Cyclical Vomiting Syndrome: Psychiatrist's View Point.

Cyclical vomiting syndrome (CVS) is an idiopathic functional disorder characterized by recurrent episodes of nausea and vomiting separated by symptom-free intervals. Even though initially described in children, it is seen in all age groups. Exact etiology is not known. Various physical, infectious, and psychosocial stressors have been implicated for CVS. High incidence of psychiatric comorbidities such as panic attacks, anxiety disorder, and depression is seen in CVS. Most children outgrow CVS with time though some may transition to migraine or continue to have CVS as adults. Frequent misdiagnosis, delay in diagnosis, or inadequate treatment often lead to years of recurrent vomiting. This case report highlights the importance of the management of CVS by a multidisciplinary team including a psychiatrist in addressing the various physical and psychological factors effectively and that would result in faster and prolonged recovery.

Joubert syndrome with autism in two siblings: A rare presentation.

Joubert syndrome is a rare autosomal recessive disorder with partial or complete agenesis of cerebellar vermis. This syndrome is identified mainly by the presence of molar tooth sign in magnetic resonance imaging of the brain since it has a varied phenotypic presentation. Of the 200 cases reported so far in the literature, only three reports show the presence of autistic symptoms in siblings suggesting a link between the cerebellar vermis and autistic spectrum disorders. In this case report of two siblings, the female child satisfied the criterion for autistic spectrum disorder in accordance with Diagnostic and Statistical Manual of Mental Disorders Fifth Editon. The boy showed developmental delay with autistic features (not amounting to diagnostic threshold). This report is important in that it adds evidence to the literature that abnormalities of cerebellum are involved in the cognitive development and autistic symptoms.

Drinking habits in ancient India.

Consumption of one or other form of intoxicating substances has been present throughout the history of the world. This article traces such use in the Indian subcontinent, both in North and South India. References to the use of intoxicants are to be found in the Vedas, the Great Epics, and the ancient Tamil literature.

P300 and neuropsychological measurements in patients with schizophrenia and their healthy biological siblings.

BACKGROUND: Patients with schizophrenia and their first-degree relatives' exhibit abnormalities in neuropsychological and electrophysiological measures especially P300. The aim was to study the P300 and neuropsychological measures together in patients with schizophrenia, their unaffected siblings, and normal controls. MATERIALS AND METHODS: Thirty patients diagnosed as schizophrenia, their unaffected biological siblings, and normal controls were included in the study. Inpatient group, the severity of symptoms was assessed by Positive and Negative Syndrome Scale. All subjects were administered P300 event-related potential, which was measured using oddball paradigm and specific neuropsychological tests from NIMHANS neuropsychiatry battery. RESULTS: Both patients with schizophrenia and their unaffected biological siblings showed lower P300 amplitude and longer P300 latency when compared with the normal controls. The three groups showed statistically significant differences in digit symbol substitution test, digit vigilance test, Trail making test B and Stroop test (P < 0.001). CONCLUSION: Patients with schizophrenia and their unaffected biological siblings show deficits in both cognitive function tests and P300 event-related potential. Our results suggest a continuum in the electrophysiological and neuropsychological measures among the three groups.

Jainism - Its relevance to psychiatric practice; with special reference to the practice of Sallekhana.

Jainism is one of the oldest religions of India. Since the founding of the religion, Jainism has given prominence to Sallekhana, death by ritual fasting facing north, as exemplified in the deaths of Bhadrabahu and Chandragupta Maurya. The controversy whether this religious form of starvation is related to suicide is debated since the time of the early Jain teachers. History is replete with instances where kings and warriors who have failed in their duty punish themselves for their sin and welcome death as expiation. Such starvation deaths are referred to as vadakirutthal (literally, facing north) and become quite prevalent during the Sangam age, probably copied from the Jain culture. The present-day thinking on Sallekhana needs to be considered here in more detail which should be brought to the knowledge of current-day psychiatrists. These ideas are relevant to psychiatric counseling of the ordinary people and would be very useful if included in the armamentarium of the mental health professionals.

Treatment of the mentally ill in the Chola Empire in 11(th) -12(th) centuries AD: A study of epigraphs.

The paper deals with the epigraphs of the Chola emperors Veera Rajendra Deva (1063-1069 AD) and Raja Raja III (1216-1256 AD), found at the temples of Thirumukkudal and Vedaranyam, with emphasis on the treatment given to the residents of the attached hospitals with special reference to treatment of mental disorders.

Adjuvant chemotherapy for bladder cancer-why does level 1 evidence not support it?

Neoadjuvant cisplatin-based combination chemotherapy provides a 5% increase in cure rate, an increase in median survival of about 3 years, and statistically significant and clinically relevant increments in overall survival for patients with invasive bladder cancer. Despite compelling level 1 data, it has become quite clear that facts that are similar to those that changed the paradigm of treatment of breast cancer in the 1970s have not had a similar influence on patterns of practice in bladder cancer care. Instead of using this proven approach, cystectomy alone or surgery followed by adjuvant chemotherapy is often used as a functional alternative for patients with deeply invasive and/or node-metastatic disease discovered at radical cystectomy. However, there is no well-powered level 1 evidence to support routine adjuvant chemotherapy for invasive bladder cancer, and some randomized trials have shown inferior outcomes. There is a clear need for a well-designed, randomized trial that tests the utility of adjuvant chemotherapy for invasive bladder cancer, but until that has been completed, neoadjuvant chemotherapy followed by definitive local treatment should be the standard of care for invasive bladder cancer.

Gender-specific effects of oral hypoglycaemic agents on cancer risk in type 2 diabetes mellitus.

AIMS: To analyse the association between cancer incidence and oral diabetes therapy (biguanide, sulphonylurea, thiazolidinedione and meglitinide) in men and women with type 2 diabetes mellitus. METHODS: A retrospective analysis of the electronic health record-based Cleveland Clinic Diabetes Registry (25 613 patients) was cross-indexed with the histology-based tumour registry (48 051 cancer occurrences) over an 8-year period (1998-2006). Multiple imputations were used to account for missing data. Cox regression with propensity scores was used to model time for the development of incident cancer in each of the imputed datasets and the results were pooled. RESULTS: During 51 994 person follow-up years, 892 incident cancer cases were identified; prostate (14.5%) and breast (11.7%) malignancies were most frequent. In women, thiazolidinedione use was associated with a 32% decreased cancer risk compared with sulphonylurea use [hazard ratio (HR) 0.68; 95% confidence interval (CI) 0.48-0.97, in the adjusted analysis]. Comparison of insulin secretagogues (sulphonylurea and meglitinide) versus insulin sensitizers (biguanide and thiazolidinedione) demonstrated a 21% decreased cancer risk in insulin sensitizers [HR 0.79 (95% CI 0.64-0.98) in the adjusted analysis]. Oral diabetes therapy showed no significant difference in men. Adjustments were made for age, body mass index (BMI), low-density lipoprotein (LDL), high-density lipoprotein (HDL), triglycerides, coronary heart disease (CHD), diabetes oral monotherapy, race, gender, haemoglobin A1c, statin use, income, insulin use, glomerular filtration rate (GFR), new diabetes status, prior cancer, prior cerebrovascular accident (stroke or transient ischaemic event), systolic/diastolic blood pressure, tobacco use (ever/never) and the propensity score for receiving a biguanide. CONCLUSIONS: Oral insulin sensitizers, particularly thiazolidinedione, are associated with decreased malignancy risk in women with type 2 diabetes mellitus.

Higher capecitabine AUC in elderly patients with advanced colorectal cancer (SWOGS0030).

BACKGROUND: The aging process is accompanied by physiological changes including reduced glomerular filtration and hepatic function, as well as changes in gastric secretions. To investigate what effect would aging have on the disposition of capecitabine and its metabolites, the pharmacokinetics between patients ≥70 years and <60 years were compared in SWOG0030. METHODS: Twenty-nine unresectable colorectal cancer patients were stratified to either ≥70 or <60 years of age, where the disposition of capecitabine and its metabolites were compared. RESULTS: Notable increase in capecitabine area under the curve (AUC) was accompanied by reduction in capecitabine clearance in ≥70 years patients (P<0.05). No difference in 5'-deoxy-5-fluorocytidine, 5'-deoxy-5-fluorouridine (DFUR), and 5-fluorouracil (5FU) AUCs between the two age groups, suggesting that carboxylesterase and cytidine deaminase (CDA) activity was similar between the two age groups. These results suggest that metabolic enzymes involved in converting capecitabine metabolites are not altered by age. An elevation in capecitabine Cmax and reduction in clearance was seen in females, where capecitabine AUC was 40.3% higher in women. Elevation of DFUR Cmax (45%) and AUC (46%) (P<0.05) was also noted, suggesting that CDA activity may be higher in females. CONCLUSION: Increases in capecitabine Cmax and AUC was observed in patients ≥70 years when compared with younger patients who were >60 years.

Characterization of Silver/Bovine Serum Albumin (Ag/BSA) nanoparticles structure: morphological, compositional, and interaction studies.

The primary objective of this study was to elucidate the structure of protein conjugated silver nanoparticles prepared by chemical reduction of AgNO(3) and bovine serum albumin (BSA) mixture. The role of BSA in the formation of Ag/BSA nanoparticles was established by UV-Vis Spectroscopy. The association of silver with BSA in Ag/BSA nanoparticles was studied by the decrease in the intensity of absorbance peak at 278 nm in UV-Vis spectra and shift in cathodic peak potential in cyclic voltammogram. The molar ratio of silver to BSA in the Ag/BSA nanoparticles is 27:1, as ascertained by thermogravimetric analysis and atomic absorption spectrometry. Based on atomic force microscopy, dynamic light scattering and transmission electron microscopy (TEM) measurements, the average particle size of nanoparticles was found to be range of 11-15 nm. TEM image showed that the nanoparticle has two distinct phases and selected area electron diffraction pattern of nanoparticles indicated that the silver phase in Ag/BSA is fcc. X-ray photo electron spectroscopy measurements of freshly prepared and argon sputtered nanoparticles provided evidence that the outer and inner region of nanoparticles are mainly composed of BSA and silver respectively. The structural and compositional findings of nanoparticles could have a strong bearing on the bioavailability and antimicrobial activity of nanoparticles.

3-[1-(4-Bromo-phen-yl)eth-oxy]-2,2,5-trimethyl-4-phenyl-3-aza-hexa-ne.

The title compound, C22H30BrNO, is an alk-oxy-amine compound, an effective initiator in nitroxide-mediated free radical polymerization. It was prepared as a mixture of two diasteromers; the crystal for the X-ray analysis showed one of these as a pair of R,S and S,R enanti-omers. The tert-butyl and isopropyl groups are in an almost anti conformation in the crystal [C-N-C-C torsion angle = -168.8 (1)°], and the methyl group of the ethoxy group is in an approximate anti relationship to the tert-butyl group. The dihedral angle between the phenyl and benzene rings is 33.12 (7)°. The Br atom is disordered over two positions, with occupancies of 0.9139 (16) and 0.0861 (16). In the crystal, weak C-H⋯Br contacts link the mol-ecules into chains along [-110].

Recruitment of ethnic minorities into cancer clinical trials: experience from the front lines.

Throughout the world there are problems recruiting ethnic minority patients into cancer clinical trials. A major barrier to trial entry may be distrust of research and the medical system. This may be compounded by the regulatory framework governing research with an emphasis on written consent, closed questions and consent documentation, as well as fiscal issues. The Leicester UK experience is that trial accrual is better if British South Asian patients are approached by a senior doctor rather than someone of perceived lesser hierarchical status and a greater partnership between the hospital and General Practitioner may increase trial participation of this particular ethnic minority. In Los Angeles, USA, trial recruitment was improved by a greater utilisation of Hispanic staff and a Spanish language-based education programme. Involvement of community leaders is essential. While adhering to national, legal and ethnical standards, information sheets and consent, it helps if forms can be tailored towards the local ethnic minority population. Written translations are often of limited value in the recruitment of patients with no or limited knowledge of English. In some cultural settings, tape-recorded verbal consent (following approval presentations) may be an acceptable substitute for written consent, and appropriate legislative changes should be considered to facilitate this option. Approaches should be tailored to specific minority populations, taking consideration of their unique characteristics and with input from their community leadership.

The need for better data about counterfeit drugs in developing countries: a proposed standard research methodology tested in Chennai, India.

WHAT IS KNOWN AND OBJECTIVE: There is still surprisingly little basic research data to support widely repeated claims about the prevalence of drug counterfeiting. To meet the need for more reliable drug quality data, we designed a study framework that includes clear definitions of measured end points, sampling methods and assay technique. Our objective was to test this research design in Chennai (formerly Madras), India, using a joint Indian and Canadian team. METHODS: The city was divided into ten areas along municipal lines. From each area, ten stores and pharmacies selling drugs were selected. At each of these 100 outlets, three study drugs (artesunate, ciprofloxacin and rifampicin) were purchased. The 300 samples were tested by Liquid Chromatography-Mass Spectrometry. Assay content was expressed as a percentage of stated tablet content. Based on assay results and their distribution, we developed drug quality definitions for normal manufacturing standards, counterfeiting, decomposition, poor quality control and adulteration. RESULTS: The group mean for ciprofloxacin was close to normal manufacturing limits (99·2 ± 7·1%) but rifampicin (91·6 ± 5·7%), and artesunate (80·1 ± 9·1%), were both below normal pharmaceutical standards. Overall, 43% of all samples fell below the widely accepted manufacturing range of 90-110% of stated content. No tablet from any sample contained less than 50% of the stated dose. WHAT IS NEW AND CONCLUSION: The quality of at least some anti-infective drugs in Chennai is below commonly accepted standards but we found no evidence of criminal counterfeiting. Poor drug quality was most likely due to decomposition during storage or poor manufacturing standards. Our research methodology worked well under practical conditions and should hopefully be of value to others working in this area.

StarClose vascular closure device: safety and efficacy of deployment and reaccess in a neurointerventional radiology service.

BACKGROUND AND PURPOSE: Obtaining safe and effective closure of the femoral access site following neurointerventional procedures can sometimes be challenging, especially in patients on anti-coagulation or anti-platelet therapy. The purpose of this study was to evaluate the safety and efficacy of a novel percutaneous closure device that employs a nitinol clip-mediated extravascular closure strategy following neurointerventional procedures. MATERIALS AND METHODS: We performed a retrospective review of all patients who underwent neurointerventional procedures at our institution between January 1, 2006 and December 31, 2008. We evaluated the safety and efficacy of the StarClose device in patients undergoing first and repeat procedures. Groin complications were classified as self-limited hematoma, hematoma requiring transfusion, other/minor (pseudoaneurysm, infection), and other/major (vascular complication). RESULTS: StarClose device use was attempted in 281 of 352 cases (79.8%) with success reported in 269 cases (95.7%). Minor and major complications occurred in 0.7% and 0.4% of patients, respectively. There was one major vascular complication. Repeat use was performed in 84 patients with 100% success and a 2.3% minor complication rate. Time to reaccess ranged from 1 to 1036 days (mean, 105 days). CONCLUSIONS: The StarClose device achieves rapid and safe femoral arterial closure in patients, both for primary closure and after reaccess.

Intra-tumoural extra-cellular pH: a useful parameter of response to chemotherapy in syngeneic tumour lines.

Reliable surrogate markers of response to anticancer therapy remain a desirable tool for preclinical modelling and clinical practice in oncology. Clinical evaluation is relatively unreliable when attempting to assess rapidly and prospectively the outcome of treatment. Fluxes in released or circulating tumour marker levels are a useful but inconsistent marker of cytotoxic response. Serial measurement of circulating tumour cells appears to have some utility as a surrogate marker, but assay systems are expensive, and many cancers are not associated with the presence of circulating tumour cells. Because tissue breakdown is associated with release of nucleic acids and other cellular products, we reasoned that serial measurement of intra-tumoural pH may correlate with the extent of tumour lysis, and thus with outcomes of cytotoxic chemotherapy. Doxorubicin-sensitive and doxorubicin-resistant sublines of P388 murine monocytic leukaemia in C57BL/6 mice were treated with increasing concentrations of doxorubicin. Tumours were serially measured by conventional bi-dimensional methods and pH was sampled using a bevelled tip electrode. Mean and median pH changes were statistically different in responsive and resistant tumours, and amplitude of change correlated with long-term responses to doxorubicin. Serial sampling of pH in tumour masses may provide a useful surrogate of long-term response to chemotherapy.

Phase II trial of neoadjuvant nab-paclitaxel in high risk patients with prostate cancer undergoing radical prostatectomy.

PURPOSE: Taxane based chemotherapy has activity in advanced prostate cancer but previous studies of neoadjuvant docetaxel demonstrated a prostate specific antigen response with no obvious antitumor activity. The efficacy and safety of neoadjuvant albumin-bound paclitaxel (nab-paclitaxel, Abraxane), a novel nanoparticle based formulation, were assessed in patients with high risk, locally advanced prostate cancer. MATERIALS AND METHODS: Eligible patients had locally advanced prostatic adenocarcinoma, clinical stage cT2b or greater, Gleason score 8 or greater, or serum prostate specific antigen 15 ng/ml or greater without metastatic disease. Patients received 2 cycles of 150 mg/m(2) nab-paclitaxel weekly for 3 weeks during each 4-week cycle, followed by radical prostatectomy with bilateral lymphadenectomy. Efficacy assessments included pathological and prostate specific antigen response. RESULTS: A total of 19 patients completed neoadjuvant therapy and 18 underwent radical prostatectomy. Median pretreatment prostate specific antigen was 8.5 ng/ml and median Gleason score was 8. Despite the lack of complete pathological responses 5 of 18 patients (28%) had organ confined disease and 9 of 18 (50%) had specimen confined disease. Post-chemotherapy prostate specific antigen was decreased in 18 of 19 (95%) patients and median decrease was 2.9 ng/ml (35%, p <0.001). An initial prostate specific antigen after radical prostatectomy of 0.02 ng/ml or less was achieved in 17 of 18 (94%) patients. There were no significant perioperative complications. Cytoplasmic vacuolization (focal in 10 and extensive in 7) was evident in all but 1 patient (94%). Ten patients (56%) had grade 3 and 1 had grade 4 neutropenia with no febrile neutropenia. CONCLUSIONS: Neoadjuvant nab-paclitaxel was well tolerated. Similar to our experience with neoadjuvant docetaxel there were no pathological complete responses, although a possible histological antitumor effect was observed.