Effects of the antimigraine compound zolmitriptan ('Zomig') on psychomotor performance alone and in combination with diazepam in healthy volunteers

Zolmitriptan (Zomig^TM) is a 5HT_1B/1D agonist which has the ability to cross the intact blood-brain barrier to access central as well as peripheral receptors. Because of the potential for central nervous system side effects, this randomized, double-blind, placebo-controlled, 6-period crossover study evaluated the effects of 2.5 and 5 mg doses of zolmitriptan on psychomotor performance and investigated any pharmacodynamic or pharmacokinetic interaction with diazepam. Twelve healthy volunteers received the following "treatments" as single doses: zolmitriptan 2.5 mg, zolmitriptan 5 mg, diazepam 10 mg, zolmitriptan 2.5 mg+diazepam 10 mg, zolmitriptan 5 mg+diazepam 10 mg and placebo. Pre-dose and at 1, 4, 8, and 24 h post-dose, the following validated battery of psychomotor tests was performed: Bond-Lader visual analogue scales (calmness, contentedness, and alertness factors), critical flicker fusion test, choice reaction time (recognition, motor, and total reaction times), finger-tapping test, number cancellation test and digit symbol substitution test. Plasma concentrations of zolmitriptan, its active metabolite, and diazepam and its active metabolites were measured at the same timepoints. Zolmitriptan 2.5 and 5 mg had no effect on psychomotor function when given alone. In contrast, diazepam 10 mg had profound effects, consistent with its sedative properties, but there was no synergism on concomitant administration of either dose of zolmitriptan. Plasma concentrations of zolmitriptan, diazepam, and their respective active metabolites were similar when the two drugs were given alone or in combination.     

Isolated lung transplantation for end-stage lung disease: a viable therapy.

Since January 1990, we have performed 29 isolated lung transplantations in 28 patients with end-stage lung disease (12 single, 16 bilateral). Recipient diagnoses were: cystic fibrosis (11), chronic obstructive pulmonary disease (6), pulmonary fibrosis (6), eosinophilic granulomatosis (1), postinfectious lung disease (1), adult respiratory distress syndrome (1), and primary pulmonary hypertension (2). There have been four deaths, two in patients with pulmonary fibrosis and two in patients with primary pulmonary hypertension. Four patients have undergone transplantation while on ventilatory support for respiratory failure (2 with cystic fibrosis, 1 having redo lung transplantation with cystic fibrosis, and 1 with adult respiratory distress syndrome); all of these have survived. Six patients required cardiopulmonary bypass, which was associated with increased transfusion requirement. All patients 2 months after discharge have returned to an active life-style, except for 2 patients who currently await retransplantation. Preoperative pulmonary rehabilitation has resulted in significant improvement in exercise performance in all patients. Immunosuppression consists of cyclosporine, azathioprine, and antilymphoblast globulin (University of Minnesota), withholding systemic steroids in the early postoperative period. We have employed bronchial omentopexy in all but four transplants; there has been one partial bronchial dehiscence, two instances of bronchomalacia requiring internal stenting, and one airway stenosis. Cytomegalovirus disease has been seen frequently (15 cases), but has responded well to treatment with ganciclovir. Other complication shave included one drug-related prolonged postoperative ventilation, thrombosis of a left lung after bilateral lung transplantation requiring retransplantation, five episodes of unilateral phrenic nerve palsy after bilateral lung transplantation (4 resolved), and the requirement of massive transfusion (greater than 10 units) in 5 patients.(ABSTRACT TRUNCATED AT 250 WORDS)     

Parenting stress among caregivers of children with congenital cataracts.

OBJECTIVE: To examine parenting stress among caregivers of young children with congenital cataracts and to assess whether diagnostic and/or treatment differences are associated with differences in perceived parenting stress. METHODS: Parents of 41 preschool-age children with congenital cataracts (13 with bilateral cataracts [BCCs] and 28 with unilateral cataracts [UCCs], of whom 14 were aphakic and 14 were pseudophakic) completed the Parenting Stress Index (PSI) and/or a disease-specific parental stress measure, ie, the Ocular Treatment Index (OTI). RESULTS: The 28-item OTI had excellent internal consistency (alpha = 0.94) and supported three of four a priori validity hypotheses. Parents of children with congenital cataracts reported normal parenting stress levels on the PSI. Parents of children with UCCs tended to report higher levels of stress, but not significantly so, than did parents of children with BCCs. Among parents of children with UCCs, those whose children were aphakic reported higher levels of stress on the OTI and all of the PSI subscales than did parents of pseudophakic children. These differences were statistically significant for two subscales (Adaptability [P =.03] and Mood [P =.01]). CONCLUSIONS: Although parents of children with congenital cataracts generally did not report increased parenting stress levels, clinicians should be aware that parenting stress can adversely impact patients' families. We did observe higher stress levels in parents with children who had UCCs and did not receive an intraocular lens-particularly stress related to their child's reaction to sensory stimulation and mood-compared with parents of pseudophakic children. Thus, clinicians may want to consider parenting stress levels when choosing a treatment for children with UCCs, especially because such stress has been associated with poor treatment compliance for children with other chronic conditions.     

Autosomal recessive microcephaly, mental retardation with nonpigmentary retinopathy and a distinctive electroretinogram

The association of microcephaly and mental retardation with a non-pigmentary retinopathy is described in three siblings of consanguineous parents. The electroretinogram showed the distinctive appearance of markedly attenuated "b" wave but normal "a" wave suggestive of a retinal dystrophy primarily affecting post-receptoral elements in the inner retina. This appears to be an autosomal recessive condition which has not been previously reported.     

Realizing the full potential of immunotoxins

When conjugated with antibodies that bind selectively to tumor cells, natural toxins from plants and bacteria represent a potentially powerful form of cancer therapy. Over the last several years, much thought and research effort has been devoted to optimizing the specificity and activity of these hybrid molecules. Here we review some of the insights that have come from detailed analyses of the so-called "first-generation immunotoxins," and discuss how these insights have prompted ideas for more effective design of "second-generation immunotoxins."