It is important to determine the size and proportion of the larynx as such information is useful in procedures such as intubation, endoscopy and surgical manipulations. Recent interest in the cases of subglottic stenosis and postintubational stenosis of the lower respiratory tract has led to renewed interest in ascertaining the measurements of the various laryngeal cartilages. The aim of the present study was to collect morphometric data of cricoid cartilage from a regional population.
Fifty laryngeal preparations from adult cadavers of Western India were assessed. Sections were prepared via dissection and the removed cricoid cartilages then measured and weighed.
The mean antero-posterior diameter (19.29±2.47) of the cricoid cartilage was greater than the average transverse diameter (18.33±2.26). The height of arch of cricoid cartilage was 6.54±1.23mm and height of lamina was 21.45±1.97mm. Mean weight of cricoid cartilage was 4.53±1.27grams. The shape of the cricoid cartilage was ovoid in 46% of cases, oval in 38%, pear shaped in 12% and narrow-oblong in 4% of cases.
Inter-subject variability in the dimensions of cricoid cartilages was observed. The large difference in almost all sizes and shapes of the cricoid cartilage makes it difficult to standardise the rigid stents used in these organs. Endotracheal tubes of the appropriate size should therefore be based on the measurements of individual patients. Clinicians should therefore be aware of morphological variations as they are of fundamental clinical importance.
Cricoid cartilage; larynx; morphometry
Earlier, we reported that CTLA4 expression is inversely correlated with CD38 expression in chronic lymphocytic leukemia (CLL) cells. However, the specific role of CTLA4 in CLL pathogenesis remains unknown. Therefore, to elucidate the possible role of CTLA4 in CLL pathogenesis, CTLA4 was down-regulated in primary CLL cells. We then evaluated proliferation/survival in these cells using MTT, 3H-thymidine uptake and Annexin-V apoptosis assays. We also measured expression levels of downstream molecules involved in B-cell proliferation/survival signaling including STAT1, NFATC2, c-Fos, c-Myc, and Bcl-2 using microarray, PCR, western blotting analyses, and a stromal cell culture system. CLL cells with CTLA4 down-regulation demonstrated a significant increase in proliferation and survival along with an increased expression of STAT1, STAT1 phosphorylation, NFATC2, c-Fos phosphorylation, c-Myc, Ki-67 and Bcl-2 molecules. In addition, compared to controls, the CTLA4-downregulated CLL cells showed a decreased frequency of apoptosis, which also correlated with increased expression of Bcl-2. Interestingly, CLL cells from lymph node and CLL cells co-cultured on stroma expressed lower levels of CTLA4 and higher levels of c-Fos, c-Myc, and Bcl-2 compared to CLL control cells. These results indicate that microenvironment-controlled-CTLA4 expression mediates proliferation/survival of CLL cells by regulating the expression/activation of STAT1, NFATC2, c-Fos, c-Myc, and/or Bcl-2.
Displaced type 2 lateral end clavicle fractures have a tendency to delayed union or non-union. Various methods of stabilisation of the displaced lateral end fractures are described. The increasing use of implants to fix such fractures also necessitates extensive dissection for implant retrieval. Adequate reduction and minimal tissue trauma during implant placement and removal would be ideal modalities for fixation of such fractures.
All displaced type 2 lateral end clavicle fractures fulfilling our inclusion criteria were reduced with a small anterosuperior incision. Anteroposterior drill holes were made in both the fragments and a nonabsorabable polyester suture was passed through. The fracture was reduced and fixed with transacromial smooth Kirshner wires. The suture was tied with the knot superiorly in a figure-eight manner. The arm was supported in an arm pouch for six weeks. The Kirshner wire was routinely removed after six weeks in an out-patient department. Clinico-radiological outcome was studied at six weeks, and monthly intervals thereafter until union.
All 16 fractures united. The mean average age of patients was 36.25 years with a SD of 11.35. There was no loss of reduction even after removal of Kirshner wires at six weeks. The mean average time of union was 10.75 weeks with a SD of 3.92. All patients regained near normal range of motion, and the mean average constant score at the end of one year was 98.37 with a SD of 2.87. All patients returned to preinjury level by the one-year follow-up. The range of motion remained the same in those who were followed up in successive years. Skin impingement with bent Kirshner wires were noted in four cases. Kirshner wires backed out in one case before six weeks but there was no loss of reduction. Infection and Kirshner wire breakage were not noted in our series.
The clinico-radiological outcomes with our modified tension band fixation for displaced type 2 lateral end clavicle fractures were encouraging and comparable with earlier studies.
The overall volume of the brain has been found to be under relatively strong genetic control, but the relative strength of genetic and environmental factors on between-person variations in regional cortical thickness in adolescence is still not well understood. Here, we analyzed structural MRI data from 108 14-year-old healthy twins (54 females/54 males) to determine the relative contributions of genes and the environment toward regional variations in gray matter thickness across the cortex. After extracting cortical thickness values at a high spatial resolution, an A/C/E structural equation model that divides the variations into additive genetic (A), shared (C), and unique (E) environmental components was fitted. There was considerable regional variability in the magnitude of genetic influences on cortical thickness after controlling for sex. Regions with genetic contributions of greater than 80% were observed in the prefrontal cortex, predominantly in the bilateral dorsolateral and mesial superior frontal regions. No region showed prominent shared environmental influences, but unique environmental influences of over 80% were found in parietal association regions. The genetic variance for cortical thickness in adolescents in prefrontal regions overlapped with previous findings in adults. However, the unique environmental effects observed in multimodal parietal association cortices with converging inputs from visual, auditory, somatosensory regions, and neighboring secondary association cortices suggest that these regional variations are more shaped by experience and could form targets for early interventions in youth with behavioral disorders.
adolescent twins; cortical thickness; heritability; MRI
India has over 62 million people with diabetes. Unfortunately, there are no trained diabetes educators in India although many are self-taught through experience. The National Diabetes Educator Program (NDEP) was initiated with the primary aim to educate and train diabetes educators in India. The first cycle of NDEP was conducted during the period June 2011 to March 2012 in 96 training centers in India and trained 1032 diabetes educators mainly drawn from various diabetes clinics across the country. Structured modules were taught by diabetologists/endocrinologists or experienced educators. A majority of the trainees attended all sessions and 95% of the trainees acknowledged that the program met its objective and was beneficial to them. This article elaborates the methodology of the program and its evaluation based on feedback received from the participants and trainers.
Diabetes; diabetes educator; India
Skeletal metastasis as a primary presentation of gall bladder carcinoma is rare. A 50-year-old lady presented with neck pain and weakness in her right upper limb of 3 months duration. Clinical and imaging work-up suggested locally advanced gall bladder carcinoma with metastasis to cervical vertebra and sternum. Only one case till date has been reported where the patient presented with neurological symptoms due to pathological fracture secondary to metastasis from an occult gall bladder carcinoma. Although rare, an occult gall bladder cancer may present with neurological symptoms due to pathological fracture of spine secondary to metastasis. We present a brief review of literature of patients who presented with skeletal metastases in clinically silent gall bladder malignancy. Palliative care issues in advanced gall bladder carcinoma have also been discussed.
Gall bladder carcinoma; Neurological symptoms; Skeletal metastases
The gold standard for diagnosis of meningitis depends on cerebrospinal fluid (CSF) examination by microscopy, biochemistry, and culture, which require an experienced microscopist and laboratory support. We conducted this study to determine if urinary reagent strip is useful to make a semi-quantitative assessment of protein, glucose, and presence of leukocyte esterase in CSF.
Materials and Methods:
All consecutive CSF samples were evaluated in a blinded fashion. CSF was tested using Combur-10 urinary reagent strip as an index test, and CSF microscopy and biochemistry as reference standards. Combur-10 (Boehringer Mannheim) is a urinary reagent strip used to estimate ten parameters including protein, glucose, and leukocytes. We estimated diagnostic accuracy of each index test using corresponding cut-off levels (glucose 1 + vs. CSF glucose >50 mg/dL; protein 1 + and 2 + vs. CSF protein >30 mg/dL and >100 mg/dL; leukocyte esterase positivity vs. >10 granulocytes in CSF sample). We constructed receiver operating curves (ROC) to evaluate overall performance of index tests and estimated area under the curve (AUC).
CSF samples of 75 patients were included in the study. All the three indicator tests (CSF cells, protein, and glucose) were normal in 17 (22.6%) samples. Of the three tests, diagnostic accuracy of protein estimation (1 + or more on reagent strip) was best for detection of CSF proteins greater than 30 mg/dL [sensitivity 98.1% (95% CI 90.1-100%); specificity 57.1% (95% CI 34-78.2%)], with AUC of 0.97. Sensitivity and specificity for 2 + on reagent strip and CSF protein > 100 mg/dL were 92.6% (95% CI 75.1-99.1) and 87.5% (95% CI 74.8-95.3), respectively, with AUC of 0.96 (95% CI 0.92-1.01). Leukocyte esterase positivity by test strip had a sensitivity of 85.2 (95% CI 66.3-95.8%) and specificity of 89.6 (95% CI 77.3-96.5%) for detection of CSF granulocytes of more than 10/mm3.
Existing urinary reagent strips can be used to diagnose meningitis in low-resource settings.
Cerebrospinal fluid; meningitis; urinary reagent strip
Atherosclerosis is a multifactorial vascular inflammatory process; however, the inciting cause for inflammation remains unclear. Two decades ago, Chlamydophila pneumoniae (formerly Chlamydia pneumoniae) infection was proposed as a putative etiologic agent. We performed a PubMed search using the keywords Chlamydia and atherosclerosis in a Boolean query to identify published studies on C. pneumoniae and its role in atherogenesis, and to understand research interest in this topic. We found 1,652 published articles on this topic between 1991 and 2011. We analyzed relevant published studies and found various serological, molecular, and animal modeling studies in the early period. Encouraged by positive results from these studies, more than a dozen antibiotic clinical-trials were subsequently conducted, which did not find clinical benefits of anti-Chlamydophila drug therapy. While many researchers believe that the organism is still important, negative clinical trials had a similar impact on overall research interest. With many novel mechanisms identified for atherogenesis, there is a need for newer paradigms in Chlamydophila-atherosclerosis research.
Atherosclerosis; Chlamydophila pneumonia; Cardiovascular disease; Infection
In the present study, we show that the combination of doxorubicin with the cyclin-dependent kinase inhibitor P276-00 was synergistic at suboptimal doses in the non-small cell lung carcinoma (NSCLC) cell lines and induces extensive apoptosis than either drug alone in H-460 human NSCLC cells.
Synergistic effects of P276-00 and doxorubicin on growth inhibition was studied using the Propidium Iodide (PI) assay. The doses showing the best synergistic effect was determined and these doses were used for further mechanistic studies such as western blotting, cell cycle analysis and RT-PCR. The in vivo efficacy of the combination was evaluated using the H-460 xenograft model.
The combination of 100 nM doxorubicin followed by 1200 nM P276-00 showed synergistic effect in the p53-positive and p53-mutated cell lines H-460 and H23 respectively as compared to the p53-null cell line H1299. Abrogation of doxorubicin-induced G2/M arrest and induction of apoptosis was observed in the combination treatment. This was associated with induction of tumor suppressor protein p53 and reduction of anti-apoptotic protein Bcl-2. Furthermore, doxorubicin alone greatly induced COX-2, a NF-κB target and Cdk-1, a target of P276-00, which was downregulated by P276-00 in the combination. Doxorubicin when combined with P276-00 in a sequence-specific manner significantly inhibited tumor growth, compared with either doxorubicin or P276-00 alone in H-460 xenograft model.
These findings suggest that this combination may increase the therapeutic index over doxorubicin alone and reduce systemic toxicity of doxorubicin most likely via an inhibition of doxorubicin-induced chemoresistance involving NF-κB signaling and inhibition of Cdk-1 which is involved in cell cycle progression.
Non-small cell lung cancer; P276-00; Doxorubicin; Cyclin-dependent kinase inhibitor; Chemotherapy
Earlier studies indicate that altered angiogenesis at birth is associated with poor birth outcome in women with preeclampsia. Now, we hypothesize that the progressive gestation dependant changes in markers of angiogenesis will be more useful to predict birth weight early even in a normotensive pregnancy. This study for the first time examines the association of gestation dependant changes in the levels of maternal angiogenic factors in addition to their levels in cord with birth weight.
Ninety two pregnant women were followed at three different time points: 16–20 weeks, 26–30 weeks and at delivery during pregnancy. Plasma levels of angiogenic and anti angiogenic factors were determined by commercial enzyme-linked immunosorbent assay (ELISA) kits.
Maternal plasma VEGF levels increased (p<0.01) till the second time point and decreased (p<0.05) up to delivery while plasma sFlt-1 levels increased (p<0.01) at delivery. PlGF levels peaked (p<0.01) at second time point and decreased (p<0.01) at delivery. Cord plasma VEGF levels were higher (p<0.01) and sFlt-1 levels were lower (p<0.01) as compared to maternal values at all time points. Maternal plasma VEGF levels at first time point and PlGF levels at delivery were positively (p<0.05 and p<0.01 respectively), while sFlt-1/PlGF ratio at delivery was negatively associated (p<0.05) with birth weight.
Levels of pro- and anti-angiogenic factors may be differentially regulated across gestation. Maternal VEGF levels at early gestation (16–20 weeks) may be predictive of birth weight in healthy term pregnancies.
To evaluate whether semen processing at 37°C yield sperm with better DNA integrity compared to centrifugation and processing at room temperature (RT) by swim-up method.
This study was done at tertiary care center attached to Reproductive Medicine Unit and Medical College.
Prospective pilot study.
Normozoospermic men (n = 50) undergoing diagnostic semen analysis.
MATERIALS AND METHODS:
Normozoospermic samples (World Health Organization, 2010 criteria) after analysis was divided into two aliquots (0.5 mL each); one was processed at 37°C and the other at RT by swim-up method. DNA fragmentation of both samples post wash was calculated by acridine orange method.
STATISTICAL ANALYSIS USED:
The values of sperm DNA fragmentation were represented as mean and standard error (mean ± SEM) of the mean. Paired t-test was used for calculating the sperm DNA integrity difference between post wash at RT and 37°C.
Statistically significant difference was not observed in post wash sperm DNA fragmentation values at 37°C compared to RT.
Our data represents that there was no significant difference in sperm DNA fragmentation values of samples processed at 37°C and at RT. Hence, sperm processing at 37°C does not yield sperm with better DNA integrity compared to centrifugation and processing at RT.
Acridine orange; semen preparation; sperm DNA integrity; temperature
Sebaceous gland carcinoma is a rare malignant tumor, which arises from the adnexal epithelium of sebaceous glands. Sebaceous glands are present all over the body and hence have variable sites of origin, histological growth patterns, and clinical presentations. Here, we report a case of recurrent extraocular sebaceous carcinoma of left occipital region with lung metastases who went into complete remission with chemotherapy for lung metastasis. Role of chemotherapy in the management ofmetastatic sebaceous carcinoma is evolving. Combination chemotherapy can result in long term remission as described in this case report.
Chemotherapy; lung metastasis; sebaceous carcinoma
P276-00 is a novel cyclin-dependent kinase inhibitor currently in Phase II clinical trials. Gemcitabine is a standard of care for the treatment of pancreatic cancer. The present study investigated the effect of the combination of P276-00 and gemcitabine in five pancreatic cancer cell lines.
Cytotoxic activity was evaluated by Propidium Iodide assay. Cell cycle and apoptosis was analyzed by flow cytometry. Genes and proteins known to inhibit apoptosis and contribute to chemoresistance were analysed using western blot analysis and RT-PCR. In vivo efficacy was studied in PANC-1 xenograft model.
The combination of gemcitabine followed by P276-00 was found to be highly to weakly synergistic in various pancreatic cancer cell lines as assessed by the combination index. Enhancement of apoptosis in PANC-1 cells and decrease in the antiapoptotic protein Bcl-2 and survivin was seen. P276-00 potentiated the gemcitabine-induced cytotoxicity by modulation of proteins involved in chemoresistance to gemcitabine and cell cycle viz. antiapoptotic proteins p8 and cox-2, proapoptotic protein BNIP3 and cell cycle related proteins Cdk4 and cyclin D1. The above results could explain the novel mechanisms of action of the combination therapy. We also show here that gemcitabine in combination with P276-00 is much more effective as an antitumor agent compared with either agent alone in the PANC-1 xenograft tumor model in SCID mice.
The chemosensitzation of pancreatic tumors to gemcitabine would likely be an important and novel strategy for treatment of pancreatic cancer and enable the use of lower and safer concentrations, to pave the way for a more effective treatment in this devastating disease. Phase IIb clinical trials of P276-00 in combination with gemcitabine in pancreatic cancer patients are ongoing.
Cdk inhibitor; P276-00; Gemcitabine; Combination studies; Pancreatic cancer
Diabetic neuropathies are a family of nerve disorders caused by diabetes. Symptoms of the disease include nerve palsy, mononeuropathy, mononeuropathy multiplex, diabetic amyotrophy, painful polyneuropathy, autonomic neuropathy, and thoracoabdominal neuropathy. In this study, type 2 diabetes in rats was induced with nicotinamide-streptozotocin. Drug treatment was initiated on the d 15, with the combination regimen of metformin, pioglitazone and glimipiride or metformin and sitagliptin or sitagliptin, amitriptyline and sitagliptin and led to significantly improved glycemic control, increased grip strength and paw jumping response on d 21, 28 and 35 (P < 0.001). Significant increases in blood protein levels and decreases in urinary protein levels were observed in the animals treated with the different regimens on d 21, 28 and 35 (P < 0.001). Combined treatment of streptozotocin and nicotinamide caused marked degeneration of nerve cells, while administration of metformin and sitagliptin showed tissue regeneration and no body weight gain. In conclusion, treatment with sitagliptin and sitagliptin combined with metformin or amitriptyline results in no body weight gain, but causes an increase in grip strength and pain sensitivity, exhibits neural protection, and reverses the alteration of biochemical parameters in rats with streptozotocin-nicotinamide induced type 2 diabetes.
diabetic neuropathy; nicotinamide-streptozotocin; metformin; pioglitazone; glimipiride; sitagliptin; amitriptyline
Resting-state MRI (rs-fMRI) is a powerful procedure for studying whole brain neural connectivity. In this study we provide the first empirical evidence of the longitudinal reliability of rs-fMRI in children. We compared rest-retest measurements across spatial, temporal, and frequency domains for each of six cognitive and sensorimotor intrinsic connectivity networks (ICNs) both within and between scan sessions. Using Kendall’s W, concordance of spatial maps ranged from .60 to .86 across networks, for various derived measures. The Pearson correlation coefficient for temporal coherence between networks across all Time one - Time two (T1/T2) z-converted measures was .66 (p<.001). There were no differences between T1/T2 measurements in low-frequency power of the ICNs. For the visual network, within-session T1 correlated with the T2 low-frequency power, across participants. These measures from resting-state data in children were consistent across multiple domains (spatial, temporal, and frequency). Resting-state connectivity is therefore a reliable method for assessing large-scale brain networks in children.
India and other countries in Asia are experiencing rapidly escalating epidemics of type 2 diabetes (T2D) and cardiovascular disease. The dramatic rise in the prevalence of these illnesses has been attributed to rapid changes in demographic, socioeconomic, and nutritional factors. The rapid transition in dietary patterns in India—coupled with a sedentary lifestyle and specific socioeconomic pressures—has led to an increase in obesity and other diet-related noncommunicable diseases. Studies have shown that nutritional interventions significantly enhance metabolic control and weight loss. Current clinical practice guidelines (CPGs) are not portable to diverse cultures, constraining the applicability of this type of practical educational instrument. Therefore, a transcultural Diabetes Nutrition Algorithm (tDNA) was developed and then customized per regional variations in India. The resultant India-specific tDNA reflects differences in epidemiologic, physiologic, and nutritional aspects of disease, anthropometric cutoff points, and lifestyle interventions unique to this region of the world. Specific features of this transculturalization process for India include characteristics of a transitional economy with a persistently high poverty rate in a majority of people; higher percentage of body fat and lower muscle mass for a given body mass index; higher rate of sedentary lifestyle; elements of the thrifty phenotype; impact of festivals and holidays on adherence with clinic appointments; and the role of a systems or holistic approach to the problem that must involve politics, policy, and government. This Asian Indian tDNA promises to help guide physicians in the management of prediabetes and T2D in India in a more structured, systematic, and effective way compared with previous methods and currently available CPGs.
Asian Indians; Diabetes; Nutrition therapy
We analyzed brain MRI data from 372 young adult twins to identify cortical regions in which gray matter thickness and volume are influenced by genetics. This was achieved using a A/C/E structural equation model that divides the variance of these traits, at each point on the cortex, into additive genetic (A), shared (C) and unique environmental (E) components. A strong genetic influence was found in frontal and parietal regions. Additionally, we correlated cortical thickness with full-scale IQ for comparison with the A/C/E maps, and several regions where cortical structure was correlated with IQ are under genetic control. These cortical measures may be useful phenotypes to narrow the search for quantitative trait loci influencing brain structure.
brain; image analysis; magnetic resonance imaging; cortex; genetics
We present an intrinsic framework for constructing sulcal shape atlases on the human cortex. We propose the analysis of sulcal and gyral patterns by representing them by continuous open curves in ℝ3. The space of such curves, also termed as the shape manifold is equipped with a Riemannian L2 metric on the tangent space, and shows desirable properties while matching shapes of sulci. On account of the spherical nature of the shape space, geodesics between shapes can be computed analytically. Additionally, we also present an optimization approach that computes geodesics in the quotient space of shapes modulo rigid rotations and reparameterizations. We also integrate the elastic shape model into a surface registration framework for a population of 176 subjects, and show a considerable improvement in the constructed surface atlases.
Heat shock protein (hsp) 90 inhibitors promote proteasomal degradation of pro-growth and pro-survival hsp90 client proteins, including CDK4, c-RAF and AKT, and induce apoptosis of human lymphoma cells. The pan-histone deacetylase inhibitor vorinostat has also been shown to induce growth arrest and apoptosis of lymphoma cells. Here, we determined the effects of the more soluble, orally bio-available, geldanamycin analogue 17-NN-dimethyl ethylenediamine geldanamycin (DMAG, Kosan Biosciences Inc) and/or vorinostat in cultured and primary human MCL cells. While vorinostat induced accumulation in the G1 phase, treatment with DMAG arrested MCL cells in the G2/M phase of the cell cycle. Both agents dose-dependently induced apoptosis of MCL cells. Vorinostat also induced hyperacetylation of hsp90 and disrupted the association of hsp90 with its co-chaperones p23 and cdc37, as well as with its client proteins CDK4 and c-RAF. Treatment of MCL cells with vorinostat or 17-DMAG was associated with the induction of p21 and p27, as well as with depletion of c-Myc, c-RAF, AKT and CDK4. Compared to treatment with either agent alone, co-treatment with DMAG and vorinostat markedly attenuated the levels of cyclin D1 and CDK4, as well as of c-Myc, c-RAF and AKT. Combined treatment with DMAG and vorinostat synergistically induced apoptosis of the cultured MCL cells, as well as induced more apoptosis of primary MCL cells than either agent alone. Therefore, these findings support the rationale to determine the in vivo efficacy of co-treatment with vorinostat and DMAG against human MCL cells.
The PRC2 complex protein EZH2 is a histone methyltransferase that is known to bind and recruit DNMT1 to the DNA to modulate DNA methylation. Here, we determined that the pan-HDAC inhibitor panobinostat (LBH589) treatment depletes DNMT1 and EZH2 protein levels, disrupts the interaction of DNMT1 with EZH2, as well as de-represses JunB in human acute leukemia cells. Similar to treatment with the hsp90 inhibitor 17-DMAG, treatment with panobinostat also inhibited the chaperone association of heat shock protein 90 with DNMT1 and EZH2, which promoted the proteasomal degradation of DNMT1 and EZH2. Unlike treatment with the DNA methyltransferase inhibitor decitabine, which demethylates JunB promoter DNA, panobinostat treatment mediated chromatin alterations in the JunB promoter. Combined treatment with panobinostat and decitabine caused greater attenuation of DNMT1 and EZH2 levels than either agent alone, which was accompanied by more JunB de-repression and loss of clonogenic survival of K562 cells. Co-treatment with panobinostat and decitabine also caused more loss of viability of primary AML but not normal CD34+ bone marrow progenitor cells. Collectively, these findings indicate that co-treatment with panobinostat and decitabine targets multiple epigenetic mechanisms to de-repress JunB and exerts antileukemia activity against human acute myeloid leukemia cells.
The misfortunate incident of formation of a urogenital fistula remains a major challenge for surgical urologists worldwide. Such fistulae may not be a life-threatening problem, but surely the women face demoralization, social boycott and even divorce and separation. The fistula may be vaginal, recto-vaginal or a combination of the two. The World Health Organization (WHO) has estimated that in the developing nations, nearly 5 million women annually suffer severe morbidity with obstetric fistulae being the foremost on the list. The objective of our study was to enunciate the patient demography, patient profile, incidence, type of surgery, as well as the long-term outcomes encountered in the management of all types of genital fistulae at a tertiary care centre.
Materials and Methods:
50 consecutive patients, attending the outpatient department with urogenital fistulae, were studied during the period of 5 years from July 2005 to July 2009. All female patients with complaints of urinary incontinence and fecal incontinence and dribbling, patients having a history of obstructed labor, radiotherapy, instrumental delivery, foreign body or trauma and with a history of hysterectomy (abdominal/ vaginal) and lower segment caesarean section (LSCS) were included. A thorough urological examination included a dye study using methylene blue, Renal function tests, X-ray KUB and intravenous urography (IVU). Cystoscopy along with examination under anaesthesia (EUA) were done to assess the actual extent of injury. All patients were subjected to appropriate surgical interventions via the same combination of surgeons . Post operatively, prophylactic antibiotics were administered to all patients and patients were managed till discharge and followed thereafter via regular outpatient visits for a period of 3 years.
Age of patients ranged from 21 to 40 years. 64% patients hailed from rural areas, 76% were from the lower socio-economic strata, 40% illiterate and 69% were short Statured. Vesico vaginal fistulae (VVF) was seen in 64% cases of which 50% were due to obstructed labor, 19% cases post LSCS and 31% cases post total abdominal hysterectomy (TAH). 68% of urogenital fistulae were between 1 to 3 cms. We obtained a 75% cure rate in UVF, 87.5% cure rate in RVF while a 93.75% cure rate was observed in patients with VVF. 76% of all patients were cured while 8% had a recurrence, probably due to the large size of fistula.
Genital fistula is preventable, yet it remains a significant cause of morbidity among females of reproductive age group. Despite facilities available, certain conditions like physical, social, economic, illiteracy, and a very casual attitude towards maternal health and children birth practices limit utilization of services for women. It is important that the modern health care providers should be aware of these aspects, so that they can recognize services that are appropriate and acceptable to the people. Thus, one must agree that in cases of urogenital fistulae, "prevention is better than cure".
Obstructed labor; urogenital fistulae; vesico vaginal fistula
To describe the normal and variant anatomy of the coronary artery ostia in Indian subjects.
Anomalous coronary origins may cause potentially dangerous symptoms, and even sudden death during strenuous activity. A cadaveric study in an unsuspected population provides a basis for understanding the normal variants, which may facilitate determination of the prevalence of anomalies and evaluation of the value of screening for such anomalies.
One hundred and five heart specimens were dissected. The number of ostia and their positions within the respective sinuses were observed. Vertical and circumferential deviations of the ostia were observed. The heights of the cusps and the ostia from the bottom of the sinus were measured.
No openings were present in the pulmonary artery or the non-coronary sinus. The number of openings in the aortic sinuses varied from 2–5 in the present series; multiple ostia were mostly seen in the anterior sinus. The majority of the ostia lay below the sinutubular ridge (89%) and at or above the level of the upper margin of the cusps (84%). Left ostial openings were mainly centrally located (80%), whereas the right coronary ostia were often shifted towards the right posterior aortic sinus (59%).
The preferential location of the ostia was within the sinus and above the cusps, but below the sinutubular ridge. On occasion, normal variants like multiple ostia, vertical or circumferential shift in the position, and slit-like ostia may create confusion in interpreting the images and pose a difficulty during procedures like angiography, angioplasty, and coronary artery bypass grafting.
Aortic cusps; Aortic sinuses; Commissures; Coronary ostium; Sinutubular ridge
Breast cancer is the most common malignancy affecting females worldwide but conventional risk factors are able to explain only a small proportion of these cases. A possible viral etiology for breast cancer has been proposed and Epstein-Barr Virus (EBV) is a widely researched candidate virus. The aim of the present study, first one of its kind from India, was to determine if there is a greater association of EBV infection with breast cancer patients as compared to patients with benign breast diseases.
We looked for expression of Epstein-Barr Virus Nuclear Antigen-1 (EBNA-1) in breast cancer tissue specimens by employing immunohistochemistry (IHC). We also measured levels of anti-EBNA-1 Immunoglobulin (IgG) antibodies in stored sera of these patients using commercial Enzyme linked Immunosorbent Assay (ELISA) kit. Patients with benign breast diseases were used as a comparison group for both immunohistochemical and serological analysis.
58 cases of malignant breast disease and 63 of benign breast disease (controls) were included in the study. Using manufacturer determined cut-off of 3 IU/ml, 50/55 tested (90.9%) cases and 27/33 tested (81.8%) controls were seropositive for anti-EBNA-1 IgG. Mean antibody levels were significantly higher for cases (54.22 IU/ml) as compared to controls (18.68 IU/ml). IHC for EBNA-1 was positive in 28/51 cases (54.9%). No IHC positivity was noted in the tested 30 controls. Our results show that EBNA-1 expression is seen in a significant proportion of breast cancer tissue specimens from rural India and as compared to patients with benign breast diseases these patients also have a higher immunological response against EBNA-1.
We investigated the mechanism of synaptic suppression by P2Y receptors in mixed hippocampal cultures wherein networked neurons exhibit synchronized Ca2+ oscillations (SCO) due to spontaneous glutamatergic synaptic transmission. Pharmacological studies suggested that SCO suppression was mediated by P2Y2/P2Y4 receptors. Immunostaining studies and characterization of ATP/UTP-stimulated Ca2+ responses in solitary neurons and astrocytes revealed that the SCO attenuation was effectuated by astrocytes. We demonstrate that nitric oxide released from activated astrocytes causes synaptic suppression by inhibiting neurotransmitter release. Physiological concentrations of ATP and UTP evoked NO production in astrocytes. SCO suppression was considerably diminished by removal of extracellular NO by membrane-impermeable scavenger c-PTIO or by pretreatment of cells with nitric oxide synthase inhibitor L-NAME. The nitric oxide donor DETA/NO effectively suppressed the SCO. ATP/UTP inhibited KCl-induced exocytosis at presynaptic terminals in an NO-dependent manner. In the absence of exogenously added ATP/UTP, both the NO scavenger and NOS inhibitor enhanced the frequency of SCO, implying that astrocytes release NO during spontaneous synaptic activity and exert a suppressive effect. We report for the first time that under physiological conditions astrocytes use NO as a messenger molecule to modulate the synaptic strength in the networked neurons.