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Biomedical subjects

B Philip

Publications and source records attributed to B Philip.

At least 19 recordsLinked to original sources

A randomized, double-blind, close-ranging, pilot study of intravenous granisetron in the prevention of postoperative nausea and vomiting in patients abdominal hysterectomy.

BACKGROUND AND OBJECTIVE: Postoperative nausea and vomiting (PONV) is a frequent and unpleasant experience that may increase postoperative complications and costs. For surgical procedures with a high risk of PONV, prevention is preferable to treatment. In this study, the authors explore the dose-response relationship between granisetron administered just prior to the end of surgery and post-operative nausea and vomiting in patients undergoing abdominal hysterectomy. METHODS: This was a randomized, double-blind, placebo-controlled, pilot study of post-operative nausea and vomiting prevention. Patients undergoing elective open abdominal hysterectomy requiring general anaesthesia received a single dose of granisetron 0.1, 0.2 or 0.3 mg or placebo administered approximately 15 min prior to the end of surgery. The primary efficacy end-point was the proportion of patients with no vomiting in the 0--6 h interval following medication administration. No inferential statistics were planned. RESULTS: The proportion of patients with no vomiting episode in the 0--6 h interval after administration of study medication was higher in each granisetron treatment group (>90%) than in the placebo group (77%). Proportions of patients with no vomiting episodes in the 0--24 h interval were similar across treatment groups. Results of analyses of proportions of patients with no moderate or severe nausea episodes, proportions of those requiring rescue medication and times to first use of rescue medication suggested a treatment effect of granisetron relative to placebo in both the 0--6 and 0--24 h intervals. Similar proportions of patients in each treatment group reported at least one adverse event. CONCLUSIONS: Granisetron at doses of 0.1, 0.2 and 0.3 mg administered just prior to the end of surgery suggested a trend of improved efficacy compared to placebo in preventing postoperative nausea and vomiting in the first 6 h after abdominal hysterectomy. This pilot study did not identify a dose-response relationship.

Adult↗

Preferential block of small myelinated sensory and motor fibers by lidocaine: in vivo electrophysiology in the rat sciatic nerve.

BACKGROUND: Controversy still surrounds the differential susceptibility of nerve fibers to local anesthetics and its relation to selective functional deficits. In the current study we report features of conduction blockade in different classes of rat sciatic nerve fibers after injection of lidocaine by a percutaneous procedure that closely resembles clinical applications. METHODS: In 30 adult male Sprague-Dawley rats (weight, 300-400 g) during general anesthesia, impulses were recorded in different classes of sensory axons (large, Aalpha and beta fibers; small, Adelta myelinated fibers and unmyelinated C fibers) and motor axons (large, Aalpha fibers; small, Agamma myelinated fibers) classified by conduction velocity. The sciatic nerve was stimulated distally, and impulses were recorded from small filaments teased from L4-L5 dorsal (sensory) and ventral (motor) roots sectioned acutely from the spinal cord. Lidocaine at concentration of 0.05-1% was injected percutaneously in 0.1-ml solutions at the sciatic notch. Both tonic (stimulated at 0.5 Hz) and use-dependent (stimulated at 40 Hz for Adelta and Agamma fibers and at 5 Hz for C fibers) impulse inhibitions by lidocaine were assayed. RESULTS: Minimal effective (threshold) lidocaine concentrations (i.e., to block conduction in 10% of fibers) were, for sensory, 0.03% for Adelta, 0.07% for Aalphabeta, and 0.09-0.1% for C fibers, and for motor, 0.03% for Agamma and 0.05% for Aalpha fibers. The order of fiber susceptibility, ranked by concentrations that gave peak tonic fiber blockade of 50% (IC50s), was Agamma > Adelta = Aalpha > Aalphabeta > C. Faster-conducting C fibers (conduction velocity > 1 m/s) were more susceptible (IC50 = 0.13%) than slower ones (conduction velocity < 1 m/s; IC50 = 0.30%). At 1% lidocaine, all fibers were tonically blocked. Use-dependent effects accounted for only a modest potentiation of block (at a lidocaine concentration of 0.25%) in Adelta and Agamma fibers, and in C fibers phasic stimulation had even smaller effects and sometimes relieved tonic block. CONCLUSIONS: Susceptibility to lidocaine does not strictly follow the "size principle" that smaller (slower) axons are always blocked first. This order of fiber blockade is qualitatively consistent with previous reports of the order of functional deficits in the rat after percutaneous lidocaine, that is, motor = proprioception > nociception, if we assume that motor deficits first arise from conduction failure in Agamma fibers and that nociception relies on C fiber conduction.

Anesthetics, Local↗

Wsc1 and Mid2 are cell surface sensors for cell wall integrity signaling that act through Rom2, a guanine nucleotide exchange factor for Rho1.

Wsc1 and Mid2 are highly O-glycosylated cell surface proteins that reside in the plasma membrane of Saccharomyces cerevisiae. They have been proposed to function as mechanosensors of cell wall stress induced by wall remodeling during vegetative growth and pheromone-induced morphogenesis. These proteins are required for activation of the cell wall integrity signaling pathway that consists of the small G-protein Rho1, protein kinase C (Pkc1), and a mitogen-activated protein kinase cascade. We show here by two-hybrid experiments that the C-terminal cytoplasmic domains of Wsc1 and Mid2 interact with Rom2, a guanine nucleotide exchange factor (GEF) for Rho1. At least with regard to Wsc1, this interaction is mediated by the Rom2 N-terminal domain. This domain is distinct from the Rho1-interacting domain, suggesting that the GEF can interact simultaneously with a sensor and with Rho1. We also demonstrate that extracts from wsc1 and mid2 mutants are deficient in the ability to catalyze GTP loading of Rho1 in vitro, providing evidence that the function of the sensor-Rom2 interaction is to stimulate nucleotide exchange toward this G-protein. In a related line of investigation, we identified the PMT2 gene in a genetic screen for mutations that confer an additive cell lysis defect with a wsc1 null allele. Pmt2 is a member of a six-protein family in yeast that catalyzes the first step in O mannosylation of target proteins. We demonstrate that Mid2 is not mannosylated in a pmt2 mutant and that this modification is important for signaling by Mid2.

Amino Acid Sequence↗

Mid2 is a putative sensor for cell integrity signaling in Saccharomyces cerevisiae.

Hcs77 is a putative cell surface sensor for cell integrity signaling in Saccharomyces cerevisiae. Its loss of function results in cell lysis during growth at elevated temperatures (e.g., 39 degrees C) and impaired signaling to the Mpk1 mitogen-activated protein kinase in response to mild heat shock. We isolated the MID2 gene as a dosage suppressor of the cell lysis defect of an hcs77 null mutant. MID2 encodes a putative membrane protein whose function is required for survival of pheromone treatment. Mid2 possesses properties similar to those of Hcs77, including a single transmembrane domain and a long region that is rich in seryl and threonyl residues. We demonstrate that Mid2 is required for cell integrity signaling in response to pheromone. Additionally, we show that Mid2 and Hcs77 serve a redundant but essential function as cell surface sensors for cell integrity signaling during vegetative growth. Both proteins are uniformly distributed through the plasma membrane and are highly O-mannosylated on their extracellular domains. Finally, we identified a yeast homolog of MID2, designated MTL1, which provides a partially redundant function with MID2 for cell integrity signaling during vegetative growth at elevated temperature but not for survival of pheromone treatment. We conclude that Hcs77 is dedicated to signaling cell wall stress during vegetative growth and that Mid2 participates in this signaling, but its primary role is in signaling wall stress during pheromone-induced morphogenesis.

ATP-Binding Cassette Transporters↗

Orbital subperiosteal hematoma, cholesterol granuloma, and infection. Evaluation with MR imaging and CT.

Orbital subperiosteal space, a potential space, is an important entity due to its unique anatomy and susceptibility to various pathologic processes. CT scan and MR imaging are important tools in the diagnosis of orbital subperiosteal hematomas, cholesterol granulomas, and infections. MR imaging has emerged as the modality of choice in the evaluation of hematomas and infections of this space due to its multiplanar capability and various imaging sequences giving better information. High-resolution CT scan offers good differentiation in most of these cases. Osseous changes in a cholesterol granuloma is better seen in CT scan, although MR imaging offers better differentiation from epidermoid or dermoid cysts and other subperiosteal process, as well as lacrimal fossa lesions. Subperiosteal abscesses are best evaluated using MR imaging.

Abscess↗

Rhabdomyosarcoma of the orbit. Evaluation with MR imaging and CT.

Rhabdomyosarcoma is the most common primary orbital malignancy of childhood. It can present insidiously, mimicking other (benign) processes clinically and radiographically. CT and MR imaging are crucial in the diagnostic evaluation, treatment planning, and follow-up monitoring of the disease. Such imaging, especially when contrast is used, can accurately detect and state the extent of tumor involvement.

Adolescent↗

Metallothionein or metallothionein like proteins and heavy metal toxicity in Oreochromis mossambicus (Peters).

Metallothioneins or metallothionein like proteins protect the biological system by encountering the influx of metal ions. These proteins are present in the contaminated as well as uncontaminated organisms. Studies show that the native metallothioneins or metallothionein like proteins of O. mossambicus is predominantly zinc bound. Increased influx of zinc causes a redistribution of this essential metal to other proteins requiring zinc as co-factor. Influx of mercury is encountered by the displacement of zinc bound to the protein and also by de novo of synthesis of metal binding proteins and subsequent binding of the incoming mercury. Data available show that "spill over" hypothesis is too simple to explain the mechanism of heavy metal toxicity.

Animals↗

Use and benefit of hearing aids in the tenth decade--and beyond.

The purpose of this study was to evaluate the use and benefit of hearing aids in 185 hearing-disabled subjects born before 1900, consecutively fitted with a hearing aid during the first 6 months of 1989. Information from 138 (75%) subjects, 117 females and 21 males with a median age of 93 years (range 90-107), was obtained from a questionnaire, which was mailed 4-6 months after the fitting procedure. The questionnaire included questions concerning use of the hearing aid(s), self-reported benefit, handling problems, overall satisfaction/dissatisfaction, social and domiciliary situation and self-reported visual capacity. Among these elderly subjects 75% had previously been provided with hearing aids, while 25% were first-time users. The results demonstrate that 76% use the hearing aid(s) at home and in small groups, and that 51% use the hearing aid(s) each day; however, 35% did not respond to this question. 64% expressed general satisfaction with their aid(s). Despite instruction and counselling, handling problems were frequently present. In those previously fitted with hearing aids a higher rate of time-related use and satisfaction was present, and handling problems were less frequent than in the first-time applicants. It is concluded that elderly hearing-impaired subjects in the tenth decade use and benefit from hearing aids; however, more problems concerning use and benefit of hearing aids are present in this age group than in the younger age groups.

Aged↗

Cortisol and lysosomal stability in normal and atheromatous rats.

The effect of cortisol on lysosomal stability has been studied in rats fed atherogenic and normal diets. beta-Glucuronidase has been taken as a lysosomal marker enzyme. Cortisol did not significantly alter total lysosomal enzyme activity in the liver or aorta or the activity present in the hepatic nuclear fraction. However, the hormone significantly increased activity in the intact lysosome and decreased soluble activity. The ratio of soluble activity (released from the lysosomes) to activity present in the intact lysosome showed that hepatic lysosomal stability was significantly increased in rats on cortisol. Cortisol tends to restore the decreased stability observed in atheromatous rats back to that in normal rats. The rate of release of enzyme from hepatic and aortic lysosomes was reduced by cortisol in both normal and atheromatous rats. Activity of serum lysosomal enzyme was also significantly lower in rats receiving cortisol. Cortisol subsequently added in vitro after the animals had been fed a normal or an atherogenic diet caused a significant in vitro decrease in the amount of enzyme released from hepatic lysosomes. The in vitro release of enzyme from lysosomes in normal rat liver progressively fell with increasing concentration of cortisol form 10(-5)--10(-4) M. Further increase in concentration up to 5 X 10(-4) M did not significantly alter enzyme release. Since cortisol was administered as its hemisuccinate the effect of succinate on lysosomal stability was also studied. It stabilized lysosomes, but the effect was much less than with cortisol.

Animals↗