Sublingual misoprostol versus intravenous oxytocin in prevention of post-partum hemorrhage

Background

Post-partum hemorrhage (PPH) is the most common direct cause of maternal mortality and timely intervention can save many lives.

Objective

To compare the effectiveness of sublingual misoprostol to intravenous oxytocin in preventing post-partum hemorrhage in low risk vaginal birth.

Methods

One hundred patients with no risk factor for PPH were randomly allocated to receive 600 μg misoprostol administered sublingually or 10 IU of intravenous oxytocin immediately after the delivery of baby. Main outcome measures were post-partum blood loss, drop in hemoglobin in 24 h, duration of third stage of labor, and drug-related adverse effects.

Results

Mean age, parity and gestational age were similar in both groups. Mean blood loss was significantly lower in oxytocin group (114.28 ± 26.75 versus 149.50 ± 30.78 ml; p = 0.00). Drop in hemoglobin was 0.31 ± 0.16 versus 0.49 ± 0.21 g% (p = 0.01) in oxytocin and misoprostol group, respectively. Duration of third stage labor was shorter in oxytocin group (median 5 min, IQR: 4.5–5.5 versus 5.5 min, IQR: 5–6 min, p < 0.01). Although fever and shivering were common adverse effects with misoprostol but were not clinically significant.

Conclusion

Intravenous oxytocin is more efficacious than sublingual misoprostol in preventing PPH in institutional deliveries.     

Fos and Jun potentiate individual release sites and mobilize the reserve synaptic-vesicle pool at the Drosophila larval motor synapse

In all nervous systems, short-term enhancement of transmitter release is achieved by increasing the weights of unitary synapses; in contrast, long-term enhancement, which requires nuclear gene expression, is generally thought to be mediated by the addition of new synaptic vesicle release sites. In Drosophila motor neurons, induction of AP-1, a heterodimer of Fos and Jun, induces cAMP- and CREB-dependent forms of presynaptic enhancement. Light and electron microscopic studies indicate that this synaptic enhancement is caused by increasing the weight of unitary synapses and not through the insertion of additional release sites. Electrophysiological and optical measurements of vesicle dynamics demonstrate that enhanced neurotransmitter release is accompanied by an increase in the actively cycling synaptic vesicle pool at the expense of the reserve pool. Finally, the observation that AP-1 mediated enhancement eliminates tetanus-induced forms of presynaptic potentiation suggests: (i) that reserve-pool mobilization is required for tetanus-induced short-term synaptic plasticity; and (ii) that long-term synaptic plasticity may, in some instances, be accomplished by stable recruitment of mechanisms that normally underlie short-term synaptic change.     

Oxaliplatin pharmacokinetics and pharmacodynamics in adult cancer patients with impaired renal function.

PURPOSE: To characterize the pharmacokinetics and pharmacodynamics of oxaliplatin in cancer patients with impaired renal function. EXPERIMENTAL DESIGN: Thirty-four patients were stratified by 24-h urinary creatinine clearance (CrCL) into four renal dysfunction groups: group A (control, CrCL, >or=60 mL/min), B (mild, CrCL, 40-59 mL/min), C (moderate, CrCL, 20-39 mL/min), and D (severe, CrCL, <20 mL/min). Patients were treated with 60 to 130 mg/m2 oxaliplatin infused over 2 h every 3 weeks. Pharmacokinetic monitoring of platinum in plasma, plasma ultrafiltrates, and urine was done during cycles 1 and 2. RESULTS: Plasma ultrafiltrate platinum clearance strongly correlated with CrCL (r2 = 0.712). Platinum elimination from plasma was triphasic, and maximal platinum concentrations (Cmax) were consistent across all renal impairment groups. However, only the beta-half-life was significantly prolonged by renal impairment, with values of 14.0 +/- 4.3, 20.3 +/- 17.7, 29.2 +/- 29.6, and 68.1 h in groups A, B, C, and D, respectively (P = 0.002). At a dose level of 130 mg/m2, the area under the concentration time curve increased in with the degree of renal impairment, with values of 16.4 +/- 5.03, 39.7 +/- 11.5, and 44.6 +/- 14.6 mug.h/mL, in groups A, B, and C, respectively. However, there was no increase in pharmacodynamic drug-related toxicities. Estimated CrCL using the Cockcroft-Gault method approximated the measured 24-h urinary CrCL (mean prediction error, -5.0 mL/min). CONCLUSIONS: Oxaliplatin pharmacokinetics are altered in patients with renal impairment, but a corresponding increase in oxaliplatin-related toxicities is not observed.     

Work-related upper extremity musculoskeletal disorders

Upper extremity musculoskeletal disorders such as DeQuervain's tendonitis, carpal tunnel syndrome, and rotator cuff tendonitis have become increasingly common among working people in the United States. Extensive epidemiological investigation indicates that the adverse ergonomic exposures of force, repetition, vibration and certain postures are risk factors for development of many of these disorders. Assessment of patients with possible work-related upper limb disorders requires eliciting information about the illness, performing an examination about the illness, and obtaining information about adverse ergonomic exposures on and off from work. Treatment can only be successful when exposure to adverse ergonomic risk factors is reduced or eliminated.     

Health-related quality of life in patients 7 months after a myocardial infarction: factors affecting the Short Form-12

We assessed patients' health-related quality of life after myocardial infarction and identified related variables. Clinical data were obtained retrospectively from medical records of consecutive patients admitted to a Midwestern university-affiliated medical center with diagnosis of myocardial infarction from July 1999-July 2000. Telephone interviews 7 months after discharge were made to administer the Short Form-12 (SF-12) and obtain patient, disease, drug, and intervention data. Complete information was obtained from 200 patients (mean age 63.4 +/- 13.1 yrs, 68% men). The mean Physical Component Summary (PCS)-12 score was 40.6 +/- 12.0, and the mean Mental Component Summary (MCS)-12 score was 52.1 +/- 10.0. Based on univariate analyses, low PCS-12 scores were associated with women; non-Q-wave infarctions; greater number of illnesses; history of myocardial infarction, chronic heart failure (CHF), transient ischemic attack (TIA), renal disease, peripheral vascular disease, or percutaneous coronary intervention (PCI); rehospitalization during the interim period; and unscheduled PCI since index myocardial infarction. Low MCS-12 scores were associated with age below 65 years, low overall self-reported drug therapy compliance, low self-reported compliance with angiotensin-converting enzyme inhibitor and lipid-lowering therapy, no history of coronary artery bypass graft, and no stress test since index myocardial infarction. A multivariate regression model for PCS-12 kept the following variables: greater number of illnesses, history of CHF or TIA, and rehospitalization since index myocardial infarction. The MCS-12 model contained age below 65 years, low overall compliance, and low compliance with lipid-lowering therapy. Further work is necessary to determine noncardiovascular predictors of quality of life and whether interventions for these patients will result in improved quality of life.     

Stability indicating LC method for the estimation of venlafaxine in pharmaceutical formulations

A rapid, selective and stability indicating high performance liquid chromatographic method was developed and validated for the estimation of venlafaxine in pharmaceutical dosage forms. The analysis was done on a Spherisorb C8 (4.6×250 mm, 5 μm) column. The mobile phase consisted of acetonitrile:sodium dihydrogen orthophosphate [0.04 M], pH 6.8 (75:25) at a flow rate of 1.5 ml/min. Detection was carried out at a wavelength of 224 nm. The developed method was found to give good separation between the pure drug and the degraded product. The polynomial regression data for the calibration plots showed good linear relationship in the concentration range of 1–10 μg/ml with r=0.9999. The method was validated for precision, accuracy, ruggedness and recovery. The minimum detectable and minimum quantifiable amounts were found to be 150 and 600 ng/ml, respectively. The drug was stable under basic and oxidative conditions. However, the sample treated with acid showed an additional peak at a retention time of 4.32 min other than the main peak at a retention time of 5.32 min. Statistical analysis proves that the method is reproducible and selective for the estimation of venlafaxine. As the method could effectively separate the drug from the degradation product, it can be employed as a stability indicating one.     

Steroidogenic alterations in testes and sera of rats exposed to formulated Fenvalerate by inhalation

Fenvalerate (Fen) is a synthetic pyrethroid, which is commonly used for destroying a variety of insect pests damaging several vegetable, fruit, and cotton crops. This insecticide is also used to mitigate household insects like flies, cockroaches, mosquitoes, and so forth. Human beings are exposed to formulated Fen preparations mostly by inhalation during spraying in fields for crop protection, for control of household insects, and also during handling and packaging at manufacturing plants. Limited online information is available regarding toxic effects of formulated Fen exposure on mammalian reproductive system. The present study has been undertaken to investigate male reproductive toxic effects of a formulated preparation of Fen (20% EC) particularly in relation to steroidogenic alterations in testes and sera of rats exposed by nose-only inhalation for (4 hours/day and five days a week) for three months. The results indicate significant reduction in the weight of testes, epididymal sperm counts, and sperm motility, along with decrease in marker testicular enzymes for testosterone biosynthesis viz. 17-beta-hydroxy steroid dehydrogenase (17-beta-HSD) and glucose-6-phosphate dehydrogenase (G6PDH), leading to net decrease in serum testosterone concentration in group of rats exposed to one-fifth LC50 of Fen (20% EC) by inhalation (4 hours/day, five days a week) subchronically for three months. These results for the first time indicate the role of testosterone in Fen (20% EC)-induced male reproductive toxicity of rats subchronically exposed by inhalation probably due to neuroendocrine-mediated phenomenon and hormone-disrupting property of the insecticide.