Human papillomavirus as an etiological factor in cervical cancer: significance for health care practice

The migration of substances from rubber packaging materials into drug products can be significant with certain packaging materials in contact with organic solvent systems. Recommendations for testing drug products for leachables are continually evolving to address new developments. Testing packaging materials using simulated solvents is not always an acceptable protocol for the pharmaceutical industry. We describe a rational strategy for evaluation of the drug product for packaging extractables. A profile of the extractables from rubber packaging materials was made with a range of organic solvents and stress conditions to provide information on substances to target in the drug product. The drug product was evaluated to determine if the matrix would cause interferences that might inhibit detection of the found extractables. Analytical methods were selected based on these findings. The procedures were validated according to FDA guidelines. A stability program using time and storage conditions as variables provided information for acceptance criteria. This same strategy can be used on other types of pharmaceuticals and packaging materials.     

Influence of an oligodendroglial component on the survival of patients with anaplastic astrocytomas: a report of Radiation Therapy Oncology Group 83-02

PURPOSE: Seven percent of patients with high grade gliomas enrolled in RTOG 83-02 had mixed astrocytoma/oligodenroglial elements on central pathology review. It has often been assumed that the most aggressive histologic component of a tumor determines biologic behavior; however in this trial, the survival of patients who had mixed glioblastomas/oligodenrogliomas was significantly longer than that of patients with pure glioblastomas (GBM). We therefore evaluated the effect of an oligodendroglial component on the survival of patients who had anaplastic astrocytomas (AAF) treated in the same trial. METHODS AND MATERIALS: One hundred nine patients who had AAF and 24 patients with mixed AAF/oligodendrogliomas (AAF/OL) were enrolled in a Phase I/II trial of randomized dose-escalation hyperfractioned radiotherapy plus BCNU. AAF/OL patients were older and more likely to have had more aggressive surgery than AAF patients. Other pretreatment characteristics were balanced between groups, as was assigned treatment. RESULTS: The median survival time for AAF was 3.0 years versus 7.3 years for AAF/OL (p = 0.019). In a multivariate analysis, adjusting for extent of surgical resection and age, an oligodendroglial component was an independent prognostic factor for survival. CONCLUSION: The results support the concept that AAFs with an oligodendroglial component have a better prognosis than pure AAF tumors, similar to the effect seen among patients with glioblastoma multiforme tumors. This better survival outcome should be taken into consideration in the design and stratification of future trials. Additionally, in contrast to patients with GBMs, patients who have AAF/OL have the potential for prolonged survival; therefore, late sequelae of treatment (both radiation and chemotherapy) must be weighed more heavily in the benefits to risks analysis.     

Pharmacological relaxation of the saphenous vein during harvesting for coronary artery bypass grafting

Spasm of the saphenous vein frequently occurs during harvesting from the leg and high-pressure distension is required to restore an adequate diameter for grafting. Forceful distention has been shown to damage the intima and media and may predispose to subsequent occlusion of the vein graft. Various pharmacologic vasodilators are capable of relaxing veins; in this study, we carried out a systematic investigation to determine the appropriate agents and concentrations for use during vein graft operations. In organ baths, human saphenous vein segments were contracted with potassium or a thromboxane mimetic, and vasodilator agents were then applied. Glyceryl trinitrate, 7.2 micrograms/mL, or papaverine hydrochloride, 11.9 micrograms/mL, caused 80% to 100% relaxation of contraction induced by potassium or thromboxane. Verapamil, 15.5 micrograms/mL, relaxed the potassium contraction by 100% and the thromboxane contraction by 75%. Comparison of the time course of action showed that glyceryl trinitrate had a rapid onset and a short duration of maximal action, whereas verapamil (like papaverine) had delayed onset and a long duration. A mixture of glyceryl trinitrate and verapamil combined rapid onset with long duration of action. We now use a mixture of glyceryl trinitrate and verapamil (pH 7.4) topically and intraluminally during harvesting of the saphenous vein to provide a relaxed conduit for coronary artery bypass grafting.     

Physiological responses to maximal treadmill and handweighted exercise

The purpose of this investigation was to compare the peak physiological responses among four protocols that employed different amounts of handweighted exercise in 16 males (aged 26.3 +/- 4.1 years). The four protocols were (a) uphill treadmill running (UR; 3.36 m.s-1, 2.5% grade increase-3 min-1); (b) uphill treadmill walking while pumping 1.36-kg handweights (HW) (UWHW; 1.79 m.s-1, 5.0% grade increase x 3 min-1; (c) treadmill walking while pumping .91-kg HW (WHW; 1.79 m.s-1, 0% grade, .91-kg HW increase x 3 min-1); and (d) standing in place and pumping HW (SHW; arm work as described in WHW). It was hypothesized that the peak responses would be inversely proportional to the estimated muscle mass activated (i.e., UR = UWHW > WHW > SHW). Dependent variables included peak oxygen uptake (VO2 peak), peak heart rate (HRpeak), peak ventilation (Ve peak), and peak respiratory exchange ratio (RERpeak). No differences were noted between UR and UWHW with respect to any of the dependent variables. All variables (except RERpeak) were greater (p < .01) in UR and UWHW than either WHW or SHW. RERpeak was greater (p < .01) in UR and UWHW than in WHW. VO2 peak and HRpeak were greater (p < .01) in WHW when compared to SHW. Mean VO2 peak was 97.5, 69.7, and 60% of UR for UWHW, WHW, and SHW, respectively. Therefore, walking and pumping handweights provides a maximal stimulus to the oxygen transport system.     

Increased dietary oxalate does not increase urinary calcium oxalate saturation in hypercalciuric rats

BACKGROUND: Human calcium oxalate (CaOx) nephrolithiasis may occur if urine is supersaturated with respect to the solid-phase CaOx. In these patients, dietary oxalate is often restricted to reduce its absorption and subsequent excretion in an effort to lower supersaturation and to decrease stone formation. However, dietary oxalate also binds intestinal calcium which lowers calcium absorption and excretion. The effect of increasing dietary oxalate on urinary CaOx supersaturation is difficult to predict. METHODS: To determine the effect of dietary oxalate intake on urinary supersaturation with respect to CaOx and brushite (CaHPO4), we fed 36th and 37th generation genetic hypercalciuric rats a normal Ca diet (1.2% Ca) alone or with sodium oxalate added at 0.5%, 1.0%, or 2.0% for a total of 18 weeks. We measured urinary ion excretion and calculated supersaturation with respect to the CaOx and CaHPO4 solid phases and determined the type of stones formed. RESULTS: Increasing dietary oxalate from 0% to 2.0% significantly increased urinary oxalate and decreased urinary calcium excretion, the latter presumably due to increased dietary oxalate-binding intestinal calcium. Increasing dietary oxalate from 0% to 2.0% decreased CaOx supersaturation due to the decrease in urinary calcium offsetting the increase in urinary oxalate and the decreased CaHPO4 supersaturation. Each rat in each group formed stones. Scanning electron microscopy revealed discrete stones and not nephrocalcinosis. X-ray and electron diffraction and x-ray microanalysis revealed that the stones were composed of calcium and phosphate; there were no CaOx stones. CONCLUSION: Thus, increasing dietary oxalate led to a decrease in CaOx and CaHPO4 supersaturation and did not alter the universal stone formation found in these rats, nor the type of stones formed. These results suggest the necessity for human studies aimed at determining the role, if any, of limiting oxalate intake to prevent recurrence of CaOx nephrolithiasis.