Pregnancy Outcome in Patients with Solitary Kidney

Background

Solitary kidney may be congenital or as a result of nephrectomy. There is a lot of literature available on quality of life in these patients, but there is limited data on pregnancy outcome.

Objectives

To study pregnancy outcome in patients with solitary kidney either congenital or due to nephrectomy.

Materials and Methods

Study Design This is a retrospective observational study conducted at tertiary health center in Ahmedabad, from 2011 to 2014. Sample Size There were 164 patients of solitary kidney, out of which two patients had congenital solitary kidney and the remaining had solitary kidney due to nephrectomy. Among 164 patients, 96 (58.53 %) patients had completed family, 37 (22.56 %) patients did not try for pregnancy, 15 (9.14 %) patients have conceived, 12 (7.3 %) were lost to follow up and 4 (2.43 %) patients were infertile. Method Patients in reproductive age group (20–40 years), with solitary kidney either congenital or due to nephrectomy, were included. Maternal and fetal outcome was studied, and patients were followed up till 2 years postpartum. Exclusion Criteria Patients with solitary kidney due to post-renal transplant were excluded.

Results

There were 15 (9.14 %) patients who had conceived, out of which 11 (73.33) patients delivered and 4 (26.67 %) patients had spontaneous abortion. Two patients developed gestational hypertension and one had preeclampsia. On follow-up, all babies were normal and none of them had delayed developmental milestones.

Conclusion

Preconceptional counseling should be done in these patients regarding risk of developing preeclampsia during pregnancy and preterm delivery. These patients can have good pregnancy outcome with close monitoring during antenatal period.

     

Evaluation of Spot Urinary Albumin–Creatinine Ratio as Screening Tool in Prediction of Pre-eclampsia in Early Pregnancy

Objective

The aim of this study was to establish whether a spot urinary albumin/creatinine ratio (ACR) measured between 20 and 28 weeks of gestation can predict subsequent pre-eclampsia in asymptomatic pregnant women.

Design

Prospective observational study.

Subjects

The patients included sixty-two women with singleton pregnancy, normal renal function and no evident proteinuria, attending antenatal clinics between 20 and 28 weeks of gestation in a tertiary care hospital.

Methods

The ACR was determined from midstream urine sample taken between 20 and 28 weeks of gestation. Estimation of albumin was done by immunoturbidimetric microalbumin method and creatinine by modified Jaffe’s method.

Results

Incidence of pre-eclampsia in the study group was 12.90%. The cut-off value for ACR was taken as 35.5 mg/mol. The mean ACR in normotensive group was 19.26 ± 7.99, and in pre-eclampsia group it was 51.95 ± 18.78. For pre-eclampsia, screening in early pregnancy, spot ACR cut-off ≥35.5 mg/mol has sensitivity of 87.5%, specificity of 96.30%, PPV of 77.78% and NPV of 98.11%.

Conclusions

Spot urinary ACR values are higher in asymptomatic women in early pregnancy, who developed pre-eclampsia later on. When measured early in the second trimester, an ACR ≥ 35.5 mg/mmol predicted pre-eclampsia well before the onset of clinical manifestations with high sensitivity and specificity. It can be used as a good screening tool for predicting pre-eclampsia in early pregnancy.

     

Expression of the bifunctional suicide gene CDUPRT increases radiosensitization and bystander effect of 5-FC in prostate cancer cells

Purpose

To test the hypothesis that, with 5-fluorocytosine (5-FC) treatment, the co-expression of cytosine deaminase (CD) and uracil phosphoribosyltransferase (UPRT) can lead to greater radiosensitization and bystander effect than CD-expression alone.

Methods and materials

R3327-AT cell lines stably expressing CD or CDUPRT were generated. The 5-FC and 5-FU cytotoxicity, and the radiosensitivity with/without 5-FC treatment, of these cells were evaluated under both aerobic and hypoxic conditions. The bystander effect was assessed by apoptosis staining and clonogenic survival. The pharmacokinetics of 5-FU and 5-FC metabolism was monitored in mice bearing CD- or CDUPRT-expressing tumors using ¹⁹F MR spectroscopy (MRS).

Results

CDUPRT-expressing cells were more sensitive to 5-FC and 5-FU than CD-expressing cells. CDUPRT-expression further enhanced the radiosensitizing effect of 5-FC, relative to that achieved by CD-expression alone. A 25-fold lower dose of 5-FC resulted in the same magnitude of radiosensitization in CDUPRT-expressing cells, relative to that in CD-expressing cells. The 5-FC cytotoxicity in co-cultures of parental cells mixed with 10-20% CDUPRT cells was similar to that in 100% CDUPRT cells. ¹⁹F MRS measurements showed that expression of CDUPRT leads to enhanced accumulation of fluorine nucleotide (FNuc), relative to that associated with CD-expression alone.

Conclusion

Our study suggests that CDUPRT/5-FC strategy may be more effective than CD/5-FC, especially when used in combination with radiation.     

Understanding the gaps in elimination of tuberculosis in India

Tuberculosis (TB) is a highly infectious disease, and it has the highest global burden on India with 21% prevalence rate and 27% of patients who do not receive pertinent medical treatment. Although India spends 23 billion dollars annually towards medical expenses for TB, India still ranks among the top 2 countries with the highest incidence and prevalence rates with more than 300,000 deaths excluding the patients with HIV and TB calling for prompt consideration. India faces a great challenge socially and economically. They lack a uniform health care system, making it burdensome to use effective surveillance techniques for prevention of TB. Currently, India is working on resolving the issue meticulously through the web-based application program ‘Nikshay’ with other strategies like Revised National Tuberculosis Control Program (RNTCP) and World Health Organization's The End TB Strategy. India's cardinal goal is to make advanced diagnostic tools made available and public-private healthcare sector collaboration. India needs to focus more on primary prevention by effective policy formation and campaign which promote proper sanitation and vaccine administration while educating the layman.     

Response of HT29 colorectal xenograft model to cediranib assessed with 18F‐fluoromisonidazole positron emission tomography,dynamic contrast‐enhanced and diffusion‐weighted MRI

Cediranib is a small‐molecule pan‐vascular endothelial growth factor receptor inhibitor. The tumor response to short‐term cediranib treatment was studied using dynamic contrast‐enhanced and diffusion‐weighted MRI at 7 T, as well as ¹⁸F‐fluoromisonidazole positron emission tomography and histological markers. Rats bearing subcutaneous HT29 human colorectal tumors were imaged at baseline; they then received three doses of cediranib (3 mg/kg per dose daily) or vehicle (dosed daily), with follow‐up imaging performed 2 h after the final cediranib or vehicle dose. Tumors were excised and evaluated for the perfusion marker Hoechst 33342, the endothelial cell marker CD31, smooth muscle actin, intercapillary distance and tumor necrosis. Dynamic contrast‐enhanced MRI‐derived parameters decreased significantly in cediranib‐treated tumors relative to pretreatment values [the muscle‐normalized initial area under the gadolinium concentration curve decreased by 48% (p = 0.002), the enhancing fraction by 43% (p = 0.003) and K^trans by 57% (p = 0.003)], but remained unchanged in controls. No change between the pre‐ and post‐treatment tumor apparent diffusion coefficients in either the cediranib‐ or vehicle‐treated group was observed over the course of this study. The ¹⁸F‐fluoromisonidazole mean standardized uptake value decreased by 33% (p = 0.008) in the cediranib group, but showed no significant change in the control group. Histological analysis showed that the number of CD31‐positive vessels (59 per mm²), the fraction of smooth muscle actin‐positive vessels (80–87%) and the intercapillary distance (0.17 mm) were similar in cediranib‐ and vehicle‐treated groups. The fraction of perfused blood vessels in cediranib‐treated tumors (81 ± 7%) was lower than that in vehicle controls (91 ± 3%, p = 0.02). The necrotic fraction was slightly higher in cediranib‐treated rats (34 ± 12%) than in controls (26 ± 10%, p = 0.23). These findings suggest that short‐term treatment with cediranib causes a decrease in tumor perfusion/permeability across the tumor cross‐section, but changes in vascular morphology, vessel density or tumor cellularity are not manifested at this early time point. Copyright © 2012 John Wiley & Sons, Ltd.     

Proton MRS detects metabolic changes in hormone sensitive and resistant human prostate cancer models CWR22 and CWR22r

17‐Allylamino, 17‐demethoxygeldanamycin (17‐AAG), an effective inhibitor of the heat shock protein hsp90, preferentially inhibiting tumor hsp90 compared to hsp90 from normal cells, has shown promising results against several cancers, including hormone‐resistant prostate cancer. Levels of several oncogenic proteins critical to tumor growth and progression, such as androgen receptor and HER2/neu, were reduced 4 h post 17‐allylamino, 17‐demethoxygeldanamycin treatment. Posttreatment metabolic changes have also been observed in several tumor cell lines. In this study, total choline distributions in hormone sensitive CWR22 and hormone resistant CWR22r prostate cancer xenograft tumors in mice were measured before and at 4 h and 48 h after a single‐bolus 17‐allylamino, 17‐demethoxygeldanamycin treatment at 100 mg/kg, using proton MR spectroscopy. Our results show that tumor total choline levels declined 4 h after the treatment for CWR22 (P = 0.001) and 48 h post treatment for CWR22r (P = 0.003). Metabolic changes, in particular of total choline intensity detected by proton magnetic resonance spectroscopic imaging (MRSI), are consistent with the observed immunohistochemistry changes, tumor growth inhibition for CWR22r (P = 0.01 at 14 days post treatment), and a constant prostate specific antigen level versus increasing prostate specific antigen for control CWR22 (P = 0.01). Metabolic changes in total choline by proton MRSI can be used as an early biomarker of response for advanced‐stage prostate cancer in targeted therapy such as 17‐allylamino, 17‐demethoxygeldanamycin. Magn Reson Med, 2009. © 2009 Wiley‐Liss, Inc.