Effects of probucol on renal function in rats with bilateral ureteral obstruction

To ascertain the potential role of reactive oxygen metabolites in the pathophysiology of obstructive uropathy, we examined the effect of probucol, an antioxidant agent, on renal function in normal rats and rats with unilateral release of bilateral ureteral obstruction (BUO) of 24 hours duration. Rats were fed either a standard diet or a standard diet containing one percent probucol for two weeks prior to study. Probucol lowered serum cholesterol in both normal and BUO rats. Probucol did not significantly affect renal function in normal rats. BUO rats given probucol had greater inulin and PAH clearances at three to five hours and three days following release of BUO than rats with BUO not given probucol. Kidneys from obstructed rats had higher levels of malondialdehyde, an index of lipid peroxidation, a greater number of leukocytes in the cortex, decreased levels of reduced glutathione and increased levels of oxidized glutathione. Renal cortex from obstructed rats treated with probucol had significantly higher levels of reduced glutathione than kidneys of obstructed rats not given probucol. A decrease in cholesterol, using another lipid-lowering agent, lovastatin, did not modify renal function in rats with BUO. The data can be interpreted to indicate a role for reactive oxygen species in the pathophysiology of obstructive nephropathy. The improved renal function seen in probucol-treated rats with BUO may be due to an effect of this agent in affecting accumulation of reactive oxygen metabolites and/or decreasing the number of leukocytes infiltrating the renal cortex.     

Effects of risk-associated human dietary macrocomponents on processes related to carcinogenesis in human-flora-associated (HFA) rats

Dietary fat, beef protein and fibre have been shown to modulatecancer risk in humans and the present study examined the biologicaleffects in human-flora-associated (HFA) rats of altering intakelevels within the normal human range. Two control groups, oneHFA and the other germfree (GF), consumed a human diet low infat, fibre and beef for 4 weeks; three other groups consumedhuman diets similar except for independent 3-fold increasesin fat, beef protein or fibre. After 2 weeks on the diets, magneticallyrecoverable microcapsules were given orally to the rats andsubsequently recovered from the faeces to assess endogenouscross-linking agents. After 4 weeks, measurements were madeof gut microfloral enzyme activities, hepatic activation ofdietary mutagens and hepatic DNA adducts by ³²P-postlabelling.Activation in vitro of the dietary mutagens 2-amino-3-methyl-3H-imidazo[4,5-f]quinolline (IQ) and 2-amino-l-methyl-6- phenytimidazo[4,5-b]pyridine(PhIP) by hepatic S9, formation of endogenous hepatic DNA adductsin vivo and the ß-glucuronidase activity of caecalcontents were all increased in the sequence high fat > highfibre > high beef = control. Of the two DNA adducts foundin all HFA rats, only one was present in GF controls, indicatingthat the human gut microflora (subject to human dietary modulation)either releases a DNA-adducting product able to act outsidethe gastrointestinal tract, or stimulates the generation ofsuch a product by mammalian processes. Caecal nitrate reductaseactivity was highest in rats fed the high beef diet, whilstentrapment of cross-linking agents was highest in those fedthe high fibre diet. These results show that risk-related componentsof human diets interact with human gut microflora to modulatethe production of endogenous DNA-adducting and cross-linkingsubstances.     

Effect of dietary fat content on the bioavailability of a sustained release quinidine gluconate tablet

Quinidine gluconate 324 mg sustained release tablets (Quinaglute) was administered as a single dose to 15 healthy male subjects following an overnight fast, immediately following a high fat (HF) breakfast or immediately following a low fat (LF) breakfast. Serum samples were obtained over a 48 h period and analyzed for quinidine content using a high performance liquid chromatographic assay. Under the conditions of the study, both the rate and extent of quinidine bioavailability was significantly affected by food. The extent of bioavailability was statistically significantly greater (p less than 0.05) following both the HF and LF meals as compared to that in the fasted state. Rate of bioavailability was significantly enhanced following the LF meal as compared to that of the other two treatment groups. Although peak concentrations were greater and time to peak concentrations somewhat later following the HF meal versus those under fasting conditions, these differences were not statistically significant. In addition, the characteristics of the serum concentration-time profile (as defined by the number, magnitude, and time of occurrence of the multiple absorption maxima) was unique for each of the three treatment groups. Possible mechanisms underlying these results are explored.     

Hypothalamic-hypophyseal-testicular abnormalities and erectile dysfunction

Forty-five men presenting with erectile dysfunction were evaluated through history and nocturnal penile tumescence, Doppler, and EMG studies. Fifteen were classified as having organic and 30 as having psychogenic impotence. Three men had mild hypergonadotropism with low testosterone levels. One had hyperprolactinemia. No case of hypogonadotropic hypogonadism was detected. Six patients who had psychogenic impotence had low levels of testosterone.     

Prevention of laryngeal stenosis in Co2 laser management of recurrent respiratory papillomatosis

Laryngeal stenosis is one of the common complications in the management of recurrent respiratory papillomatosis. The authors have compared the results with regard to development of laryngeal stenosis, when surgical treatment was given with CO₂ laser alone in the early 34 cases plus 7 advanced cases, while in the remaining 13 advanced cases the CO₂ laser ablation was combined with the conventional cup forceps removal. Age, extent of disease, duration of the procedure and interval between two procedures were also noted. The incidence of laryngeal stenosis was found to be reduced in advanced cases when CO₂ laser was combined with the conventional cup forceps removal.     

A human immunodeficiency virus-resistant airway for cardiopulmonary resuscitation.

Due to fear of transmitted disease, mouth-to-mouth cardiopulmonary resuscitation (CPR) is now rare, even though early CPR is associated with a fivefold to 30-fold increase in survival. The authors have devised a one-piece silicone mask (Kiss of Life [KOL], Brunswick Biomedical Technologies, Inc, Warehom, MA) with a one-way valve and circular recess to form a no-contact lip seal, enabling mouth-to-mouth CPR to be given. The ventilatory volume during mannequin CPR using the KOL mask was 0.75 +/- 0.235 L. This volume was significantly (P less than .05) greater than that generated by alternate widely used airways (range, 0.195 +/- 0.147 to 0.617 +/- 0.208 L). To assess mask performance in vivo, the authors measured exhaled volumes in 10 apneic anesthetized patients under three conditions: with the KOL mask, a standard anesthetic mask and bag, and an anesthetic mask with an endotracheal tube. The results were: anesthetic mask and tube, 1.5 L (range, 1.2 to 1.7 L); KOL mask, 1.1 L (range, 1.0 to 1.3 L); anesthetic mask alone, 0.7 L (range, 0.5 to 0.8 L). To test permeability, we exposed two KOL masks to a high titer of human immunodeficiency virus (HIV)-1 soup (10(6) culture infection doses/mL) for 10 and eight masks for 60 minutes, respectively, and cultured swabs of the interior of the valve for 1 month. There was no growth in any culture. These data suggest that the KOL mask has excellent ventilating characteristics, is practical (pocket-portable, disposable), experimentally impermeable to HIV-1, and inexpensive.(ABSTRACT TRUNCATED AT 250 WORDS)     

Capsazepine: a competitive antagonist of the sensory neurone excitant capsaicin.

1. Capsazepine is a synthetic analogue of the sensory neurone excitotoxin, capsaicin. The present study shows the capsazepine acts as a competitive antagonist of capsaicin. 2. Capsazepine (10 microM) reversibly reduced or abolished the current response to capsaicin (500 nM) of voltage-clamped dorsal root ganglion (DRG) neurones from rats. In contrast, the responses to 50 microM gamma-aminobutyric acid (GABA) and 5 microM adenosine 5'-triphosphate (ATP) were unaffected. 3. The effects of capsazepine were examined quantitatively with radioactive ion flux experiments. Capsazepine inhibited the capsaicin (500 nM)-induced 45Ca2+ uptake in cultures of rat DRG neurones with an IC50 of 420 +/- 46 nM (mean +/- s.e.mean, n = 6). The 45Ca2+ uptake evoked by resiniferatoxin (RTX), a potent capsaicin-like agonist was also inhibited. (Log concentration)-effect curves for RTX (0.3 nM-1 microM) were shifted in a competitive manner by capsazepine. The Schild plot of the data had a slope of 1.08 +/- 0.15 (s.e.) and gave an apparent Kd estimate for capsazepine of 220 nM (95% confidence limits, 57-400 nM). 4. Capsazepine also inhibited the capsaicin- and RTX-evoked efflux of 86Rb+ from cultured DRG neurones. The inhibition appeared to be competitive and Schild plots yielded apparent Kd estimates of 148 nM (95% confidence limits, 30-332 nM) with capsaicin as the agonist and 107 nM (95% confidence limits, 49-162 nM) with RTX as agonist. 5. A similar competitive inhibition by capsazepine was seen for capsaicin-induced [14C]-guanidinium efflux from segments of adult rat vagus nerves (apparent Kd = 690 nM; 95% confidence limits, 63 nM-1.45 microM).(ABSTRACT TRUNCATED AT 250 WORDS)     

Cervical Anterior Spinal Cord Infarction

Spinal cord infarction or ischemia predominates in the thoracic region, less so in the cervical and lumbar regions. Different etiological factors have been implicated in anterior spinal artery syndrome. Magnetic resonance imaging (MRI) allows in vivo imaging of spinal cord disease, including infarction. A 31-yearold, previously healthy man had an acute onset of interscapular pain, followed by rapid development of quadriparesis associated with paresthesias and mild bladder dysfunction. Initial MRI of the cervicothoracic region demonstrated normal findings. A repeat study obtained 6 days later showed marked increase in the cervical cord size, especially at the C6-7 level. On the T2-weighted sagittal series and after gadolinium injection, increased signal in the anterior portions of the cord extending from C-4 to the T2-3 interspace was noted. This was most prominent at the C-6 and C-7 levels. The coronal views revealed abnormal high signal in the region of the anterior horns of the gray matter, a finding that is recognized as an “owl's eyes” pattern. Because the MRI changes of cerebral infarction may succeed a clinical event by hours or days, accurate diagnosis may require delayed or repeated studies. This report suggests that the diagnosis of spinal cord disease requires a similar evaluation.     

Three balanced anesthetic techniques for neuroanesthesia: infusion of thiopental sodium with sufentanil or fentanyl compared with inhalation of isoflurane.

STUDY OBJECTIVE: To compare emergence from anesthesia and the hemodynamic and respiratory depressant effects of thiopental sodium infusion plus sufentanil or fentanyl with those of isoflurane as the primary component of a balanced technique for neuroanesthesia. DESIGN: Randomized, double-blind, prospective study. SETTING: University hospital and its affiliated Veterans Affairs Medical Center. PATIENTS: Thirty patients undergoing elective craniotomy for aneurysm or tumor. INTERVENTIONS: Thiopental with infusion of sufentanil 0.1 microgram/kg/hr, thiopental with infusion of fentanyl 1 microgram/kg/hr, or inhalation of 0.25% to 2% isoflurane as the major component of a balanced anesthesia technique that included nitrous oxide (N2O) and vecuronium (potency ratio of sufentanil to fentanyl, 10:1). MEASUREMENTS AND MAIN RESULTS: Intraoperative stress response (as indicated by intraoperative hypertension) was said to be the percentage of time the patient required administration of an antihypertensive drug, measuring from the first dose of thiopental to discontinuation of N2O at the end of the procedure, excluding any period of induced hypotension. Rapidity of emergence was measured by the number of minutes from discontinuation of N2O to first opening of the eyes on command. Adequacy of spontaneous ventilation was evaluated by determining partial pressure of arterial carbon dioxide 1, 2, and 3 hours after discontinuation of N2O. Extent of vasoactive drug administration for control of intraoperative hypertension (as determined by the clinicians caring for the patients) was described by minutes of vasodilator infusion and milligrams of propranolol or labetalol administered. The frequency of postoperative hypertension was defined as the number of patients in each group who required medication for postoperative hypertension. No significant differences in variables were found for thiopental/sufentanil, thiopental/fentanyl, or isoflurane when these drugs were used with N2O and vecuronium. CONCLUSIONS: Any one of these balanced anesthetic techniques appears appropriate for craniotomy.