Studies on carboxymethylcellulose: Conductivity measurements of solutions, 2

The conductivity behaviour of carboxymethylcellulose (CMC) solutions was studied using different types of neutralizing reagents (LiOH, NaOH, KOH); the following order of conductance of CMC solutions was observed: Li⁺ < Na⁺ < K⁺. This conductance behaviour of CMC solutions with respect to the size of counterions is explained qualitatively as well as quantitatively. Binding of Li⁺, Na⁺ and K⁺ ions onto the polymer molecule and the influence of the degree of substitution, ,DS , on the conductivity of CMC were also investigated. The conductivity of CMC solutions as well as the fraction of bound counterions increase with increasing DS , at a given degree of neutralization (α) for each type of counterion. The effect of DS on the polymer charge fraction, i/s, is in line with the counterion condensation phenomena of Oosawa. The results regarding the dependence of the equivalent conductance of the polyion, Δ_p, on DS are compared with literature data.     

Reproductive tract immune cells from pregnant women or those using depot medroxyprogesterone acetate show no excess susceptibility to HIV-1: Results of an ex vivo fusion assay

IntroductionEx vivo fusion assays offer an efficient method for studying HIV-1 entry associated with contraceptive use and pregnancy outside of cohort studies of HIV-1 incidence.MethodsWe measured ex vivo HIV-1 fusion to cervical or endometrial immune cells from three groups of women: pregnant, non-pregnant not using hormonal or intrauterine contraception, and using depot medroxyprogesterone acetate (DMPA).Results and conclusionsThere was no excess susceptibility to HIV-1 fusion of cells from pregnant women or DMPA users compared to controls. Although the number of target cells in endometrium was higher in DMPA users compared to controls, HIV-1 fusion was lower.ImplicationsIn ex vivo assays, HIV-1 showed no enhanced fusion to cervical immune cells from pregnant women or DMPA users compared to controls, and lower fusion to endometrial immune cells from DMPA users. This assay is useful for studying hormonal and contraceptive effects on HIV-1 entry into reproductive tract immune cells.     

High prevalence of type 2 diabetes in an urban settlement in Kerala, India

Background. Prevalence of type 2 or non insulin dependent diabetes mellitus is high among Indians living in India as well as abroad. Prevalence among persons of Indian origin in many countries is greater than that of people of other ethnic extraction. The Indian state of Kerala is distinguished by a high level of achievement in the health sector, characterised by both lower mortality rates and greater density of health care institutions that ensure access to most people. These attributes make the prevalence of diabetes and the pattern of its management in Kerala worth studying. Objective. To estimate the prevalence of diabetes among persons 20 years or older in an urban housing settlement in Trivandrum city, the capital of Kerala, as well as study the management of the disease in subjects affected. Design. Cross sectional survey for detecting diabetes and other chronic diseases in all willing residents of an urban housing settlement in Trivandrum, the capital city of Kerala, as part of a preventive campaign against lifestyle diseases. Fasting plasma glucose, serum triglycerides, cholesterol, height, weight and blood pressure were measured, and a detailed questionnaire administered to ascertain previous diabetic status and management. Results. Overall prevalence of type 2 diabetes is 16.3%. In the 30-64 age group, age standardised prevalence is 13.7%. Gender differences in prevalence are negligible. Greater prevalence is associated with advancing age, body mass index above 24.99, sedentary habits, serum total cholesterol > 239, serum triglycerides > 149, hypertension and smoking. Compared to non-diabetics, diabetics have greater mean and range of fasting plasma glucose values (8.87 + /-3.6 mM/l as against 4.34 + /-0.53 mM/l). 32 out of 38 diabetics among the subjects (82.4%) were already diagnosed even before the survey; of them, 89% were on medication. 3% of subjects had impaired fasting glucose, or FPG level between 110-125 mg/dl. Conclusion. Prevalence of type 2 diabetes among a group of urban residents in Trivandrum city in Kerala is very high. This is associated also with a high detection rate and compliance to treatment.     

An intrasubject comparison of two doses of succinylcholine in modified electroconvulsive therapy.

The electroconvulsive therapy (ECT) guideline of the Royal College of Psychiatrists recommends a 0.5 mg/kg of succinylcholine for ECT modification. Our clinical experience suggests that this dose is insufficient for Indian patients. The dose recommended by the Royal College of Psychiatrists (0.5 mg/kg) and a larger dose (1 mg/kg) were compared in 50 patients referred for ECT. In one ECT session, patients were equally randomized to receive one of the two doses and in the next session they were switched to the other dose. The extent of motor seizure modification was rated on a five-point scale by two independent raters who were blinded to the succinylcholine dose. The interrater reliability was good (K = 0.85). "Poor" seizure modification occurred in 48% and 12% of patients with the 0.5 and 1 mg/kg doses, respectively. Of the 24 patients who had poor modification with 0.5 mg/kg, 20 had "good" modification in the session with 1 mg/kg (P < 0.001). A small delay (mean = 55 s) occurred in time to recover from the respiratory paralysis with the 1 mg/kg dose of succinylcholine. No patient, however, had prolonged apnea requiring special measures. We recommend 1 mg/kg of succinylcholine dose be used in the first ECT session. For subsequent sessions, the dose may be altered, depending on the response for optimal motor seizure modification. IMPLICATIONS: The dose of muscle relaxant (succinylcholine) recommended in modified electroconvulsive therapy is not based on empirical research. In the same patients (n = 50), two doses-0.5 mg/kg and 1 mg/kg-were compared during different electroconvulsive therapy sessions. The larger dose was more effective in modifying the peripheral convulsion.     

Design and synthesis of novel alpha(1)(a) adrenoceptor-selective antagonists. 1. Structure-activity relationship in dihydropyrimidinones

Dihydropyrimidinones such as compound 12 exhibited high binding affinity and subtype selectivity for the cloned human alpha(1a) receptor. Systematic modifications of 12 led to identification of highly potent and subtype-selective compounds such as (+)-30 and (+)-103, with high binding affinity (K(i) = 0.2 nM) for alpha(1a) receptor and greater than 1500-fold selectivity over alpha(1b) and alpha(1d) adrenoceptors. The compounds were found to be functional antagonists in human, rat, and dog prostate tissues. Compound (+)-103 exhibited excellent selectively to inhibit intraurethral pressure (IUP) as compared to lowering diastolic blood pressure (DBP) in mongrel dogs (K(b)(DBP)/K(b)(IUP) = 40) suggesting uroselectivity for alpha(1a)-selective compounds.     

Unusual presentation of a giant glomus tumor

Giant glomus tumors pose a challenge to the Otologist by virtue of their location and vascularity. A vast majority of them present with tinnitus, conductive hearing loss and cranial nerve palsies. We report the case of a 16-year-old male patient who presented with sudden right-sided sensorineural hearing loss. This is an unusual presentation of a giant glomus tumor. We present the clinical features and management of this unusual case.     

Results of a phase II upfront window of pharmacokinetically guided topotecan in high-risk medulloblastoma and supratentorial primitive neuroectodermal tumor.

PURPOSE: To assess the antitumor efficacy of pharmacokinetically guided topotecan dosing in previously untreated patients with medulloblastoma and supratentorial primitive neuroectodermal tumors, and to evaluate plasma and CSF disposition of topotecan in these patients. PATIENTS AND METHODS: After maximal surgical resection, 44 children with previously untreated high-risk medulloblastoma were enrolled, of which 36 were assessable for response. The topotecan window consisted of two cycles, administered initially as a 30-minute infusion daily for 5 days, lasting 6 weeks. Pharmacokinetic studies were conducted on day 1 to attain a topotecan lactone area under the plasma concentration-time curve (AUC) of 120 to 160 ng/mL.h. After 10 patients were enrolled, the infusion was modified to 4 hours, with dosage individualization. RESULTS: Of 36 assessable patients, four patients (11.1%) had a complete response and six (16.6%) showed a partial response, and disease was stable in 17 patients (47.2%). Toxicity was mostly hematologic, with only one patient experiencing treatment delay. The target plasma AUC was achieved in 24 of 32 studies (75%) in the 30-minute infusion group, and in 58 of 93 studies (62%) in the 4-hour infusion group. The desired CSF topotecan exposure was achieved in seven of eight pharmacokinetic studies when the topotecan plasma AUC was within target range. CONCLUSION: Topotecan is an effective agent against pediatric medulloblastoma in patients who have received no therapy other than surgery. Pharmacokinetically guided dosing achieved the target plasma AUC in the majority of patients. This drug warrants testing as part of standard postradiation chemotherapeutic regimens. Furthermore, these results emphasize the importance of translational research in drug development, which in this case identified an effective drug.