Clonidine and Dexmedetomidine Potently Inhibit Peristalsis in the Guinea Pig Ileum In Vitro

Background: Inhibition of intestinal peristalsis is a major side effect of drugs used for anesthesia or for analgesia and sedation of patients in the intensive care unit. This in vitro study examined the effect of clonidine and dexmedetomidine on intestinal peristalsis and analyzed some of their mechanisms of action.

Methods: In isolated segments of the guinea pig small intestine, peristalsis was triggered by a perfusion-induced rise of the intraluminal pressure. The peristaltic pressure threshold to elicit a peristaltic wave was used to quantify drug effects on peristalsis. Vehicle (Tyrode's solution), clonidine (10 nm-100 [mu]m), or dexmedetomidine (0.1-100 nm) were added extraserosally to the organ bath. In other series of experiments, clonidine or dexmedetomidine was administered after pretreatment with yohimbine, prazosin, apamin, naloxone, or vehicle. Clonidine was also tested after blockade of NO synthase with l-NAME and in the presence of the inactive enantiomer d-NAME.

Results: Clonidine and dexmedetomidine concentration-dependently increased peristaltic pressure threshold and inhibited peristalsis (clonidine: EC50 = 19.6 [mu]m; dexmedetomidine: EC50 = 12.0 nm). The inhibition caused by clonidine could be prevented by pretreatment with yohimbine, naloxone, and apamin, but not by prazosin, l-NAME, or d-NAME. Inhibition caused by dexmedetomidine was prevented by yohimbine only.     

Reconstruction of complex and unusual defects of the thoracic wall

Summary From 1981 to. 1989, a total of 13 procedures were performed on 12 patients requiring complex reconstructions of the thoracic wall. The most common cause of these defects was cancer. Muscle flaps remain the treatment of choice for thoracic wall reconstruction and have been used in 10 cases. Microsurgical tissue transfer opens even larger therapeutic perspectives. A team approach is recommended.     

A simple method for measurement of inulin in nanoliter samples using glass capillaries

Summary A simple method using glass capillaries instead of microcuvettes for measurement of inulin in nanoliter samples is given. Inulin was determined with anthron reagent (5 or 10 nl samples +3 l anthron reagent). Glass capillary tubes (o.d.=1 mm, i.d.=0.68 mm, length=150 mm) in which the chemical reaction took place during incubation at 56°C were directly introduced into the optical system of a Zeiss spectrophotometer PMQ II with sphere attachment and objective.Extinction was measured vertically to the axis of the capillary. The changes of extinction of 20 different capillaries with the blank at different positions was only 1.13×10^–3. The exactness of measurement in the concentration range of 100 200 400 750 1500 3000 mg-% inulin was for 5nl/3 l: 19.8 11.0 6.7 4.7 3.0 2.2%. 10nl/3 l: 13.0 8.4 5.1 3.9%.This method of measurement may also be applicable for other colorimetric reactions with nanoliter samples.This work was supported by Fonds zur Förderung der wissenschaftlichen Forschung.     

The relationship between demographic factors and attitudes toward mental health services.

Considerable effort has been exerted in recent years toward educating the public concerning mental illness and the efficacy of various treatment modalities. Most previous studies of attitudes have focused solely on attitudes toward the mentally ill. In this study we investigated attitudes toward mental health services and found that most people are positively disposed toward the use of these services. Attitudes toward the use of mental health services were affected by the age, sex, race, education, and income of the subjects. In general, differences of attitude lie in the direction that would tend to inhibit utilization among those most at risk.     

Controlled release levodopa-benserazide and changes in efficacy during treatment of Parkinson's disease

Twenty-five patients, 12 men and 13 women, 42 to 79 years (mean 62) were studied to determine possible interest of a controlled release preparation of L. dopa combined with benserazide. All patients were experiencing fluctuations in efficacy over the last 8 +/- 4 years. Their Parkinson disease was of long duration, (16 +/- 5 years), severe (Hoehn and Yahr's stages III to V) and treated with L. dopa for 12 +/- 4 years. Results were evaluated in the short, medium and long term. During the initial period the new treatment was substituted for previous therapy on a dose for dose basis. Long term (300 days) results showed that "end of dose" fluctuations had been improved in 40 p. 100 of cases without concomitant reduction in therapeutic effects, duration of "ON" periods progressing by 60%. The frequency of drug intake was unaltered but daily dosage could be increased by 30% without increasing severity of abnormal movements to a similar degree. The administration of this new presentation can be recommended, especially when frequent fluctuations compromise long term therapeutic effects.     

Exclusion criteria of DSM-III. A study of co-occurrence of hierarchy-free syndromes

The diagnostic criteria of the third edition of the DSM-III often state that one diagnosis cannot be made if it is "due to" another disorder. Using data from the National Institute of Mental Health Diagnostic Interview Schedule, with a sample of 11,519 subjects from a community population, we found that if two disorders were related to each other according to the DSM-III exclusion criteria, then the presence of a dominant disorder greatly increased the odds of having the excluded disorder. We also found that disorders, which DSM-III says are related to each other, were more strongly associated than disorders, which DSM-III says are unrelated. However, we also found there was a general tendency toward co-occurrence, so that the presence of any disorder increased the odds of having almost any other disorder, even if DSM-III does not list it as a related disorder. We concluded that empirical studies are needed to study the assumptions underlying the use of a diagnostic hierarchy.     

Pneumococcal vaccine. Efficacy and associated cost savings

We evaluated the efficacy and cost savings of the pneumococcal pneumonia vaccine in a retrospective cohort study of 762 vaccinated and 1161 randomly selected unvaccinated age-sex matched persons in Blue Cross/Blue Shield of Minnesota using medical and pharmaceutical claims. The pneumonia incidence and the ratio of incidence in the postvaccination to prevaccination periods (rate ratio) were examined in the vaccine group by sex and risk factors. Vaccination significantly reduced pneumonia incidence, with overall efficacy of 69% and higher efficacy in women (86%) than in men (33%). We assigned persons to risk categories based on disease conditions as recorded in the claims by the ICD-9-CM (International Classification of Diseases, Ninth Revision, Clinical Modification) diagnostic codes. In the risk categories, efficacy varied from 50% to 75% and was confounded by sex. Immunocompromised and immunocompetent women had high efficacy (83% to 88%), while immunocompetent and immunocompromised men had lower efficacy (33%). Persons with a precondition of pneumonia exhibited similar vaccine efficacy to the overall cohort relative to the comparison group. Projected costs of pneumonia cases are 3.6 times the observed costs of vaccination and postvaccination pneumonia costs. We conclude that the pneumococcal pneumonia vaccine is efficacious in persons having had pneumonia, persons "at risk" of developing pneumonia, or persons over 50 years of age, and it corresponds to overall savings of $141 per person.     

The inhibitory modulation of guinea-pig intestinal peristalsis caused by capsaicin involves calcitonin gene-related peptide and nitric oxide

The effect of capsaicin-induced stimulation of afferent neurons on peristalsis and the possible neural mediators involved in this action were examined in the guinea-pig isolated ileum. The intraluminal pressure threshold for eliciting peristaltic waves was used to quantify facilitation (decrease in threshold) or inhibition (increase in threshold) of peristalsis. Capsaicin (0.1–1 M) caused an initial short-lasting stimulation of peristalsis followed by a prolonged inhibition of peristaltic activity. Capsaicin (1 M) was ineffective when the gut segments had been pretreated with 3.3 M capsaicin, which is indicative of an afferent neuron-dependent action of the drug. In contrast, the abolition of peristalsis caused by a high concentration of capsaicin (33 M) was fully reversible on removal and reproducible on readministration of capsaicin, a feature characteristic of a nonspecific depression of smooth muscle excitability. Baseline peristalsis and the excitatory/inhibitory effect of capsaicin (1 M) on peristalsis remained unaltered by a combination of the tachykinin NK₁ receptor antagonist ( + )-(2S, 3S)-3-(2-methoxybenzylamino)-2-phenyl piperidine (CP-99,994; 0.3 M) and the tachykinin NK₂ receptor antagonist L(-)-N-methyl-N[4-acetylamino-4-phenyl-piperidino-2-(3,4-dichlorophenyl)butyl]-benzamide (SR-48,968; 0.1 M). Further experiments, performed in the presence of a low concentration of atropine (10 nM) showed that the catcitonin gene-related peptide (CGRP) antagonist human -catcitonin gene-related peptide (8–37) [hCGRP (8–37); 10 M] attenuated the delayed inhibitory effect of capsaicin on peristalsis, but did not influence baseline peristaltic activity and the capsaicin-induced facilitation of peristalsis. Blockade of nitric oxide (NO) synthesis by N ^G-nitro-l-arginine methylester (l-NAME, 300 M) facilitated baseline peristaltic activity and reduced the delayed inhibition of peristalsis caused by capsaicin (1 M) without affecting the initial peristalsis-stimulating action of capsaicin. The effects of l-NAME were prevented by l-arginine (1 mM). The data of the current study indicate that capsaicin-sensitive afferent neurons do not participate in the neural pathways subserving peristalsis in the guinea-pig small intestine, but modulate peristaltic activity upon stimulation with capsaicin. The initial stimulant action of capsaicin on peristalsis is independent of tachykinins acting via NK₁ or NK₂ receptors, while the delayed capsaicin-induced depression of peristalsis involves CGRP and NO.