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Biomedical subjects

K Sharp

Publications and source records attributed to K Sharp.

11 recordsLinked to original sources

Hypercarbia during carbon dioxide gas insufflation for therapeutic laparoscopy: a note of caution.

During the past decade, the number of laparoscopic procedures performed in the United States, primarily with cholecystectomy, has increased phenomenally. We recently had a patient who developed hypercarbia and cardiovascular compromise during laparoscopic cholecystectomy. The cardiovascular compromise was caused by mechanical factors directly related to increasing intra-abdominal pressures affecting ventilation and venous return as well as the absorption of carbon dioxide (CO2) into the circulation, leading to acidosis and further depression of the cardiopulmonary system. Cardiovascular compromise can be avoided with early recognition of increased end-tidal CO2 concentrations and by preventing intra-abdominal pressures from exceeding 16 mm Hg.

Aged

Voluntary and involuntary maternal separation in guinea pig pups with mothers required to forage.

Lactating guinea pigs required to leave a nest box to obtain food were observed to be separated from their pups almost 10% of the time on Days 13-15 postpartum. The duration of separation was greater in the dark than in the light, and was not different for mothers/litters exposed to low (LFD) versus high (HFD) foraging demand. Subsequently, LFD and HFD pups as well as pups reared under standard laboratory conditions (SLC) all exhibited vocalization and plasma cortisol responses to involuntary maternal separation. However, several effects of rearing were also observed. HFD pups vocalized less during separation and had higher resting cortisol levels than did SLC pups; LFD and HFD males spent less time in contact with the mother in a test cage than did SLC males. These effects are discussed in terms of the importance of the physical environment in shaping infant-mother interactions and the infant's perception of control.

Animals

An analysis of the fourth year of medical school for students pursuing surgical careers.

A fourth-year curriculum survey was forwarded to surgery resident program directors, clerkship directors, and residents. A 37 percent response rate was achieved with comparable representation of each respondent type from 130 institutions. The purpose of the survey was to determine how each of the 3 respondent types rated the importance of 42 subjects or clinical experiences to be taken in the fourth year of medical school for students pursuing surgical careers. The survey also included questions on such issues as externships, early match programs, and guidelines used at their institutions for their fourth year students. The results indicated a significantly high agreement among respondent types on what should comprise surgical students' fourth-year curriculum content. The majority feel the fourth year should be planned by students with an electives advisor to equally add breadth to their general professional education as well as provide prerequisite experiences in the career-chosen discipline.

Clinical Clerkship

Fatal and disastrous complications following percutaneous endoscopic gastrostomy.

Percutaneous endoscopic gastrostomy (PEG) has become the preferred method of nutritional support in virtually every patient in whom this procedure is technically feasible because of its apparent technical facility, cost containment, and bedside insertion. PEG can, however, be associated with serious complications and death. This is a report of three patients who developed life-threatening abdominal wall abscesses and four patients who died after PEG insertion. The patients ranged in age from 30 to 80 years, four female and three male. Complicating medical conditions included cirrhosis, diabetes, heart-lung transplantation, neurological dysfunction, and psychosis. The four patients who died were all noted to have had unsatisfactory adhesion between the gastric serosa and the anterior abdominal wall, resulting in large gastric defects where the PEG had been placed and intraperitoneal contamination with gastric contents and feedings. Three additional patients developed abdominal wall abscesses requiring operative debridement. The patient considered to be high risk for surgical gastrostomy may be a higher risk for PEG. Alternatives to PEG should be considered in patients with poor nutritional status or debilitating medical conditions, or in patients undergoing immunosuppressive therapy and steroid use. Psychosis and dementia should be considered relative contraindications to PEG because these patients may dislodge the gastrostomy tube, resulting in severe wound infection and, possibly, death.

Adult

Computer simulations of the diffusion of a substrate to an active site of an enzyme.

Computer simulations of the diffusion of a substrate to an enzyme active site were performed. They included the detailed shape of the protein and an accurate description of its electrostatic potential. Application of the method to the diffusion of the superoxide anion to the protein superoxide dismutase revealed that the electric field of the enzyme enhances the association rate of the anion by a factor of 30 or more. Calculated changes in the association rate as a function of ionic strength and amino acid modification paralleled the observed behavior. Design principles of superoxide dismutase are considered with respect to insights provided by the simulations. A possible means of enhancing the enzyme turnover rate through site-directed mutagenesis is proposed.

Binding Sites

Focusing of electric fields in the active site of Cu-Zn superoxide dismutase: effects of ionic strength and amino-acid modification.

In this paper we report the implementation of a finite-difference algorithm which solves the linearized Poisson-Boltzmann equation for molecules of arbitrary shape and charge distribution and which includes the screening effects of electrolytes. The microcoding of the algorithm on an ST-100 array processor allows us to obtain electrostatic potential maps in and around a protein, including the effects of ionic strength, in about 30 minutes. We have applied the algorithm to a dimer of the protein Cu-Zn superoxide dismutase (SOD) and compared our results to those obtained from uniform dielectric models based on coulombic potentials. We find that both the shape of the protein-solvent boundary and the ionic strength of the solvent have a profound effect on the potentials in the solvent. For the case of SOD, the cluster of positive charge at the bottom of the active site channel produces a strongly enhanced positive potential due to the focusing of field lines in the channel-a result that cannot be obtained with any uniform dielectric model. The remainder of the protein is surrounded by a weak negative potential. The electrostatic potential of the enzyme seems designed to provide a large cross-sectional area for productive collisions. Based on the ionic strength dependence of the size of the positive potential region emanating from the active site and the repulsive negative potential barrier surrounding the protein, we are able to suggest an explanation for the ionic strength dependence of the activity of the native and chemically modified forms of the enzyme.

Amino Acids

Electrokinetic and electrostatic properties of bilayers containing gangliosides GM1, GD1a, or GT1. Comparison with a nonlinear theory.

We formed vesicles from mixtures of egg phosphatidylcholine (PC) and the gangliosides GM1, GD1a, or GT1 to model the electrokinetic properties of biological membranes. The electrophoretic mobilities of the vesicles are similar in NaCl, CsCl, and TMACl solutions, suggesting that monovalent cations do not bind significantly to these gangliosides. If we assume the sialic acid groups on the gangliosides are located some distance from the surface of the vesicle and the sugar moieties exert hydrodynamic drag, we can describe the mobility data in 1, 10, and 100 mM monovalent salt solutions with a combination of the Navier-Stokes and nonlinear Poisson-Boltzmann equations. The values we assume for the thickness of the ganglioside head group and the location of the charge affect the theoretical predictions markedly, but the Stokes radius of each sugar and the location of the hydrodynamic shear plane do not. We obtain a reasonable fit to the mobility data by assuming that all ganglioside head groups project 2.5 nm from the bilayer and all fixed charges are in a plane 1 nm from the bilayer surface. We tested the latter assumption by estimating the surface potentials of PC/ganglioside bilayers using four techniques: we made 31P nuclear magnetic resonance, fluorescence, electron spin resonance, and conductance measurements. The results are qualitatively consistent with our assumption.

Egg Yolk

Control by H-2 genes of murine antibody responses to protein antigens of Mycobacterium tuberculosis.

The genetic control of antibody responses after immunization with Mycobacterium tuberculosis soluble antigens was examined in inbred and H-2 congenic mouse strains. Antibody levels to five distinct epitopes were determined by a competitive inhibition test using radiolabelled murine monoclonal probes. High or low responder antibody levels were associated with either the H-2b (TB23, TB71 and TB72 specificities) or the H-2k (TB68) allele on both B10 and BALB backgrounds. The high response of TB78 specificity associated with the H-2k on the BALB but with H-2b haplotype on B10 background. The phenotype of (C57BL/6 X CBA)F1 hybrids reflected the high response for four and the low or intermediary response for one (TB68) of the tested paratopes. This is the first demonstration of immune response gene control in respect of defined mycobacterial protein epitopes. The implications towards the analysis of pathogenic or protective mechanisms during mycobacterial infection are briefly outlined.

Animals