Cyclophosphamide-induced agenesis of cerebral aqueduct resulting in hydrocephalus in mice

The present work was undertaken to reveal the mechanism of cerebral aqueduct agenesis found to result in hydrocephalus following intrauterine exposure to model teratogen, cyclophosphamide, in murine fetuses. A single dose of 10-mg/kg body weight cyclophosphamide was injected intaperitoneally to pregnant mice on day 10, 11 or 12 of gestation. Fetuses were collected through abdominal incision on day 18 and studied for various malformations of brain and cranium including hydrocephalus. Incomplete development and failure of canalization of the cerebral aqueduct were detected when serial sections of brain in coronal and transverse planes were studied under the microscope. Biotechnological investigations such as % DNA fragmentation, % viable cell count and cell proliferation assay were carried out on brain cells for further studies. Agenesis and non-canalization of the cerebral aqueduct resulted in increased pressure of CSF, which led to rupture of the aqueduct complicated by leakage and accumulation of CSF in brain substance forming a cavity containing CSF parallel and lateral to the unopened part of the cerebral aqueduct. Incomplete development along with non-canalization of the cerebral aqueduct resulted in blockage of CSF flow through the ventricles that manifest as internal hydrocephalus. External hydrocephalus on the other hand was detected where the CSF accumulated in the cavity formed inside the brain substance and established communication with the CSF in the subarachnoid space. Cyclophosphamide induced inhibition of mitosis and cell differentiation of ependymal cells reflecting a decreased % viable cell count and cell proliferation assay along with augmentation of apoptosis of brain cells quantified as increased % DNA fragmentation count, which were identified as the contributing factors underlying the agenesis and incomplete development of the cerebral aqueduct. The study also suggests that cell survival, proliferation, migration or differentiation of ependymal cells might have been affected, and we speculate that CSF may have an inducing role in the development and canalization of the cerebral aqueduct.     

High prevalence of malnutrition and inflammation in undialyzed patients with chronic renal failure in developing countries: a single center experience from eastern India

BACKGROUND: Malnutrition is common in patients with chronic renal failure (CRF), and its prevalence before the initiation of dialysis is poorly characterized in these patients in developing countries. There is a paucity of data on the quantification of malnutrition and inflammation in undialyzed patients of CRF from India. This study analyzed the prevalence and causes of malnutrition in patients with CRF before the initiation of dialysis treatment. MATERIAL AND METHODS: In the present study, assessments of nutritional and inflammatory status were carried out in patients with CRF. Serum albumin, body mass index (BMI), triceps skin fold thickness (TST), mid-arm muscle circumference (MAMC), and subjective global assessment (SGA) scoring were used for assessment of nutritional parameters. Serum C-reactive protein and serum ferritin level were used to assess the inflammatory state of the patient. RESULTS: Two hundred and three (146 male, 57 female) patients with CRF were included in the study from August 2004 to April 2006. Overall, the prevalence of malnutrition was 65% (131/203). The age of malnourished patients (93 male, 38 female) ranged from 11-82, with mean age of 52 +/- 12.68 years. The mean serum total protein and albumin were also significantly lower in patients with malnutrition in comparison to non malnourished cases (5.50 +/- 0.40 gm/dL vs. 5.74 +/- 0.38 gm/dL; p < 0.05, and 3.18 +/- 0.58 gm/dL vs. 3.68 +/- 0.55 gm/dL; p < 0.05). The C-reactive protein and serum ferritin were significantly elevated in the malnourished group as compared to non-malnourished patients (63% vs. 33%; p < 0.05, and 301.2 +/- 127.1 mg/dL vs. 212.7 +/- 124.9 mg/dL; p < 0.05). CONCLUSION: Thus, malnutrition was common in patients with CRF before the commencement of dialysis. These data indicate that an emphasis should be placed on the assessment and prevention or correction of malnutrition in patients with CRF because of its documented adverse effect on the outcome on maintenance dialysis.     

No role for antiseptics in routine pin site care in Ilizarov fixators: A randomised prospective single blinded control study

Introduction

Pin site infection is the commonest complication of Ilizarov external fixation. The aim of the study was to examine if use of antiseptics was superior over control and further if daily dressing was superior to weekly dressing in regular pin site care in reducing the burden of pin site infection in Ilizarov fixators.

Efficacy of three doses of ketamine with bupivacaine for caudal analgesia in pediatric inguinal herniotomy

BACKGROUND AND OBJECTIVES: Ketamine administered systemically is a potent analgesic at subanesthetic plasma concentrations. Addition of ketamine to bupivacaine for caudal epidural block significantly prolongs the duration of postoperative analgesia. The purpose of this prospective, randomized double-blind study is to identify the optimal dose of ketamine that produces the maximum duration of caudal analgesia with minimal adverse effects as an adjuvant to bupivacaine for caudal epidural block. METHODS: Sixty children, aged 6 months to 10 years, undergoing inguinal herniotomy were allocated randomly to receive 1 of 3 solutions for caudal epidural block. Group 1 received 0.75 mL/kg of bupivacaine 0.25% with preservative-free ketamine 0.25 mg/kg, group 2 received 0.75 mL/kg of bupivacaine 0.25% with ketamine 0.5 mg/kg, and group 3 received 0.75 mL/kg of bupivacaine 0.25% with ketamine 1 mg/kg. Postoperative pain was assessed using the All India Institute of Medical Sciences pain discomfort scale. Rescue analgesia in the form of pethidine 1 mg/kg intramuscularly was administered when this score exceeded 4. RESULTS: The mean duration of caudal analgesia was 8.8 hours in group 1 compared with 22.1 hours in group 2 (P <.001) and 25.2 hours in group 3 (P <.001). Supplemental analgesia requirements with pethidine were significantly less in group 2 (4 subjects) and group 3 (no subject) when compared with group 1 (18 subjects). There were no differences between the groups in the incidence of motor blockade, urinary retention, emesis, or sedation. Group 3 had a significantly higher incidence of behavioral side effects such as odd behavior, agitation, or restlessness than groups 1 and 2. CONCLUSIONS: The optimal dose of ketamine in our study was 0.5 mg/kg added to 0.75 mL/kg bupivacaine 0.25% for caudal epidural block without an increase in side effects.     

Calcified atherosclerotic plaque - where exactly is the calcium and what does it contain?

Objective  

To understand the morphology and mineral content in calcified atherosclerotic plaques.     

Tourniquets in orthopedic surgery

Tourniquets are commonly used in limb surgeries, be it orthopedic or plastic surgeries. But the inflation pressures, the duration, and release guidelines are still not clear. According to a survey, majority of orthopedic surgeons inflate the tourniquet to fixed pressures for the upper and the lower limbs without considering the baseline blood pressure of the patient on whom the tourniquets are being applied. This review was designed to recall and review the safe use of tourniquets and the various techniques that can be employed to minimize the complications of tourniquet use. Google, science direct, and pubmed were searched for appropriate literature and relevant articles were identified.     

Worldwide variability in deceased organ donation registries

The variability in deceased organ donation registries worldwide has received little attention. We considered all operating registries, where individual wishes about organ donation were recorded in a computerized database. We included registries which recorded an individual's decision to be a donor (donor registry), and registries which only recorded an individual's objection (non-donor registry). We collected information on 15 characteristics including history, design, use and number of registrants for 27 registries (68%). Most registries are nationally operated and government-owned. Registrations in five nations expire and require renewal. Some registries provide the option to make specific organ selections in the donation decision. Just over half of donor registries provide legally binding authorization to donation. In all national donor registries, except one, the proportion of adults (15+) registered is modest (<40%). These proportions can be even lower when only affirmative decisions are considered. One nation provides priority status on the transplant waiting list as an incentive to affirmative registration, while another nation makes registering a donation decision mandatory to obtain a driver's license. Registered objections in non-donor registries are rare (<0.5%). The variation in organ donor registries worldwide necessitates public discourse and quality improvement initiatives, to identify and support leading practices in registry use.     

Autosomal dominant progressive nephropathy with deafness: linkage to a new locus on chromosome 11q24

Focal segmental glomerulosclerosis (FSGS) and Alport syndrome (AS) are two major causes of end-stage renal disease (ESRD). A few families with autosomal dominant FSGS have been reported with linkage to chromosome 19q13 or 11q22, while AS is usually linked to mutations in type IV collagen (COL4) subunit genes. A phenotype resembling AS may also be seen with myosin heavy chain-9 (MYH9) gene mutations. This study ascertained a multigeneration family (CHP-177) with clinical aspects of both FSGS and AS where we identified a new locus for the trait. A genome-wide scan was performed with 400 markers, and fine mapping was performed for chromosome 11 markers. Data were analyzed by GENEHUNTER and VITESSE under various models. CHP-177 is a 39-member kindred residing near New Delhi, India, with seven affecteds and showed male-to-male transmission. Two members had ESRD. Renal biopsies showed both FSGS lesions and thin glomerular basement membranes. Five of the affecteds also had sensorineural deafness, which involved both low and high frequency in some members. The AS loci, i.e., COL4A3/COL4A4 and MYH9 (LOD scores: -6.1 and -4.3, respectively) and FSGS loci, on 19q13 and 11q22, were excluded from linkage. A significant evidence of linkage was observed for 11q24 region, with a multipoint LOD (z-score) of 3.2 for marker D11S4464 at theta = 0. The z-1 confidence interval for the linked region spans a genetic distance of 7 cM. This study thus reports an autosomal dominant nephropathy with features of both FSGS and AS in which linkage to currently known loci for such phenotypes was excluded and a new locus on 11q24 was identified. The findings suggest further locus heterogeneity for the autosomal dominant nephropathy phenotype.