Protection of CGS 10078B against ouabain-induced arrhythmia in the cat

CGS 10078B (CGS; 1-[2,3-dihydro-1,4-(2S)-benzodioxin-2-yl]-5-[2,3-dihydro-1,4-(2R)- benzodioxin-2-yl]-3-(1R,5S)-aza-1,5-pentanediol methane sulfonate) is an agent with alpha- and beta-receptor and calcium channel blocking actions. To study its antiarrhythmic activity, cats were anesthetized with alpha-chloralose, ventilated, and given atropine and gallamine. CGS (10 or 20 mg/kg, i.v.) was infused 15 min prior to ouabain. Bolus injections of ouabain (25 micrograms/kg, i.v.) were given every 15 min until death (D). Some cats were pretreated with reserpine (R; 5 mg/kg, i.p.) 24 h prior to the experiment. In other cats 6-hydroxydopamine (6-OHDA; 20 mg/kg, i.v.) was administered 3 days prior to CGS 20 mg/kg and ouabain. Data were compared with those of Lathers [Eur. J. Pharmacol. 64: 95, 1980], i.e., with 12 cats who received only ouabain and with 11 pretreated with timolol (T; 5 mg/kg, i.v.) prior to ouabain. After CGS (10 or 20 mg/kg, i.v.), but just prior to the first dose of ouabain, the blood pressure (BP) was decreased (p less than 0.05) from control (165 +/- 6 vs. 96 +/- 7, and 136 +/- 5 vs. 90 +/- 10 mm Hg, respectively). Comparable heart rate (HR) values were also decreased (p less than 0.05) from 225 +/- 17 to 166 +/- 14 and from 193 +/- 8 to 152 +/- 6 beats/min. 11 min after T, BP and HR had decreased (p less than 0.05) from 133 +/- 6 to 103 +/- 7 mm Hg and from 134 +/- 4 to 104 +/- 6 beats/min, respectively. Ouabain did not influence these decreases in BP and HR. CGS (10 or 20 mg/kg, i.v.) increased (p less than 0.05) the time to ouabain-induced arrhythmia (AR) and D. The magnitude of the protection appeared to be similar to that afforded by T. R given prior to CGS (20 mg/kg, i.v.) also increased the time to ouabain-induced AR and D while 6-OHDA increased the time to AR. The CGS protection against ouabain-induced AR was still present in animals pretreated with R or 6-OHDA. This indicates that the antiarrhythmic affect is not dependent upon adrenergic neuronal blockade.     

Imipenem (N-F-thienamycin) versus netilmicin plus clindamycin. A controlled and randomized comparison in intra-abdominal infections

In a randomized study the clinical and bacteriologic effectiveness of imipenem was compared with the classical combination of netilmicin with clindamycin in patients who had surgery for an intraperitoneal infection, localized or generalized, with positive bacteriologic findings of the specimen taken at surgery. Excluded were all patients who received other antibiotics before surgery, or who died within 3 days after antibiotic therapy was started. Imipenem was given at a dose of 500 mg t.i.d., clindamycin 600 mg t.i.d., and netilmicin according to serum levels. The diagnoses ranged from postoperative peritonitis, gallbladder empyema, perforated gastroduodenal ulcer, small bowel perforation with and without obstruction, and perforated appendicitis to perforation of the colon. The bacteriologic work-up included examination of the primary specimen (aerobic and anaerobic), the urine, feces, and serologic testing for Candida albicans once or twice a week and after the course of antibiotic therapy. In addition, pH measurements of abscesses and drainage fluids were performed. Ninety-three patients entered the study. Forty-seven patients were treated with imipenem (test group), and 46 patients were treated with the combination therapy (control group). The two groups did not show significant differences in age, sex, diagnostic groups, risk factors, primary bacteriology, and duration of therapy (mean: 6.7 days). Thirty-eight patients (80.9%) treated with imipenem were cured, six patients (12.8%) were improved, and there were three (6.4%) failures. The respective numbers for the control group were 31 (67.4%), 10 (21.7%), and 5 (10.9%). The mean duration of hospitalization was 19 days for the test group and 24.5 days for the control group. There were four wound infections in the test group and 11 wound infections in the control group. Imipenem is at least as effective in the adjuvant therapy of intra-abdominal infections as the combination of netilmicin with clindamycin.     

Behavior of acid secretion and clinical results following selective proximal vagotomy in uncomplicated duodenal ulcer

Reported in this paper are postoperative results recorded from 120 patients, 3 years after selective proximal vagotomy for uncomplicated duodenal ulcer. There was no intraoperative lethality and no recurrence in 96.7 per cent of all cases, while Visick grades I on II were recorded from 98.2 per cent. Radiologically and gastroscopically detected pathological processes receded soon. Average postoperative reduction in acid secretion was 66.2 per cent in BAO and 46.8 per cent in MAO. Acid values re-increased thereafter, and three years later reduction rates still amounted to 43.7 per cent in BAO and 28.6 per cent in MAO. Indications for proximal gastric vagotomy are discussed in some detail.     

Acute obstruction by enterolith complicating jejunal diverticulosis. Case report

Two cases are presented in which the cause of small-bowel obstruction was enterolith originating in jejunal diverticula.     

Functional blockage of open comedones

Sebum excretion rate was measured by a photometric technique. We demonstrated a high correlation between sebum excretion rates on the left and right sides of the upper back and between back and forehead skin. Sebum excretion rate measurements overlying an open comedone (blackhead) were significantly lower than those obtained from normal skin. This observation demonstrates a functional obstruction to the outflow of sebum and would suggest that the lack of involvement of open comedones in inflammatory acne is not because of the maintenance of a free flow of sebum.     

A surgically recovered case of spontaneous rupture of the esophagus--the significance of preoperative esophagoscopy for direct suture

A 65-year-old man with spontaneous rupture of the esophagus survived with a direct suture of the esophagus 15 hours after the onset of symptoms. Endoscopic examination of the esophagus was especially of great help in determining the surgical procedure in this patient, and we want to stress the importance of prompt diagnosis and immediate surgery for this disease.     

Comparison of PET, MRI, and CT with pathology in a proven case of Alzheimer's disease

Positron emission tomography (PET) with fluorodeoxyglucose (FDG), magnetic resonance imaging (MRI), and CT were carried out in a patient with Alzheimer's disease 16 months before he died. At autopsy, the gross appearance of the brain correlated with MRI and CT, which showed some regional atrophy. These were much less revealing than PET, which correlated with microscopic findings of neuronal loss and proliferation of glia. In areas of moderately impaired local cerebral metabolic rate of glucose, as revealed by reduced FDG uptake, there was some gliosis, primarily around the numerous senile plaques. In areas of severe metabolic impairment, there was a profound loss of neurons, extensive gliosis, and a diminished appearance of plaques. PET-FDG is a better measure of the severity of Alzheimer's disease than MRI or CT, because it reflects the degree of neuronal pathology.     

gamma-Aminobutyric acid (GABA) causes consistent depolarization of neurons in the guinea pig supraoptic nucleus due to an absence of GABAB recognition sites

The action of gamma-aminobutyric acid (GABA) in the supraoptic nucleus was investigated using guinea pig brain slices. GABA produced a membrane depolarization accompanied by a decrease in the input resistance. The action of GABA was concentration-dependent throughout a wide range of concentrations (10(-7)-10(-3) M). In none of the cells examined, a membrane hyperpolarization was observed. The reversal potential for the depolarization induced by GABA was about 25 mV positive to the resting membrane potential. The amplitude of the GABA-induced depolarization was increased to 1.5 X the control by reducing the external Cl- from 134.2 mM to 10.2 mM. The action of GABA was readily antagonized by relatively low concentrations of bicuculline (10(-5) M). The action of GABA in the hippocampus or in the anterior hypothalamus was markedly different from that in the supraoptic nucleus, i.e. GABA produced both depolarizing and hyperpolarizing responses in the hippocampus and consistently a hyperpolarization in the anterior hypothalamus. The depolarizing but not the hyperpolarizing response in the hippocampus was selectively blocked by picrotoxin (2 X 10(-5) M) or by bicuculline (10(-5) M). The depolarizing component was dependent on the external Cl- concentration and had a reversal potential similar to that of the depolarization induced by GABA in the supraoptic nucleus. The hyperpolarizing component was resistant to bicuculline and had a reversal potential about 30 mV negative to the resting membrane potential.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effects of dexamethasone on central and peripheral ACTH systems in the rat

To investigate the simultaneous effects of dexamethasone on peripheral and central adrenocorticotropic hormone (ACTH) systems, rats were treated with dexamethasone or saline for 4 days. Pituitary, plasma, hypothalamus and cerebrospinal fluid (CSF) were then collected and analyzed for ACTH immunoreactivity. Additionally, hypothalamic tissue extracts were analyzed for corticotropin-releasing hormone (CRH) immunoreactivity. Dexamethasone significantly lowered peripheral levels of ACTH as measured in pituitary and plasma. Hypothalamic ACTH content significantly increased while CSF ACTH significantly decreased with dexamethasone treatment. Hypothalamic CRH concentrations showed a small but statistically insignificant decrease. These results suggest that prolonged exposure to dexamethasone affects central as well as peripheral ACTH activity, corroborate our previous findings in rhesus monkeys of decreased CSF ACTH in response to prolonged dexamethasone treatment, suggest that dexamethasone may inhibit the release of ACTH from hypothalamic neurons into the CSF, and provide evidence that the effect of dexamethasone on pituitary ACTH content is of greater magnitude than its effect on hypothalamic CRH.