Randomized, controlled, proof-of-concept trial of MK-7622 in Alzheimer's disease.

Introduction: We evaluated the selective M1 muscarinic positive allosteric modulator, MK-7622, as adjunctive cognitive enhancing therapy in individuals with Alzheimer's disease.

Methods: A randomized, double-blind, proof-of-concept trial was performed. Participants with mild-to-moderate Alzheimer's disease, being treated with an acetylcholinesterase inhibitor, were randomized 1:1 to 45 mg of MK-7622 or placebo for 24 weeks.

Suvorexant in Patients With Insomnia: Results From Two 3-Month Randomized Controlled Clinical Trials.

Background: Suvorexant is an orexin receptor antagonist for treatment of insomnia. We report results from two pivotal phase 3 trials.

Methods: Two randomized, double-blind, placebo-controlled, parallel-group, 3-month trials in nonelderly (18-64 years) and elderly (≥65 years) patients with insomnia.

Randomized, controlled trial of telcagepant over four migraine attacks.

Methods: This study evaluated the calcitonin gene-related peptide (CGRP) receptor antagonist telcagepant (tablet formulation) for treatment of a migraine attack and across four attacks. Adults with migraine were randomized, double-blind, to telcagepant 140 mg, telcagepant 280 mg, or control treatment sequences to treat four moderate-to-severe migraine attacks. Control patients received placebo for three attacks and telcagepant 140 mg for one attack.

Efficacy and tolerability of MK-0974 (telcagepant), a new oral antagonist of calcitonin gene-related peptide receptor, compared with zolmitriptan for acute migraine: a randomised, placebo-controlled, parallel-treatment trial.

Background: Calcitonin gene-related peptide (CGRP) probably has a role in migraine pathophysiology, and antagonism of its receptors might provide treatment without the vasoconstrictor effects of triptans. We aimed to assess the clinical profile of MK-0974 (telcagepant), an orally bioavailable antagonist of CGRP receptor.

Methods: In a randomised, parallel-treatment, placebo-controlled, double-blind, trial at 81 sites in the Europe and the USA, adults with migraine diagnosed by International Headache Society criteria treated moderate or severe attacks with either oral telcagepant 150 mg or 300 mg, zolmitriptan 5 mg, or placebo.

Efficient assessment of neuropathic pain drugs in patients with small fiber sensory neuropathies.

We sought to develop an enrichment crossover study design that would allow us to efficiently evaluate and compare promising candidate neuropathic pain drugs. We evaluated the efficacy of gabapentin or tramadol vs. active placebo (diphenhydramine) in subjects with biopsy-proven painful idiopathic small fiber neuropathy (SFN) who were self-reported gabapentin responders.

Isolation and identification of nontuberculous mycobacteria from foods as possible exposure sources.

A variety of foods collected from local supermarkets and produce stands were examined as possible sources of nontuberculous mycobacterial exposure. Food samples were combined with sterile ultrapure water and manually shaken. To remove large particles, the suspensions were filtered through a sterile strainer, centrifuged, and the supernatants were discarded.

PCR comparison of Mycobacterium avium isolates obtained from patients and foods.

Mycobacterium avium is a cause of disseminated disease in AIDS patients. A need for a better understanding of possible sources and routes of transmission of this organism has arisen. This study utilized a PCR typing method designed to amplify DNA segments located between the insertion sequences IS1245 and IS1311 to compare levels of relatedness of M.

Comparison of large restriction fragments of Mycobacterium avium isolates recovered from AIDS and non-AIDS patients with those of isolates from potable water.

We examined potable water in Los Angeles, California, as a possible source of infection in AIDS and non-AIDS patients. Nontuberculous mycobacteria were recovered from 12 (92%) of 13 reservoirs, 45 (82%) of 55 homes, 31 (100%) of 31 commercial buildings, and 15 (100%) of 15 hospitals. Large-restriction-fragment (LRF) pattern analyses were done with AseI.

Examination of Bottled Water for Nontuberculous Mycobacteria.

The objective of this study was to examine bottled water for the presence of nontuberculous mycobacteria as a potential source of infection in AIDS patients. Twenty brands of bottled water commonly used in the Los Angeles area were tested for the presence of nontuberculous mycobacteria. The three brands most commonly used in the Los Angeles area were tested most frequently.

Molecular technique for rapid identification of mycobacteria.

Identification of mycobacteria through conventional microbiological methods is cumbersome and time-consuming. Recently we have developed a novel bacterial identification method to accurately and rapidly identify different mycobacteria directly from water and clinical isolates. The method utilizes the PCR to amplify a portion of the small subunit rRNA from mycobacteria.

Phage typing of Staphylococcus intermedius.

Staphylococcus intermedius, a coagulase-positive staphylococcal species, is a common canine pathogen and a rare human wound pathogen. A total of 145 strains of S. intermedius (ATCC 29663, 4 reference strains, 4 human isolates, 44 canine infection isolates, and 92 isolates from canine gingiva) were screened for lysogenic phage by a modified Fisk method.

A co-operative numerical analysis of Mycobacterium gastri, Mycobacterium kansasii and Mycobacterium marinum.

A co-operative taxonomic study has been performed on slowly growing photochromogenic mycobacteria (Runyon Group I) and closely related organisms. Phenetic data on 54 strains, studied in seven laboratories, were collected and analysed by numerical taxonomic methods. Immunological properties and phage susceptibility patterns were analysed independently to establish correlation with numerical classification.

Tuberculin activity of mycobacterial fractions obtained by chromatography.

Commercial purified protein derivatives (PPD), old tuberculin (OT), the bacillary extract, and the culture filtrate of Mycobacterium tuberculosis H37Ra were submitted to Sephadex G-25 and diethylaminoethyl (DEAE)-cellulose chromatography. The ability of the fractions obtained to elicit delayed dermal hypersensitivity in M. tuberculosis H37Ra-infected guinea pigs was studied.

Antigens of mycobacterial cell walls.

Three antigenic fractions from the cell walls of eight strains of mycobacteria were studied. Isolation and purification of these antigens were effected by enzymatic digestions, differential and sucrose gradient centrifugations, dialyses, and column chromatography. Two of the fractions were termed cell wall tuberculins (CWT-1, solubilized with lipase; CWT-2, solubilized with lysozyme); the third was termed "C" (cross-reacting) antigen.

MYCOBACTERIA: LABORATORY METHODS FOR TESTING DRUG SENSITIVITY AND RESISTANCE.

In its seventh report, published in 1960, the WHO Expert Committee on Tuberculosis "noted the need for international standards for the definition and determination of drug resistance which will permit comparisons to be made from one area to another, and recommended that the World Health Organization take appropriate steps to establish such standards".(10) Acting on this recommendation, WHO took the first step towards standardization by convening in Geneva, in December 1961, an informal international meeting of specialists in the bacteriology of tuberculosis. At this meeting an attempt was made to formulate prerequisites for reliable sensitivity tests and to specify the technical procedures for them.