Long-term effects of physical exercise on working capacity and pulmonary function in cystic fibrosis

Seven patients with cystic fibrosis aged 6 to 20 were enrolled for 30 months in a daily exercise program. After 12 months conventional chest physiotherapy was withdrawn. Patients with low initial Shwachman scores improved as regards maximal working capacity. Spirometric data and volume of trapped gas indicated opening of closed airways. We suggest that physical exercise in general should be the basis of pulmonary therapy in cystic fibrosis. Other forms of physiotherapy are advisable when hard physical exercise is not feasible.     

Labially displaced ectopically erupting maxillary permanent canine: interceptive treatment and long-term results.

This case report demonstrates how extracting a maxillary deciduous canine affects the eruption path of a labially displaced ectopically erupting permanent canine. A long-term follow-up is presented, and the biologic mechanisms are discussed.     

Innervation of the child urinary bladder

Muscle strips from the fundus, trigonum and distal ureters obtained from children at operations for vesico-ureteric reflux were studied using histochemical and immunohistochemical methods, and electrical nerve stimulation in an organ bath. A rich supply of cholinergic nerves was found and despite a partial atropine resistance the neurophysiological experiments indicated that the transmitter causing contraction of the detrusor muscle is acetylcholine. Imipramine, which is used in the treatment of enuresis, had no anticholinergic effect on the bladder in the doses used clinically. The adrenergic innervation was very sparse except around the ureter orifices. No contractile alpha-adrenoceptors could be detected but beta receptor mediated relaxation was found, which was neither of the beta 1 nor beta 2 type. A third type of beta receptor is postulated. Peptidergic nerves containing vasoactive intestinal peptide, VIP, were demonstrated in a few nerve terminals running along bundles of smooth muscle. No nerves containing enkephaline, somatostatine or substance P were found. VIP affected the detrusor muscle indicating a possible role as a modulator of transmitter action, while substance P had no effect. The anticholinergic and calcium antagonistic drug terodiline inhibited all muscle activity, whether it was induced by nerve stimulation, cholinergic drugs or a potassium rich solution, making it suitable for treatment of diurnal enuresis.     

Early spontaneous hematoma in cerebral infarct: is primary cerebral hemorrhage overdiagnosed?

We identified 15 patients (63 +/- 8 years) in whom CT showed no bleeding within 6 hours of stroke onset but showed ganglionic or lobar hemorrhage less than 18 hours later, without visible underlying infarct (early spontaneous intra-infarct hematoma [ESIH]). No patient had antithrombotic therapy or a coagulation disorder, but eight had hypertension. The second CT was prompted by rapid worsening (in 10) or because the first CT was not available (in five). Prior transient ischemic attacks, silent infarcts on CT, and a potential cardiac source of embolism were more common in patients with ESIH than in 200 patients with primary cerebral hemorrhage (PCH) admitted during the same period. Distal occlusions were present in four of five patients who underwent intracranial studies within the first 2 days. Most of these patients probably had embolism with early and extensive bleeding in the ischemic area. Our findings suggest that ESIH may be under-recognized, while PCH may be overdiagnosed.     

Correlation between 5-HT7 receptor affinity and protection against sound-induced seizures in DBA/2J mice

Audiogenic seizures can be induced in DBA/2J mice following intense auditory stimulation. A number of neurotransmitters, including 5-hydroxytryptamine (5-HT), are believed to be involved in mediating this effect since it has been shown previously that depletion of 5-HT or blockade of 5-HT receptors protects DBA/2J mice from these audiogenic seizures. The present study was undertaken to determine whether antagonism of the newly identified 5-HT₇ receptor may protect DBA/2J mice from audiogenic seizures by attempting to correlate in vivo potency of compounds with their affinity at the 5-HT₇ receptor. All compounds used in the correlation were shown to be antagonists at the 5-HT₇ receptor and a statistically significant correlation was observed between 5-HT₇ affinity and doses for half-maximal response (ED₅₀) for protection of DBA/2J mice from sound-induced seizures (r = 0.80; P < 0.05). No significant correlation was observed between in vivo activity and affinity at either 5-HT_1A, 5-HT_2A or 5-HT_2C receptors. It is also unlikely that interactions between the 5-ht₅ receptor will protect DBA/2J mice from audiogenic seizures since metergoline and mesulergine which are both active in this in vivo model have no affinity for the 5-ht₅ receptor. There are similarities between the pharmacology of the 5-HT₇ receptor and that of the 5-HT_1A receptor, however the correlation between the in vivo potency in DBA/2J mice and 5-HT_1A affinity was not significant. Furthermore, the 5-HT_1A receptor antagonist WAY 100135 did not protect DBA/2J mice from audiogenic seizures at doses that antagonise 5-HT_1A receptor-mediated effects in mice. These data suggest that antagonism of 5-HT₇ receptors may protect against audiogenic seizures in DBA/2J mice although a definitive conclusion must await studies with selective 5-HT₇ antagonists. Received: 20 March 1997 / Accepted: 10 August 1997     

Effects of haloperidol and amisulpride on motor and cognitive skill learning in healthy volunteers

Buprenorphine is a mu opioid partial agonist currently used as an analgesic, and being developed for the treatment of opioid dependence. The purpose of this study was to determine the abuse liability of parenteral buprenorphine in volunteers maintained on daily sublingual (SL) buprenorphine (8 mg). In a residential laboratory, eight volunteers underwent pharmacologic challenges two times per week. Medication challenges were 16 h after the daily dose of buprenorphine, and consisted of double-blind IM injections of buprenorphine (4, 8, 16 mg), the prototypic mu opioid agonist hydromorphone (9 and 18 mg), or saline. Assessments consisted of physiologic monitoring, subjects’ self-reports, and a trained observer’s ratings of drug effects, and were collected for 0.5 h before and 2.0 h following injection. Supplemental doses of IM buprenorphine produced opioid agonist-like effects, indicating some abuse potential of parenteral buprenorphine in buprenorphine-maintained patients. There was incomplete cross-tolerance to the effects of hydromorphone, suggesting that higher maintenance doses of buprenorphine may be needed to maximize clinical efficacy. However, there was a lack of graded dose-effects for hydromorphone, suggesting that buprenorphine’s combination of partial agonist effects and high affinity for opioid receptors may limit the magnitude of effects of supplemental full agonists. Finally, participants tolerated cumulative doses of maintenance buprenorphine plus challenge buprenorphine without adverse effects, suggesting higher doses of buprenorphine can be safely administered to opioid dependent patients. Received: 22 February 1996/Final version: 23 August 1996     

Cost savings of using EMLA cream for split-skin harvesting

Split-skin harvesting is a procedure which requires effective anaesthesia. The application of EMLA® cream to the skin effectively serves this purpose as was shown as early as 1985 [7]. This study with 146 patients indicated that dermal analgesia with EMLA cream is less risky for patients and also cheaper, although there were no data to support the latter. Accordingly, another 122 patients were selected retrospectively. They were from the same department and had undergone split-skin harvesting for the same indications and over a similar period but under general or regional block anaesthesia. In addition, these 122 patients received postanaesthesia care in a recovery ward. These 122 patients and the 146 patients from the previous study are compared in this analysis of economy and risk. The analysis indicated considerable cost savings and less risk for patients treated with EMLA.     

Effects of scopolamine,trimipramine and diazepam on explicit memory and repetition priming in healthy volunteers

The effects of scopolamine, an anticholinergic drug, of trimipramine, a tricyclic antidepressant with both anticholinergic and sedative properties, of diazepam and a placebo, on explicit memory and repetition priming were assessed using a free-recall task and a word-stem completion task. Forty-eight healthy volunteers took part in this double-blind study. Diazepam provoked a dissociation between free recall, which was profoundly impaired, and word completion, which was spared. No significant changes in memory performances were observed in the scopolamine group; however, a significant correlation between explicit and implicit memory performances was observed in this group. At the low dose used, the effects of trimipramine on memory were mild. The results suggest that the cholinergic system is involved in the priming effect.