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PubMed1992

[Sumatriptan and its use in treatment of migraine and cluster headaches].

The methods used presently for abortion of the attacks of migraine and cluster headache are not fully satisfactory which causes that the search for new therapies is continuing. Although the mechanism of migraine attacks remains unexplained, it is thought that an important role in it is played by serotonin receptors, vasodilation in certain regions and opening of arteriovenous communications in the head. Sumatriptan is an agonist of 5-HT1 -like receptors and exerts a selective vasoconstricting effect on the arteries of the head, particularly in the rami of the carotid artery. In 1988 the first reports appeared on the effectiveness of the drug in migraine attacks. In the following years extensive, multicentre and international studies of the drug were carried out on over 600 healthy volunteers and nearly 6000 patients with migraine. The studies demonstrated that Sumatriptan was effective in abortion of migraine attacks. After oral administration of 100 mg or subcutaneous injection of 6 mg in nearly 70% of cases the attack regressed or was greatly alleviated, similarly as other symptoms accompanying the headache such as photophobia, nausea, vomiting. Studies were undertaken also on the effectiveness of Sumatriptan in emergency treatment of cluster headache, and good results were again achieved. The tolerance of the drug is good, although in some cases side effects develop, usually transient and mild, among them tingling, feeling of pressure, heat or heaviness of the head or chest, taste change and burning sensation at the site of injection. Sumatriptan, similarly as all novel drugs, requires caution in its use, particularly in patients with coronary heart disease and hypertension, and also in old patients. As yet, the use of the drug in paediatric migraine or in pregnancy is not recommended.

Cluster Headache↗
PubMed2005

Alcohol withdrawal severity in inbred mouse (Mus musculus) strains.

Male mice (Mus musculus) from 15 standard inbred strains were exposed to a nearly constant concentration of ethanol (EtOH) vapor for 72 hr, averaging 1.59 +/- 0.03 mg EtOH/mL blood at withdrawal. EtOH- and air-exposed groups were tested hourly for handling-induced convulsions for 10 hr and at Hours 24 and 25. Strains differed markedly in the severity of withdrawal (after subtraction of control values), and by design these differences were independent of strain differences in EtOH metabolism. Correlation of strain mean withdrawal severity with other responses to EtOH supported previously reported genetic relationships of high EtOH withdrawal with low drinking, high conditioned taste aversion, low tolerance to EtOH-induced hypothermia, and high stimulated activity after low-dose EtOH. Also supported were the positive genetic correlations among EtOH, barbiturate, and benzodiazepine withdrawal. Sensitivity of naive mice to several chemical convulsant-induced seizures was also correlated with EtOH withdrawal.

Alcohol Withdrawal Delirium↗
PubMedDate not supplied

Somatoform symptoms, anxiety, and depression in the context of traumatic life experiences by comparing participants with and without psychiatric diagnoses.

The present study examines somatoform symptoms, anxiety and depression in connection with traumatic life experiences by comparing participants with and without psychiatric diagnoses. Significant group differences in the quantity of somatoform symptoms and the degrees of anxiety and depression could be found between participants with and without psychiatric diagnoses. Experience of sexual abuse leads to significantly more somatoform symptoms. Experience of repeated physical abuse as an additional factor significantly increased the depression score in all groups. This study reveals that the type of somatic complaint allows a prediction of the kind of traumatic life experience suffered. Physical abuse may be predicted by discomfort in and around the precodium, loss of appetite and stomach discomfort or a churning feeling in the stomach. Sexually abused participants reported significantly more anal pain, bad taste in the mouth or an excessively coated tongue, sexual indifference, and urinary retention. The findings of this study also revealed an association between depression, anxiety and somatoform symptoms and the type of traumatic life experience. The experience of physical and sexual abuse was found to be the most highly discriminative function.

Adolescent↗
PubMed1995

Nicotine and addiction. The Brown and Williamson documents.

OBJECTIVE: To learn how nicotine has been regarded by a major tobacco company. DATA SOURCES: Documents from Brown and Williamson Tobacco Corporation (B&W), the British American Tobacco Company (BAT), and other tobacco interests provided by an anonymous source, obtained from Congress, and received from the private papers of a former BAT officer. STUDY SELECTION: All available materials, including confidential reports regarding research and internal memoranda exchanged between tobacco industry lawyers. CONCLUSIONS: During a period of 22 years (1962 to 1984), employees of B&W and BAT conducted research and commented on the pharmacology of nicotine. They consistently regarded nicotine as the pharmacological agent that explained tobacco use. In the early part of the period under study, officials of the companies wrote about nicotine addiction explicitly. Inhalation of cigarette smoke by the consumer was recognized throughout the period as necessary for the normal function of a cigarette. The documents contain little indication that research was conducted on either the taste or the flavor of nicotine. The documents reveal an intention on the part of B&W and its corporate parent to affect the function of the body with nicotine.

Commerce↗
PubMed1997

Sensitization, somatization, and subjective health complaints.

More than half of the days lost due to sickness absence are due to diagnostic groups that solely or mainly depend on subjective statements from the patient The most frequent subjective health complaints are musculoskeletal pain. These conditions do not seem to qualify as psychiatric or mental disorders, but are not strictly somatic states either. Terms like somatization may be inadequate terms for states that may be best understood as psychobiological feedback loops. Subjective health complaints is suggested as a neutral, descriptive term. Only a minority requires treatment and sickness compensation for prolonged periods for these very common states. In these patients the neurons in feed-forward and positive feedback loops may have developed sensitization. These patients tend to show an abnormal sensitivity to sensory input from muscles, the gastrointestinal tract, and to smell and taste. It seems to be futile to search for single-factor solutions. This approach opens up for the possible effectiveness of many different types of treatment, breaking the feedback loops.

Journal Article↗
PubMed2001

Treatment of migraine attacks with intranasal alniditan: an open study.

In this open phase-II clinical tolerability trial 17 neurologists enrolled a total of 112 patients and instructed them to administer a maximum of two doses of intranasal alniditan, a 5-HT1B/D receptor agonist, for the treatment of three consecutive migraine attacks of moderate to severe intensity. A second dose of the trial medication was allowed within 1-24 h after the first administration. At 1 h after intranasal administration, 70/103 (68%) patients had responded to treatment (reduction from severe or moderate headache before treatment to mild or no headache) after their first migraine attack, 65/94 (69%) after their second and 52/75 (71%) after their third. In 187/270 (69%) of all attacks, patients were considered responders at 1 h. The median time to onset of effect was 30 min. The migraine headache recurred in 44% (attack 1), 55% (attack 2) and 44% (attack 3) after 4-5 h. Sixty-eight per cent of the patients reported nasal irritation, 19% taste disturbance and 44% throat irritation. Alniditan 2 mg, administered via the intranasal route, was effective in relieving migraine headaches in over two-thirds of the patients at 1 h.

Administration, Intranasal↗
PubMedDate not supplied

Antiepileptic drugs in migraine prevention.

Migraineurs may continue to experience attacks, despite daily use of one or more agents from a wide range of drugs, including beta-blockers, calcium channel blockers, serotonin antagonists, tricyclic antidepressants, monoamine oxidase inhibitors, and antiepileptic agents. Divalproex sodium is the only antiepileptic drug approved for migraine prevention. Gabapentin, topiramate, and other antiepileptic agents are being evaluated for migraine prevention and treatment. Prospective, double-blind, placebo-controlled clinical trials of divalproex, gabapentin, and topiramate for migraine prevention generally were composed of a prospective baseline period, a dose titration period, and a fixed-dose treatment period. The primary efficacy variable was a reduction in the 28-day frequency of migraine headache. Patients receiving divalproex for 12 weeks at doses up to 1500 mg/day achieved significant decreases in the migraine frequency (P<.05), corresponding to reductions of 30% to 40% compared with baseline. Nearly half of the divalproex-treated patients had a 50% or more reduction from baseline in headache frequencies (P< or =.05). Asthenia, vomiting, somnolence, tremor, and alopecia were common adverse events associated with divalproex. Significant reductions in migraine frequency were also observed with gabapentin (1800 to 2400 mg/day) when compared with placebo (P<.01), and nearly half of all patients treated at the highest dose experienced a reduction in headache rate of 50% or more. Somnolence was the most commonly reported adverse event among the gabapentin-treated patients. Two single-center, double-blind, placebo-controlled clinical trials evaluated topiramate for migraine prevention. A lower 28-day migraine frequency was seen during 18 weeks of administration at a maximum daily dose of 200 mg (P =.09). In a second study, a significantly lower mean 28-day migraine frequency was observed during 16 weeks of treatment with topiramate (P =.0015). Mean reduction in migraine frequency was also significantly greater in topiramate-treated patients (P =.0037). Paresthesias, diarrhea, somnolence, and altered taste were commonly reported adverse events in the topiramate-treated patients. Unlike some patients given divalproex or gabapentin, some given topiramate reported weight loss. Large, double-blind, placebo-controlled trials may prove the effectiveness of novel antiepileptic drugs in migraine prevention.

Acetates↗
PubMedDate not supplied

Topiramate in migraine prevention: a double-blind, placebo-controlled study.

OBJECTIVE: To evaluate the efficacy of topiramate in the preventative treatment of episodic migraine. BACKGROUND: Topiramate is a broad-spectrum antiepileptic drug effective for treatment of multiple seizure types in adults and children. Antiepileptic agents have demonstrated efficacy in migraine prevention, and open-label experience from our clinic has suggested that topiramate might be effective for this use. We consequently conducted a single-center, double-blind, placebo-controlled trial to evaluate the efficacy and safety of topiramate for the preventative treatment of migraine. METHODS: Forty patients, aged 19 to 62 years (mean, 38.2 years), were randomly assigned in a 1:1 ratio to receive topiramate (n = 19; all women) or placebo (n = 21; 20 women, 1 man). Following a prospective baseline phase of 4 weeks, the study drug dose was titrated weekly in 25-mg increments over 8 weeks to 200 mg per day or to the maximum tolerated dose. The titration phase was followed by an 8-week maintenance phase. RESULTS: During the entire double-blind phase, topiramate-treated patients experienced a significantly lower 28-day migraine frequency (3.31 +/- 1.7 versus 3.83 +/- 2.1; P =.002) compared to placebo, irrespective of use of concomitant migraine prevention medications. The mean 28-day migraine frequency was reduced by 36% in patients receiving topiramate as compared with 14% in patients receiving placebo (P =.004). Twenty-six percent of the patients on topiramate and 9.5% of the patients on placebo achieved a 50% reduction in migraine frequency (P >.05). The mean dose of topiramate was 125 mg per day (range, 25 to 200 mg per day). Topiramate was well tolerated; 2 of 19 topiramate-treated patients discontinued treatment due to adverse events. Adverse effects that occurred more frequently in topiramate-treated patients included paresthesia, weight loss, altered taste, anorexia, and memory impairment. CONCLUSIONS: Preventative therapy with topiramate significantly reduced migraine frequency. Larger multicenter clinical studies may further delineate the role of topiramate in migraine prevention.

Adolescent↗
PubMed2006

Disruption of glycine transporter 1 restricted to forebrain neurons is associated with a procognitive and antipsychotic phenotypic profile.

The NMDA receptor is thought to play a central role in some forms of neuronal plasticity, including the induction of long-term potentiation. NMDA receptor hypofunction can result in mnemonic impairment and has been implicated in the cognitive symptoms of schizophrenia. The activity of NMDA receptors is controlled by its endogenous coagonist glycine, and a local elevation of glycine levels is expected to enhance NMDA receptor function. Here, we achieved this by the generation of a novel mouse line (CamKIIalphaCre;Glyt1tm1.2fl/fl) with a neuron and forebrain selective disruption of glycine transporter 1 (GlyT1). The mutation led to a significant reduction of GlyT1 and a corresponding reduction of glycine reuptake in forebrain samples, without affecting NMDA receptor expression. NMDA (but not AMPA) receptor-evoked EPSCs recorded in hippocampal slices of mutant mice were 2.5 times of those recorded in littermate controls, suggesting that neuronal GlyT1 normally assumes a specific role in the regulation of NMDA receptor responses. Concomitantly, the mutants were less responsive to phencyclidine than controls. The mutation enhanced aversive Pavlovian conditioning without affecting spontaneous anxiety-like behavior in the elevated plus maze and augmented a form of attentional learning called latent inhibition in three different experimental paradigms: conditioned freezing, conditioned active avoidance, conditioned taste aversion. The CamKIIalphaCre;Glyt1tm1.2fl/fl mouse model thus suggests that augmentation of forebrain neuronal glycine transmission is promnesic and may also offer an effective therapeutic intervention against the cognitive and attentional impairments characteristic of schizophrenia.

Animals↗
PubMed1992

[The participation of the sensorimotor cortex in assessing the quality of food reinforcement against a background of thirst].

In trained cats, unilateral extirpation of the sigmoid gyri's cortex disinhibited the unreinforced runs while preserving the positive conditioned reflexes associated with differentiation of different salt food reinforcement. The bilateral extirpation induced a disorder of differentiated inhibition while preserving the conditioned runs reinforced with the highly salted food. The unilateral extirpation did not affect the food-motor conditioning against the background of the salt diet. The bilateral extirpation delayed the differentiation inhibition and facilitated the positive conditioning.

Animals↗
PubMed2002

[Efficacy of tea blends in the treatment of dyspeptic disorders--an application observation].

BACKGROUND: Medicinal teas present one of the oldest galenic preparations of herbal remedies. Their use is primarily determined by tradition and empirics. One of their traditional domains are gastrointestinal disorders, which belong to the most frequent wellness disorders. While the effectiveness and compatibility of essential oils, modern drug extracts, and alcoholic extracts from bitters and etheric-oil drugs in the treatment of dyspeptic disorders have been documented in placebo-controlled clinical trials, little attention has so far been given to aqueous extracts from bitters and etheric-oil drugs, which are equivalent to the standard method of preparing herbal teas. PURPOSE: The presented application observation in clinical practice tried to give evidence for effectiveness and tolerability of medicinal teas in the treatment of dyspeptic disorders and to quantify their extent. MATERIAL AND METHODS: We collected information about effectiveness, compatibility, and side effects of herbal teas from 89 patients (w = 56; m = 33) suffering from dyspeptic disorders. The data were reported with a questionnaire that was sent to physicians and pharmacists experienced in phytotherapy. RESULTS: It could be shown that complaints in patients with primary dyspeptic symptoms (n = 79) decreased by an average of 74%. Final overall assessment revealed that the physicians as well as the patients estimated an effectiveness of 2.9 points as good (3 = good). Compatibility was considered as good to very good (4 = very good), with an average rating of 3.3 points. Two patients stopped therapy because of an extreme aversion to the bitter taste of the teas. No other serious side effects were reported. CONCLUSION: The herbal teas can be considered effective, very well tolerable and to a large extent free from serious side effects. However, due to the limited observation time, no final conclusion could be given concerning long-term compatibility.

Beverages↗
PubMed2001

Oral drug self-administration: an overview of laboratory animal studies.

Many abused drugs can be established as orally delivered reinforcers for rhesus monkeys and other animals. Benzodiazepines, barbiturates, opioids, psychomotor stimulants, dissociative anesthetics, and ethanol can come to serve as reinforcers when taken by mouth. The principal problems in establishing drugs as reinforcers by the oral route of administration are (1) aversive taste, (2) delay in onset of central nervous system effects, and (3) consumption of low volumes of drug solution. Strategies have been devised to successfully overcome these problems, and orally delivered drugs can be established as effective reinforcers. Reinforcing actions are demonstrated by consumption of greater volumes of drug solution than volumes of the water vehicle, and supporting evidence for reinforcing effects consists of the maintenance of behavior under intermittent schedules of reinforcement and the generation of orderly dose-response functions. This article presents an overview of studies of behavior reinforced by oral drug reinforcement. Factors that control oral drug intake include dose, schedule of reinforcement, food restriction, and alternative reinforcers. Many drugs, administered by the experimenter, can alter oral drug reinforcement. Relative reinforcing effects can be assessed by choice procedures and by persistence of behavior across increases in schedule size. In general, reinforcing effects increase directly with dose. Rhesus monkeys prefer combinations of reinforcing drugs to the component drugs. The taste of drug solutions may act as a conditioned reinforcer and a discriminative stimulus. Consequences of drug intake include tolerance and physiological dependence. Findings with orally self-administered drugs are similar to many findings with other positive reinforcers, including intravenously self-administered drugs.

Administration, Oral↗
PubMedDate not supplied

Alterations in the solitary tract nucleus of the rat following perinatal food restriction and subsequent nutritional rehabilitation.

Newborn of altricial species maintain functional gustatory communication with the mother because the neural substrate and the capacity to discriminate and promote gustofacial responses are already operating. Because little is known about the effects of perinatal food restriction upon gustatory neuronal brain stem structures, we characterized neuronal Golgi-Cox alterations of the solitary tract rostral portion (NSTr) where gustatory information is known to convey in neonatal Wistar rats. Pre-and neonatally undernourished rats exhibited a general reduction in the number and extension of distal dendrites particularly in small neurons but little effect upon perikarya measurements of the NSTr neuronal population. By contrast, in nutritional and sensory rehabilitated rats the number of distal dendrites increased, although the dendritic extensions were less affected compared to perinatally underfed and control subjects. The data indicate that perinatal food restriction interferes with the NSTr dendritic arbor organization, while nutritional and sensorial rehabilitation given by normally lactating dams induced plastic changes presumably modifying the integrative processes underlying early taste discriminative capabilities. Moreover, since perinatal food restriction is a powerful stressor influence and the NST forms a part of a complex system underlying adaptive stress responses, the neuronal alterations observed here may be partly due to this noxious perinatal influence.

Animal Nutritional Physiological Phenomena↗
PubMed2004

[Topiramate in the preventive treatment of migraine: experience in a tertiary center].

Frequent migraine attacks require prophylactic treatment. Anticonvulsants have been suggested due to the progressive knowledge that cortical hyperexcitability is involved in migraine pathophysiology. Topiramate is one of these drugs and its efficacy has been demonstrated in several studies. The aim of this study is to evaluate the adherence and response to topiramate in migraineurs under treatment in a tertiary center. During a 2-year period, all of the patients receiving topiramate for migraine were evaluated after 3 months. The parameters evaluated were adherence to treatment, frequency reduction of attacks >50% and adverse events. Among 175 patients included, 134 (76.6%) returned. Among the 134 patients evaluated, 82 (61.2%) revealed frequency reduction >50% and 105 (78.4%) patients presented weight loss (average 3.4Kg). The most frequent side effects were paresthesias (39.6%); emotional disturbances (including depression, irritability and anxiety) in 17,9%; thinking impairment (12.7%); memory disturbances (12.7%) and altered taste (11.9%). Despite methodological limitations we concluded that adherence to its use and efficacy occurred in most of the patients. In addition, the side effect profile was acceptable. Further controlled studies are necessary to confirm these observations.

Adolescent↗
PubMed2006

NMDA Partial agonist reverses blocking of extinction of aversive memory by GABA(A) agonist in the amygdala.

The ability to extinguish aversive memories is of significant clinical interest. The amygdala plays an important role in emotional conditioning and its experimental extinction. It has been suggested that gamma-aminobutyric acid (GABA) agonists retard extinction and that consolidation of extinction involves N-methyl-D-aspartate receptor (NMDAR)-mediated plasticity. The aim was to further explore the interaction between GABA and NMDA in the amygdala in consolidation of experimental extinction in the rat. To that end conditioned taste aversion (CTA) was used. In CTA, the amygdala has been reported to subserve both acquisition and extinction. The GABA(A) receptor agonist, muscimol, administered into the amygdala immediately after the first extinction session, caused lasting disruption of extinction of CTA for at least 2 weeks. However, the administration of GABA(A) receptor antagonists had no effect on extinction kinetics. Microinfusing the partial NMDA agonist D-cycloserine together with or after muscimol infusion reversed the blocking effects of muscimol. These findings could bear relevance to the potential involvement of extinction abnormalities in behavioral disorders, and their amelioration.

Amygdala↗
PubMed1995

Smell impairment. Can it be reversed?

Patients who have lost the sense of smell usually come to a doctor on their own, reporting loss of the sense of taste. Inflammation (often due to allergy), viral infection, and head trauma are common causes of olfactory disturbance. History taking may provide clues to these and other problems (eg, toxin exposure, congenital dysosmia). Workup should not begin until a standardized test has been given that established impairment of the sense of smell. The only truly reversible cause is inflammation, which is confirmed when smell returns after a course of corticosteroid. Sinus computed tomography is necessary to view the olfactory cleft; lack of obstruction indicates that smell impairment is nonreversible. Patients deserve an explanation for their disorder and a prognosis. If restoration of their sense of smell is unlikely, patients should be cautioned to take steps to ensure safety in regard to such dangers as gas leaks, smoke, and spoiled foods.

Algorithms↗
PubMed1991

Characterizing organic delusional syndrome.

We present a first comprehensive description of the clinical features of patients with organic delusional syndrome. This description is based on information from 39 patients with organic delusional syndrome among 14,889 patients who presented for initial evaluation over a 5-year period at our institution. This description includes an enumeration of the common clinical symptoms of this syndrome and the respective prevalence and mean severity of each symptom. The severity of the symptoms of organic delusional syndrome are compared with those of schizophrenia to determine which symptoms distinguish between these two diagnostic categories. Patients with organic delusional syndrome demonstrated significantly more symptoms of "acquired intellectual impairment," "impaired sensorium," and "hallucinations of smell, taste, or touch," while schizophrenic patients demonstrated more "flat affect," "emotional coldness," and "thought disorganization." In addition, associated factors are presented concerning demographics, modes of treatment, level of functioning, and current physical problems associated with organic delusional syndrome.

Delusions↗