Clinical and Molecular Characterization of Prader-Willi Syndrome

Objectives

To describe the clinical presentations and molecular diagnosis to aid the clinicians in early diagnosis and appropriate management of Prader-Willi syndrome (PWS).

Methods

Thirty-four clinically diagnosed PWS cases were enrolled after obtaining informed consent/assent. Demographic details, clinical data and anthropometry were recorded using structured proforma. The facial dysmorphology was evaluated. Appropriate genetic testing was performed to confirm the diagnosis.

Results

At diagnosis, the most common clinical features included obesity (59%) and short stature (53%). Distinct dysmorphic features were observed in 67%. Neonatal hypotonia with feeding difficulty, delayed development in infancy and childhood behavioral problems were reported in 94%, 94% and 74% respectively. Food seeking behavior and hyperphagia was reported in 67%. Seizures were reported in 47%. All children had underdeveloped external genitalia. Growth hormone (GH) deficiency and impaired glucose tolerance were found in 56% and 50% respectively. Sleep related problems were seen in 67%. Skin and rectal picking were reported in 67%. FISH confirmed micro-deletion was found in 64.7% and abnormal methylation in 35%, of which uniparental disomy was confirmed in 14.7%.

Conclusions

Clinical suspicion is vital for early detection of PWS. Confirmation of the diagnosis requires complex multi-tier molecular genetic testing.

     

Relation of occupation to presence or absence of coronary artery disease: an angiographic study.

To determine the relation of occupation to the presence or absence of coronary artery disease (CAD) and cardiovascular risk factors, the authors compared the occupations of a series of 116 consecutive patients who underwent coronary angiography and were found to have normal or near-normal coronary arteries (< 30% stenosis of all major coronary arteries) with those of a series of 116 patients with moderate to severe CAD (> or = 60% stenosis of one or more major coronary artery). The usual lifetime occupational status of each study participant was classified as sedentary, intermediate, or strenuous. The presence of the usual cardiovascular risk factors in the patients was also recorded. There was no significant difference in the frequency of the three occupational categories between the two groups (those with or without CAD) when subjects of all ages were considered or when subjects less than 40 years or more than 60 years old were considered. However, the results indicate that among 40-60-year-old individuals CAD occurred significantly more frequently in those engaged in strenuous occupations than in those engaged in sedentary occupations. Cardiovascular risk factors occurred significantly more frequently in patients with CAD than in those with normal coronary arteries and in those engaged in strenuous occupations compared with those in sedentary occupations.     

Successful nonsurgical removal of a knotted and entrapped pulmonary artery catheter

Knotting of a balloon-tipped, flow-directed catheter leading to difficulty in its removal is a rare but serious complication. Several methods have been used to remove such catheters with nonsurgical techniques. A case of knotted catheter that was also entrapped in a surgical suture in a patient undergoing emergency mitral valve replacement is presented and a method for its nonsurgical removal is described. Cathet. Cardiovasc. Diagn. 43:87–89, 1998. © 1998 Wiley-Liss, Inc.     

Management of steroid sensitive nephrotic syndrome: revised guidelines

JUSTIFICATION: In 2001, the Indian Pediatric Nephrology Group formulated guidelines for management of patients with steroid sensitive nephrotic syndrome. In view of emerging scientific evidence, it was felt necessary to review the existing recommendations. PROCESS: Following a preliminary meeting in March 2007, a draft statement was prepared and circulated among pediatric nephrologists in the country to arrive at a consensus on the evaluation and management of these patients. OBJECTIVES: To revise and formulate recommendations for management of steroid sensitive nephrotic syndrome. RECOMMENDATIONS: The need for adequate cortico-steroid therapy at the initial episode is emphasized. Guidelines regarding the initial evaluation, indications for renal biopsy and referral to a pediatric nephrologist are updated. It is proposed that patients with frequently relapsing nephrotic syndrome should, at the first instance, be treated with long-term, alternate-day prednisolone. The indications for use of alternative immunosuppressive agents, including levamisole, cyclophosphamide, mycophenolate mofetil and cyclosporin are outlined. The principles of dietary therapy, management of edema, and prevention and management of complications related to nephrotic syndrome are described. These guidelines, formulated on basis of current best practice, are aimed to familiarize physicians regarding management of children with steroid sensitive nephrotic syndrome.     

Role of sensory input and muscle strength in maintenance of balance, gait, and posture in Parkinson's disease: a pilot study

OBJECTIVE: The purpose of this study was to simultaneously evaluate multiple components of disequilibrium in patients with idiopathic Parkinson's disease (PD) in ON and OFF states and healthy age- and sex-matched controls on tests of balance, gait, and dynamometry. DESIGN: Thirty subjects with Parkinson's disease and 30 controls were matched for age and sex. Isokinetic and balance laboratories of a clinical research center were used for assessment. Performance results for static and dynamic balance by dynamic posturography for sensory organization tests (SOT), limits of stability, clinical gait assessment, and dynamometric assessment for the trunk, hip, and ankle at different speeds for concentric muscle strength were obtained. Tests were done both in ON and OFF state in Parkinson's disease patients and results compared. RESULTS: Between OFF state and controls, a significant difference was observed for SOT-2 (proprioception, P < 0.005), SOT-6 (conflicting vision, P < 0.001), and SOT-4 (eyes open with sway support, P < 0.038), and there was less use of ankle strategy in SOT-3 (sway vision, P < 0.04). No significant difference was observed for vestibular function (SOT-5). Significant difference was also observed (P < 0.001) for all variables in limits of stability except for reaction time and for muscle strength of trunk, hip, and ankle (P < 0.001) between OFF state and controls. After antiparkinsonian medications, significant improvement was observed for gait velocity (P < 0.002), muscle strength (P < 0.001), and strategy score in SOT-3 between OFF and ON states. A positive correlation was observed between muscle strength (ankle, hip, and trunk) and gait velocity (ON state r = 0.37, OFF state r = 0.56) and movement velocity (ON state r = 0.39). A positive correlation was also seen between ankle strength and gait velocity in both ON (r = 0.393) and OFF states (r = 0.397) and between ankle strength and ankle strategy in all SOTs except SOT-3 in the OFF state. CONCLUSIONS: The quantitative reduction of muscle strength in the spine, hip, and ankle, along with impaired proprioception, visual sense, and smaller base of support, were the main causes for postural instability in Parkinson's disease patients. A correlation was seen between muscle strength, static and dynamic balance, and gait in both ON and OFF states. In contrast to the previous studies, the present study showed that medications improved the muscle strength, gait speed, and use of ankle strategy but did not worsen proprioceptive sense.     

Second trimester termination of pregnancy: a review by site and procedure type

BACKGROUND: We hypothesized that complications for second trimester terminations are higher in a low-volume residency training program than in a high-volume private practice. STUDY DESIGN: Complications and cost were compared between three groups undergoing second trimester terminations: patients undergoing dilation and evacuation (D&E) at a university hospital (Hospital D&E, n=83) or medical pregnancy termination at a university hospital (Hospital Induction, n=89) and D&E at a private outpatient facility (Clinic D&E, n=253). RESULTS: Major complications occurred in 11% of the Hospital D&E, 10% of the Hospital Induction, and 1% of the Clinic D&E patients (p=.0019). Complication rates remained statistically significant when a logistic regression model was applied to the data. The mean total charge for the three respective groups was US$4625, US$5029 and US$1105 (p<.001). CONCLUSION: Second trimester terminations of pregnancy by D&E in well-selected patients in a dedicated outpatient facility can be safer and less expensive than hospital-based D&E or induction of labor.     

L-arginine stimulates immune response in chickens immunized with intermediate plus strain of infectious bursal disease vaccine

Infectious bursal disease continues to pose an important threat to the commercial poultry industry, especially after the emergence of virulent infectious bursal disease virus (IBDV). L-arginine, a ubiquitous, basic amino acid is used as an immunostimulant in variety of human and animal studies with great success in immunosuppressed hosts. In the present study, we evaluated the immunomodulatory effects of L-arginine on humoral and cellular immune response in chickens immunized with live intermediate plus (IP) strain of IBDV vaccine. Chickens vaccinated with IP strain and supplemented with 2% L-arginine showed 100% protection after challenge with virulent IBDV compared to 80% protection induced by IP strain alone. IP strain vaccine elicited good antibody titres in both the groups, IP + L-arginine and IP alone, however, the antibody titres in IP + L-arginine group were significantly higher (P < 0.05) than IP vaccinated chickens. Mitogenic response of peripheral blood lymphocytes to specific IBDV antigen stimulation was significantly higher in IP + L-arginine group (P < 0.05). Peripheral blood lymphocytes were able to rapidly clear the suppressive effects of IP strain and virulent challenge virus in IP + L-arginine group. These results strongly suggest that l-arginine plays a vital role in modulation of protective immune response against IBDV.     

Targeting breast stem cells with the cancer preventive compounds curcumin and piperine

The cancer stem cell hypothesis asserts that malignancies arise in tissue stem and/or progenitor cells through the dysregulation or acquisition of self-renewal. In order to determine whether the dietary polyphenols, curcumin, and piperine are able to modulate the self-renewal of normal and malignant breast stem cells, we examined the effects of these compounds on mammosphere formation, expression of the breast stem cell marker aldehyde dehydrogenase (ALDH), and Wnt signaling. Mammosphere formation assays were performed after curcumin, piperine, and control treatment in unsorted normal breast epithelial cells and normal stem and early progenitor cells, selected by ALDH positivity. Wnt signaling was examined using a Topflash assay. Both curcumin and piperine inhibited mammosphere formation, serial passaging, and percent of ALDH+ cells by 50% at 5 μM and completely at 10 μM concentration in normal and malignant breast cells. There was no effect on cellular differentiation. Wnt signaling was inhibited by both curcumin and piperine by 50% at 5 μM and completely at 10 μM. Curcumin and piperine separately, and in combination, inhibit breast stem cell self-renewal but do not cause toxicity to differentiated cells. These compounds could be potential cancer preventive agents. Mammosphere formation assays may be a quantifiable biomarker to assess cancer preventive agent efficacy and Wnt signaling assessment can be a mechanistic biomarker for use in human clinical trials.