Residual Paralysis in the PACU after a Single Intubating Dose of Nondepolarizing Muscle Relaxant with an Intermediate Duration of Action

Background: Residual neuromuscular blockade remains a problem even after short surgical procedures. The train-of-four (TOF) ratio at the adductor pollicis required to avoid residual paralysis is now considered to be at least 0.9. The incidence of residual paralysis using this new threshold is not known, especially after a single intubating dose of intermediate-duration nondepolarizing relaxant. Therefore, the aim of the study was to determine the incidence of residual paralysis in the postanesthesia care unit after a single intubating dose of twice the ED95 of a nondepolarizing muscle relaxant with an intermediate duration of action.

Methods: Five hundred twenty-six patients were enrolled. They received a single dose of vecuronium, rocuronium, or atracurium to facilitate tracheal intubation and received no more relaxant thereafter. Neuromuscular blockade was not reversed at the end of the procedure. On arrival in the postanesthesia care unit, the TOF ratio was measured at the adductor pollicis, using acceleromyography. Head lift, tongue depressor test, and manual assessment of TOF and DBS fade were also performed. The time delay between the injection of muscle relaxant and quantitative measurement of neuromuscular blockade was calculated from computerized anesthetic records.

Results: The TOF ratios less than 0.7 and 0.9 were observed in 16% and 45% of the patients, respectively. Two hundred thirty-nine patients were tested 2 h or more after the administration of the muscle relaxant. Ten percent of these patients had a TOF ratio less than 0.7, and 37% had a TOF ratio less than 0.9. Clinical tests (head lift and tongue depressor) and manual assessment of fade showed a poor sensitivity (11-14%) to detect residual blockade (TOF < 0.9).     

Contributions of ovarian failure and aging to blood pressure in normotensive perimenopausal women: a mixed longitudinal study

Epidemiologic studies have shown that blood pressure increases more rapidly in middle-aged women than in middle-aged men. Whether or not ovarian failure contributes to this rapid rise is still not clear. In a follow-up study begun in 1979 and to continue for 10 years, the blood pressure of 193 healthy normotensive perimenopausal women, who lived in the mixed rural/industrial community of Ede, the Netherlands and who were initially aged between 49 and 56 years, was measured annually. During the course of the study, the onset of menopause of each participant could be established. Because of the mixed longitudinal design of the study, it was possible to evaluate the effects of both chronologic aging and time pre- or postmenopause on blood pressure. After the first seven years of follow-up, it was demonstrated that blood pressure did not increase in 168 women whose body weight was relatively stable. After multivariate analyses, systolic as well as diastolic pressure showed a significant negative relation (slope, 1.34 mmHg per year and 0.63 mmHg per year, respectively) with the years since menopause. On the other hand, the observed positive relation (slope, 0.81 mmHg per year) of systolic pressure with chronologic aging was not significant. No consistent association was found between diastolic pressure and chronologic aging. It is concluded that menopause cannot be regarded as a cause of hypertension; on the contrary, ovarian failure appears to have a protective effect on the increase in blood pressure as a result of chronologic aging. on the increase in blood pressure as a result of chronologic aging.     

Tape stripping of human stratum corneum yields cell layers that originate from various depths because of furrows in the skin

Received: 21 November 1996     

6-Mercaptopurine metabolism in Crohn's disease: correlation with efficacy and toxicity.

BACKGROUND: 6-Mercaptopurine (6-MP) has confirmed short and longterm efficacy in the treatment of IBD. However, the relation between its metabolism, efficacy, and side effects is not well understood. AIMS: To assay 6-MP metabolites and to correlate levels with drug compliance, disease activity, and adverse effects of treatment. PATIENTS: Heparinised blood was obtained prior to daily administration of 6-MP in 25 adolescent Crohn's disease patients (14 ileocolitis, 11 colitis) receiving 1.2 (range 0.4-1.6) mg/kg/day for a mean of 17 (range 4-65) months. METHODS: Erythrocyte free bases 6-thioguanine (6-TG) and 6-methyl-mercaptopurine (6-MMP) were measured (pmol/8 x 10(8) red blood cells) using reverse phase high performance liquid chromatography. RESULTS: Disease activity (modified Harvey-Bradshaw index) improved significantly with 6-MP (p = 0.001). Clinical remission was achieved in 72% of patients, who stopped taking prednisone, or were successfully weaned to a low alternate day dose (< 0.4 mg/kg/OD). Remission correlated well with erythrocyte 6-TG (p < 0.05), but not 6-MMP levels. Neutropenia was associated with 6-MP use (p < 0.005), but did not correlate with erythrocyte 6-MP metabolite levels. One patient refractory to 6-MP had 6-TG, but no measureable 6-MMP production, suggesting deficient thiopurine methyl-transferase activity or poor compliance. 6-MP induced complications (hepatitis, pancreatitis, and marrow suppression) were generally associated with increased 6-MMP levels. CONCLUSIONS: These results suggest that high performance liquid chromatography measurement of erythrocyte 6-MP metabolites may provide a quantitative assessment of patient responsiveness and compliance to treatment. The data support an immunosuppressive role for 6-TG, and potential cytotoxicity of raised 6-MMP levels.     

Behavioral models in mice. implication of the alpha noradrenergic system

1. The mechanism of action of drugs might change according to the test used. Several noradrenergic drugs were tested in order to understand their implication in the mobility tests.

2. It was found that clonidine, an Alpha 2 agonist, acted differently according to the tast used. It provoked sedation in spontaneous activity test, and anti-immobility effects in the other tests.

3. Tall suspension test is able to show the double acting of clonidine.

4. Idazoxan might act either as an alpha 2 antagonist or as partial alpha 2 agonist. TST shown the unexpected partial alpha agonist effect of the molecule.

5. Forced swimming test is more specific for predicting antidepressant activity than tail suspension test which is close to a spontaneous activity model.     

Distension-induced gastric accommodation in functional dyspepsia: effect of autonomic manipulation

Functional dyspepsia (FD) is associated with impaired gastric accommodation and autonomic dysregulation. The aim of this study was to investigate the effects of autonomic manipulation on distension-induced gastric accommodation in subjects with and without FD, using a newly developed gastric barostat paradigm. Twelve healthy subjects (HS) and 18 subjects with FD had four barostat examinations each: no intervention, intravenous atropine (1 mg), vagal stimulation (mental relaxation with deep breathing) and acute stress stimulation (serial subtraction task). Intrabag pressure increased from 1 to 15 mmHg in 5 min (ramp phase), and was maintained at 15 mmHg for 5 min (tonic phase). Volume responses were analysed using predefined parameters. There were no significant group differences in accommodation variables between HS and subjects with FD. The FD group could be subdivided into two distinct subgroups: subgroup 1 (n = 7, 38%) with low maximum volume and accommodation rate, and subgroup 2 with normal accommodation (n = 11). In subgroup 1, but not in subgroup 2 atropine increased maximum volume and accommodation rate substantially. Neither mental stress nor mental relaxation changed any of the accommodation variables. In a subgroup of subjects with FD, impairment of distension-induced gastric accommodation can be improved by cholinergic blockade, but not by acute physiological autonomic manipulation.     

Effect of female sex hormone supplementation and withdrawal on gastrointestinal and colonic transit in postmenopausal women

Females are disproportionately affected by constipation, which is often aggravated during pregnancy. Bowel function also changes during the luteal phase of the menstrual cycle. The aim was to compare the effects of acute administration of female sex steroids on gastric emptying, small bowel transit and colonic transit in healthy postmenopausal subjects. A second aim was to determine whether withdrawal of the hormones was associated with a change in transit. Forty-nine postmenopausal females were randomized to receive for 7 days 400 mg day(-1) micronized progesterone, 0.2 mg day(-1) oestradiol, combination of the two, or placebo. Treatment groups were balanced on age. Participants underwent whole gut transit measurement by scintigraphy using a 99m-labeled technetium-egg meal and 111-labeled indium-charcoal via a delayed-release capsule. Transit measurement was repeated after withdrawal of the study medications. The primary endpoints were ascending colon (AC) emptying half-life time (t1/2) and colonic geometric centre (GC) at 24 h. Secondary analysis variables were GC at 4 and 48 h, gastric emptying t1/2 and colonic filling at 6 h. There was a significant overall effect of progesterone on colonic transit with shorter AC emptying t1/2 and significantly greater colonic GC at 48 h. No transit endpoints were altered by oestradiol or combined hormonal treatment relative to placebo. Oestradiol and progesterone resulted in looser stool consistency. Withdrawal of the hormone supplement was not associated with significant alteration in transit. Micronized progesterone does not retard colonic transit in postmenopausal females.     

Zinc takes the center stage: its paradoxical role in Alzheimer’s disease

There is compelling evidence that the etiology of Alzheimer’s disease (AD) involves characteristic amyloid-β (Aβ) deposition, oxidative stress, and anomalous metal–Aβ protein interaction. New studies have implicated redox active metals such as copper, iron, and zinc as key mediating factors in the pathophysiology of Alzheimer’s disease. There is also evidence that drugs with metal chelating properties could produce a significant reversal of amyloid-β plaque deposition in vitro and in vivo. This paper reviews current observations on the etiologic role of zinc in AD. We also discuss the interactions of zinc and copper with Aβ, a factor that purportedly facilitates disease processes. Finally, we review the protective role of zinc against Aβ cytotoxicity and hypothesize how the apparent effect of zinc on AD pathology may be paradoxical, The Zinc Paradox. Indeed, complex pathologic stressors inherent to the Alzheimer’s diseased brain dictate whether or not zinc will be neuroprotective or neurodegenerative. Further research on the zinc paradox in AD is needed in order to elucidate the exact role zinc plays in AD pathogenesis.