Otitis externa among users of private swimming pools

The purpose of this study was to detect risk factors for developing otitis externa (OE) with special regard to swimming in private pools in holiday houses. Data were collected in a retrospective case-control study from June to October in 1993 and over the same period in 1994. Patients who had OE diagnosed by a general practitioner were included. In 1993 controls were 134 guests from 27 holiday houses where nobody got o.e. during their stay. The number of cases was 35. In 1994 the design was changed so that controls were the 95 healthy inhabitants from the same houses as the 23 cases. The amounts of time spent in the pools and the total bacteria count in the water were significant risk factors for developing OE. Pseudomonas aeruginosa was found in 80% of the ear swabs of the casegroup. In 1993 30% and in 1994 83% of the pools fulfilled the requirements for public pools set by the Danish authorities.     

Peptides and anxiety: a dose-response evaluation of pentagastrin in healthy volunteers

A large body of data suggest that brain cholecystokinin (CCK) systems are involved in the regulation of anxiety, and numerous studies have demonstrated that CCK-4, a CCKB agonist, reliably induces panic attacks in patients with panic disorder. Recently, pentagastrin, a commercially available CCKB agonist, has been reported to have similar anxiogenic properties. To further explore the utility of pentagastrin as a challenge agent and to determine whether its effects are dose-related, a dose-response study was conducted in ten healthy volunteers. Pentagastrin (0.2 microgram/kg, 0.6 microgram/kg and 1.0 microgram/kg) and inactive placebo were infused over one minute on four separate challenge days in a double-blind fashion. Subjects received pentagastrin while participating in a structured social interaction task. Repeated measures of anxiety, blood pressure, pulse, ACTH, and cortisol were taken at baseline and postinfusion. Pentagastrin administration led to increases in anxiety, pulse, ACTH, cortisol and physical symptoms of panic, in a dose-related manner. Participation in the social interaction task led to increases in measures of anxiety as well as increases in pulse and blood pressure. Few differences were found between the 0.2 microgram/kg dose of pentagastrin and placebo, or between the 0.6 microgram/kg and the 1.0 microgram/kg doses of pentagastrin. These findings support the notion that CCK systems are involved in the regulation of anxiety, and suggest that the 0.6 microgram/kg dose may be optimal for increasing symptoms of anxiety while minimizing unpleasant side effects. The powerful anxiogenic effects of the social interaction task underscore the importance of contextual variables in challenge studies.     

Microanatomy of the dopaminergic system in the rainbow trout retina

We have investigated the morphology of dopaminergic interplexiform cells as well as the distribution of two classes of dopamine receptors in the retina of the rainbow trout. Interplexiform cells were visualized using an antiserum against tyrosine hydroxylase and PAP immunocytochemistry. In whole amounts, these cells have a density of between 91 and 182 cells per mm2 with highest values in the lower temporal quadrant. Their cell bodies lie at the inner margin of the inner nuclear layer with only 12-17 cells per retina displaced to the ganglion cell layer. There are three levels of stratification in the inner plexiform layer, one at the distal and proximal borders respectively, and one in the middle. They arise mostly from a radially oriented, stout primary dendrite. Tangential processes are about 1 micron in diameter and show a number of varicosities. The density of processes is greatest in sublayer 5, but no major difference in the general organization is apparent between the three sublayers. In the outer retina, there are two levels of dense ramification confined to the layer of horizontal cells. Light and electron microscopic analysis shows synaptic input to horizontal cells, but not to photoreceptors. The distribution of D1 receptors was assessed by studying the binding pattern of a specific, fluorescent-labelled antagonist, SCH 23390, in unfixed frozen sections. We found displaceable binding in the inner and outer plexiform layers and in the region of horizontal cell perikarya. We used an anti-peptide antibody directed to an extracellular domain of the rat D2 receptor and a fluorescent secondary antiserum to study the localization of D2 receptors. In addition to marked label in both plexiform layers, the outer, and especially the inner segments of rods and cones show specific immunoreactivity. In addition, there is distinct label at the level of the horizontal cell bodies; in the inner retina, specific fluorescence is found in somata of some amacrine cells. The significance of the connectivity pattern and the distribution of the two receptor types is discussed with respect to the role of dopamine in controlling adaptational processes in the outer retina, such as retinomotor movements and changes in horizontal cell morphology and physiology.     

Straightforward solid-phase extraction method for the determination of verapamil and its metabolite in plasma in a 96-well extraction plate

Straightforward solid-phase extraction (SPE) methods were developed for the determination of verapamil and its metabolite in a plasma matrix. The spiked plasma sample was pretreated with 2% phosphoric acid followed by two different SPE methods using a Waters Oasis HLB 96-well extraction plate. Recoveries greater than 90% were obtained using both a generic and a selective SPE methods. The generic method is a good starting protocol, and it is applicable to a wide range of compounds. This generic method consists of using 5% methanol as the wash solvent, and 100% methanol for the elution. The limitation of the non-specific method is that it does not remove all plasma constituents that interfere with the quantitation of the metabolite, norverapamil. A second, more specific method was developed using the same Oasis HLB sorbent which removes more plasma interferences and provides cleaner extracts for the HPLC-UV analysis. This selective method uses both the methanol concentration and the pH advantageously to preferentially isolate the analytes of interest from a complex sample matrix. Recoveries of greater than 90% with R.S.D.s less than 3.8% were obtained with this selective method.     

Brain serotonin neurotoxicity and primary pulmonary hypertension from fenfluramine and dexfenfluramine. A systematic review of the evidence

OBJECTIVES: Obesity is an important clinical problem, and the use of dexfenfluramine hydrochloride for weight reduction has been widely publicized since its approval by the Food and Drug Administration. However, animal and human studies have demonstrated toxic effects of fenfluramines that clinicians should be aware of when considering prescribing the drugs. Our purpose was to systematically review data on brain serotonin neurotoxicity in animals treated with fenfluramines and the evidence linking fenfluramines to primary pulmonary hypertension (PPH). DATA SOURCES: Archival articles and reviews identified through a computerized search of MEDLINE from 1966 to April 1997 using "fenfluramine(s)," "serotonin," "neurotoxicity," "behavior," "anorexigens," "weight loss," and "primary pulmonary hypertension" as index terms. STUDY SELECTION: Reports dealing with long-term effects of fenfluramines on brain serotonin neurons, body weight, and pulmonary function in animals and humans. DATA EXTRACTION: Reports were reviewed by individuals with expertise in serotonin neurobiology, neurotoxicity, neuropsychiatry, and pulmonary medicine and evaluated for appropriateness for inclusion in this review. DATA SYNTHESIS: Fenfluramines cause dose-related, long-lasting reductions in serotonin axonal markers in all the animal species tested and with all the routes of drug administration used. Doses of fenfluramines that produce signs of brain serotonin neurotoxicity in animals are on the same order as those used to treat humans for weight loss when one takes into account known relations between body mass and drug clearance. However, no human studies have been conducted, and the pathological and clinical potential for neurotoxicity in humans is unknown. Appetite suppressants-most commonly fenfluramines-increase the risk of developing PPH (odds ratio, 6.3), particularly when used for more than 3 months (odds ratio, >20). CONCLUSIONS: Fenfluramine and dexfenfluramine have been demonstrated to damage brain serotonin neurons in animal studies. It is not known if such damage occurs in humans or if there are clinical consequences. Use of fenfluramines is associated with an increased risk of PPH. Future studies should address the long-term consequences of prolonged use of fenfluramines.