Comparative assessment of in vitro release kinetics of calcitonin polypeptide from biodegradable microspheres

The objective of our study was to compare the in vitro release kinetics of a sustained-release injectable microsphere formulation of the polypeptide drug, calcitonin (CT), to optimize the characteristics of drug release from poly-(lactide-co-glycolide) (PLGA) copolymer biodegradable microspheres. A modified solvent evaporation and double emulsion technique was used to prepare the microspheres. Release kinetic studies were carried out in silanized tubes and dialysis bags, whereby microspheres were suspended and incubated in phosphate buffered saline, sampled at fixed intervals, and analyzed for drug content using a modified Lowry protein assay procedure. An initial burst was observed whereby about 50% of the total dose of the drug was released from the microspheres within 24 hr and 75% within 3 days. This was followed by a period of slow release over a period of 3 weeks in which another 10-15% of drug was released. Drug release from the dialysis bags was more gradual, and 50% CT was released only after 4 days and 75% after 12 days of release. Scanning electron micrographs revealed spherical particles with channel-like structures and a porous surface after being suspended in an aqueous solution for 5 days. Differential scanning calorimetric studies revealed that CT was present as a mix of amorphous and crystalline forms within the microspheres. Overall, these studies demonstrated that sustained release of CT from PLGA microspheres over a 3-week period is feasible and that release of drug from dialysis bags was more predictable than from tubes.     

Sexually transmitted diseases in children

Sexually transmitted diseases (STDs) cause considerable morbidity among their victims. This is true even for children. Unfortunately, this aspect has not received due attention and remains a relatively ignored field. We carried out a study of the clinico-epidemiological profile of STDs among the pediatric patients who attended the STD clinic of a tertiary care hospital. Pediatric patients who presented with STDs from January of 1995 to February of 2001 constituted the subject material of this study. A detailed clinical examination and relevant laboratory investigations were carried out in all patients. A total of 15,453 STD patients were seen during this period, out of which 127 were children, giving a prevalence of 0.82% pediatric STD cases. The peak incidence of STDs was seen in the age group of 10-14 years (66.1%). Most of them were illiterate (61.4%) and from low socio-economic backgrounds (70.9%). Notably, 17.3% were from remand homes. The predominant STDs observed among these children were syphilis (25.2%), including six cases of congenital syphilis, vulvo-vaginal candidiasis (11.8%), condyloma-acuminata (14.2%), herpes progenitalis (8.7%) and traumatic lesions (7.9%). Histories or signs of abuse were present in 74% of the patients. Only two cases during the span of the study were HIV positive. Pediatric STDs remain a hidden and neglected problem. Children constituted 0.82% of all STD patients in our series. This may represent only the tip of the iceberg, because several features, including some operational problems, are responsible for underdiagnosis of pediatric STDs. If not treated promptly and adequately, they may result in significant physical and emotional sequelae in children. Thus, it is essential to develop strategies to prevent sexual abuse and to have adequate counselling measures, especially in juvenile delinquents.     

Splenic infarction in pregnancy

We present a case of splenic infarction in pregnancy, secondary to acute bacterial endocarditis. Left upper quadrant pain in pregnancy can be due to a variety of causes and in the septic or unwell patient, splenic infarct should be considered in the differential diagnosis. The diagnosis of splenic infarct should be considered especially in those at increased risk of bacterial endocarditis. Acute bacterial endocarditis can occur even in patients without any risk factors. Bacterial endocarditis is rare in pregnancy and splenic infarction is even rarer. However when it occurs, rapid diagnosis and management are necessary to minimize embolic phenomena. With the increasing use of intravenous drugs and with increasing numbers of Pacific Islanders in our pregnant population, it is important to be alert to the risk of bacterial endocarditis and to avoid serious sequelae. Patient education to the importance of medical follow-up in order to prevent such a life-threatening condition, and to avoid more complicated acute treatment, is imperative.     

Transdermal lontophoretic delivery of colchicine encapsulated in liposomes

Iontophoresis is useful for the transdermal delivery of charged drugs. However, nonionized drugs either have a low flux (due to electro-osmosis) or cannot be delivered using this technique. Because ionized or nonionized drugs can be encapsulated in charged liposomes, it was hypothesized that charged liposomes can deliver neutral or nonionized drug efficiently by iontophoresis. Colchicine, a neutral drug, was encapsulated in large unilamellar vesicles (LUVs), prepared with 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC), 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC), and 1,2-distearoyl-sn-glycero-3-phosphocholine (DSPC) along with cholesterol (1:0.5 mole ratio). Multilamellar vesicles (MLVs) were prepared by the thin-film hydration method and LUVs were obtained by extruding MLVs through polycarbonate filters of 200 nm pore size. Positive charge was induced in the liposomes by adding stearylamine and negative charge by adding dicetyl phosphate. Nonencapsulated drug was separated from LUVs by the Ficoll density gradient method. Positively charged LUVs were delivered under the anode, negatively charged LUVs under the cathode, and neutral LUVs without current using Franz cells and human cadaver skin. Plain colchicine as well as colchicine encapsulated in positively charged LUVs was delivered better under the anode compared with the cathode and passive conditions. Delivery of colchicine encapsulated in positively charged DSPC liposomes was four to five times greater than that of plain colchicine and two to three times greater than that of colchicine encapsulated in DMPC or DPPC liposomes. Because LUVs prepared with DMPC and DPPC were fluid at 37°C, the encapsulated drug leaked during iontophoresis and therefore the delivery was less. Delivery of colchicine was lower under the cathode due to the change in pH during iontophoresis, which, as observed in high-performance liquid chromatographic analysis, caused degradation of the drug. Thus, it can be concluded that iontophoresis of colchicine encapsulated in positively charged DSPC liposomes can improve its delivery across human cadaver skin     

Variation in outcomes in Veterans Affairs intensive care units with a computerized severity measure

OBJECTIVE: To quantify the variability in risk-adjusted mortality and length of stay of Veterans Affairs intensive care units using a computer-based severity of illness measure. DESIGN: Retrospective cohort study. SETTING: A stratified random sample of 34 intensive care units in 17 Veterans Affairs hospitals. PARTICIPANTS: A consecutive sample of 29,377 first intensive care unit admissions from February 1996 through July 1997. INTERVENTIONS: Standardized mortality ratio (observed/expected deaths) and observed minus expected length of stay (OMELOS) with 95% confidence intervals were estimated for each unit using a hierarchical logistic (standardized mortality ratio) or linear (OMELOS) regression model with Markov Chain Monte Carlo simulation. We adjusted for patient characteristics including age, admission diagnosis, comorbid disease, physiology at admission (from laboratory data), and transfer status. MEASUREMENTS AND MAIN RESULTS: Mortality across the intensive care units for the 12,088 surgical and 17,289 medical cases averaged 11% (range, 2-30%). Length of stay in the intensive care units averaged 4.0 days (range, mean unit length of stay 3.0-5.9). Standardized mortality ratio of the intensive care units varied from 0.62 to 1.27; the standardized mortality ratio and 95% confidence interval were <1 for four intensive care units and >1.0 for seven intensive care units. OMELOS of the intensive care units ranged from -0.89 to 1.34 days. In a random slope hierarchical model, variation in standardized mortality ratio among intensive care units was similar across the range of severity, whereas variation in length of stay increased with severity. Standardized mortality ratio was not associated with OMELOS (Pearson's r = .13). CONCLUSIONS: We identified intensive care units whose indicators for mortality and length of stay differ substantially using a conservative statistical approach with a severity adjustment model based on data available in computerized clinical databases. Computerized risk adjustment employing routinely available data may facilitate research on the utility of intensive care unit profiling and analysis of natural experiments to understand process and outcome links and quality efforts.