Pharmacogenetic allele nomenclature: International workgroup recommendations for test result reporting.

This article provides nomenclature recommendations developed by an international workgroup to increase transparency and standardization of pharmacogenetic (PGx) result reporting. Presently, sequence variants identified by PGx tests are described using different nomenclature systems. In addition, PGx analysis may detect different sets of variants for each gene, which can affect interpretation of results. This practice has caused confusion and may thereby impede the adoption of clinical PGx testing. Standardization is critical to move PGx forward.

Evaluation of regional limb perfusion with amikacin using the saphenous, cephalic, and palmar digital veins in standing horses.

Previous studies have shown that regional limb perfusion (RLP) using the palmar digital (PD) vein delivers therapeutic concentration of amikacin to the distal limb. Our hypothesis was that using the cephalic and saphenous veins for RLP will enable delivery of therapeutic concentrations of amikacin to the distal limb. Nineteen healthy horses participated in the study. The cephalic, saphenous, or PD vein was used to perfuse the limb with amikacin. Two grams of amikacin was used for RLP using the saphenous and the cephalic veins, and one gram was used in the PD vein. Synovial samples were collected from the metacarpo-/metatarsophalangeal (MCP/MTP) joint, and blood samples were collected from the jugular vein. Maximum concentration (Cmax) of amikacin in the MCP/MTP joint using the cephalic and the saphenous vein was 277 and 363 mg/L, respectively. The amikacin concentrations achieved in the synovial fluid of the MCP/MTP joint in the current study were between 69 and 91 times the minimally inhibitory concentration of common susceptible bacterial pathogens causing orthopedic infections in horses. To conclude, this study shows that use of the proximal veins for RLP to treat distal limb infections is a viable alternative to using the palmar or plantar digital vein.

General practitioners' attitudes to randomised clinical trials for women with breast cancer.

OBJECTIVE: To determine general practitioners' attitudes to randomised clinical trials for women with breast cancer. DESIGN: Cross-sectional survey with structured face-to-face interviews conducted between December 1997 and May 1998. PARTICIPANTS: A random sample of GPs in central Sydney. MAIN OUTCOME MEASURES: GPs' attitudes to referring women with breast cancer to specialists who enrol patients in randomised clinical trials, and to randomised clinical trials in general. RESULTS: 85 of 158 GPs (54%) consented to be interviewed. Of these 85 GPs, 47% stated that they would refer a woman with breast cancer to a specialist who was likely to enrol the woman in a clinical trial; 50% believed that clinical trials increase knowledge about treatment options; and 15% thought that randomised trials may make a valuable scientific contribution. However, 43% of GPs expressed concerns that their patients may be disadvantaged, 39% said that they wanted optimum treatment for their patients, 18% that they would want to know what the trial was about, and 12% were worried about ethical considerations. CONCLUSIONS: Many of the GPs in this survey have concerns about randomised clinical trials for women with breast cancer. Improved communication between specialists and GPs about the conduct of and treatments offered in clinical trials for breast cancer may change this attitude.

Implementing the US preventive services guidelines in a family practice residency.

BACKGROUND: Despite growing emphasis on preventive services, physicians still provide low levels of these services to their patients. Barriers to providing preventive services might be modified by more effective teaching models at the residency level. The purpose of this study was to evaluate a practice-based teaching model designed to increase resident compliance with the US Preventive Services Task Force Guidelines. METHODS: In Phase One of this study, physicians received didactic education about the US Preventive Services Task Force Guidelines. Subsequently, physicians' compliance with these recommendations was monitored. During Phase Two of the study, a comprehensive two-visit "Health Check" appointment was instituted. It incorporated a computerized health risk appraisal that was reviewed with patients. After the Health Check program was implemented, physicians' compliance with the guidelines was again audited. RESULTS: The chart audits revealed an overall increase in the level of preventive services provided by physicians from 31% in Phase One to 74% in Phase Two (P < .01). CONCLUSIONS: This type of teaching model can effectively increase the level of preventive services provided to patients in a family practice residency.

Distribution of substance P-like immunoreactive fibres and terminals in the medulla oblongata of the human infant.

This study provides a detailed report of the distribution and density of substance P-like immunoreactive fibres and terminals within the human infant medulla. Seven brains with no signs of macroscopic alteration fixed usually within 24-48 h after death were used. Free floating transverse sections (50-60 microns) were then immunostained with a monoclonal antibody against substance P using the avidin-biotin-peroxidase technique. Morphologically three types of substance P-like immunoreactive fibres were observed: those with small varicosities of less than 1 micron, those with medium varicosities of 1-2 microns and those with large varicosities of 2-4 microns. Very dense substance P-like immunoreactivity was present within the spinal trigeminal nucleus, parts of the gracile and cuneate fasciculi and the paracommissural subnucleus of the solitary nucleus; dense substance P-like immunoreactivity was present within the dorsal nucleus of the vagus nerve, commissural, medial, dorsal, dorsolateral ventral and ventrolateral subnuclei of the solitary nuclear complex, parasolitary nucleus, raphe obscurus, inferior olivary complex (medial, dorsal, dorsomedial nuclei) and ventrolateral part of the dorsal reticular nucleus; moderate substance P-like immunoreactivity was present within the gelatinosus nucleus of the solitary tract, lateral reticular nucleus proper, intermediate reticular zone and parvocellular reticular nucleus; sparse substance P-like immunoreactivity was present within the hypoglossal nucleus, retroambigual nucleus and much of the reticular formation (dorsal, parvocellular, ventral gigantocellular, dorsal paragigantocellular nuclei): and very sparse substance P-like immunoreactivity was present within the nucleus ambiguus, medial vestibular nucleus and parts of the reticular formation (ventral, medial, gigantocellular, ventral gigantocellular, dorsal paragigantocellular nuclei). Substance P-like immunoreactivity was absent in the area postrema, intercalated nucleus, gracile and cuneate nuclei, in the epiolivary, subtrigeminal and parvocellular divisions of the lateral reticular nucleus, spinal vestibular nucleus, and in the solitary and pyramidal tracts. In several regions the substance P-like immunoreactive fibres formed distinct pericellular arrays around the somata and dendrites of neurons (hypoglossal nucleus, dorsal nucleus of the vagus nerve, retroambigual nucleus, intermediate reticular zone). The results indicate the high specificity of the localization of substance P in various structures of the brainstem and underline the presumed significance of this peptide in autonomic and sensorimotor functions of the brain.

Continuous-flow apneic ventilation with small endobronchial catheters.

This study compares gas exchange and hemodynamic parameters during bronchial insufflation with two different internal diameter (ID) catheters (2.5 and 1.4 mm) at a constant mean gas exit velocity. Anesthetized, paralyzed dogs were instrumented to monitor arterial, central venous, and airway pressures, blood gases, temperature, ECG, and ventilated using continuous flow apneic ventilation (CFAV) via 2.5-mm or 1.4-mm ID bronchial insufflation catheters positioned 1.25 bronchial diameter units (BDU) beyond the carina. Initially, flow was adjusted to provide adequate oxygenation and ventilation through the 2.5-mm ID catheters. After a 30-min stabilization, physiological parameters were recorded and the mean gas exit velocity was calculated. The 2.5-mm ID insufflation catheters were then replaced by 1.4-mm ID catheters and the bronchial insufflation flow adjusted so as to produce the same mean gas exit velocity as for the 2.5-mm ID catheters. After a 30-min stabilization period, physiological parameters were again recorded. No significant differences were noted in arterial, central venous, or airway pressures, temperature, heart rate, pH, PaCO2, and PaO2 between the 2.5-mm and 1.4-mm ID bronchial insufflation catheters. However, significantly less bronchial insufflation flow (69.7%) was required to maintain oxygenation and ventilation for the 1.4-mm ID bronchial insufflation catheters.

Low-compliance, volume-controlled, high-frequency positive-pressure ventilation versus conventional ventilation during coronary artery bypass grafting.

Low-compliance, volume-controlled, high-frequency positive-pressure ventilation (HFPPV) was compared to conventional intermittent positive-pressure ventilation (IPPV) immediately before and after surgery in a series of ten patients who underwent coronary artery bypass grafting (CABG). Direct and indirect hemodynamic and respiratory variables were recorded and calculated. All patients were adequately ventilated with either HFPPV or IPPV. No significant differences in hemodynamic stability were noted either before or after cardiopulmonary bypass (CPB). Airway pressures were lowered significantly by HFPPV as compared to IPPV. This may be useful in cases in which increased airway pressure might be harmful due to decreased venous return and cardiac output (CO).

Distribution of corticospinal motor fibres within the cervical spinal cord with special reference to the phrenic nucleus: a WGA-HRP anterograde transport study in the cat.

The anterograde transport of wheat germ agglutinin conjugated with horseradish peroxidase (WGA-HRP) was used to demonstrate the corticospinal fibres which originate in the motor cortex and project to the cervical spinal cord, specifically to the phrenic nucleus, in the cat. Following injections of WGA-HRP into the pericruciate cortex large numbers of fibres were labelled in the contralateral lateral and ventral funiculi and fewer fibres were labelled in the ipsilateral lateral and ventral funiculi. Labelled corticospinal motor fibres entered the gray matter laterally in laminae V and VI and terminated within these two laminae as well as throughout the entire extent of lamina VII. A few labelled fibres were present in medial lamina VIII and also in lamina IX where they were in close association with the phrenic motoneuron pool. Labelling was present in the gray matter at both sides, with a stronger labelling contralaterally. Labelled axons were also seen crossing from each side of the gray matter to the other side. The results suggest that in the cat the corticospinal motor fibres have a wider distribution in the spinal gray matter than has been previously shown, and that corticospinal motor axons may be in direct contact with phrenic motoneurons.

The identification of brainstem neurones projecting to thoracic respiratory motoneurones in the cat as demonstrated by retrograde transport of HRP.

Brainstem neurones which project to the immediate vicinity of the spinal motoneurones which supply the intercostal and abdominal respiratory muscles were identified by means of the retrograde transport of horseradish peroxidase (HRP). A combined electrophysiological and histological technique was used in which recording of phasic inspiratory or expiratory motoneurone activity within upper (T3-T4) or lower (T8-T9) thoracic segments was followed by the ion-tophoretic injection of HRP at these recording sites. HRP labelled cells were concentrated in those brainstem regions known to contain phasic respiratory neurones, namely the ventrolateral nucleus of the solitary tract (vl-NTS) or dorsal respiratory group (DRG), the ambiguus complex or ventral respiratory group (VRG) and the parabrachial pontine (PB) nuclei. In 18 cats, 248 cells were labelled in these three respiratory regions of the brainstem while 668 were much more diffusely distributed in other regions of the medulla and pons. The ipsilateral and contralateral contributions within the respiratory regions were respectively; 23%:77% (DRG), 33%:67% (VRG), 95%:5% (PB). These results are considered in the general context of previous electrophysiological and histological findings, but also with particular reference to a related study of the projections from brainstem neurones to the phrenic nucleus [32].

Cells of origin of corticospinal projections to phrenic and thoracic respiratory motoneurones in the cat as shown by retrograde transport of HRP.

A combined electrophysiological and histological approach was employed to identify neurones within the motor cortex which project to the vicinity of spinal respiratory motoneurones, and which may be involved in the alteration of the pattern of breathing under certain conditions. Recording of respiratory phased activity from phrenic, or from thoracic motoneurones within either the upper (T3-4) or lower (T8-9) segments, was followed by the iontophoretic injection of HRP at these recording sites. After injections within the cervical or thoracic ventral horn, 219 cells were retrogradely labelled in 14 experiments. The majority of these cells (88%) were labelled contralateral to the injection site. Following the injection of HRP into the phrenic nucleus, labelling was observed at two major sites within the anterior sigmoid gyrus (ASG), one along the anterolateral edge of the cruciate sulcus, and the other along the ventrolateral border of the ASG. In contrast, cells labelled after injections into the thoracic ventral grey matter were located more medially within the ASG and the posterior sigmoid gyrus (PSG). The populations of cells labelled following phrenic and thoracic injections overlapped, primarily at the lateral edge of the cruciate sulcus. The somas of labelled cells were pyramidal, round or oval. The mean diameters of cortical cells labelled after injections into the lower or upper thoracic segments were 30.5 +/- 6.2 and 31.5 +/- 5.6 respectively, which were not significantly different in size. However, they were significantly larger than the mean diameter of the cells labelled from injections into the phrenic nucleus (22.7 +/- 4.2 micron).(ABSTRACT TRUNCATED AT 250 WORDS)

Brainstem projections to the phrenic nucleus: a HRP study in the cat.

Brainstem neurones which project to the phrenic nucleus were identified using retrogradely transported horseradish peroxidase (HRP) as a marker. Following iontophoretic injection of HRP into the phrenic nucleus, labelled cells were encountered throughout large areas of the medulla and pons, but occurred with characteristic high densities in those regions known to contain phasic respiratory neurones: namely, the ventrolateral solitary tract nucleus (vl-NTS), known as the dorsal respiratory group (DRG), the ambiguus complex or ventral respiratory group (VRG) and the parabrachial pontine nuclei (BCM-KF). In 12 cats a total of 1540 cells was identified within these regions, the relative contralateral and ipsilateral contributions were respectively 72%:28% (vl-NTS), 65%:35% for the ambiguus complex, and 5%:95% (BCM-KF). In addition, labelled cells, predominantly ipsilateral, were observed in the pontine and medullary reticular formation and the vestibular nuclei. The labelled cells of the DRG had round, oval or triangular perikarya. Their mean soma diameter was 18.3 micrometers. The HRP-positive cells of the VRG had slightly larger somas (mean 21.2 micrometers) and they were fusiform and triangular. The neurones labelled in the BCM-KF nuclei were more heterogeneous with a mean soma size of 14.9 micrometers. The bilateral projections to the phrenic nucleus from the DRG and the VRG, and the predominantly ipsilateral projection from the BCM-KF are discussed in relation to current electrophysiological and autoradiographic findings.

Evalution of mechanical ventilators in a hyperbaric environment.

Four mechanical ventilators, the pneumatic Emerson, IMV bird, Urgency bird, and the Modified Mark 2 bird were tested in a hyperbaric chamber at depths up to 165 ft of sea water (FSW). All failed except the Emerson, which is the only machine recommended for chamber use at this time.

Acidosis, local anesthetics, and the newborn.

Four newborn infants were studied following maternal epidural block with lidocaine or mepivacaine. Each of these neonates, born with a pH of 7.23 or below in the umbilical vein blood, showed an elevated fetal-to-maternal concentration ratio, a possible manifestation of ion trapping of a weak base.