Pneumocandins from Zalerion arboricola. III. Structure elucidation.

Pneumocandin B0 (6) and six related lipopeptides are antifungal and anti-Pneumocystis carinii agents from mutants of Zalerion arboricola, whose structures were determined mainly on the basis of spectroscopic analysis. They belong, along with pneumocandin A0 (L-671,329) previously isolated from these laboratories, to the echinocandin class of antifungal agents. The product from base-catalyzed ring opening involving the hemiaminal position of the dihydroxyornithine residue of B0, has been clearly defined as 6b. Modifications were limited to the 3-hydroxy-4-methylproline, 3,4-dihydroxyhomotyrosine and 4,5-dihydroxyornithine residues of pneumocandin A0.     

Executive function impairments in children with attention-deficit hyperactivity disorder: do they differ between school and home environments?

OBJECTIVE: The primary purpose of this study was to compare parent and teacher reports of executive function (EF), as measured by the Behavior Rating Inventory of Executive Function (BRIEF), on a sample of children who had been diagnosed with attention-deficit hyperactivity disorder (ADHD). If differences were found, the secondary purpose was to explore these differences by determining which of the 8 BRIEF scales, each representing a different EF, would best predict symptoms of ADHD by the 2 proxy reporters. METHOD: We performed a secondary data analysis on the assessment information pertaining to 240 children, aged 5 to 15 years, accessing services at an urban Toronto psychiatric program specializing in ADHD. We compared parent and teacher ratings and applied logistical binary regressions to predict the probability of a child's meeting the criteria for clinically significant inattention and hyperactivity-impulsivity on the ADHD Rating Scale-IV. RESULTS: As expected, teachers reported more variety and severity of EF impairments than did parents. In addition, teachers used inhibition, organization of materials, and planning and organizing as predictors of ADHD symptoms, whereas parents relied predominantly on inhibition, working memory, and planning and organizing as the risk factors. CONCLUSION: Consistent with the current theory, EF impairments, particularly in inhibition, appear to underlie the behavioural manifestation of ADHD. However, parents and teachers do not always agree when reporting EF impairments at home and in school. Thus information from both types of informants is essential for understanding and treating children with this disorder.     

Local cerebral glucose metabolic rates in obsessive-compulsive disorder. A comparison with rates in unipolar depression and in normal controls

We studied 14 patients with obsessive-compulsive disorder (OCD) by positron emission tomography and the fluorodeoxyglucose method, looking for abnormalities in local cerebral metabolic rates for glucose in brain structures that have been hypothesized to function abnormally in OCD. These patients were compared with 14 normal controls and 14 patients with unipolar depression. The patients with unipolar depression and OCD did not differ in levels of anxiety, tension, or depression. In OCD, metabolic rates were significantly increased in the left orbital gyrus and bilaterally in the caudate nuclei. This was apparent on all statistical comparisons with both controls and unipolar depression. The right orbital gyrus showed at least a trend to an increased metabolic rate in all comparisons. The metabolic rate in the left orbital gyrus, relative to that in the ipsilateral hemisphere (orbital gyrus/hemisphere ratio), was significantly elevated compared to controls and subjects with unipolar depression, and stayed high even with successful drug treatment. Though it was in the normal range in the morbid state, with improvement in OCD symptoms after drug treatment, the caudate/hemisphere metabolic ratio increased uniformly and significantly bilaterally. This ratio did not increase in patients who did not respond to treatment. Thus, OCD showed cerebral glucose metabolic patterns that differed from controls in both the symptomatic and recovered states.     

Investigation of an outbreak of Moraxella conjunctivitis at a Navajo boarding school

In 1986, an outbreak of Moraxella follicular conjunctivitis occurred in girls attending a Navajo boarding school in New Mexico. We diagnosed 19 cases of culture-proven, and 21 of clinical conjunctivitis based on isolation of Moraxella from conjunctival cultures and the occurrence of symptoms significantly associated with positive culture. Sharing eye makeup was significantly associated with Moraxella-positive conjunctivitis (odds ratio [OR] = 7.2, P = .004) and showed a trend toward significance in those with clinical conjunctivitis (OR = 2.9, P = .09). Eyeliner and eye shadow were implicated (OR = 4.1, P less than .05). We cultured samples of 13 students' makeup; one third of the eyeliners were positive for Moraxella. Nasal carriage of Moraxella was found in 35 (44%) of the 79 female boarders and in 20 (21%) of 97 Navajo patients at two nearby clinics. In a prospective evaluation of the effect of patient education and rifampin therapy on the occurrence of conjunctivitis during an 11-month follow-up period, both types of intervention were successful in significantly reducing the rate of conjunctivitis when compared with that in a control group.     

Physician motivations for nonscientific drug prescribing

Although there is increasing concern about inappropriate physician prescribing and how to devise programs to improve drug therapy decisions, little research has been published documenting the reasons for such misprescribing. We analyzed the motivations reported by 141 physicians who were part of a large multi-state randomized controlled trial of 'academic detailing.' The physicians were identified from state Medicaid prescribing records as moderate to high prescribers of cerebral or peripheral vasodilators, propoxyphene, or cephalexin, and were visited by clinical pharmacists serving as outreach educators in a medical school-based prescribing improvement program. Physicians' motivations for their prescribing patterns were discussed in an informal, interactive manner; all responses were recorded in detail by the pharmacists immediately following each visit. Of the 110 responses elicited, the most common reason offered by physicians for use of these medications was patient demand (51 statements, or 46%). Physicians also frequently attributed their prescribing of these drugs to intentional use of placebo effect (24%). An equally common reason was prescribers' assertion that their own clinical experience indicated that these drugs were actually therapies of choice in the conditions presented (26%), despite evidence from the research literature that this was not the case. Such indications included the use of the 'vasodilators' for senile dementia or peripheral vascular disease, cephalexin for viral upper respiratory infections, and propoxyphene instead of acetaminophen or aspirin for mild pain. Greater attention must be paid to physicians' attitudes and motivations concerning suboptimal prescribing if programs are to succeed in replacing these practices with more rational clinical decision-making.     

Aspergillus pancarditis following bone marrow transplantation for chronic myelogenous leukemia

A 34-year-old man with chronic myelogenous leukemia developed hemoptysis, pain in the left side of the chest, and a systolic heart murmur eight weeks following an allogeneic bone marrow transplant. His clinical status deteriorated, and he died ten weeks after transplantation. Autopsy revealed unsuspected disseminated aspergillosis, including the unusual finding of Aspergillus pancarditis and pericarditis. Cardiac aspergillosis is a uniformly lethal disease in immunocompromised persons and must be aggressively diagnosed following early symptoms.