Influence of serum protein on polycarbonate-based copolymer micelles as a delivery system for a hydrophobic anti-cancer agent.

A new micelle system formed from methoxy (polyethylene glycol)-b-poly (5-benzyloxy-trimethylene carbonate; MePEG-b-PBTMC 5000-b-4800) was investigated as a delivery system for the hydrophobic anti-cancer agent, ellipticine. The ellipticine was loaded into the MePEG-b-PBTMC micelles with a loading efficiency of 95% using a high-pressure extrusion technique. The ellipticine-loaded micelles have a spherical morphology and an average diameter of 96 nm. The anti-cancer activity of ellipticine was confirmed to be retained following formulation in the MePEG-b-PBTMC micelles. The extent of protein adsorption to the MePEG-b-PBTMC micelles was investigated by transmission electron microscopy, dynamic light scattering and gel filtration chromatography. Overall, the amount of protein both loosely and tightly associated with the micelles was found to be minimal and insignificant. The partitioning properties of ellipticine between an aqueous medium containing protein and the MePEG-b-PBTMC micelles were examined over a range of protein concentrations. Under physiologically relevant conditions, it was found that 61% of the drug remained within the micelle fraction while 39% was in the protein-containing aqueous phase. In addition, the in vitro drug release profile of ellipticine from the micelles was fit using a modified Higuchi model and found to be accelerated in the presence of protein. These studies demonstrate that although there are no significant interactions between micelle and protein, the properties of the micelle as a delivery vehicle may be strongly influenced by protein-drug interactions.     

Human immunodeficiency virus infection in urban Rwanda. Demographic and behavioral correlates in a representative sample of childbearing women

OBJECTIVE.--To determine behavioral and demographic risk factors for human immunodeficiency virus (HIV) infection in central Africa. DESIGN.--Cross-sectional survey. SETTING.--Kigali, Rwanda. PARTICIPANTS.--A representative sample of 1458 childbearing women aged 19 to 37 years who were recruited from outpatient prenatal and pediatric clinics at the only community hospital in the city. MAIN OUTCOME MEASURE.--Antibodies to HIV assessed by enzyme immunoassay and confirmed by Western blot or indirect immunofluorescence. RESULTS.--The HIV seroprevalence was 32% overall. Infection rates were higher in women who were single, in those in steady relationships that began after 1981, and in the 33% of women reporting more than one lifetime sexual partner. Women in legal marriages or monogamous partnerships had lower rates of infection, but even low-risk women had prevalences on the order of 20%. History of venereal disease in the past 5 years, although the strongest risk factor in a multiple logistic analysis (odds ratio, 2.7; 95% confidence interval, 2.0 to 3.7), was reported by only 30% of those infected. Having a male sexual partner who drank alcohol or who had higher income were significant risk factors for HIV infection in the multivariate analysis, but use of oral contraceptives and having an uncircumcised partner were not. CONCLUSIONS.--The epidemic of the acquired immunodeficiency syndrome in Rwanda has spread beyond high-risk groups to the general population of women without known risk factors. For most of these women, a steady male partner is the source of their HIV risk and therefore a vital target for intervention efforts.     

Fertility in Persons with Epilepsy: 1935–1974

Data from the Rochester-Olmsted County Medical Records Linkage Project were utilized to assess fertility in persons with epilepsy. Population age-specific reproduction rates for Rochester residents for the years 1935-1974 were estimated using the number of live births from the Minnesota Department of Health Statistics and Vital Statistics of the U.S. for comparison with rates in affected persons. Overall, fertility rates were significantly reduced to 80% of expected for affected males and 85% for affected females. Individuals with partial seizures (simple and complex) were disadvantaged, whereas those with generalized onset were not. During the last 20 years of the study period, males were more disadvantaged than females. The male-female difference was greatest during the time of low population fertility (after 1965). Male deficits were more marked after diagnosis; female deficits were more marked before diagnosis. Differences in the proportion of ever-married person-years between the sexes only partially explain the observed differences.     

Brain and spinal cord hemorrhage in long-term survivors of malignant pediatric brain tumors: a possible late effect of therapy

Three children with malignant primary CNS tumors treated with craniospinal radiotherapy developed intraparenchymal hemorrhages a median of 5 years following therapy in sites distant from the primary tumor. Radical surgical procedures disclosed fresh and old hematoma, gliosis, and necrosis in all 3 patients and an aggregation of abnormal microscopic blood vessels in two. No tumor was found. All 3 patients remain in long-term (greater than 10 years) continuous remission.     

Preoperative screening for perioperative cardiac risk

Preoperative screening for potential cardiac complications is crucial in making rational decisions about surgery. A number of classification schemes are available to aid the primary care physician in assessing a patient's perioperative cardiac risk. In general, these schemes enable the physician to place patients in low-risk, moderate-risk and high-risk categories. Patients at low risk can often be safely referred for surgery with minimal preoperative evaluation, while those at potentially high risk frequently need further assessment and medical or surgical treatment of cardiac disease prior to surgery. The classification schemes are most accurate in identifying patients at high risk for perioperative cardiac complications. However, patients with silent underlying cardiac disease are often underclassified with respect to potential risk. For those patients, accurate prediction of perioperative cardiac complications can be challenging.     

Daptomycin disrupts membrane potential in growing Staphylococcus aureus.

Daptomycin (LY146032) caused a calcium-dependent dissipation of the membrane potential (delta psi) in Staphylococcus aureus without noticeably affecting the chemical gradient (delta pH) across the membrane. The effect of daptomycin on membrane energization may account for many of the inhibitory effects on macromolecular biosyntheses and membrane function reported for this antibiotic. Our evidence indicates that the bactericidal activity of daptomycin is dependent on an available delta psi.     

Fluoroscopic percutaneous lumbar zygapophyseal joint cyst rupture: a clinical outcome study

Background contextLumbar zygapophyseal joint (Z-joint) synovial cysts can cause low back pain (LBP), spinal stenosis, and lower extremity radiculopathy. In the literature, there are several minimally invasive techniques described with mixed results. Typical recommended treatment is surgical resection of the cyst. Currently, there is little information available concerning the efficacy and outcome with treatment of Z-joint synovial cyst by percutaneous, fluoroscopic, contrast-enhanced distention, and rupture.PurposeTo evaluate the therapeutic value and safety of Z-joint cyst rupture in symptomatic patients.Study design/settingRetrospective cohort study in an academic outpatient physiatric spine practice.Patient sampleThirty-two patients with moderate-to-severe LBP and leg pain (18 women and 14 men with an age range of 46–86 y; mean age, 66 y) with an average preprocedure symptom duration of 5 months. The patient's clinical symptoms correlated with magnetic resonance imaging studies documenting the presence of a synovial cyst at the corresponding level and side of symptoms. Patients had at least 6 months follow-up (range, 6–24).Outcome measuresNumerical Pain Rating Scale, Roland-Morris Disability Questionnaire, North American Spine Society four-point patient satisfaction survey, recurrence of synovial cyst requiring repeat rupture, and need for surgical intervention.MethodsPatients with symptomatic lumbar Z-joint synovial cyst were identified and their charts were reviewed. Patients included in the study either had symptomatic lumbar LBP or LBP with associated lower extremity radiculopathy. All patients in the study had magnetic resonance imaging's documenting Z-joint synovial cyst that corresponded with the patients' clinical symptoms. All patients received fluoroscopically guided, contrast-enhanced, percutaneous facet cyst distention and rupture followed by an intra-articular facet joint injection of 1 cc kenalog and 1 cc of 1% lidocaine. Seventeen of the patients also received a transforaminal epidural steroid injection just before facet cyst rupture. Telephone follow-up was conducted on all patients.ResultsExcellent long-term (average follow-up 1 y; range, 6–24 mo) pain relief was achieved in 23 (72%) of 32 patients undergoing facet cyst rupture. Twelve patients (37.5%) had synovial cyst recurrence and 11 chose to undergo repeat rupture, which resulted in 5 patients (45%) obtaining complete relief of symptoms and 6 patients (55%) requiring surgical intervention for cyst removal. Fisher exact test demonstrated that all patients who did not have a cyst recurrence were a success and obtained complete relief of symptoms (p<.0002). Patients who underwent a repeat rupture had a 50% chance of a successful outcome. There was no statistical significance between a successful outcome and level of facet cyst rupture, the presence of spondylolisthesis, sex, age, or having a transforaminal epidural steroid injection at the time of the procedure. Wilcoxon signed-rank test demonstrated that the difference in Numerical Pain Rating Scale and Roland-Morris Disability Questionnaire scores before and after the procedure was statistically significant (p<.0001). No complications were reported.ConclusionsFluoroscopic percutaneous Z-joint cyst rupture appears to be a safe and effective minimally invasive treatment option. This procedure should be considered before surgical intervention.