Effect of inhaled methanol on pituitary and testicular hormones in chamber acclimated and non-acclimated rats.

Two experiments were conducted in which the acute effects of inhaled methanol on serum hormones associated with reproductive function in the male rat were evaluated. In the first experiment, rats exposed to methanol (0, 200, 5000 and 10,000 ppm) for 6 h were killed at the end of the exposure period (6 h) or the following morning (24 h). Also, because the process of exposure itself could modify neuroendocrine function, the effect of the handling associated with placing the rat in the exposure chamber was evaluated further by dividing the exposed animals into acclimated (2 weeks of prior handling) and non-acclimated groups. At 6 h, an effect of prior handling was noted in the sham-exposed rats, with serum luteinizing hormone (LH) of the non-acclimated group being greater than that of the acclimated group. Serum LH concentrations were altered by methanol exposure, but the direction of change and the exposure level at which an effect was noted differed between the acclimated and non-acclimated rats. Methanol (5000 ppm) reduced serum LH in the non-acclimated animals, while 10,000 ppm increased LH in the acclimated rats. Follicle stimulating hormone (FSH) and testosterone were unchanged by methanol in rats killed at 6 h. Thus, this experiment did not confirm earlier reports that exposure to 200 ppm for 6 h reduced serum testosterone. At 24 h, an effect of prior handling was still present in the hormonal measures, with serum and interstitial fluid testosterone concentrations being greater in the non-acclimated rats. Also, there was a dose x handling interaction with methanol exposure inducing an increase in serum testosterone in the non-acclimated rats (up to 5000 ppm) and a decrease in the acclimated rats (up to 10,000 ppm). In the second experiment, groups of acclimated and non-acclimated rats were exposed to 0 or 5000 ppm methanol for 1, 2 and 6 h and killed immediately after removal from the chamber. Serum LH, testosterone and FSH values were not different in sham- vs methanol-exposed rats at any time point. As in experiment 1, an effect of prior handling was noted. In general, the concentrations of these hormones and serum prolactin in the non-acclimated rats were greater than those observed for acclimated rats. Methanol exposure resulted in increased prolactin concentrations under both handling conditions.(ABSTRACT TRUNCATED AT 400 WORDS)     

Risk for suicide attempts among adolescents who engage in non-suicidal self-injury.

The current study examined whether common indicators of suicide risk differ between adolescents engaging in non-suicidal self-injury (NSSI) who have and have not attempted suicide in an effort to enhance clinicians' ability to evaluate risk for suicide within this group. Data were collected from 540 high school students in the Midwest who completed the RADS, RFL-A, SIQ, and SHBQ as part of a larger adolescent risk project. Results suggest that adolescents engaging in NSSI who also attempt suicide can be differentiated from adolescents who only engage in NSSI on measures of suicidal ideation, reasons for living, and depression. Clinical implications of the findings are discussed.     

Physician knowledge of herbal toxicities and adverse herb-drug interactions.

OBJECTIVE: To determine how knowledgeable physicians are regarding the toxic effects and drug interactions of herbal remedies. METHODS: An anonymous voluntary demographic survey and 16-question, multiple-choice quiz was distributed at educational meetings of emergency medicine and internal medicine physicians. The primary outcome measures were to determine whether significant associations existed between quiz scores and the amount of clinical experience, or between quiz scores and self-assessed familiarity with the topic of herbal toxicities and adverse herb-drug interactions. RESULTS: A total of 142 surveys and quizzes were completed by 59 attending physicians, 57 resident physicians, and 26 medical students. The mean subject score on the quiz was only slightly higher than would have occurred from random guessing. Neither the amount of the subjects' clinical experience, nor their self-assessed familiarity with herbal toxicities and drug interactions correlated significantly with the score on the quiz. CONCLUSION: The physicians and medical students surveyed had little training in herbal toxicities and drug interactions. They generally rated their familiarity with these topics as 'poor', and their scores on the quiz bore out this assessment as correct. Educational efforts might improve physician knowledge of the adverse effects of herbal remedies.     

Intensity-dependent regional cerebral blood flow during 1-Hz repetitive transcranial magnetic stimulation (rTMS) in healthy volunteers studied with H215O positron emission tomography: I. Effects of primary motor cortex rTMS.

BACKGROUND: Repetitive transcranial magnetic stimulation (rTMS) affects the excitability of the motor cortex and is thought to influence activity in other brain areas as well. We combined the administration of varying intensities of 1-Hz rTMS of the motor cortex with simultaneous positron emission tomography (PET) to delineate local and distant effects on brain activity. METHODS: Ten healthy subjects received 1-Hz rTMS to the optimal position over motor cortex (M1) for producing a twitch in the right hand at 80, 90, 100, 110, and 120% of the twitch threshold, while regional cerebral blood flow (rCBF) was measured using H(2)(15)O and PET. Repetitive transcranial magnetic stimulation (rTMS) was delivered in 75-pulse trains at each intensity every 10 min through a figure-eight coil. The regional relationship of stimulation intensity to normalized rCBF was assessed statistically. RESULTS: Intensity-dependent rCBF increases were produced under the M1 stimulation site in ipsilateral primary auditory cortex, contralateral cerebellum, and bilateral putamen, insula, and red nucleus. Intensity-dependent reductions in rCBF occurred in contralateral frontal and parietal cortices and bilateral anterior cingulate gyrus and occipital cortex. CONCLUSIONS: This study demonstrates that 1-Hz rTMS delivered to the primary motor cortex (M1) produces intensity-dependent increases in brain activity locally and has associated effects in distant sites with known connections to M1.     

Phosphorylation of neurofilament proteins and chromatolysis following transection of rat sciatic nerve

States of phosphorylation of neurofilament proteins were examined in the perikarya of rat sensory and motor neurons between 3 and 28 d following either a distal transection [6-7 cm from the L4-L5 dorsal root ganglia (DRG)] or a proximal transection (1-2 cm from the L4-L5 DRG) of the sciatic nerve. Paraffin sections of the right (experimental) and left (control) L4 and L5 DRG from animals with unilateral transection of the right distal sciatic nerve were stained immunocytochemically with monoclonal antibodies to phosphorylation-dependent (NF-P), dephosphorylation-dependent (NF-dP), or phosphorylation-independent (NF-ind) epitopes on the largest (NF200), mid-sized (NF150), or smallest (NF68) neurofilament protein subunits. Increased immunoreactivity to NF-P on NF200 and NF150 was detected in experimental DRC at 10 d, peaking by 20 d, and declining to near control levels by 28 d. Conversely, immunoreactivity to NF-dP declined in experimental DRG beginning at 6 d, reaching a maximum decline at 10-16 d, and returning to near control levels by 28 d. Immunocytochemical changes were confirmed with biochemical studies on tissue homogenates that demonstrated an increase of immunoreactivity to NF-P and a decrease of reactivity to NF-dP in the experimental DRG. Changes in immunoreactivities to NF-P and NF-dP were observed only in the perikarya of large neurons and were closely associated with chromatolytic changes in these neurons. Marked enhancement of chromatolysis, as well as the immunoreactivities to NF-P and NF-dP, occurred following a proximal (left side) versus distal (right side) transection in the same animal.(ABSTRACT TRUNCATED AT 250 WORDS)     

Physical fitness and all-cause mortality. A prospective study of healthy men and women

We studied physical fitness and risk of all-cause and cause-specific mortality in 10,224 men and 3120 women who were given a preventive medical examination. Physical fitness was measured by a maximal treadmill exercise test. Average follow-up was slightly more than 8 years, for a total of 110,482 person-years of observation. There were 240 deaths in men and 43 deaths in women. Age-adjusted all-cause mortality rates declined across physical fitness quintiles from 64.0 per 10,000 person-years in the least-fit men to 18.6 per 10,000 person-years in the most-fit men (slope, -4.5). Corresponding values for women were 39.5 per 10,000 person-years to 8.5 per 10,000 person-years (slope, -5.5). These trends remained after statistical adjustment for age, smoking habit, cholesterol level, systolic blood pressure, fasting blood glucose level, parental history of coronary heart disease, and follow-up interval. Lower mortality rates in higher fitness categories also were seen for cardiovascular disease and cancer of combined sites. Attributable risk estimates for all-cause mortality indicated that low physical fitness was an important risk factor in both men and women. Higher levels of physical fitness appear to delay all-cause mortality primarily due to lowered rates of cardiovascular disease and cancer.     

Barrett's oesophagus: a clinical study of 52 patients

This paper reports a series of 52 patients with Barrett's (or columnar-lined) oesophagus from one medical unit diagnosed over a six-year period. The commonest associated symptoms were heartburn, regurgitation and dysphagia but 10 patients had no oesophageal symptoms and two had no symptoms at all. Gastrointestinal bleeding (overt or occult) was observed in almost one-third of patients. At diagnosis, 26 patients had oesophagitis, 23 had oesophageal ulceration and 10 had benign oesophageal strictures. An association between oesophageal ulceration and non-steroidal anti-inflammatory drug ingestion was suggested by the data and patients with oesophageal ulceration were significantly older than patients with uncomplicated Barrett's oesophagus. No patient had adenocarcinoma of the oesophagus at diagnosis and neither carcinoma nor dysplasia were seen during a mean period of 16.4 months. However, 17 per cent of patients in the series had malignancies in other sites. Most patients did well on medical treatment and only two were referred for anti-reflux surgery (both for non-healing oesophageal ulcers). Barrett's oesophagus was seen in 10 per cent of patients with gastro-oesophageal reflux at endoscopy. Oesophageal ulceration in patients with Barrett's oesophagus made up 21 per cent of oesophageal ulcers seen and benign oesophageal stricture in patients with Barrett's oesophagus constituted 13 per cent of all benign strictures seen. Barrett's oesophagus is common in our population and despite complications, it can be managed successfully, at least in the short term, by conservative means.     

Final surgical results with a suction trephine

The suction trephine was studied in 31 aphakic and pseudophakic penetrating keratoplasty patients (31 eyes). The postoperative corneal astigmatism averaged 3.9 +/- 2.8 diopters overall. The 15 pseudophakic cases in nonscarred corneas showed a marked reduction in postoperative corneal astigmatism (3.59 diopters) when compared to previous reports. Our results have encouraged us to continue use of the suction trephine in all aphakic or combined keratoplasty procedures.     

Acute cardiovascular effects of tranylcypromine: correlation with plasma drug, metabolite, norepinephrine, and MHPG levels

BACKGROUND: Recent case reports, small series, and uncontrolled, unblinded studies have suggested that tranylcypromine may produce pressor reactions in some patients. However, the physiologic mechanism underlying this cardiovascular change is unknown. METHOD: The authors studied the acute cardiovascular effects of tranylcypromine in 13 patients and attempted to correlate these changes with plasma measures of parent drug, possible pressor metabolites, norepinephrine, and 3-methoxy-4-hydroxyphenylglycol. RESULTS: Significant elevations in supine blood pressure occurred after administration of tranylcypromine and correlated with tranylcypromine dose. Similar changes were not observed in standing blood pressure measurements. In fact, an orthostatic decrease in blood pressure and increase in heart rate were observed. Amphetamine-like metabolites were not found. CONCLUSIONS: The authors speculate on possible mechanisms underlying these opposite cardiovascular effects.