Semantic (verbal) and figural memory impairment in alcoholics

In two separate studies, episodic semantic (verbal) and figural-memory abilities as measured by the Wechsler Memory Scale (Russell Method) are compared in middle-aged detoxified male alcoholics and controls. Both studies gave rise to similar findings. Alcoholics recalled significantly less verbal and figural material at both immediate recall and 30-min delayed recall than did the controls. Contrary to expectation, compared to controls, alcoholics did not have a greater differential deficit for the figural material as compared with the verbal or a greater differential deficit on delayed than on immediate memory. The percentage of material recalled at the delayed testing, when taken as a function of the amount of material recalled immediately, did not differ for the two groups on the semantic or figural tasks in either study. Thus, rates of forgetting were equivalent in alcoholics and controls suggesting that the alcoholics' deficit lies in the initial acquisition process. Whether that deficit is in encoding or initial retrieval processes remains to be investigated. Implications for future research are given.     

Adrenergic and purinergic neurotransmission in arterial resistance vessels of the cat intestinal circulation

The contribution of adrenoceptors and purine receptors in mediating neurogenic vasoconstriction was investigated in the autoperfused intestinal circulation of anaesthetised cats treated with atropine and propranolol. Prazosin (0.5 mg/kg) and yohimbine (1.5 mg/kg) reduced but did not abolish the vasoconstrictor responses to stimulation of the efferent sympathetic nerves. The inhibitory actions of the two antagonists were additive but even after alpha 1- and alpha 2-adrenoceptor blockade nerve stimulation still elicited a residual, frequency-related vasoconstriction. The initial, rapid, phase of this response was completely abolished after desensitisation of P2x-purinoceptors with a high dose (1.5 mg i.a.) of alpha,beta-methylene ATP. In the absence of alpha-adrenoceptor antagonists, alpha,beta-methylene ATP reduced neurogenic vasoconstriction particularly at low frequency (1 Hz) nerve stimulation, but also caused a short-lasting decrease in noradrenaline and methoxamine responses which indicates that the drug may have some non-specific effects on arterial smooth muscle. The results suggest that neurotransmission in arterial resistance vessels of the cat intestinal circulation is predominantly under adrenergic control mediated by postsynaptic alpha 1- and alpha 2-adrenoceptors, with a possible purine involvement in the initial rapid response of the blood vessels, particularly to low frequency nerve stimulation.     

Mild renal ischemia activates primed neutrophils to cause acute renal failure.

The role of neutrophils (PMN) in acute renal failure (ARF) is controversial. Although the development of acute renal failure (ARF) frequently occurs in situations where there is partial activation of PMN (primed PMN) and mild renal ischemia, the interaction between primed PMN and ischemic organs has not been studied in any biological system. To define the interaction between primed PMN and mild renal ischemia, kidneys were made ischemic for 10 minutes in situ and reperfused by the isolated kidney technique with untreated PMN or PMN primed with low concentrations of lipopolysaccharide (LPS) or phorbol myristate acetate (PMA). We found that primed PMN had no effect on control (non-ischemic) kidneys and that untreated PMN did not cause injury to kidneys previously subjected to mild ischemia. However, addition of primed PMN to mildly ischemic kidneys caused severe injury. To determine the nature of renal injury, ischemic kidneys were reperfused with primed PMN and catalase (CAT) or the elastase inhibitor, Eglin C. In ischemic kidneys reperfused with LPS-primed PMN, Eglin C (but not CAT) was partially protective while in ischemic kidneys reperfused with PMA-primed PMN, CAT (but not Eglin C) was partially protective. Reperfusion with both CAT and Eglin C completely prevented the damaging effects of either LPS- or PMA-primed PMN. In conclusion, addition of primed but not untreated PMN causes ARF in mildly ischemic kidneys by PMN oxidant- and/or protease-mediated mechanisms. This synergism could account for the high frequency of ARF in conditions associated with prerenal azotemia and primed PMN.     

Class III antiarrhythmic activity of novel substituted 4-[(methylsulfonyl)amino]benzamides and sulfonamides.

The synthesis and Class III antiarrhythmic activity of a series of 4-[(methylsulfonyl)amino]benzamides and sulfonamides are described. Selected compounds show a potent Class III activity and are devoid of effects on conduction both in vitro (dog Purkinje fibers) and in vivo (anesthetized dogs). Compounds having a 2-aminobenzimidazole group were found to be the most potent, and one compound having this heterocycle (5, WAY-123,398) was selected for further characterization. Compound 5 was shown to have good oral bioavailability and a favorable hemodynamic profile to produce a 3-fold increase of the ventricular fibrillation threshold and to terminate ventricular fibrillation, restoring sinus rhythm in anesthetized dogs. Voltage-clamp studies in isolated myocytes show that 5 is a potent and specific blocker of the delayed rectifier potassium current (IK) at concentrations that cause significant prolongation of action potential duration.     

Simple reaction time event-related potentials: Effects of alcohol and diazepam

1. 1. Acute effects of alcohol and diazepam on reaction time (RT) and event-related potential (ERP) measures were examined in 108 healthy male volunteers.

2. 2. The subjects engaged in a simple RT task at two levels of stimulus intensity during baseline and treatment sessions.

3. 3. Lower stimulus intensity produced increased RTs, increased ERP peak latencies, and suppression of peak amplitudes.

4. 4. Moderate and high doses of alcohol, and high doses of diazepam produced increased RTs. Alcohol suppressed P100 and N100 amplitudes, while diazepam suppressed P100 amplitudes only. P100 amplitudes were correlated to RTs under baseline and treatment conditions.

5. 5. These results were taken as evidence for impaired stimulus detection during alcohol and diazepam intoxication, with both drugs influencing sensory-perceptual processes and alcohol alone influencing the degree of attentiveness.

Healthy choices: motivational enhancement therapy for health risk behaviors in HIV-positive youth.

This study piloted a brief individual motivational intervention targeting multiple health risk behaviors in HIV-positive youth aged 16-25. Interviews about sexual behavior and substance use and viral load testing were obtained from 51 HIV-positive youth at baseline and post intervention. Youth were randomized to receive a four-session motivational enhancement intervention (N = 25) or to a wait-list control (N = 26). Of the eligible youth approached, 88% agreed to participate, and 80% percent of participants completed at least three of four sessions. The treatment group showed significantly greater reductions in unprotected sex acts and in viral load compared with controls. Although change scores for substance use were not significantly different between the two groups, paired t tests demonstrated that reductions in alcohol use and marijuana use were significant for the treatment group at the trend level. There were no significant differences in substance use from baseline to posttest for the control group. Findings demonstrate the potential of a brief motivational enhancement intervention to improve health risk behaviors in HIV-positive youth. Larger randomized clinical trials are warranted. Resources required for retention should not be underestimated.     

Mandibular lingual releasing approach.

The mandibular lingual releasing approach to oral cavity and oropharyngeal tumors provides excellent visualization for resection while integrity of the mandibular arch is preserved. A lingual floor-of-mouth flap is created, which allows delivery of these structures directly into the neck without lip splitting, mandibulotomy, or mandibulectomy. The procedure was carried out on 15 patients between 1987 and 1991, with followup ranging from 2 to 50 months. Nine patients had received previous radiation, whereas planned postoperative radiation was administered to five patients. The visualization afforded by this technique was very good, in that 12 patients had clear margins of resection. Three patients had close margins; recurrent disease developed in one of these patients 18 months later. Twelve of the patients were able to maintain their weight with an oral diet alone. Four postoperative fistulae occurred, three of these were in patients who had not been previously irradiated. The single fistula that did not spontaneously heal occurred in a patient who had received previous radiation and was also on long-term corticosteroids. Mandibular osteoradionecrosis developed in two patients who received postoperative radiation. The complication rate after previous radiation is acceptable; however, there is risk of mandibular osteoradionecrosis after high-dose postoperative radiation.