Selective inhibition of excitatory amino acids by divalent cations. A novel means for distinguishing N-methyl-D-aspartic acid-, kainate- and quisqualate-mediated actions in the mouse spinal cord

Biting and scratching behaviors produced by intrathecal injection of excitatory amino acid (EAA) agonists were examined to determine whether the biting and scratching behavioral effects produced by these compounds are altered selectively in vivo by coadministration with divalent cations. N-methyl-D-aspartate (NMDA)-induced behavior was inhibited by both magnesium and calcium but not by zinc. Kainic acid (KA)-induced behavioral activity was also inhibited by coadministration with calcium but not by magnesium or zinc. In contrast to both NMDA and KA, calcium, magnesium and zinc failed to alter the intensity of quisqualic acid (Quis)-induced biting and scratching behaviors. Based on this selective inhibition of the three EAA subtypes by divalent cations, we examined the behavioral responses produced by Glu and Asp in combination with calcium or magnesium to identify the receptor population involved in these motor effects. Calcium antagonized the biting and scratching behavior produced by i.t. injected Glu in contrast with Asp which was inhibited significantly by magnesium. Our results support the concept that Glu and Asp produce biting and scratching behaviors by an interaction with distinct receptor populations in the spinal cord. To date, there are no selective antagonists at the KA or Quis receptors. Thus, a systematic examination of the selective inhibition of EAA activity by divalent cations in addition to currently available pharmacologic antagonists may prove to be a useful approach to the identification of NMDA, KA and Quis receptor interactions.     

Tetanus: an uncommon cause of dysphagia

A 53-year-old woman was examined at our medical center because of progressive dysphagia of 14 days' duration and a severe inability to open her mouth and swallow saliva. A barium esophagogram showed no obstruction, but pooling of barium in the hypopharynx suggested a neuromuscular disorder. The clinical diagnosis of tetanus was confirmed by electromyography. With appropriate therapy, the patient recovered during a period of 6 weeks. This case illustrates both an uncommon cause of dysphagia and an uncommon initial manifestation of tetanus.     

On the relation of PAG neurons to laryngeal and respiratory muscles during vocalization in the monkey

Despite evidence from previous unit recording, microstimulation, lesioning and anatomical studies, the functions of the midbrain periaqueductal gray (PAG) remain unclear. We attempted to clarify the function of the PAG by recording activity of PAG units along with laryngeal and respiratory electromyograms (EMG) during vocalization in awake monkeys. PAG units were classified with respect to vocalization on the basis of their discharge patterns as 'early burst', 'late burst', 'tonic-increase' and 'tonic-off', with the vast majority being of the early- and late-burst type. Early-burst cells were correlated most frequently with inspiratory muscles of the respiratory system and laryngeal abductor muscles. Late-burst cells were most clearly correlated with laryngeal adductor and expiratory respiratory muscles. Data from spike-triggered averaging and parametric correlations indicate that most cells are related to single muscles, but a significant number were related to functionally related groups of two or more muscles. The results suggest that the PAG determines qualitative aspects of vocalization by the multisynaptic action its cells have on laryngeal and respiratory motoneurons.     

Travel distance, age, and sex as factors in follow-up visit compliance in the post-gastric bypass population

BACKGROUND: There is no consensus regarding the optimal rate of follow-up in the post-bariatric surgery patient population. METHODS: The records of all patients who underwent laparoscopic Roux-en-Y gastric bypass from 2001 to 2003 were reviewed. Using patient zip codes, travel distances were calculated between the patients' places of residence and our clinic. Patients were then assigned to 1 of 3 cohorts according to the following distances: (1) < 50 miles, (2) 50 to 100 miles, and (3) > 100 miles. Patient compliance with follow-up appointments at 3 weeks, 3 months, 6 months, 9 months, and 12 months was analyzed. Linear trends were identified using the Mantel-Haenszel test. Age and sex were analyzed as possible predictors of compliance using the chi(2) test. P values < .05 were considered statistically significant. RESULTS: The study group comprised 150 patients (127 females and 23 males). The 3 cohorts contained 115, 21, and 14 patients, respectively. All patients in each cohort were compliant with the 3-week follow-up appointment. Although there were differences in compliance between cohorts at each of the remaining appointments, only the 9-month (70.3% vs 61.9% vs 35.7%) visit showed statistical significance (P = .035). The 6-month visit trended toward significance (85.2% vs 76.2% vs 64.3%; P = .088). Males were more likely to be compliant with the 12-month follow-up (P = .040). When controlling for sex, travel distance was also a predictor of compliance at this follow-up visit (P = .024). Age was not predictive of compliance (P = .827). CONCLUSION: Based on our findings, we conclude that travel distance from the clinic does not significantly affect compliance at the initial follow-up, 3-month, and 12-month appointments. However, distance does tend to affect compliance at the 6-month appointment and significantly affects compliance at the 9-month appointment. Males are more likely to be compliant at the 12 month follow-up visit. We must continue to strive for 100% follow-up in our post-bariatric surgery patients.     

Distribution and disposition of trospectomycin sulfate in the in vivo rat, perfused rat liver, and cultured rat hepatocytes

Trospectomycin sulfate is an experimental, aminocyclitol antibiotic. It has been shown in preclinical, chronic safety studies in the dog and rat to elicit a reversible, lysosomal phospholipidosis in liver. The present experiments were conducted to characterize the tissue distribution and disposition of 3H]trospectomycin sulfate in the male rat, perfused rat, perfused rat liver, and cultured rat hepatocytes. Following a 5 mg/kg iv dose to four rats, approximately 70% of the dose was recovered within 24 hr primarily in urine as unchanged drug, and the remainder was eliminated with a terminal phase half-life in blood and tissues of 3 days. Fecal excretion was relatively minor (16% of the dose recovered in feces in 7 days) until later timepoints, when it was the principal pathway of terminal phase elimination. The liver sequestered approximately 10% of the dose and had the highest tissue levels of drug at all times measured. Liver perfusion experiments indicated that trospectomycin accumulated in a hepatic depot compartment as parent drug by a first-order process which was nonsaturable up to a 1 mM concentration of drug. Biliary excretion of unchanged trospectomycin by the perfused liver was slow (approximately 3% of the dose in 2 hr) and occurred by both paracellular and transcellular mechanisms. The hepatic depot compartment appeared to be responsible for transcellular biliary excretion, and thus for the sustained fecal excretion observed in vivo. Subcellular distribution experiments indicated that at least 50% of the drug in the hepatic depot was sequestered in organelles having a broad density range. The existence of a trospectomycin depot compartment was also demonstrated in cultured hepatocytes.(ABSTRACT TRUNCATED AT 250 WORDS)     

Danazol administration after gonadotrophin-releasing hormone analogue reduces rebound of uterine myomas [published erratum appears in Hum Reprod 1998 Mar;13(3):780]

We report the results of administration of danazol after suspension of gonadotrophin-releasing hormone analogue (GnRHa) therapy for uterine myomas. A total of 21 women with uterine myomas was treated with 100 mg danazol for 6 months after GnRHa therapy. Uterine volume and endocrine status were monitored monthly by ultrasound and assay of plasma gonadotrophins, oestradiol and progesterone. The results show a rebound of uterine volume about 30% less than in controls at the end of danazol therapy. Menstrual cyclicity returned after 65 +/- 3 days in 16 subjects and five patients remained amenorrhoeic. Hormone assays confirmed renewed ovarian function in the women whose menstrual periods returned. Bone mineral content was substantially reduced during GnRHa treatment but improved significantly during danazol therapy even in the women who remained amenorrhoeic. These results show the utility of danazol in prolonging the therapeutic effects of GnRHa. The mechanism by which danazol inhibits rebound of uterine volume may be due to its antiprogesterone effects on uterine myomas.