CD44 expression is a feature of prostatic small cell carcinoma and distinguishes it from its mimickers

Small cell neuroendocrine carcinoma of the prostate is a rare variant of prostatic cancer that shares morphologic similarity with prostatic adenocarcinoma of Gleason 5 pattern. It has also been considered morphologically and immunohistochemically indistinguishable from small cell neuroendocrine carcinomas of other origins. CD44 is a cell-surface molecule proposed to identify cancer stem/progenitor cells in prostate cancer. We performed immunohistochemical study for CD44 expression in 11 cases of prostatic small cell neuroendocrine carcinoma and compared its patterns of expression with 73 cases of prostatic adenocarcinoma and 47 cases of small cell neuroendocrine carcinomas of other organs. Strong and diffuse membrane staining for CD44 was observed in 100% of the prostatic small cell neuroendocrine carcinomas. In conventional adenocarcinomas of the prostate, positive staining was only seen in rare, scattered tumor cells; and CD44 staining was negative in most of the small cell neuroendocrine carcinomas of nonprostate origin. The difference in CD44 expression between small cell neuroendocrine carcinomas of the prostate and those of other organs are statistically significant (P < .001). Our study demonstrates the utility of immunohistochemical staining for CD44 in distinguishing prostatic small cell neuroendocrine carcinoma from its mimickers including prostatic adenocarcinoma of Gleason 5 pattern and small cell neuroendocrine carcinomas of other organs. CD44 is the first marker that shows a high degree of tissue/organ specificity for small cell neuroendocrine carcinomas. Because CD44 is a putative marker of prostate cancer stem cells, the strong and diffuse expression of CD44 and the lack of expression of prostate luminal differentiation markers androgen receptor and prostatic specific antigen in prostatic small cell neuroendocrine carcinomas suggest that the tumor cells may retain cancer stem cell features.     

Laparoscopic Colonic Resection for Rectosigmoid Colonic Tumours: A Retrospective Analysis and Comparison with Open Resection

Laparoscopic approach for treatment of colorectal malignancy is gaining acceptance gradually; however the benefits of laparoscopic surgery in colonic and rectal tumours is still open to debate. This study aims at a retrospective analysis of operative and short term outcome of patients with rectosigmoid tumours. A retrospective analysis of operative, postoperative and short-term outcome of 62 patients who underwent laparoscopic colorectal resection for cancer of rectosigmoid region were compared with a same number of parameters-matched patients who underwent open colorectal resection. Blood transfusion requirement was significantly more in the open group compared to the laparoscopy group (38.7% versus 6.4%, p = 0.001). ICU stay was less in the laparoscopy group (p = <0.05) and they were started on oral liquid diet earlier (p = 0.013). The number of the lymph nodes retrieved, positive distal margin and radial involvement were similar in both groups. The hospital stay was significantly shorter in laparoscopy group (8.4 versus 13.8 days, p < 0.05). Radical operation for rectosigmoid tumors is technically feasible with laparoscopic surgery. Laparoscopic approach is associated with less blood loss, transfusion and significantly less ICU stay. Laparoscopic group recovers early and needs less hospital stay     

Behavioral effects of the novel cannabinoid full agonist AM 411

AM 411 ((-)-1-adamantyl-Delta8-tetrahydrocannabinol) is a novel full agonist at cannabinoid CB1 receptors. The present studies were conducted to provide behavioral characterization of this compound in rats. It was hypothesized that AM 411 should produce behavioral effects similar to known cannabinoid agonists, and that these effects should be inhibited by co-treatment with a CB1 antagonist. In Experiments 1 and 2, AM 411 dose-dependently produced behaviors consistent with CB1 agonism, including analgesia, hypothermia, catalepsy and reductions in locomotion, which were blocked by a CB1-selective antagonist. In Experiment 3, AM 411 produced a dose-dependent suppression of lever-pressing on a fixed-ratio 5 (FR5) schedule, a task known to be sensitive to administration of CB1 agonists. Detailed analysis of the temporal patterns of operant responding showed that AM 411 altered the distribution of interresponse times. Experiment 4 showed that AM 411 decreased relative interior activity in the open field, which is suggestive of an anxiogenic effect. It is concluded that AM 411 produces CB1 agonist-like behavior with potency between that of WIN 55,212-2 and AM 356. AM 411 could be a useful tool for understanding the behavioral and neural effects of CB1 receptor stimulation.     

Adamantyl cannabinoids: a novel class of cannabinergic ligands

Structure-activity relationship studies have established that the aliphatic side chain plays a pivotal role in determining the cannabinergic potency of tricyclic classical cannabinoids. We have now synthesized a series of analogues in which a variety of adamantyl substituents were introduced at the C3 position of Delta(8)-THC. Our lead compound, (-)-3-(1-adamantyl)-Delta(8)-tetrahydrocannabinol (1a, AM411), was found to have robust affinity and selectivity for the CB1 receptor as well as high in vivo potency. The X-ray crystal structure of 1a was determined. Exploration of the side chain conformational space using molecular modeling approaches has allowed us to develop cannabinoid side chain pharmacophore models for the CB1 and CB2 receptors. Our results suggest that although a bulky group at the C3 position of classical cannabinoids could be tolerated by both CB1 and CB2 binding sites, the relative orientation of that group with respect to the tricyclic component can lead to receptor subtype selectivity.     

Glycosylated hemoglobin-defined prediabetes and cardiovascular risk markers in rural India: the Nallampatti noncommunicable disease study

The aim of this study is to assess the associations between glycosylated hemoglobin in the prediabetes range and cardiovascular risk markers in a rural South Indian population. Local Ethics Committee approval and informed consent was obtained from all participants. Inclusion criteria were participants, aged ≥20 and ≤85 years, from Nallampatti, a classical farming village from Tamil Nadu State, India. Those with known history of diabetes were excluded from this analysis. All participants were administered a detailed questionnaire, had anthropometric measurements including height, weight, and waist circumference. Bloods were drawn for random blood glucose, glycosylated hemoglobin, nonfasting lipid profile, cystatin C, uric acid, and hemoglobin. All participants had carotid intima thickness done by high-resolution B-mode carotid ultrasound. Progressive hyperglycemia across the glucose tolerance continuum based on glycosylated hemoglobin levels in a rural South Indian population seems to be associated with worsening cardiovascular risk markers. A cut-off value of ≥6% (42 mmol/mol) seems to herald a much more significant increase in such markers. Long-term follow-up of this cohort for incident cardiovascular disease will help to substantiate the associations between glycosylated hemoglobin levels within the prediabetes range and cardiovascular disease in an Indian population. Evidence-based race-specific criteria for diagnosis of prediabetes and diabetes are the need of the hour for risk stratification and appropriate management.     

Multimodality Screening for Lower Genital Tract Infections Between 18 and 24 Weeks of Pregnancy and its Efficacy in Predicting Spontaneous Preterm Delivery

Background

Predicting spontaneous preterm birth (SPTB) during mid-trimester would be very useful. We used a multimodality screening approach mainly focusing on urogenital infections among unselected obstetric population between 18 and 24 weeks in a tertiary center.

Method

Diagnosis of lower genital tract infection (LGTI) was attempted among 228 pregnant women using several factors—symptom of vaginal discharge, characteristic appearance of discharge on speculum, point of care tests using Amsel’s criteria and gram staining of vaginal swab. Nugent’s scoring was taken as gold standard. Urine microscopy/culture was obtained. Serum inflammatory markers were done. Total leukocyte count, neutrophil/lymphocyte ratio and C-reactive protein were obtained. Data on cervical length were obtained from mid-trimester scan.

Results

Thirty patients complained of vaginal discharge. Speculum examination revealed discharge in 221 (96.92%), appearing pathological in 192 (86.87%). Amsel’s criteria showed poor sensitivity to detect full (57%) and partial (24%) bacterial vaginosis (BV). On gram staining, 104 (45.61%) showed evidence of LGTI; 14 full BV (6.1%); 45 partial BV (19.5%); 40 candidiasis (17.5%); and two each of trichomoniasis and aerobic vaginitis. Appearance of vaginal discharge and microscopic diagnosis of LGTI were poorly correlated. Forty women (17.5%) had SPTB, 24 following membrane rupture and 16 following spontaneous labor. The presence of BV (specifically partial) increased the likelihood of SPTB with OR of 3.347 (CI 1.642, 6.823). Three of seven women with short cervix delivered preterm. No other screening modality was associated with SPTB.

Conclusion

Active screening for LGTI between 18 and 24 weeks shows high prevalence of BV in Indian setting. There is a strong link between partial BV and SPTB.

     

Benzathine penicillin, metronidazole and benzyl penicillin in the treatment of tetanus: a randomized, controlled trial

Penicillin, the drug of choice in tetanus, may potentiate the effect of tetanus toxin by inhibiting the type-A (GABAA) receptor for gamma-amino-n-butyric acid. Metronidazole has therefore been suggested as an alternative. Intramuscular benzathine penicillin (1.2 million units as a single dose; N=56), enteral metronidazole (600 mg every 6 h for 10 days; N=55) and intravenous benzyl penicillin (2 million units every 4 h for 10 days; N=50) were therefore compared, in a randomized, controlled trial, among patients with all grades of tetanus. On presentation, the three treatment groups were similar in terms of age and sex distributions, immune statuses, durations of illness, and their APACHE-II scores and Ablett's grades of tetanus. Of the patients given benzathine penicillin, 36 required tracheostomy, 10 neuromuscular blockade, and 23 mechanical ventilation; the corresponding numbers for the metronidazole (34, 12 and 18, respectively) and benzyl-penicillin groups (39, 12 and 25, respectively) were similar (P>0.10). The incidences of dysautonomia and nosocomial pneumonia and the numbers of in-hospital deaths (26 with benzathine penicillin, 19 with metronidazole and 22 with benzyl penicillin; P=0.392) were also similar in each treatment arm. The length of the hospital stay was longer in the patients receiving benzyl penicillin than in the benzathine-penicillin or metronidazole groups, with means (S.D.) of 21.9 (15), 16.9 (11) and 19.9 (15) days, respectively, but the difference was not statistically significant (P=0.09). Although the three antibiotic regimens investigated appear equally effective, benzathine penicillin offers the convenience of a single, intramuscular injection instead of the 10 days of therapy needed with the other two drugs.