be the first manifestation of a systemic disease. Prompt diagnosis and treatment are important to improve survival.

Animals↗

Correlation between CMV genotypes, multiple infections with herpesviruses (HHV-6, 7) and development of CMV disease in kidney recipients in Kuwait.

The possible correlation between cytomegalovirus, human herpesvirus types 6, 7 and cytomegalovirus-related clinical symptoms was studied in kidney transplant patients in Kuwait. Cytomegalovirus infection was diagnosed using the pp65 antigenemia assay. DNA of cytomegalovirus was detected by nested polymerase chain reaction (nested-PCR). PCR was also used to amplify the genes coding for structural proteins of human herpesvirus-6 (240 bp) and human herpesvirus-7 (186 bp). Glycoprotein B genotypes of cytomegalovirus were determined by restriction fragment length polymorphism. The average number of cells positive for cytomegalovirus pp65 antigen showed a steady increase with the severity of the cytomegalovirus-related symptoms. Furthermore, cytomegalovirus pp65 antigen positivity was significantly more frequent among recipients of cadaver kidney (45.5%) than among those who received live related kidneys (22.6%). Cytomegalovirus gB genotype 1 was detected more frequently (P<0.036) in recipients with live related donor kidney (38%) than in patients of cadaver kidney (13%). The genome of human herpesvirus-6 was detected at the same rate in patients with or without cytomegalovirus-related symptoms. However, the genome of human herpesvirus-7 was detected significantly more frequently (P<0.0001) in asymptomatic patients (41.7%) than in recipients with symptomatic cytomegalovirus infection (17%). We conclude that cytomegalovirus gB genotypes are not associated with the outcome of a cytomegalovirus infection in kidney transplant patients, that human herpesvirus-6 does not play a role in cytomegalovirus pathogenesis and that the role of human herpesvirus-7 in cytomegalovirus-related morbidity in kidney recipients remains unclear.

Adolescent↗

High incidence of post-transplant diabetes mellitus in Kuwait.

Post-transplant diabetes mellitus (PTDM) has been reported to occur in 5-15% of non-diabetic renal transplant recipients. During a 15-year period (January 1983-January 1998), 631 renal transplant recipients (TxR) were followed-up in our Centre of whom 79 (12.5%) had pre-transplant diabetes mellitus. Among the 552 TxR who were non-diabetic at pre-transplantation, 117 (21.2%) developed PTDM. The gender, native renal disease and the mode of pre-transplant dialysis did not differ in those with and without PTDM. Of the 117 TxR who developed PTDM, 63 (53.8%) were above the age of 45 years where as only 90 (20.7%) of the 435 who remained non-diabetic (NDM) were above this age (P<0.05). PTDM occurred in 115 (29.6%) recipients of Arab origin (Kuwaitis and non-Kuwaitis) where as only two (1.7%) non-Arabs developed it. There was no difference in the incidence of PTDM when prednisone and azathioprine (two drug regime) were used or with cyclosporine (triple drug regime). The incidence of acute rejection episodes did not differ among PTDM and NDM groups. The over all incidence of infections requiring hospitalisation was higher in PTDM group (1.8 episodes per patient) compared to NDM group (one episode per patient) during the study period (P<0.001). Coronary heart disease was also more frequent in PTDM (15 vs. 6%, P<0.05). The cumulative graft survival at 1, 5, 10 and 14 years in the PTDM (97, 92, 74 and 67%, respectively) and NDM groups (97, 91, 80 and 73%, respectively) was similar. However, an important cause of graft loss was death of the recipient in PTDM compared to NDM (10.7 vs. 3.6%). Similarly, the patient survival up to 14 years did not differ between PTDM and NDM groups (80 and 82%, respectively), although infection related deaths were more frequent in the PTDM group (65 vs. 49%) although not statistically significant. In conclusion, there is a high incidence of PTDM in Kuwait; age and race being the two important contributory factors. The overall patient and graft survival are not adversely affected by PTDM although infections and coronary heart disease are more frequently encountered in this group.

Adult↗