Further experience with radiation therapy and concomitant intravenous chemotherapy in advanced carcinoma of the lower female genital tract

Sixty-seven patients with advanced carcinoma of the lower female genital tract (cervix, vagina, and vulva) were treated with radiation and concomitant intravenous cisplatin and/or 5-fluorouracil. Fifty-seven patients (85%) responded completely clinically. Thirty-five (61%) complete responders recurred with a median time to recurrence of 6 months. Twenty-six of the thirty-five patients who recurred had some component of local failure. The 22 complete responders who have not recurred have been followed a median of 13 months. Acute toxicity was minimal, with only 6 patients requiring interruption of therapy. Nine (13%) patients developed severe late complications and eight required surgery. The actuarial 5-year survival is 22%. This treatment regimen is disappointing in terms of both survival and local control.     

High school football injuries: field conditions and other factors

This study was conducted to identify factors that were associated with injuries during 59 varsity high school football games in 1987. For each injury, medical personnel recorded data on the type and body location of each injury, player position, specific player activity at the time of injury, the quarter of the game, the week of the season, playing field conditions, and ambient air temperature. We found injury frequencies, types, body locations and seasonal and game quarter distributions similar to previous reports. This study demonstrated a previously unreported association between playing field condition and injury rate.     

3-Hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors. 3. 7-(3,5-Disubstituted [1,1'-biphenyl]-2-yl)-3,5-dihydroxy-6-heptenoic acids and their lactone derivatives

The syntheses of a series of 7-(3,5-disubstituted [1,1'-bephenyl]-2-yl)-3,5-dihydroxy-6-heptenoic acids and their lactones are reported. Intrinsic 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitory activity is enhanced markedly when the biphenyl moiety is substituted by chloro or methyl groups at positions 3 and 5 and a fluoro group at position 4'. These substitutions, followed by resolution, provided compounds 100(+) and 110(+) with 2.8 times the intrinsic inhibitory activity of compactin. Compound 100(+) was shown to possess the same chirality in the lactone ring as compactin by single-crystal X-ray crystallography.     

Comparison of three intracellular markers for combined electrophysiological, morphological and immunohistochemical analyses.

Hypothalamic paraventricular and supraoptic neurons were recorded intracellularly in coronal slices and injected with Lucifer yellow, ethidium bromide or biocytin. Electrical properties, morphological staining and neurophysin immunohistochemistry were compared among the 3 markers. Lucifer yellow electrodes had a high resistance and frequently blocked during experiments. Neurons recorded with Lucifer yellow electrodes had low input resistances and low-amplitude, broad spikes. Lucifer yellow labeling in whole mount was highly fluorescent, revealing distal dendrites and axons. Of cells injected with Lucifer yellow, 64% were recovered but were faint after immunohistochemical processing. Recordings with ethidium bromide electrodes were similar to controls, although electrode blockage sometimes occurred. Only somata and proximal dendrites of ethidium bromide-filled neurons were visible in whole-mount. Forty percent of cells injected with ethidium bromide were recovered after immunohistochemical processing; these were invariably faint. Recordings with biocytin-filled electrodes were similar to control recordings. Biocytin-filled, HRP-labeled cells showed distal dendrites and often dendritic spines and axons in 50-75-microns sections. Seventy percent of biocytin-injected cells labeled with fluorescent markers were recovered and remained strongly labeled after immunohistochemical processing. Biocytin had the best electrical and staining properties for combined electrophysiological and anatomical studies.     

Brain tissue oxygenation in patients with cerebral occlusive disease and arteriovenous malformations

It is not clear if ventilation with oxygen increases brain tissue oxygen pressure (PO2) during ischaemia. We have measured brain tissue PO2, carbon dioxide pressure (PCO2) and pH during baseline anaesthesia and oxygen ventilation in non-ischaemic control patients (n = 9), patients with cerebral occlusive disease (n = 11) and patients with arteriovenous malformations (AVM, n = 12). The same anaesthetic treatment was given to all groups and anaesthesia was constant during the study. Arterial pressure, brain temperature and arterial blood-gas tensions were similar between groups. Under baseline conditions, brain tissue PO2 was mean 4.2 (SD 1.4) kPa in the controls and was 70% lower in patients with ischaemia and AVM. Patients with occlusive disease also had elevated tissue PCO2 and acidosis. During oxygen ventilation, PO2 increased to 7.5 (2.9) kPa in controls and this was 50% greater than the increase in the ischaemia and AVM patients. The results showed that baseline tissue oxygenation and increases in PO2 during hyperoxia were attenuated in patients with ischaemia or AVM.      

Kinetics of drug action in disease states. XXIX. Effect of experimental nephrotic syndrome on the pharmacodynamics of heptabarbital: implications of severe hypoalbuminemia

The purpose of this investigation was to determine the effect of nephrotic syndrome (NS) on the pharmacodynamics of a barbiturate. NS was induced in male rats by puromycin aminonucleoside; it caused hypoproteinemia, increased liver and kidney weight and elevated serum creatinine and urea nitrogen concentrations. Serum albumin concentration decreased from 3.5% in controls to 0.90% in NS animals. The rats were infused i.v. with heptabarbital, 1 mg/min, until they lost their righting reflex. The total dose (mean +/- S.D.) required by rats with NS, 40.2 +/- 4.2 mg/kg, was substantially lower than that required by normal animals (68.6 +/- 6.2 mg/kg, P less than .001). Serum protein binding of heptabarbital was reduced from 49% in controls to 26% in NS rats. However, the drug concentration in cerebrospinal fluid (CSF) at the pharmacologic endpoint was not significantly different in controls and NS rats (18.9 +/- 1.5 vs. 18.3 +/- 1.4 mg/l). Serum, CSF and the brain contained appreciable concentrations of a metabolite of heptabarbital. To determine if the metabolite contributes to the pharmacologic effect of the parent drug, rats received an i.v. injection of 46, 60 or 100 mg/kg of heptabarbital. Concentrations of heptabarbital in CSF at return of righting reflex (which occurred after 15, 25 and 50 min, respectively) were independent of dose whereas metabolite concentrations increased with increasing dose. Thus, the metabolite of heptabarbital in male rats is pharmacologically inactive.(ABSTRACT TRUNCATED AT 250 WORDS)