Evaluation of a new bipyridine inotropic agent--milrinone--in patients with severe congestive heart failure

Milrinone, a derivative of amrinone, has nearly 20 times the inotropic potency of the parent compound and does not cause fever or thrombocytopenia in normal volunteers or in animals sensitive to amrinone. In 20 patients with severe congestive heart failure, intravenous milrinone resulted in significant decreases in left ventricular end-diastolic pressure (from 27 +/- 2 to 18 +/- 2 mm Hg), pulmonary wedge pressure, right atrial pressure, and systemic vascular resistance, as well as a slight reduction in mean arterial pressure. Significant increases occurred in cardiac index (from 1.9 +/- 0.1 to 2.9 +/- 0.2 liters per minute per square meter) and the peak positive first derivative of left ventricular pressure, with a slight increase in heart rate. Hemodynamic improvement was sustained during a 24-hour continuous infusion. Nineteen of the 20 patients subsequently received oral milrinone (29 +/- 2 mg per day) for up to 11 months (mean, 6.0 +/- 0.8), with sustained improvement in symptoms of heart failure. In 10 patients receiving long-term oral milrinone (greater than or equal to 6 months) radionuclide ventriculography showed continued responsiveness, with a 27 per cent increase in left ventricular ejection fraction after 7.5 mg of the drug. Four patients died after a mean of 4.8 months of therapy, and three patients with severe underlying coronary-artery disease and angina pectoris required additional antianginal therapy. No patient had fever, thrombocytopenia, gastrointestinal intolerance, or aggravation of ventricular ectopy. We conclude that milrinone shows promise for the longterm treatment of congestive heart failure.     

Early tracheostomy tube change in children

OBJECTIVE: To review the safety of early tracheostomy tube change in children. DESIGN: Retrospective case series. SETTING: Pediatric tertiary care hospital. PATIENTS: Twenty-one consecutive pediatric patients undergoing routine tracheotomy. INTERVENTION: First tracheostomy tube change performed at patient's bedside at 3 (n = 15) or 4 (n = 5) days after surgery. OUTCOME MEASURE: The ability to safely change a tracheostomy tube at the patient's bedside 3 or 4 days after surgery. RESULTS: The first tracheostomy tube change was safely performed at 3 or 4 days after surgery in 20 patients. All changes were accomplished without complication or difficulty on the first attempt. The patients' ages ranged from 4 days to 16 years. The smallest child weighed 1.6 kg. Early tracheostomy tube change was not attempted in one obese 10-year-old girl whose pediatric tracheostomy tube became dislodged and formed a false tract 2 days after surgery. CONCLUSIONS: Most pediatric tracheostomy tubes can be safely changed at the patient's bedside approximately 3 days after surgery. Clinical applications of early tracheostomy tube change may include facilitating better hygiene, earlier completion of family caregiver tracheotomy education, and shorter hospital stays. It appears safe and advantageous for surgeons to consider early initial tracheostomy tube change for pediatric patients.     

Genome-wide search for asthma susceptibility loci in a founder population. The Collaborative Study on the Genetics of Asthma

Founder populations offer many advantages for mapping genetic traits, particularly complex traits that are likely to be genetically heterogeneous. To identify genes that influence asthma and asthma-associated phenotypes, we conducted a genome-wide screen in the Hutterites, a religious isolate of European ancestry. A primary sample of 361 individuals and a replication sample of 292 individuals were evaluated for asthma phenotypes according to a standardized protocol. A genome-wide screen has been completed using 292 autosomal and three X-Y pseudoautosomal markers. Using the semi-parametric likelihood ratio chi2 test and the transmission-disequilibrium test, we identified 12 markers in 10 regions that showed possible linkage to asthma or an associated phenotype (likelihood ratio P < 0.01). Markers in four regions (5q23-31, 12q15-24.1, 19q13 and 21q21) showed possible linkage in both the primary and replication samples and have also shown linkage to asthma phenotypes in other samples; two adjacent markers in one additional region (3p24.2-22) showing possible linkage is reported for the first time in the Hutterites. The results suggest that even in founder populations with a relatively small number of independent genomes, susceptibility alleles at many loci may influence asthma phenotypes and that these susceptibility alleles are likely to be common polymorphisms in the population.     

Brain-derived neurotrophic factor modulates hippocampal synaptic transmission by increasing N-methyl-D-aspartic acid receptor activity

Neurotrophins (NTs) have recently been found to regulate synaptic transmission in the hippocampus. Whole-cell and single-channel recordings from cultured hippocampal neurons revealed a mechanism responsible for enhanced synaptic strength. Specifically, brain-derived neurotrophic factor augmented glutamate-evoked, but not acetylcholine-evoked, currents 3-fold and increased N-methyl-D-aspartic acid (NMDA) receptor open probability. Activation of trkB NT receptors was critical, as glutamate currents were not affected by nerve growth factor or NT-3, and increased open probability was prevented by the tyrosine kinase inhibitor K-252a. In addition, the NMDA receptor antagonist MK-801 blocked brain-derived neurotrophic factor enhancement of synaptic transmission, further suggesting that NTs modulate synaptic efficacy via changes in NMDA receptor function.     

Benzalkonium chloride. A potential disinfecting irrigation solution for orthopaedic wounds

The efficacy of benzalkonium chloride was evaluated as an irrigating solution for the eradication of Staphylococcus aureus from a contaminated orthopaedic wound. Thirty Sprague Dawley rats were randomized into two groups. A stainless steel wire was placed in a lumbar spinous process, and the wound was inoculated with 10(7) or 10(6) colony forming units of Staphylococcus aureus. The wound was irrigated with 1 L of normal saline or 0.1% benzalkonium chloride solution. The animals were sacrificed, and cultures were obtained. Rats inoculated with 10(7) colony forming units of Staphylococcus aureus and irrigated with benzalkonium chloride had a significant decrease in the total number of positive cultures, deep wound cultures, and stainless steel wire cultures. Rats inoculated with 10(6) colony forming units of Staphylococcus aureus and irrigated with benzalkonium chloride also had a significant decrease in the total number of positive cultures, deep wound cultures, and stainless steel wire cultures. In a parallel noninoculation study, histologic evaluation of tissues did not show toxicity in the rats irrigated with benzalkonium chloride. This study shows that benzalkonium chloride is more effective than normal saline as an irrigating agent for eradicating Staphylococcus aureus from a contaminated orthopaedic wound.     

Pelvic inflammatory disease: the importance of aggressive treatment in adolescents

Pelvic inflammatory disease (PID), an infection of the female genital tract, presents a number of difficult challenges in diagnosis and management. Adolescents in particular require aggressive care of PID to prevent the long-term sequelae of chronic pelvic pain and infertility. This article reviews the etiology, microbiology, diagnosis, and management of PID, with an emphasis on treating adolescents with PID.     

Making progress: does clinical research lead to breakthroughs in basic biomedical sciences?

Beta-catenin is a pivotal player in the signaling pathway initiated by Wnt proteins, mediators of several developmental processes. beta-catenin activity is controlled by a large number of binding partners that affect the stability and the localization of beta-catenin and is thereby able to participate in such varying processes as gene expression and cell adhesion. Activating mutations in beta-catenin and in components regulating its stability can contribute to the formation of certain tumors.     

Human visual evoked potentials during the recognition of facial emotional expression

Visual evoked potentials (VEPs) were recorded in 22 right-handed healthy subjects in the occipital, parietal, central, frontal and posterotemporal cortical areas during recognition and passive viewing of positive, negative, and neutral emotional facial expression. Peak latencies of N90, P150, and N180 VEP components appeared to be significantly shorter in response to the negative emotional expression than during administration of other facial stimuli. The differences were observed both during active recognition and passive viewing. Correct recognition was characterized by involvement of both hemispheres and high level of interhemispheric correlation between the peak latencies of P150 in the posterotemporal and of N180 in the frontal areas. It is suggested that the facial expressions are primarily recognized at the subthreshold level with participation of the posterotemporal areas. The role of the frontal areas is discussed in the completion of this process and making the correct decision about the image.     

The adhesive system of the planarian Dendrocoelum lacteum: its structure and innervation

Light and electron microscopy of ventral surface of triclada D. lacteum allowed to distinguish four regions, containing ducts of adhesive glands. Every zone described has several morphological features connected to their role in various physiological processes. In every case structural unit of adhesive system is a complex of two unicellullar glands which according to the structure of secretory granules secrete different chemical products and are responsible for different processes such as adhesion an secretion. Adhesive structures of D. lacteum involved in vital behavior acts as movement on substrate surface, food capture an reaction of avoiding are heavily innervated. Cerebral ganglion neurons play the leading role in innervation of adhesive channel and area of additional secretion. The margin and caudal sucktio are innervated by axons originated from lateral neural cord. Neurons of peripheral plexuses play an important role in innervation of the whole adhesive system. Most dense accumulation of nerve endings is located in the vicinity of ducts of adhesive glands.