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BACKGROUND: Human platelet antigens (HPAs) are alloantigens derived from polymorphisms in platelet-surface glycoproteins. The occurrence of alloantibodies against HPAs can lead to platelet destruction and subsequent thrombocytopenia. Brazilians have a high rate of racial admixture, and the knowledge of HPA polymorphisms in particular donors from north Brazil, who have a large Amerindian influence, is a relevant strategy to prevent alloimmunisation. OBJECTIVE: Our aim was investigate the HPA allele's frequencies in the Amazonas blood donors. METHODS: We performed HPA genotyping among 200 Amazonas blood donors by microarray for 11 HPA biallelic systems, including six of the most clinically significant systems (HPA-1 to -5 and -15) and five others (HPA-6 to -9 and -11) that have been also associated with alloimmunisation, amounting to 22 HPA alleles. RESULTS: The obtained allele frequencies were compared with data of 38 populations worldwide to determine the hierarchical relationship and estimated the probability of mismatch platelets. The allele frequencies were 0·862 for HPA-1a, 0·137 for HPA-1b, 0·852 for HPA-2a, 0·147 for HPA-2b, 0·665 for HPA-3a, 0·335 for HPA-3b, 0·995 for HPA-4a, 0·005 for HPA-4b, 0·892 for HPA-5a, 0·107 for HPA-5b, 0·997 for HPA-9a, 0·005 for HPA-9b, 0·502 for HPA-15a and 0·497 for HPA-15b. The incompatibility risks are higher for HPA-15 and HPA-3, followed by HPA-1, -2 and -5. CONCLUSION: We found differences among populations worldwide, and it is interesting to note the indigenous and European influences in this region, reinforcing the heterogeneity in the ancestry of Brazilians. The results will be helpful in providing information for platelet transfusion to avoid alloimmunisation.

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Virulence factors and antimicrobial resistance patterns of Escherichia coli isolates were evaluated. A total of 80 E. coli isolates were evaluated, being 64 from clinical samples (intestinal content and fragments of organs from diarrheic piglets), seven from feces of clinically healthy piglets and sows, and nine environmental samples (five from facilities, two from feed, one from insect, and one from waste). Molecular characterization was performed by PCR detection of fimbriae and toxin genes and plasmid content determination. The isolates were also characterized according to their resistance or sensitivity to the following drugs: ampicillin, trimethoprim:sulfamethoxazole, tetracycline, amikacine, colistin, norfloxacin, florfenicol, enrofloxacin, cefalexin, trimethoprim, neomycin, chloramphenicol, and gentamicin. From 80 E. coli isolates, 53.8 percent were classified as enterotoxigenic E. coli (ETEC), 2.5 percent were shiga toxin-producing E. coli (STEC), and 43.8 percent showed a non specific pattern and were unclassified. One fecal isolate from non-diarrheic piglet was classified as ETEC by PCR. Clinical isolates showed resistance mainly for tetracycline and trimethoprim:sulfamethoxazole. Plasmidial DNA was observed in 70 isolates, being 78.5 percent of clinical isolates, 8.57 percent of non-diarrheic feces, and 12.8 percent of environment.

Os fatores de virulência e a resistência aos antimicrobianos foram avaliados em Escherichia coli. Um total de 80 isolados de E. coli, sendo 64 de amostras clínicas (conteúdo intestinal e fragmentos de órgãos de leitões diarreicos), sete das fezes de porcas e leitões saudáveis e nove de amostras ambientais (cinco de instalações, dois de alimentos, um de inseto e um de esterqueira). A caracterização molecular feita pela PCR objetivou detectar fimbrias e toxinas, bem como a determinação do conteúdo de plasmídeos. Os isolados foram caracterizados quanto à resistência ou sensibilidade às seguintes drogas: ampicilina, sulfazotrim, tetraciclina, amikacina, colistina, norfloxacina, florfenicol, enrofloxacina, cefalexina, trimetoprim, neomicina, cloranfenicol e gentamicina. Dos 80 isolados, 53,8 por cento foram classificados como E. coli enterotoxigênica (ETEC), 2,5 por cento como E. coli produtora de shiga toxina (STEC) e 43,8 por cento, por não apresentarem padrão específico, não foram classificadas. Pela PCR, um isolado de fezes de suíno sem diarreia foi classificado como ETEC. Os isolados das amostras clínicas foram principalmente resistentes à tetraciclina e à sulfazotrim. Em 70 isolados, observaram-se DNA plasmidial, destes 78,5 por cento foram obtidos de amostras clínicas, 8,57 por cento de leitões sadios e 12,8 por cento de amostras ambientais.

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OBJECTIVE: To review the pharmacology, pharmacokinetics, clinical investigations, and adverse effects of sulpiride as a treatment for schizophrenia. DATA SOURCES: Information was selected from a MEDLINE search of English-language medical literature using "sulpiride" as the search term. Manual searches of pertinent journal article bibliographies also were performed. STUDY SELECTION: Clinical investigations with a blind, controlled, randomized design and treatment durations of at least 6 weeks were preferred. Formal assessment of a patient's schizophrenia was required. One clinical investigation using a 4-week treatment duration and 1 open investigation were included for purposes of adverse reaction assessment. DATA EXTRACTION: Clinical investigations were evaluated for design, sample size, diagnosis, duration, and outcome. Data from all investigations were selected by 1 author and reviewed by both authors. DATA SYNTHESIS: Sulpiride is a substituted benzamide with selective dopaminergic blocking activity. Early pharmacology reports hypothesized that sulpiride was selective for dopamine (D)2 receptors only, but sulpiride also blocks D3 and D4 receptors. Sulpiride does not block D1, adrenergic, cholinergic, gamma-aminobutyric acid-ergic, histaminergic, or serotonergic receptors to an appreciable extent. The oral bioavailability of sulpiride is poor, with estimates approximating 35%. Sulpiride does not appear to have an extensive first-pass metabolism, nor is it extensively protein-bound. There have been no identified active metabolites, and elimination appears to depend primarily on the kidneys. Clinical studies support sulpiride as being equally effective as active controls in the acute treatment of patients with schizophrenia. Daily doses permitted in these clinical investigations ranged from 100 to 3200 mg. Further investigation is required to determine the usefulness of sulpiride as a chronic treatment of schizophrenia and its effectiveness in treating the negative symptoms of schizophrenia. Sulpiride may cause extrapyramidal effects, autonomic effects, tardive dyskinesia, and the neuroleptic malignant syndrome. The incidence of these adverse reactions has not been established. CONCLUSIONS: Sulpiride is a safe and effective pharmacotherapeutic treatment for the acute management of schizophrenia. A unique pharmacology does not appear to provide sulpiride with a greater effectiveness than the standard antipsychotics, but may provide it with minor safety advantages.

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OBJECTIVE: To review the pharmacology, pharmacokinetics, clinical investigations, adverse effects, and dosing strategies of paroxetine as a treatment of major depression. DATA SOURCES: Specific paroxetine information was selected from a MEDLINE search using paroxetine as the search term. Other sources included manual searches of pertinent journal article references, meeting abstracts, and the manufacturer. STUDY SELECTION: Clinical investigations with a blind, controlled (placebo and/or active), randomized design were selected. With the exception of treatment-resistant depression, no short-term, open investigations were selected. DATA EXTRACTION: Clinical investigations were evaluated for design, sample size, diagnosis, duration, definition of response, and outcome. Data from all investigations were selected by one author and reviewed by both authors. DATA SYNTHESIS: Paroxetine is a selective serotonin reuptake inhibitor (SSRI) recently approved for the treatment of major depression. It is a potent and selective inhibitor of serotonin reuptake and has weak or no activity on the other monoamines; it is also weakly anticholinergic. Although pharmacokinetic parameters are variable, paroxetine is generally well absorbed, highly protein bound, hepatically cleared, and has no active metabolites. Clinical investigations support paroxetine's effectiveness as an antidepressant in an outpatient population with moderately severe depression. Its effectiveness is superior to that of placebo and is comparable to that of active controls. The majority of investigations have been six weeks in duration. Additional data are required to support paroxetine's promise for longer treatment periods (i.e., > or = 1 y), in the elderly, and for treatment-resistant depression. Adverse effects appear to be similar to those caused by the other SSRIs; some of the most common are nausea, diarrhea, insomnia, dry mouth, and nervousness. Significant drug interactions may occur with the monoamine oxidase inhibitors, phenobarbital, and phenytoin. CONCLUSIONS: Paroxetine is safe and effective for treatment of outpatients with moderately severe depression. Further clinical data and experience are necessary to determine this agent's place in the long-term treatment of major depression.

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Clozapine is an antipsychotic without the extra-pyramidal adverse effects associated with currently marketed antipsychotics. In animals, this drug has not been shown to induce catalepsy and only weakly antagonizes the stereotypic movements induced by apomorphine and the amphetamines. Clozapine is rapidly absorbed after both single and repeated oral doses, with steady-state concentrations attained within eight to ten days after beginning therapy. It is metabolized to N-oxideclozapine and N-desmethylclozapine, which have less pharmacological activity than the parent compound and are excreted in the urine and, to a lesser extent, in the feces. Clozapine has overall therapeutic efficacy and/or superiority to currently marketed antipsychotics in the treatment of refractory schizophrenia. Usual doses (25-900 mg/d) of clozapine cause fewer extrapyramidal adverse reactions than available antipsychotics. Hypotension, dizziness, salivation, and sedation are the most frequently reported adverse effects and tend to subside over time. Agranulocytosis is the most serious adverse reaction, and those receiving clozapine should undergo weekly white blood cell count determinations. Clozapine is useful for those treatment-resistant patients who have not responded to adequate trials of other antipsychotics.

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Bupropion is a trimethylated monocyclic phenylaminoketone that is an effective antidepressant in humans. It neither is sedating, anticholinergic, nor cardiotoxic. Its mechanism of action may be related to dopamine, but remains uncertain at this time. Clinical trials comparing bupropion 300-750 mg/d with placebo show it to be superior to placebo in efficacy and as well tolerated. Bupropion, in controlled clinical trials, is as effective as amitriptyline or imipramine, with fewer side effects. The only clinically significant adverse reaction to bupropion in more than 1000 patients studied has been seizure induction at a frequency comparable with that of imipramine. Bupropion appears to be safe and effective in both adult and geriatric depressed patients. Although it appears to be safer and equally efficacious when compared with currently used antidepressants, it has not been tested by routine clinical use.

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The in vitro interaction of selected drugs with coffee, tea, gallic acid, and gallotannic acid was examined by mixing solutions of drug with each of these four preparations. Results of these experiments indicate that significant precipitation occurs for a variety of agents, including several phenothiazines, amitriptyline, haloperidol, imipramine, and loxapine. The strong complex which is formed between these drugs and tannins is probably the basis of the interaction of these drugs with coffee and tea. Although precipitates did occur with a number of neuroleptics, two members of this drug class, thiothixene and molindone, failed to interact with the solutions used.

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Pirprofen, a nonsteroidal antiinflammatory drug (NSAID) undergoing Phase III investigation as Rengasil (Ciba-Geigy Corp.), is useful in the management of both rheumatoid arthritis and osteoarthritis and as an analgesic. In doses of 600-800 mg/d, pirprofen has been found to be as effective as, but not superior to, aspirin 3.6 g/d in relieving the more common symptoms of rheumatoid arthritis. Pirprofen is as effective as, but not superior to, other available NSAIDs in terms of efficacy, tolerability, and incidence of adverse effects. The recommended dosage in osteoarthritis is 450-600 mg/d. As with all NSAIDs, including aspirin, the side effects most commonly seen with pirprofen are gastrointestinal in nature. Peptic ulceration and occult gastrointestinal blood loss have been reported in a small percentage of patients receiving pirprofen. Central-nervous-system-related side effects that are frequently associated with high-dose aspirin therapy appear less frequently with pirprofen. Although it does not offer distinct advantages over other NSAIDs, pirprofen offers an effective therapeutic alternative for patients who are unable to tolerate aspirin or other existing compounds.

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Tardive dyskinesia, a syndrome of involuntary motor movements, can be a permanent consequence of the long-term use of antipsychotic drugs. While there is no well-established drug treatment, case reports and the results of a few clinical studies suggest that drugs that facilitate the GABA-ergic system may decrease the abnormal movements. One such class of drugs is the benzodiazepines. We administered diazepam to 13 subjects in a 24-week, crossover design study. Tardive dyskinesia and psychopathology were assessed by blind raters using the Abnormal Involuntary Movement Scale and the Brief Psychiatric Rating Scale (BPRS). The means of all movement measurements improved from the baseline, with orofacial, subtotal, symptom severity, and total reaching significance. However, we were unable to demonstrate a drug effect; the patients improved to a similar degree whether or not they received diazepam. Their psychiatric disorders did not worsen with diazepam administration and, in fact, improved slightly; the activation factor of the BPRS was significantly improved over baseline. Our results suggest that diazepam is not effective in managing the movements of tardive dyskinesia and that behavior modification strategies be investigated to help patients control symptoms.

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Using an ABA' research design, the effects of a benzodiazepine gamma-aminobutyric acid (GABA)-ergic agent, diazepam, on various aspects of tardive dyskinesia (TD) were investigated in 21 patients. Videotaped recordings of the examinations were rated blind on the Abnormal Involuntary Movements Scale. In nonsedating amounts, diazepam had a significant anti-TD effect, especially in terms of limb dyskinesia. A significant portion of the therapeutic effect persisted after the medication was withdrawn. The results suggest that diazepam has a specific anti-TD action and that in some cases it may be able to produce a somewhat lasting correction of the deranged neurobiological mechanisms in TD. Since the main sites of action of benzodiazepines and the highest concentrations of benzodiazepine-linked GABA receptors are in the limbic and cortical structures that provide principal sources of inputs to the basal ganglia, it is suggested that the supra-striato-pallidal mechanisms of voluntary movement control should be considered in understanding the pathogenesis and treatment of TD.

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Amoxapine is a tricyclic antidepressant agent, which is chemically related to the antipsychotic agent loxapine, but which appears to block selectively the neuronal reuptake of norepinephrine; it is qualitatively similar to desipramine. In studies of patients with mixed depressive illnesses, amoxapine is at least as effective as amitriptyline and imipramine and probably more effective than placebo in ameliorating depressive symptoms. Claims of more rapid onset of therapeutic effects are based on group mean data obtained from small samples of depressed patients with heterogeneous and imprecisely defined diagnostic types. Amoxapine has yet to be compared with desipramine or maprotiline, the most pharmacologically similar antidepressants. Biopharmaceutical and pharmacokinetic data are limited, and a relationship between serum concentrations and efficacy has not yet been shown. Acute toxicity and drug interaction documentation are also lacking. At this time, amoxapine represents a chemical alternative to traditional tricyclic antidepressants. There are no consistent data indicating superiority of amoxapine over any other antidepressant agent for any specific symptom constellation, in rate or extent of improvement, or in any particular diagnostic or demographic population. Studies in which amoxapine is compared with pharmacologically similar agents at therapeutically equivalent doses in diagnostically homogeneous groups are needed to establish the drug's true place in the treatment of depressions.

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The effect of Mylanta on naproxen bioavailability was studied in 11 healthy volunteers. In separate experiments, single oral doses of naproxen (250 mg) and multiple oral doses (250 mg twice daily for 7 days) were administered with and without Mylanta. Coadministration of naproxen with Mylanta in the single-dose experiment did not significantly affect the area under the curve (579 vs. 580 microgram/ml X hr with and without Mylanta, respectively), time to peak serum concentration (2.5 vs. 2.6 hr), peak serum concentration (37.2 vs. 34.8 microgram/ml) or plasma half-life (16.1 vs. 16.4 hr). There was no significant difference between trough level naproxen concentrations at steady state (29.6 microgram/ml with Mylanta vs. 30.7 microgram/ml without Mylanta). The data were also used to investigate naproxen pharmacokinetics predicted by two different pharmacokinetic models, one of which allowed for protein binding. The nonlinear protein-binding model accurately predicted steady-state concentration, while the values predicted by the linear model exceeded actual values by 33-54%.

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A case describing the effect of hemodialysis on naproxen plasma levels in a 48-year-old anuric man with chronic glomerulonephritis is reported. The patient received 500 mg of naproxen daily for rheumatoid arthritis while undergoing hemodialysis thrice weekly. The patient's mean pre-dialysis plasma concentrations were similar to those seen in normal volunteers, suggesting no accumulation of the drug. Plasma concentrations were higher after dialysis, probably because of fluid loss during dialysis. Naproxen is not cleared from the body during hemodialysis and, therefore, a post-dialysis naproxen dose is not necessary.

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The effect of the following variables on insulin loss from total parenteral nutrient solutions was examined: (1) time of infusion sample; (2) insulin concentration; (3) amino acid or polypeptide source; (4) electrolytes and vitamins; (5) inline filters; (6) glass and polyvinyl chloride (PVC) infusion containers; and (7) human albumin. I125-tagged insulin was added to various parenteral nutrient solutions in liter containers. These solutions were prepared and drained to simulate actual clinical use. The drained solutions were collected and measured for radioactivity, and the percent of insulin remaining in the infusion container was calculated. Basic solutions of amino acids and protein hydrolysates in dextrose with 30 units of insulin failed to deliver approximately 44 to 47% of the added insulin. Varying the concentration of insulin had a small but statistically significant effect on the degree of insulin loss. The use of inline filters and PVC bags caused an even greater loss of insulin. The addition of albumin or electrolytes and vitamins decreased the insulin loss.

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