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Sumatriptan nasal spray: a dose-ranging study in the acute treatment of migraine.

This multicentre, randomized, double-blind, placebo-controlled, parallel group dose-ranging study compared the efficacy and tolerability of four doses of sumatriptan nasal spray (2.5, 5, 10 and 20 mg) with a placebo, in the acute treatment of a single migraine attack. In total, 544 patients received the study medication as a single spray in one nostril, to treat a single migraine attack in the clinic. Efficacy assessments included the measurement of headache severity, clinical disability, and the presence/absence of associated symptoms. The incidence of headache recurrence was also assessed. The three highest doses of sumatriptan (5 mg 49%, 10 mg 46%, 20 mg 64%) were significantly better than the placebo (25%) at providing headache relief (moderate or severe headache improving to mild or none) 120 min after treatment (P </= 0. 01). Also, the 20 mg dose was significantly superior to both the 10 and 5 mg doses at this time point (P < 0.05). The proportion of patients who were headache-free 120 min after treatment, was also higher following 20 mg (42%) rather than following any other sumatriptan dose (14-24%, P < 0.005 20 vs 10 mg) or placebo (11%). Headache recurrence in patients who had responded to initial treatment was reported by 30-41% of patients who received sumatriptan, compared with 33% of patients in the placebo group. Sumatriptan nasal spray was well tolerated, the incidence of adverse events with each dose of sumatriptan being similar to the placebo (20-27 and 23%, respectively). Apart from bad/bitter taste, the events were comparable with those reported following sumatriptan treatment by other routes of administration.

Adult↗

Discrimination of intranasal cocaine.

In the development of medications for the treatment of cocaine abuse, the drug discrimination paradigm can be used to identify medications that can attenuate the discriminative stimulus effects of cocaine. To ascertain that participants are basing the discrimination on the drug's central effects, this paradigm requires that the drug and placebo administrations do not produce any peripheral effects on which the discrimination can be based. This study examined whether intranasal cocaine (50 mg) can be discriminated from placebo (46 mg lactose + 4 mg cocaine), how quickly this discrimination can be made, and whether pretreatment with intranasal benzocaine can affect this discrimination. Results showed that subjects were generally able to discriminate the drug conditions correctly 15 s after administration, and this was unaffected by benzocaine. These results suggest that subjects base the discrimination on peripheral drug effects (e.g. taste) that are not affected by anaesthesia of the nasal passage, and that the intranasal route of cocaine administration is unlikely to be feasible with a drug discrimination paradigm.

Administration, Intranasal↗

Zinc, the brain and behavior.

The total content of zinc in the adult human body averages almost 2 g. This is approximately half the total iron content and 10 to 15 times the total body copper. In the brain, zinc is with iron, the most concentrated metal. The highest levels of zinc are found in the hippocampus in synaptic vesicles, boutons, and mossy fibers. Zinc is also found in large concentrations in the choroid layer of the retina which is an extension of the brain. Zinc plays an important role in axonal and synaptic transmission and is necessary for nucleic acid metabolism and brain tubulin growth and phosphorylation. Lack of zinc has been implicated in impaired DNA, RNA, and protein synthesis during brain development. For these reasons, deficiency of zinc during pregnancy and lactation has been shown to be related to many congenital abnormalities of the nervous system in offspring. Furthermore, in children insufficient levels of zinc have been associated with lowered learning ability, apathy, lethargy, and mental retardation. Hyperactive children may be deficient in zinc and vitamin B-6 and have an excess of lead and copper. Alcoholism, schizophrenia, Wilson's disease, and Pick's disease are brain disorders dynamically related to zinc levels. Zinc has been employed with success to treat Wilson's disease, achrodermatitis enteropathica, and specific types of schizophrenia.

Animals↗

Psychotherapies for the person with HIV disease.

Work with patients with HIV infections demands the highest degree of professional skill, empathy, and self-understanding on the part of the therapist. He or she must be an excellent diagnostician, must be knowledgeable about the use of medications in a wide array of clinical conditions, and must be willing to confront both psychodynamic issues of the past and realistic medical and social concerns of the present and future. The therapy must be driven not by the disease but informed by the evolving needs, of the individual patient for self-understanding and a sense of enhancing competence. Although decline and death must be confronted during therapy, its center is on living and creating an engaged quality of life "in spite of". To help a person find the sweet-tasting strawberry of life in the face of what would otherwise be an intolerable situation can be one of the most meaningful acts we engage in as therapists.

AIDS Dementia Complex↗

A new animal model of binge eating: key synergistic role of past caloric restriction and stress.

Dieting and stress are important in the etiology and maintenance of eating disorders, and dieting strongly predicts stress-induced overeating in humans. We hypothesized that caloric restriction and stress interact in a unique manner to promote binge eating. To test this hypothesis, a group of young female rats were cycled through a restriction period (4 days of 66% of control food intake) followed by 6 days of free feeding prior to being stressed by acute foot shock. After three of these cycles, the food intake of rats exposed only to restriction (R), or only to stress (S), did not differ from controls. However, R+S rats that were restricted and refed, despite normal body weight and food intake after free feeding, engaged in a powerful bout of hyperphagia when stressed (Experiment 1). The R + S effect was replicated in an older group of rats (Experiment 2). The hyperphagia was characteristically binge-like, it constituted a 40% selective increase in highly palatable (HP) food (P < .001) over a discrete period of time (within 24 h post-stress), and reflected feeding for reward (higher HP:chow ratio) over metabolic need as occurred after restriction (higher chow:HP ratio). Subsequent experiments revealed that binge eating did not occur if only chow was available (Experiment 3) or if restriction-refeeding (R-R) did not proximally precede stress (Experiment 4). Experiment 5 revealed that a history of R-R cycles followed by only one stress episode was sufficient to increase intake to 53% above controls as early as 2 h after stress (P < .001). This animal model of binge eating should facilitate investigations into the neurochemical changes induced by dieting and environmental stress to produce disordered eating and provide a preclinical tool to test preventive strategies and treatments more relevant to bulimia nervosa, multiple cases of binge eating disorder (BED) and binge-purge type anorexia nervosa.

Animals↗

Amplification of the erotic enema deviance.

Use of enemas for sexual stimulation has been observed and named klismaphilia. Some klismaphiliacs indulge their taste for enemas in other wise normal sexual settings. Others combine it with fetishes, excretory and otherwise or with masturbation. Still others practice klismaphilia in homosexual or sadomasochistic settings or in group sex.

Ego↗

Dietary concerns associated with the use of medications.

Medications can affect, and be affected by, nutrition. The interactions between drugs and various components in the diet are in part responsible for the erratic drug responses observed in patients. Because of the diversity of food consumption patterns among individuals and the widespread use of drugs, an array of varied and complicated side effects can occur. When vitamins, minerals, or other food components alter drug utilization or when drugs induce nutritional deficiencies, the effect poses a risk to the patient. Drugs can also affect many nutrition-related factors, such as appetite, taste acuity, and gastrointestinal function. Dietary habits or metabolic changes should be examined carefully and evaluated in any patient who unexpectedly gains or loses weight while taking drugs. Medicated patients need to be aware of good nutrition practices and to understand the importance of dietary modifications associated with certain diseases. A nutritious diet not only makes an important contribution to the health of those individuals but also reduces the risk of nutrition disorders or altered drug efficacy. Nutrition counseling should be considered for medicated patients to help them make rational decisions about their food choices.

Absorption↗

[Parasitosis in an adult population with chronic gastrointestinal disorders].

We worked with 185 middle-class patients above 18 years of age, both sexes, who presented diarrhea and/or chronic gastrointestinal disorders. The faeces were collected serially in formol 10% and processed in the following way: direct microscopy, with and without wet staining, concentration by Ritchie's method, 1% safranine technique for a specific investigation of Cryptosporidium sp., and faecal sieving macroparasites. Twenty eight point six of the studied patients showed at least one enteroparasite in their faeces, 48 harboured one parasite and 5 harboured two parasites. The following parasites were found and their corresponding percentages in the entire studied population are given below: Blastocystis hominis 15.7%, Giardia lamblia 7.5%, Cryptosporidium sp. 1.6%, Entamoeba coli 3.3%, Chilomastix mesnilii 1.1%, Ancylostoma duodenale-Necator americanus 0.5%, Ascaris lumbricoides 0.5%, Enterobious vermicularis 0.5% y Endolimax nana 0.5%. The most frequently found enteroparasites in the positive patients were B. hominis and G. lamblia. Cryptosporidium sp. was diagnosed in only three patients. The source of infection could be presumed in all of them. The symptomatology coincided with that described for this coccid in the bibliography. In spite of the fact that they were HIV seronegative patients the diarrhea was not self-limiting, but the immunologic profile of their relatives remained unknown and no other cause of immunosuppression could be detected with justified chronicity. The treatment with spiramycin was effective. Giardiasis was found in 17 patients, and the source of infection could not be inferred in any of them. They all had chronic diarrhea and their most frequent symptoms were abdominal pain, metallic taste, flatulency and nausea. Most of these patients were harboured one parasite, and only 2 of them simultaneously presented another faecal parasite associated to G. lamblia. Treatment with metronidazole was successful in all of them. Twenty nine patients were found to have B. hominis. The source of infection could not be inferred, this amoeboid was present as the only parasite in 25 patients. Predominant symptoms were flatulence, abdominal distention and colis. All patients suffered from chronic diarrhea, alternating, in some cases, with constipation. Good therapeutic results were obtained with metronidazole. Considering that one third of the patients examined presented faecal parasites associated to chronic disorders, it is important to insist on the detection of parasites to chronic disorders, it is important to insist on the detection of parasites using appropriate diagnostic techniques since the application of specific therapy made their eradication possible as well as relieving the patients' symptomatology.

Adolescent↗

Lansoprazole: an update of its place in the management of acid-related disorders.

Lansoprazole is an inhibitor of gastric acid secretion and also exhibits antibacterial activity against Helicobacter pylori in vitro. Current therapy for peptic ulcer disease focuses on the eradication of H. pylori infection with maintenance therapy indicated in those patients who are not cured of H. pylori and those with ulcers resistant to healing. Lansoprazole 30 mg combined with amoxicillin 1g, clarithromycin 250 or 500mg, or metronidazole 400 mg twice daily was associated with eradication rates ranging from 71 to 94%, and ulcer healing rates were generally >80% in well designed studies. In addition, it was as effective as omeprazole- or rabeprazole-based regimens which included these antimicrobial agents. Maintenance therapy with lansoprazole 30 mg/day was significantly more effective than either placebo or ranitidine in preventing ulcer relapse. Importantly, preliminary data suggest that lansoprazole-based eradication therapy is effective in children and the elderly. In the short-term treatment of patients with gastro-oesophageal reflux disease (GORD), lansoprazole 15, 30 or 60 mg/day was significantly more effective than placebo, ranitidine 300 mg/day or cisapride 40 mg/day and similar in efficacy to pantoprazole 40 mg/day in terms of healing of oesophagitis. Lansoprazole 30 mg/day, omeprazole 20 mg/day and pantoprazole 40 mg/day all provided similar symptom relief in these patients. In patients with healed oesophagitis. 12-month maintenance therapy with lansoprazole 15 or 30 mg/day prevented recurrence and was similar to or more effective than omeprazole 10 or 20 mg/day. Available data in patients with NSAID-related disorders or acid-related dyspepsia suggest that lansoprazole is effective in these patients in terms of the prevention of NSAID-related gastrointestinal complications, ulcer healing and symptom relief. Meta-analytic data and postmarketing surveillance in >30,000 patients indicate that lansoprazole is well tolerated both as monotherapy and in combination with antimicrobial agents. After lansoprazole monotherapy commonly reported adverse events included dose-dependent diarrhoea, nausea/vomiting, headache and abdominal pain. After short-term treatment in patients with peptic ulcer, GORD, dyspepsia and gastritis the incidence of adverse events associated with lansoprazole was generally < or = 5%. Similar adverse events were seen in long-term trials, although the incidence was generally higher (< or = 10%). When lansoprazole was administered in combination with amoxicillin, clarithromycin or metronidazole adverse events included diarrhoea, headache and taste disturbance. In conclusion, lansoprazole-based triple therapy is an effective treatment option for the eradication of H. pylori infection in patients with peptic ulcer disease. Preliminary data suggest it may have an important role in the management of this infection in children and the elderly. In the short-term management of GORD, lansoprazole monotherapy offers a more effective alternative to histamine H2-receptor antagonists and initial data indicate that it is an effective short-term treatment option in children and adolescents. In adults lansoprazole maintenance therapy is also an established treatment option for the long-term management of this chronic disease. Lansoprazole has a role in the treatment and prevention of NSAID-related ulcers and the treatment of acid-related dyspepsia; however, further studies are needed to confirm its place in these indications. Lansoprazole has emerged as a useful and well tolerated treatment option in the management of acid-related disorders.

2-Pyridinylmethylsulfinylbenzimidazoles↗

Effect of citric acid and citric acid-sucrose mixtures on swallowing in neurogenic oropharyngeal dysphagia.

The ability of sour and sweet-sour mixtures to improve swallowing in 11 nursing home residents with neurogenic oropharyngeal dysphagia was investigated using fiberoptic endoscopic evaluation of swallowing. Citric acid (2.7%) significantly reduced aspiration and penetration compared with water. Teaspoon delivery of liquids significantly reduced aspiration and penetration compared with natural cup drinking. Subjects tended to appropriately self-regulate the cup volume they consumed after the first trial. A significant increase in spontaneous dry swallows was observed after both taste stimuli. The mechanisms for improved swallowing due to citric acid are not understood but may be due to increased gustatory and trigeminal stimulation of acid to the brainstem in neurologically impaired subjects.

Aged↗

Ageusia associated with thalamic plaque in multiple sclerosis.

Ageusia and the cheirooral syndrome developed in a patient with a relapse of multiple sclerosis. Magnetic resonance imaging revealed an area of demyelination in the thalamus. This lesion presumably affected the most medial part of the ventralis posterior nucleus, where taste information is located. Given the proximity of the taste area and somatosensory representation of the hand and oral cavity in the ventralis posterior nucleus, we propose that a diagnosis of thalamic lesion should be considered when ageusia occurs with the cheirooral syndrome.

Adult↗

Zopiclone: a new nonbenzodiazepine hypnotic used in general practice.

Ninety-one insomniacs completed a four-week study of the efficacy and safety of zopiclone (Z), 7.5 mg. Patients were randomly allocated to one of two groups, each of which received placebo (P) during one week of the study. Forty-six subjects received medication in the sequence of ZPZZ, and 45 received it in the sequence of ZZPZ. Twice each week, patients filled out presleep and postsleep questionnaires and reported their morning complaints. Compared with placebo, zopiclone produced statistically significant improvements (P less than 0.05) in sleep induction time, duration of sleep, number of awakenings per night, quality and soundness of sleep, morning state of rest, and daytime sleepiness. Headache, dizziness, nausea, and bitter taste were the predominant complaints. Zopiclone can be considered an efficient and safe hypnotic for chronic insomnia.

Adult↗

Epithelial cells and their neighbors. II. New perspectives on efferent signaling between brain, neuroendocrine cells, and gut epithelial cells.

Surface sensory enteroendocrine cells are established mucosal taste cells that monitor luminal contents and provide an important link in transfer of information from gut epithelium to the central nervous system. Recent studies now show that these cells can also mediate efferent signaling from the brain to the gut. Centrally elicited stimulation of vagal and sympathetic pathways induces release of melatonin, which acts at MT2 receptors to increase mucosal electrolyte secretion. Psychological factors as well mucosal endocrine cell hyperplasia are implicated in functional intestinal disorders. Central nervous influence on the release of transmitters from gut endocrine cells offers an exciting area of future gastrointestinal research with a clinical relevance.

Brain↗

Combined naloxone and fluoxetine on deprivation-induced binge eating of palatable foods in rats.

Opioid antagonism and serotonergic stimulation is associated with macronutrient-specific hypophagia in animals. In the present study we evaluated their systemic effect alone, and in combination, at various doses, on the intake of sweet carbohydrate-rich and sweet fat-rich foods, tastes, and nutrients that are typical of binge-food items. Low-dose (1 mg/kg) naloxone, alone, preferentially suppressed fat-rich intake while low-dose (2.5 mg/kg) fluoxetine, alone, preferentially suppressed carbohydrate-rich intake. Each drug at these doses, combined with various doses of the other (2.5-10 mg/kg fluoxetine; 0.01-1 mg/kg naloxone) additively suppressed both kinds of the sweet foods. Naloxone and fluoxetine have therapeutic potential in treating binge-eating disorders. This animal study suggests what shortcomings and benefits might be expected when combining these two agents.

Animals↗

Screening and rehabilitation of olfaction after total laryngectomy in Swedish patients: results from an intervention study using the Nasal Airflow-Inducing Maneuver.

OBJECTIVES: To examine the olfactory function in patients with laryngectomy and to assess the results of the Nasal Airflow-Inducing Maneuver (NAIM) odor-rehabilitation technique. DESIGN: A prospective intervention study. SETTING: University hospital. PATIENTS: Twenty-four patients, 21 men and 3 women, mean age 68 years, who underwent laryngectomy at least 5 months prior to intervention. INTERVENTION: Speech therapists trained patients in the NAIM technique: simultaneous lowering of the jaw, floor of the mouth, tongue, base of the tongue, and soft palate while the lips are closed. Three interventions were given within 6 weeks. MAIN OUTCOME MEASURE: Olfactory testing with semistructured interview, the Questionnaire on Olfaction, Taste, and Appetite (QOTA), and the Scandinavian Odor-Identification Test (SOIT). Quality of life was measured with European Organization for Research and Treatment of Cancer QLQ-C30 and QLQ-H&N35 questionnaires. The patients were categorized as smellers or nonsmellers based on the SOIT results. RESULTS: Before the treatment, 10 patients (42%) were smellers (ie, 6 had normosmia and 4 hyposmia), while 14 patients (58%) were nonsmellers (ie, all had anosmia). Thus, 18 patients had impaired olfaction. Using the NAIM technique, 13 (72%) of 18 patients with impaired olfaction showed improvement. Of the 14 nonsmellers, 7 converted to smellers after only 1 intervention session, giving us a success rate of 50% in anosmic patients after 1 session. CONCLUSIONS: Olfactory impairment is common in patients who underwent laryngectomy. The NAIM method is easy to learn and rapidly improves smell and taste. A single intervention session is sometimes sufficient, but many patients benefit from repeated training. The SOIT test is an effective and simple test for the assessment of olfaction acuity after laryngectomy.

Aged↗

Melatonin and insomnia.

The hypnotic action of melatonin 5 mg p.o. was explored in 15 subjects with psychophysiological insomnia in a double-blind controlled self-report questionnaire study. Melatonin or placebo was taken at 20.00 hours for a 1-week period in random order. Effects on sleep and wakefulness were monitored by visual analogue scale and structured interview. Bedtime, sleep onset time, estimated total sleep and wake time, as well as self-rated sleep quality, were not altered by melatonin, and estimates of next-day function did not change. The period of melatonin, treatment was retrospectively correctly identified by 8 of 15 subjects. Despite unchanged ratings of night sleep quality on the last night of each treatment, 7 of 15 subjects reported that sleep had subjectively improved to a minor extent in the week of active treatment. Side-effects attributed to melatonin included headache and an odd taste in the mouth. These data indicate that melatonin is probably of no clinical value in the management of psychophysiological insomnia.

Adult↗

Building a virtual reality temporal bone dissection simulator.

The temporal bone is one of seven bones that comprise the human skull, and has an intimate relationship with many vital structures. Anatomically, its three-dimensional relationships make it one of the most challenging areas for surgeons to understand and master. In addition, the temporal bone contains minute structures that are among the most sophisticated and delicate in the human body. These structures include the cochlea and vestibular organs, which are responsible for hearing and balance; the middle ear, including the ossicles, which conduct acoustic energy to the cochlea; and the facial nerve, which is responsible for controlling the muscles of facial expression, and contributes to the sensation of taste. Additionally, the temporal bone forms a major portion of the skull base, and has intimate relationships to vital structures including the carotid artery, jugular vein, cerebral cortex, brainstem, and cranial nerves. Surgical procedures performed on the temporal bone include: procedures to eradicate chronic and acute infections; procedures to remove malignant and benign tumors within the temporal bone, from the skull base, or from the posterior cranial fossa; procedures to restore the hearing mechanism; procedures to eliminate balance disorders; and procedures to correct congenital anomalies. For surgeons-in-training, and even surgeons-in-practice, mastery of the anatomy of the temporal bone and the many complex approaches necessary to treat patients takes years of focused endeavor. This is typically accomplished through the dissection of human cadaver temporal bones, which are scarce, and require a dedicated laboratory facility. Efforts are currently underway to develop a realistic simulator for temporal bone procedures. Users immersed in the simulator will interact with a three-dimensional temporal bone, derived from patient-specific data, using a haptic interface to simulate traditional surgical procedures. Feedback from experts in otologic surgery will be built into the system for additional instruction. This presentation will include an overview of the application being developed, a report of its current state of development, and plans for the future.

Computer Simulation↗

[Clinical evaluation of 99mTc-hexakis 2-methoxy isobutyl isonitrile (MIBI): multicenter phase III clinical trial].

Multicenter Phase III clinical trial on a new myocardial imaging agent, 99mTc-hexakis 2-methoxy isobutyl isonitrile (99mTc-MIBI), was carried out in 464 patients with various cardiac disorders. Both planar and tomographic images provided high-quality regional myocardial perfusion images which correlated well with 201TlCl images. The positive ratios of myocardial infarction and angina pectoris by the agent were as high as that of 201TlCl. In addition, ventricular function and wall motion could be assessed with first-pass and ECG gated studies. There was no serious adverse reaction which were attributed to 99mTc-MIBI in any of patients studied. A transient metallic taste was observed immediately after the injection in approximately 64% of the patients. Based on its safety and efficacy, the clinical usefulness of 99mTc-MIBI was observed in 562 (93.1%) of 604 injections. In conclusion, 99mTc-MIBI was useful as a imaging agent of myocardial blood flow.

Adolescent↗