Alpha-blockade and thiazide treatment of hypertension. A double-blind randomized trail comparing doxazosin and hydrochlorothiazide.

This trial involved 107 patients in a two-group, parallel, double-blind, randomized study comparing the diuretic, hydrochlorothiazide (HCTZ) (dose 25 to 50 mg) and the alpha 1 antagonist, doxazosin (dose 2 to 16 mg). All randomized participants were followed for at least 1 year. Participants were recruited from the community. The study was carried out in four phases: Phase I-Baseline; Phase II-Monotherapy Titration; Phase III-Combination Therapy Titration; and Phase IV-Maintenance. The following measures were carried out: blood pressure, biochemistries, lipids/lipoproteins, quality of life, ambulatory electrocardiograms, echocardiograms, adverse experiences, and drug adherence. Both drugs were well tolerated, with only 4% taken off doxazosin and 7% off HCTZ. Adverse experiences were uncommon and mostly mild. Both drugs were effective in managing hypertension over 1 year of therapy. There was no difference noted in terms of efficacy of blood pressure lowering between the two study drugs, nor was there any evidence of tolerance developing or of any serious adverse effects. Average final doses for drugs were 7.8 mg for doxazosin and 36 mg for HCTZ. The results show that, over the course of 1 year, both drugs significantly lowered systolic and diastolic pressures compared to baseline; doxazosin (-19 and -16 mm Hg); HCTZ (-22 and 15 mm Hg). Blood pressure lowering was not significantly different between drugs. Sitting heart rate was not affected by drugs. Changes in quality of life measures were similar between groups. Echocardiographic measures at 1 year showed significant between-drug differences in change in left internal end systolic and diastolic dimensions and end systolic stress. Both doxazosin and HCTZ were effective drugs over 1 year for treating hypertension.

Naltrexone plasma levels, clinical response and effect on weight in autistic children.

This research measured naltrexone levels in plasma, to assess the relationship between behavioral response to naltrexone and plasma levels, and the effects of naltrexone on weight in hospitalized autistic children (n = 41). A double-blind, placebo-controlled, parallel groups design with fixed dose was used, with random assignment to naltrexone or placebo. Drug plasma levels were analyzed by gas chromatography/mass spectrometry, and weights were obtained weekly. Naltrexone levels measured in 17 children ranged from 0.12 to 5.60 ng/mL (mean = 0.71, standard error of the mean = 0.32). There was no relationship between plasma levels and age, level of intellectual functioning, scores on the 14 selected Children's Psychiatric Rating Scale (CPRS) items, Clinical Global Impressions, Global Clinical Consensus, and the CPRS hyperactivity factor. There was a trend (p = .06) for children receiving naltrexone in the highest weight percentile (> or = 90th) to lose weight (mean = -0.42 kg) but this was not the case for those in the lower weight percentiles (mean = +0.03 kg).

Naltrexone in autistic children: behavioral symptoms and attentional learning.

OBJECTIVE: To assess critically the short-term efficacy and safety of naltrexone in autistic children and its effects on discrimination learning in the laboratory. METHOD: A parallel group design was employed. After a 2-week placebo baseline period, children were randomly assigned either to naltrexone or to placebo for a period of 3 weeks followed by a one-week posttreatment placebo period. Multiple raters and rating scales were employed in a variety of conditions. Forty-one children, all inpatients, ages 2.9 to 7.8 years, completed the study. Naltrexone reduced hyperactivity and had no effect on discrimination learning in the laboratory. There was a suggestion that it had a beneficial effect on decreasing self-injurious behavior. Untoward effects were mild and transient. CONCLUSION: In the present study, naltrexone significantly reduced only hyperactivity, and no serious untoward effects were observed. The effectiveness of naltrexone in the treatment of autism and self-injurious behavior requires additional assessment in a sample of children with moderate to severe self-injurious behavior.

Acute dystonic reaction with low-dose pimozide.

It is essential to recognize individual susceptibility to neuroleptic-induced side effects for treatment guidelines. This paper reports on a 6.9-year-old autistic male who developed repeated episodes of acute dystonic reactions associated with pimozide administration at the doses of 0.096 mg/kg/day and 0.032 mg/kg/day and 32 hours following pimozide withdrawal, as well as during subsequent thioridazine administration. It draws the clinician's attention to unusual susceptibility to extrapyramidal side effects and suggests that if a child shows this type of susceptibility to one neuroleptic, he/she may react similarly to other neuroleptics as well.

Autistic children on followup: change of diagnosis.

The present study compared baseline assessments of 30 autistic children studied at ages 2.8 to 6.3 years (mean = 4.5; median = 4.5) with assessments at followup 0.38 to 14.3 years later (mean = 5.05; median = 4.33). The assessments included diagnosis, Severity of illness, and intellectual functioning. At the time of followup, when they participated in the American Psychiatric Association's DSM-IV Field Trial, the subjects' ages ranged from 5.5 to 19.25 years (mean = 9.60). At followup, a clinical diagnosis of autistic disorder was made in 22 of the 30 children; autistic disorder, residual state was diagnosed in 6 children, and pervasive developmental disorder not otherwise specified (PDDNOS) was diagnosed in 2 children. The group of children who, on followup, no longer met the diagnosis of autistic disorder had lower severity of illness ratings and higher intellectual functioning at baseline and at followup than those children who remained diagnosed as autistic disorder; they also showed a rise in intellectual functioning over time whereas those children who remained diagnosed as autistic did not. Both groups showed decreases in severity of illness over time.

Plasma beta-endorphin levels, naltrexone, and haloperidol in autistic children.

Plasma beta-endorphin levels were measured in 13 autistic children, aged 3.67 to 11.67 years at the end of treatment (naltrexone, haloperidol, pimozide, or placebo) and in 5 of the 13 children also at baseline. Baseline plasma beta-endorphin levels were lower than those reported in the literature. There was a strong correlation between plasma beta-endorphin levels and severity of sterotypies in all children. Naltrexone did not seem to have a specific effect on plasma beta-endorphin levels; short-term haloperidol treatment was associated with an increase, whereas long-term haloperidol treatment seemed to have a depressive effect on plasma beta-endorphin levels, which rose after withdrawal of haloperidol.

Experimental models of hypersensitivity pneumonitis.

Experimental models of hypersensitivity pneumonitis are important tools for the study of the pathogenesis of this disease. In this paper we review the characteristics of the main animal models developed until now. The HP models in rats seem to be particularly appropriate for studying pigeon fancier's disease and the HP induced by chemicals, as well as for studying mediators of acute lesions induced by immunocomplexes. However, the HP models developed in rats are of less value in the evaluation of other aspects of the pathogenesis of this clinical entity in humans. The murine models of HP offer several advantages: the ease and simplicity of intranasal administration, the ability to produce acute and subacute pulmonary lesions similar to those found in humans, the possibility of reproducing lesions similar to those of nonaffected exposed subjects and the possibility of pharmacologically modulating the process. Their disadvantages lie in the different pulmonary lymphocyte response and the difficulty in reproducing a model of chronic fibrosis. The HP models in rabbits are extraordinarily useful for evaluating the immunological mechanisms through which subjects repeatedly exposed to the antigen do not develop clinical manifestations. However, the rabbit has several immunological differences when compared to humans, and the effect of some immunomodulators in this animal is different. The models of HP in guinea-pigs have as advantages the ease in handling the animals, the possibility of pharmacological manipulation, and the ability to induce an acute phase that is very similar to that observed in humans. The drawback, however, is the low lymphocyte response and the striking eosinophilic reaction that contrast with the bronchoalveolar data found in HP in humans. In conclusion, there is no ideal model to reproduce all the findings observed in humans, suggesting that the experimental animal and the method of developing HP should be selected on the basis of concrete research aims.

The pharmacologic treatment of conduct disorders and rage outbursts.

Although this article focuses on psychopharmacology, pharmacotherapy is only part of a comprehensive treatment program. Treatment should be individualized to the patient's condition and level of intellectual functioning (e.g., conduct disorder, mental retardation). Clinicians should be acquainted with the Food and Drug Administration's regulations and the Physician's Desk Reference's guidelines. Psychoactive agents should be prescribed judiciously under careful clinical and laboratory monitoring, especially when given on a long-term basis. Knowledge of potential short- and long-term side effects is imperative to minimize impairment (cognitive, sedation) and to maximize achievement of adaptive behaviors. Aggressiveness is a low-frequency behavior and therefore difficult to assess. Aggressiveness with an explosive affective component and rage seems to be more responsive to pharmacotherapy than aggressiveness alone. Children who present with covert conduct disorder symptoms, such as stealing and lying, might not be as responsive to psychoactive agents as the conduct disorder with explosive characteristics. The neuroleptics are considered the standard drugs for the treatment of aggression but sedation and concern over tardive dyskinesia have led investigators to explore and study other classes of drugs. Lithium carbonate has been studied in short-term clinical trials and has been shown to be an effective alternative to the neuroleptics. Carbamazepine and propranolol seem to be promising agents but require further critical assessment in children and adolescents. Stimulants should be considered the first choice of treatment in coexisting conduct disorder and ADHD or in milder forms of aggression. In conclusion, there is a need for systematic investigation of the effectiveness and safety of psychoactive agents in children and adolescents with aggressiveness, explosiveness, and rage outbursts. There is some supportive evidence that some patients with these target symptoms are good responders to certain drugs. Future research should compare pharmacotherapy to psychosocial treatment and the combination of both.

Pimozide in autistic children.

This open pilot study explored the efficacy and safety of pimozide, over a 3-week period, in hospitalized autistic children. Eight males, ages 4.2 to 8.3 years, completed the study. Intellectual functioning ranged from moderate to profound mental retardation. Symptoms included severe withdrawal, stereotypies, hyperactivity and/or hypoactivity, aggressiveness, and temper tantrums. Therapeutic daily doses of pimozide ranged from 3.0 mg to 6.0 mg with a mean of 4.9 mg (0.12-0.32 mg/kg; mean, 0.22). Laboratory studies including electrocardiogram and liver function tests remained within normal limits. Untoward effects were minimal and transient. Decreases of behavioral symptoms were evidenced on all measures including the Children's Psychiatric Rating Scale, Clinical Global Impressions, and Global Clinical Judgments Scale (consensus rating). Of the 5 hypoactive children, 4 showed a decrease in hypoactivity, whereas 1 child showed worsening. These findings are promising and indicate the need for further study.

Predictors of side effects associated with lithium administration in children.

Data were pooled from three controlled and double-blind studies of lithium carbonate involving a total of 48 hospitalized children, and secondary data analyses were conducted. The objective was to assess whether there is a relationship between a child's chronological age and side effects associated with lithium administration. Two dependent measures of side effects were investigated: number of side effects per child and number of episodes of side effects per child. The children were diagnosed as having conduct disorder with a profile of severe aggressive and explosive behavior; their ages ranged from 5.08 to 12.92 yrs (mean, 9.23 yrs). For the entire sample of 48 children, the effect of age on side effects was statistically significant (p = .057); younger children had more side effects than older children. This relationship continued to hold after adjustment for weight, serum lithium levels, optimal dose, and duration of optimal dose.

[Primary malignant melanoma of the esophagus]. / Melanoma maligno primario de esófago.

Primary malignant melanoma of the esophagus is very rare, and only 139 cases have been described in all the world literature. We present one case of primary malignant melanoma of the esophagus in a 76-year-old woman who reported the symptoms of dysphagia and recent weight loss; the radiography showed a large polypoid mass filling the entire lower half of the esophagus, dark brown-black in the endoscopy. Histologic analysis demonstrated the existence of a malignant melanoma infiltrating the esophageal mucosa, composed of anaplastic cells with abundant brown pigment which had positive immunoreactivity for the S-100 protein.

Use of antihypertensive agents with particular comorbid problems.

This article reviews the use of several classes of antihypertensive drugs in elderly hypertensive patients who may also have one of eight concomitant medical conditions. Specific contraindications in various disease states as well as preferred choice(s) of drugs exist. The rationale for drug choice is supported by explanations that relate to the pathophysiology of hypertension in the elderly population and the disease under consideration.

Embolomycotic aneurysm of external iliac artery: producing ipsilateral hydronephrosis and venous insufficiency.

We report a case of embolomycotic aneurysm of the right iliac artery secondary to bacterial endocarditis. The patient, a 33-year-old woman, presented with unilateral hydronephrosis and lower extremity edema caused by aneurysmal compression of the ipsilateral ureter and the external iliac vein. She was treated with ligation and an extraperitoneal left-external-iliac-artery to right-femoral-artery bypass using a knitted Dacron prosthesis. Since her surgery, our patient has been well except for persistence of moderate leg edema. To the best of our knowledge, we are reporting the 1st case of embolomycotic external-iliac-artery aneurysm secondary to bacterial endocarditis and resulting in hydronephrosis and venous insufficiency.

HLA-linked control of predisposition to lepromatous leprosy.

In a study of the relation between HLA and lepromatous leprosy, HLA haplotype segregation was analyzed in 28 families with multiple cases of different types of leprosy. The inheritance of HLA-DR2, HLA-DR3, and HLA-MT1, which had previously been shown to be associated with susceptibility to leprosy or with a leprosy type, was analyzed separately. Segregation occurred in a significantly nonrandom fashion in both polar tuberculoid leprosy and lepromatous leprosy. This finding indicated HLA-encoded control of a predisposition to both of these forms of the disease. In both cases the segregation observed among healthy siblings was random. Thus, susceptibility to leprosy per se is probably not controlled by HLA-linked genes. HLA-DR3 was inherited preferentially by children with polar tuberculoid leprosy rather than lepromatous disease (P = .02), and HLA-MT1 was inherited preferentially by children with lepromatous leprosy (P = .04). The results confirmed the association of these genetic markers with leprosy type.

Association of HLA specificity LB-E12 (MB1, DC1, MT1) with lepromatous leprosy in a Venezuelan population.

To investigate whether an association could be found between HLA and lepromatous leprosy a population study was performed in Tachira, Venezuela. This was done in the same endemic area in which recently both non-random parental HLA-haplotype and preferential segregation of the HLA specificity LB-E12 (MB1, DC1, MT1) was demonstrated in lepromatous leprosy patients from multicase families. In this study 32 lepromatous patients and 32 healthy controls were typed for HLA-A, -B, -C, -DR and the specificities MB and MT. The frequency of LB-E12 (MB1, DC1, MT1) showed a significant increase in lepromatous leprosy patients (p = 0.04). This is the first report concerning HLA and leprosy which confirms in the same endemic area an association observed in families on the population level.