The total percentage of biopsy cores with cancer improves the prediction of pathological stage after radical prostatectomy

OBJECTIVE: To examine whether the simple variable 'percentage of cancer-positive biopsy cores' is a significant predictor of true pathological stage after radical prostatectomy and can be used to improve pathological stage prediction by simple means. PATIENTS AND METHODS: In all, 375 patients had a radical prostatectomy for localized prostate cancer in two UK centres; 260 had complete preoperative staging information. Logistic regression was used and predicted probability graphs constructed to assess predictors of pathological stage. RESULTS: In this study, only PSA (P = 0.004) and percentage cancer-positive biopsy cores (P < 0.001) were significant predictors of pathological stage. The final model was an acceptable classifier for pathological stage (area under the receiver operating characteristic curve 0.76, specificity 85%, sensitivity 47%). A patient with a PSA of 10 ng/mL and one of six cores positive for cancer would have a predicted probability of extraprostatic disease of 20%, whereas the same patient with all six biopsy cores positive would have a predicted probability of extraprostatic disease of 80%. CONCLUSIONS: The percentage of cancer-positive biopsy cores significantly predicts the disease stage after radical prostatectomy. This variable is easy to obtain by the clinician and avoids the need to estimate the percentage of biopsy tissue infiltrated by cancer. This readily available information can easily be computed and may help to counsel patients about realistic expectations of organ-confined disease in relation to surgery as a treatment option.     

Phosphodiesterase and thymidine phosphorylase-inhibiting salirepin derivatives from Symplocos racemosa

A re-investigation of the chemical constituents of the stem bark of Symplocos racemosa Roxb. led to the isolation of four new glycosides, symplocomoside (1), symponoside (2), symplososide (3) and symploveroside (4). Benzoylsalireposide (5) and salireposide (6) were re-isolated from this plant. The structures of the new compounds were determined by 1D and 2D-homonuclear and heteronuclear NMR spectroscopy, chemical evidence, and by comparison with the published data of the closely related compounds. The glycosides 1-4 displayed in vitro inhibitory activity against phosphodiesterase I with IC50 values of 122 +/- 0.017, 698 +/- 0.06, 722 +/- 0.03, 909 +/- 0.09 microM, respectively. The compounds 1-6 also showed in vitro inhibitory activity against thymidine phosphorylase with IC50 values of 189.96 +/- 1.02, 195.56 +/- 2.36, 207.61 +/- 1.06, 488.89 +/- 4.10, 427.20 +/- 5.36, 354.2 +/- 5.69 microM, respectively while 1 was also found to be a urease inhibitor with an IC50 value of 54.13 +/- 0.71 microM.     

Interleukin-12 redirects murine immune responses to soluble or aluminum phosphate adsorbed HSV-2 glycoprotein D towards Th1 and CD4+ CTL responses

The type of immune response elicited against HSV-2 infection may be a factor in the frequency and severity of recurrent disease, with non-recurrent status being associated with a Th1-like response. As administration of glycoprotein D subunit formulated with an aluminum-based adjuvant induces predominantly Th2-like immune responses, we sought to assess the ability of IL-12 to redirect anti-HSV immunity towards a Th1 response. Co-administration of gD with IL-12 resulted in gD-specific antibody subclass switching from predominantly IgG1 observed in mice immunized with either gD or gD/AlPO4 to a more balanced combination of IgG1 and IgG2a, and enhanced virus neutralizing activity. Spleen cells from mice immunized with gD and IL-12, and restimulated in vitro with HSV-2, developed into effector cells capable of secreting IFN-gamma and lysing HSV-2 infected targets, while those obtained from gD or gD/ALPO4 immunized mice did not express lytic activity. In vitro studies determined that these CTLs were CD4+ and that the cytotoxicity was primarily perforin dependent. Vaginal challenge with HSV-2 demonstrated that IL-12 co-administration with gD resulted in increased efficacy of this vaccine as compared to administration of gD antigen alone. This acquired protection persisted up to 1 year. Finally, adsorbing gD and IL-12 to AlPO4 decreased the optimal dose of IL-12 required to enhance gD immunogenicity and shift responses towards a Th1-like profile.     

Obstetric and gynecologic complications in women with Marfan syndrome

OBJECTIVE: To analyze the maternal and fetal outcomes of pregnancy and gynecologic problems in women with Marfan syndrome. STUDY DESIGN: The outcomes of 14 pregnancies in 4 women with Marfan syndrome were prospectively observed between January 1988 and December 2000. The cardiovascular and obstetric complications were analyzed. During pregnancy all the patients were carefully monitored with serial echocardiography and close attention to symptoms. RESULTS: Of the 14 pregnancies, 5 (35.7%) ended in abortion, and 3 of them occurred in the early second trimester due to cervical incompetence. Premature onset of labor occurred in 2 pregnancies at 31 and 34 weeks. Postpartum hemorrhage complicated 3 deliveries, and inversion of the uterus occurred in 1 patient. Significant cardiovascular complications occurred in 2 patients, who required surgical correction of the aortic aneurysm and replacement of the aortic valve. In one patient the operation was performed within hours of vaginal delivery, and the other patient underwent surgery 8 weeks postpartum. No maternal death occurred in the study. One infant in the series was diagnosed as having Marfan syndrome. A premature infant delivered at 31 weeks died on the second day of life. CONCLUSION: Women with Marfan syndrome are at high risk of aortic dissection in pregnancy even in the absence of preconceptional aortic root dilatation. Obstetric complications in patients with this condition have been underreported in the past. Women with aortic root dilatation of < 40 mm usually tolerate pregnancy well, with good maternal and fetal outcomes. Women with Marfan syndrome should be counseled regarding the risk of pregnancy to both mother and fetus. Patients who have cardiac decompensation or aortic dilatation > 40 mm are advised to avoid pregnancy.     

Agricultural produce in the dry bed of the River Ganga in Kanpur, India--a new source of pesticide contamination in human diets.

Vegetables grown in the dry bed field of the River Ganga in Kanpur, an important industrial city of North India, were analysed for the pesticides hexachlorocyclohexane (HCH), dichlorodiphenyl trichloroethane (DDT), their isomers and metabolites at three different sites. Residues of both the pesticides were found in all the samples. Mean levels of 109.35, 136.76 and 145.93 microg HCH/kg and 6.64, 49.3 and 46.70 microg DDT/kg were found in the rural upstream, city and downstream industrial areas, respectively. The mean total HCH and DDT levels were within safe limits as per the Indian Standard but some samples had HCH levels above the WHO/FAO limit. The pesticide residue level in vegetables was several fold higher than their surrounding sandy soil and could pose health problems since these popular vegetables are consumed regularly by the population.     

Identification of a novel zinc finger gene, zf5-3, as a potential mediator of neuroblastoma differentiation.

We established a unique parental neuroblastoma cell line, NUB-7, which mimics the bipotentiality of neuroblastoma in vivo along neuronal and Schwann cell lineages following dibutyryl cAMP and retinoic acid treatments, respectively. Differential display identified a putative novel zinc finger gene as a potential differentiation-responsive gene coincident with retinoic acid treatment of NUB-7. This cDNA clone, now designated zf5-3, was mapped to chromosome 19 using somatic cell hybrids, and a larger cDNA clone further localized this gene to band 13.1-13.2 by fluorescent in situ hybridization. zf5-3 possesses 4 characteristic zinc finger DNA-binding motifs as determined by its nucleic acid and proposed amino acid sequence. Expression of zf5-3 is restricted to fetal neuronal, hepatic and renal tissues and their tumor-derived cell lines, including 8/9 neuroblastomas and 2/2 malignant rhabdoid tumors of kidney. The restricted expression in the kidney of zf5-3 to collecting tubules and ureter epithelium is suggestive of an ectodermal histogenesis of malignant rhabdoid tumors of kidney. During development of the fetal human brain, high levels of zf5-3 mRNA are restricted to the mitotically active, undifferentiated neuroblasts. Morphological evidence of overt differentiation was generally accompanied by a marked loss in zf5-3 expression. Therefore, the neuronal tissue expression profile and the down-regulation coincident with retinoic acid-induced neuroblastoma maturation implicate zf5-3 as a potential mediator of their differentiation.     

Antioxidant properties of methanolic extracts from leaves of Rhazya stricta

Because of increased safety concerns about synthetic antioxidants, exploitation of cheaper and safer sources of antioxidants based on natural origin is the focus of research nowadays. Rhazya stricta is a medicinally important plant native to South Asia. Extraction of antioxidants was carried out in different solvent systems, i.e., water, 80% methanol, 70% ethanol, and diethyl ether. The methanolic extract exhibited the highest total phenolic content among the extracts; therefore for further studies the methanolic extract was employed. Antioxidant activity measurement in the linoleic acid system, metal chelating activity, reducing power, scavenging effect on 1,1-diphenyl-2-picrylhydrazyl free radical, and superoxide anion radical scavenging activity were taken as the parameters for assessment of antioxidant potential of methanolic extracts. Results were compared with alpha-tocopherol and the synthetic antioxidant butylated hydroxyanisole. The antioxidant potential of methanolic extracts of R. stricta leaves was comparable with previously exploited potent antioxidants and is strongly concentration dependent.     

Student quality-of-life declines during third year surgical clerkship

INTRODUCTION: Choosing surgery as a career is declining among U.S. medical students. The 8-wk third year surgery clerkship at our institution can be an intense learning experience, and we hypothesized that during this clerkship medical student quality-of-life would drop significantly from baseline, and that this drop would be greater among certain subgroups, such as women students not interested in pursuing a surgical career, and those who place a high value on a controllable lifestyle. METHODS: At clerkship orientation (baseline), students were asked to complete a survey that measured quality-of-life on an 84-point scale, and depression on a 40-point scale. The quality-of-life scale was composed of select questions from the Medical Outcomes Study, and the Harvard Department of Psychiatry/NDSD brief screening instrument was used to measure depression. Students were also asked the typical number of hours they slept per night. Demographics, attitude toward a controllable lifestyle, and top three specialties of interest were also gathered at baseline. On week 6 of the clerkship, students were surveyed on the same quality-of -life and depression scales, and asked average hours of sleep per night for the previous week. RESULTS: From June 2005 through December 2006, 143 of 177 (81%) students agreed to participate, and after exclusions for missing data, 137 students were included in the analysis. Sixty-nine students were women (51%), and the average age was 25.8 (sd 2.6). Mean quality-of-life at baseline was 57.0 (sd 11.3) and at week 6 was 50.4 (sd 10.1) representing a statistically significant average decline of 6.6 points (P < 0.0001). Mean depression at baseline was 14.4 (sd 3.8) and at week 6 was 15.1 (sd 3.6), representing a small but significant average decline of 0.7 points (P = 0.0155). Mean sleep at baseline was 6.3 h/night (sd 0.9) and at week 6 was 5.7 h/night (sd 1.2), representing a statistically significant average decline of 0.6 h/night (P < 0.0001). Declines were similar on all outcomes between men versus women, those who ranked surgery in their top three career choices versus those who did not, and those who ranked controllable lifestyle as "very important" versus all other categories. CONCLUSION: Quality-of-life and sleep declines and depression increases significantly in third-year medical students from orientation to week 6 of their surgery clerkship at our institution. We look forward to studying quality-of-life on other clerkships for comparison, assessing whether the magnitude of this decline in quality-of-life predicts students avoiding a future career in surgery, and testing interventions to prevent this decline in quality-of-life during the clerkship.     

Evaluation of a culturally adapted cognitive behavior therapy-based,third-wave therapy manual

BACKGROUND Recommendations for psychotherapy have evolved over the years, with cognitive behavioral therapy(CBT) taking precedence since its inception within clinical guidelines in the United Kingdom and United States. The use of CBT for severe mental illness is now more common globally.AIM To investigate the feasibility and acceptability of a culturally adapted, CBT-based, third-wave therapy manual using the Comprehend, Cope, and Connect approach with individuals from a diverse population prese...