Risk of endometrial cancer among women with benign ovarian tumors - A Danish nationwide cohort study.

OBJECTIVE: The few studies on the association between benign ovarian tumors and endometrial cancer have been inconclusive. Using data from a large Danish register-based cohort study, we assessed the overall and type-specific risk of endometrial cancer among women with a benign ovarian tumor. METHODS: We identified all Danish women diagnosed with a benign ovarian tumor during 1978-2016 in the Danish National Patient Register (n = 149,807). The study population was followed for subsequent development of endometrial cancer by linkage to the Danish Cancer Register and standardized incidence ratios (SIRs) with corresponding 95% confidence intervals (CIs) were calculated after correction for hysterectomy. RESULTS: After a one-year delayed study entry, women with benign ovarian tumors had a decreased incidence of endometrial cancer (SIR = 0.74, 95% CI: 0.68-0.81) compared with women in the general Danish population. Both solid benign ovarian tumors (SIR = 0.79, 95% CI 0.70-0.88) and cystic benign ovarian tumors (SIR = 0.68, 95% CI 0.58-0.78) were associated with decreased incidences of endometrial cancer. Likewise, women with benign ovarian tumors had decreased incidences of both type I and type II endometrial cancer. The incidence of endometrial cancer was decreased to virtually the same magnitude irrespective of the age at diagnosis of a benign ovarian tumor and the reduction persisted throughout the follow-up period. CONCLUSIONS: The risk of endometrial cancer was decreased beyond the first year after a benign ovarian tumor and the decrease persisted for 20 or more years. The possible underlying mechanisms are not known and should be investigated further.

The short-term impact of protocol biopsies in a live-related renal transplant program using tacrolimus based immunosuppression.

The aim of the study was to assess the impact of protocol biopsies in a live-related renal transplant program using tacrolimus-based immunosuppression in the short term. Eighty-three live-related transplant recipients were randomly allocated to protocol biopsy group (Group I, n = 40) and a control group (Group II, n = 43). Other immunosuppressants in these groups consisted of either mycophenolate mofetil or azathioprine and steroids. Protocol biopsies were conducted in biopsy group at 1, 6, and 12 months post-transplant. The non-biopsy group was followed by serial serum creatinine and biopsies in them were conducted as and when clinically indicated. Both groups were analyzed at 12 months with respect to graft function and survival. The two groups were similar with respect to age, number of dialysis pre-operatively, tacrolimus levels, induction therapy, donor age, and donor glomerular filtration rate. Forty protocol biopsies were conducted at 1 month, 31 at 6 months, and 26 at 12 months. The prevalence of sub-clinical rejection at 1, 6, and 12 months in these biopsies was 17.5%, 11.2%, and 10.3%, respectively. The prevalence of calcineurin inhibitor toxicity during same period was 15%, 15.5%, and 14.4%, respectively. The cumulative rejection rate in Group I and Group II at 12-month follow-up was 10.3% and 11.3% (P = 0.78), respectively, and cumulative calcineurin inhibitor toxicity at 12 months was 14.4% and 9.3% (P = 0.59), respectively, were not statistically significant. There was no difference in graft survival and function at 1 year. Protocol biopsies have a limited role in a well-matched renal transplant program with tacrolimus-based immunosuppression in the short term. However, the long-term impact of protocol biopsies needs further evaluation.

Effect of pre-cooling, fruit coating and packaging on postharvest quality of apple.

Freshly harvested apple fruits cv.'Royal Delicious' were subjected to Surface coating with 1, 1.5, 2% neem oil (Azadirachta indica) and 10, 15, 20% marigold flower (Tagetes erectus) extracts with pre cooling on apple storage quality was tested. Then the fruits were analyzed for physicochemical and physiological characters such as loss in weight, fruit firmness, total soluble solids (TSS) content, titratable acidity (TA), pH, reducing sugar contents, pectin, total anthocyanin, polygalacturonase (PG) activity and fruit spoilage. The results revealed that, the 1.5-2% concentration of neem oil as a surface coating along with pre-cooling was the most effective by retaining better physiochemical characteristics, in addition, significantly lowering disease incidence. Similarly, packaging of fruits with corrugated fiber board (CFB) boxes + paper mould trays, CFB + Polyethylene (PE) liners and shrink wrapped tray packing during storage (18-25 °C and 65-75% RH), revealed that 2% neem oil surface coating with shrink wrap tray packing resulted the better retention of storage life and, whereas, the treatment effect on physico-chemical characteristics of fruits were significant (p < 0.05). However, the treatment effect was statistically at par with the marigold extract application with shrink wrapped tray packing in pre cooled fruits (10-15 °C, 70-75% RH) during ambient storage (18-25 ° C, 65-75% RH).

A pilot study on area under curve of mycophenolic acid as a guide for its optimal use in renal transplant recipients.

BACKGROUND & OBJECTIVES: The immunosuppressants administered to renal transplant subjects are usually monitored therapeutically to prevent graft rejection and drug toxicity. Mycophenolic acid (MPA) is an immunosuppressant. The present prospective study was undertaken to establish the utility of plasma level monitoring of MPA and to correlate it with clinical outcomes in renal transplant receipients. METHODS: MPA plasma level at 2, 4 and 9 h and the area under concentration-time curve (AUC) were estimated using high performance liquid chromatography in 24 renal transplant recipients receiving immunosuppressant MPA plus tacrolimus and steroid. RESULTS: There was wide inter-individual variation in MPA plasma level and the AUC. The incidences of gastrointestinal adverse drug events (diarrhoea and acidity) were significantly more in the high MPA AUC patients. Though biopsy proven acute rejection was not found, of the six subjects with lower MPA AUC (<30 mg.h/l), three were clinically diagnosed to develop tacrolimus nephrotoxicity. The Gastrointestinal Symptom Rating Scale (GSRS) and Gastrointestinal Quality of Life Index (GIQLI) scores represented better health related quality of life in lower MPA AUC than in the higher MPA AUC (>60 mg.h/l). INTERPRETATION & CONCLUSIONS: The present findings suggest the MPA AUC of 30 - 60 mg.h/l in the maintenance stage of renal transplant patients to have optimum clinical benefit and relegated adverse events profile indicating the usefulness of AUC of MPA with limited sampling strategy in optimizing its use.

Frequency of T cell expressing Th1 and Th2 associated chemokine receptor in patients with renal allograft dysfunction.

Acute rejection of human renal allografts is a frequent, serious posttransplantation complication, occurring in up to 50% of recipients. Leukocyte recruitment is a central feature of acute allograft rejection. Chemokine receptors are expressed on leukocytes in a cell type-specific manner. Recently CCR5+ and CXCR3+ cells have been observed in allograft biopsy specimens of patients undergoing acute cellular rejection (ACR). Herein we investigated the expression of Th1 (CCR5, CXCR3, and CCR2) and Th2 (CCR4, CCR3, and CCR8)-associated chemokine receptors on CD4 and CD8 T-cell populations. We sought to correlate chemokine receptor expression in peripheral blood T-cell subsets with the types of graft dysfunction (biopsy-proven rejections). In the peripheral blood CD4+ and CD8+ T-cell populations of patients with graft dysfunction, we observed a high frequency of Th1-associated chemokine receptors CCR5+ and CCR2+ but not CXCR3.

An Atypical Case of Chiari II Malformation Mimicking Partial Rhombencephalosynapsis.

Partial rhombencephalosynapsis in the presence of Chiari II malformation has been proposed as a "new abnormality of the hindbrain and spine". We describe a case of Chiari II malformation with imaging features mimicking partial rhombencephalosynapsis. Our case demonstrates how the imaging findings of Chiari II malformation can be confused with the above entity and highlights the differentiating features to help radiologists make an accurate diagnosis.

The quality of life of women volunteering as live-related kidney donors in India.

BACKGROUND: Women outnumber men 6:1 as live-related donors in our renal transplant programme. Women donors in developing regions are often illiterate and unemployed. This study was done to assess the change in quality of life of women who donate kidneys. METHODS: We prospectively studied 73 consecutive women volunteering as live-related kidney donors over a 6-month period using the World Health Organization Quality of Life Brief (WHO QoL Bref) Questionnaire and Hospital Anxiety and Depression Scale (HADS). Each woman was interviewed 2 weeks before and 6 months after kidney donation. RESULTS: There was a significant improvement in all the domains, namely physical (p=0.0001), psychological (p<0.0001), social relationship (p=0.037) and environment (p<0.0001) of the WHO QoL Bref questionnaire. Donors who were mothers had a greater improvement in all 4 domains than donors with other relationships. There was a significant decrease in the depression score (p<0.0001), but no change in the anxiety scores (p=0.065) following kidney donation. All donors would donate again, if possible. CONCLUSION: In live-related women kidney donors, quality of life improves and depression scores decline after kidney donation.

Risk factors for the development of new-onset diabetes mellitus in a living related renal transplant program.

New-onset diabetes mellitus is associated with considerable morbidity after transplantation. We evaluated 78 living related renal transplant recipients due to all causes except diabetic nephropathy a waiting a living related renal transplantation. We evaluated demographic characteristics, pretransplant glycemic profile, fasting C-peptide levels, plasma insulin levels, pretransplant insulin resistance, and immunosuppression protocols. Among the 16.7% of patients developing diabetes mellitus at the end of 1 year, age, family history, and impaired glucose tolerance at the time of transplantation correlated with the development of diabetes mellitus in the posttransplant period.

Generic tacrolimus (Pan Graf) in renal transplantation: an experience of 155 recipients in India.

BACKGROUND: The safety and efficacy of tacrolimus in transplantation are well established. However, tacrolimus (Pan Graf) has only been available in India for the last 2 years. We conducted this study to assess the safety and efficacy of tacrolimus in living related kidney transplantation. Herein we have reported our experience with tacrolimus as de novo therapy in a living related renal transplant program. MATERIALS AND METHODS: One hundred fifty-five consecutive recipients of living donor renal allografts were included in this study after consent and ethical clearance. Immunosuppression consisted of tacrolimus, mycophenolate mofetil or azathioprine, and steroids. The dose of tacrolimus was adjusted according to levels done on a regular basis. All patients were followed for periods ranging from 3 to 33 months. All episodes of graft dysfunction were evaluated by a graft biopsy. We evaluated the effects of this regimen on the incidence of graft rejection, graft survival, patient survival, and new onset diabetes mellitus. Six patients were diabetic prior to transplantation and 9 patients were hepatitis C virus (HCV) positive. RESULTS: There were 137 male and 18 female patients. The incidence of acute rejection was 3.87%; 17.93% developed new onset diabetes mellitus; and 77.7% of HCV-positive patients and 14.07% of HCV-negative patients developed posttransplantation diabetes mellitus. The patient survival at the current follow-up was 94.19%. CONCLUSION: This generic form of tacrolimus is a safe, effective immunosuppressant in living related renal transplantation.

A prospective analysis of testicular androgenic function in recipients of a renal allograft.

Eighteen adult males with end stage renal disease (ESRD) were studied to determine the serum levels of gonadotropins (LH and FSH), prolactin (PRL) and testosterone. All of the patients were studied longitudinally while undergoing maintenance hemodialysis (HD) and six months after renal transplantation. Prior to transplantation, significantly high levels of gonadotropins and PRL were observed. During HD the serum testosterone levels tended to be subnormal in most of the uremic patients and low normal in some of the subjects. Renal transplantation led to a significant improvement (P < 0.05) in serum testosterone. Elevated gonadotropin and PRL levels observed in patients on HD returned to the normal range in most of the patients after successful renal transplantation.

Fungal panniculitis in renal transplant recipients.

Panniculitis may result due to various etiologies. In post-transplant immunosuppressed patients infection is the foremost cause of panniculitis. We present 2 cases of fungal panniculitis in renal transplant recipients. The first patient presented with non-tender firm erythematous plaques on the left thigh. Biopsy showed panniculitis with cryptococci. Subsequent investigations revealed the presence of cryptococcal antigens in the blood, urine, and bronchoalveolar lavage fluid. There was no evidence of cryptococcal meningitis. The second patient complained of subcutaneous nodules on the trunk and right thigh. Biopsy of one of the nodules showed panniculitis with histoplasma. This patient had been treated earlier (inadequately) for disseminated histoplasmosis. Both the cases responded well to conventional amphotericin B therapy. Their renal functions remained stable.

Tacrolimus (Pan Graf) in live related renal transplantation: an initial experience of 101 recipients in India.

BACKGROUND: Success of modern transplantation is in large part due to the successful development of effective immunosuppressive agents. The safety and efficacy of tacrolimus in transplantation is well established. However, tacrolimus (Pan Graf, Panacea Biotec Ltd, India) has only been available in India for the last 2 years. This study was conducted to assess the safety and efficacy of tacrolimus in live related kidney transplantation. We report an initial experience of tacrolimus as de novo therapy in a live related renal transplantation program. MATERIALS AND METHODS: One hundred one consecutive recipients of a live renal allograft were commenced on triple immunosuppression consisting of tacrolimus, mycophenolate mofetil or azathioprine, and steroids. The dose of tacrolimus was adjusted to keep trough levels at 10-12 ng/mL in the first 3 months, 8-10 ng/mL in the next 3 months, and 5-8 ng/mL thereafter. All patients were followed up for a period ranging from 4 weeks to 24 months. The effect of this regimen on the incidence of graft rejection, graft survival, patient survival, and new-onset diabetes mellitus was evaluated. Any evidence of graft dysfunction was evaluated using a graft biopsy. RESULTS: There were 89 male and 12 female patients with mean age of 32.08 years. The incidence of acute rejection was 3.96%; 21.05% developed new-onset diabetes mellitus. Six patients were diabetic prior to transplantation and 9 patients were hepatitis C virus (HCV)-positive; 77.7% of HCV-positive patients and 15.1% of HCV-negative patients developed posttransplantation diabetes mellitus. The patient survival rate at the current follow-up was 92.07%. No graft was lost due to rejection. CONCLUSION: Tacrolimus is a safe and effective immunosuppressant in live related renal transplantation.

Effect of bisphosphonates on bone mineral density after renal transplantation as assessed by bone mineral densitometry.

INTRODUCTION: Steroid-induced osteoporosis is a major problem after organ transplantation. There is considerable evidence that bisphosphonates are effective in decreasing osteoporosis. AIM: This prospective study was carried out to see the effects of bisphosphonates on bone mineral density (BMD) after successful renal transplantation. MATERIAL AND METHODS: Fifty consecutive patients of successful renal transplantation were randomized into two groups. Group A (n = 27) received 35 mg/wk of Alendronate for 6 months after transplantation. Group B (n = 23) did not receive Alendronate and served as a control. Both groups underwent a pretransplant baseline dual-energy X-ray absorptiometry (DEXA) scan of their hips and lumber spines. Both groups received oral calcium and vitamin D supplement. Both groups were matched for the regimen and dose of immunosuppressive drugs. BMD was measured at 3 months and 6 months after transplantation. RESULTS: Both groups showed a decline in BMD in early months posttransplantation. However, the 6-month DEXA scans showed a significant rise in BMD in group A as compared to group B. CONCLUSION: Bisphosphonates appear to have a beneficial effect on steroid-induced bone loss.

Monitoring of anti-HLA and anti-Major histocompatibility complex class I related chain A antibodies in living related renal donor transplantation.

This study was undertaken with the aim to analyze the clinical relevance of posttransplant anti-HLA and anti-major histocompatibility complex class I related chain A (MICA) antibodies in response to living related donor renal transplantation. A total of 185 consecutive post-renal transplant recipient serum samples were analyzed for the detection of anti-HLA and MICA antibodies using enzyme-linked immunosolvent assay techniques. Patients carrying both anti-HLA as well as anti-MICA antibodies (MICA(+)/HLA(+)) were the worst affected, showing significantly poorer graft survival compared with the MICA-/HLA-negative group (17% vs 89%, chi(2) = 19.63, P = .000). Similarly, patients with only MICA antibodies or those with only HLA antibodies also had significantly lower graft survival (P = .035 and P = .001, respectively) as compared to the nonsensitized group. The study illustrated that posttransplant monitoring antibodies to both MICA as well as HLA could be good predictors of renal allograft failure.

Allosensitization to HLA and MICA is an important measure of renal graft outcome.

The objective of this study was to evaluate the donor-specific antibody repertoire against T and B cells and monocytes, as well as the non-donor anti-HLA, and MICA (MHC class I-related chain A) antibodies in recipients of the live related donor renal transplantation. Sera collected before and after transplantation were tested by ELISA for the presence of HLA class I- and class II-specific antibodies and by Luminex MICA single-antigen bead assay for the detection of MICA antibodies. Patients having a combination of both anti-HLA and MICA antibodies had worse graft survival and more rejection episodes as compared to the group without antibodies. Further, presence of IgG antibodies against the donor cells (T, B & monocytes) led to a compromised graft survival along with higher incidence of acute rejection as compared to the negative groups. These results suggest that a comprehensive assessment of anti-donor antibody repertoire and monitoring of anti-HLA, MICA antibodies following transplantation is a useful exercise to detect the sensitization status of the recipient and this can prove to be of immense prognostic value in renal transplantation.

Significance of protocol biopsies in living related renal transplant recipients.

INTRODUCTION: Subclinical rejection (SCR) in a normally functioning renal allograft may have an impact on long-term graft outcome. SCR detection is best done by protocol biopsies in clinically normal grafts. METHODS: We evaluated 20 stable living related renal allografts with protocol biopsies on days 7 and 90 posttransplant. SCR when detected was treated with a 3-day pulse of methylprednisolone therapy. The outcomes of these grafts were compared with 63 other clinically stable renal allografts that did not undergo protocol biopsies. RESULTS: SCR was observed in 60% of cases. The patients who received antirejection therapy for SCR based on protocol biopsies showed better graft survival and mean serum creatinine values at the end of the follow-up period.

Tacrolimus (Pan Graf) as de novo therapy in renal transplant recipients in India.

The safety and efficacy of tacrolimus in transplantation is well established. However, tacrolimus has only recently been available in India. We report an initial experience using tacrolimus as de novo therapy in a living related renal transplant program. Fifty-two consecutive recipients of living renal allografts were treated with tacrolimus, mycophenolate mofetil, or azathioprine and steroids. The dose of tacrolimus was adjusted to keep trough levels at 10 to 12 ng/mL in the first 3 months, 8 to 10 ng/mL in the next 3 months, and 5 to 8 ng/mL thereafter. Any evidence of graft dysfunction was evaluated by graft biopsy. The effect of this regimen on the lipid profile as well as the incidence of posttransplant diabetes mellitus was evaluated in an Indian population. All patients were followed for periods ranging from 6 to 72 weeks (mean = 29 weeks). The incidence of acute rejection was 3.84%; 17.3% developed posttransplant diabetes mellitus. Graft and patient survivals at the current follow-up were 100% and 96.26%. In conclusion, tacrolimus is a safe and effective immunosuppressant in a living related renal transplant program.

Functional assessment of immune markers of graft rejection: a comprehensive study in live-related donor renal transplantation.

A better understanding of the immunobiological processes and predictors of graft rejection holds promise for the development of potential therapeutic strategies and also individualization of immunosuppression. The objective of this study is to analyze the clinical relevance of immune parameters such as antidonor antihuman leukocyte antigen (anti-HLA) antibodies, monitoring of cytokines and their receptors on the graft outcome following live-related donor renal transplantation. Flow cytometry-based methods were used to detect antidonor antibodies (flow cytometry crossmatch, FCXM) and intracellular cytokines. Enzyme-linked immunosorbent assay (ELISA) methods were employed to detect anti-HLA class I and class II antibodies and quantitative serum-soluble interleukin-2 receptor (sIL-2R) levels. The data revealed that patients with HLA class I-specific IgG antibody experienced higher acute rejection (AR) episodes at 1 yr in comparison to the antibody negative group (82% vs. 56%, p = 0.01). On the contrary, donor-specific class II antibodies (B+) did not have any influence on the graft survival. However, 15 recipients having both T- and B-cell antidonor antibodies (T+B+) had significantly poor graft survival (60%) as compared to the antibody-negative group (T-B-, 82%, p = 0.05). Additionally, patients having non-donor but HLA-specific antibodies (FCXM-/ELISA+) had poor graft survival as compared to the antibody-negative group (64% vs. 88%, p < 0.05). Further, patients undergoing AR episodes had significantly higher expression of IFN-gamma-producing T cells (19.16 +/- 7.4% median 17.50) as compared to their pre-transplant levels (5.68 +/- 1.63%, Median 5.20) and the non-rejecter group (5.97 +/- 4.39%, median 4.3, p = 0.0004). Similarly sIL-2 was significantly increased in AR episodes during the first month of transplantation (292 +/- 131.5 pmol/L) as compared to those with well-functioning grafts (p = 0.01) and healthy controls (p = 0.001). Evaluation of antidonor antibodies by flow cytometry is found to be relatively more sensitive and a better predictor of graft outcome. Further monitoring of cytokine expression profile of primed peripheral T-helper cells and quantitative analysis of sIL-2R offer additional valuable diagnostic and prognostic tools for follow-up of transplant subjects and a better alternative for functional assessment of immunosuppression.