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Biomedical subjects

M S Harris

Publications and source records attributed to M S Harris.

At least 37 records · Page 2Linked to original sources

Streamlining the management of defecation disorders.

Obstinate constipation is a frequent but elusive gastrointestinal symptom. Increased understanding of defecation physiology and recent availability of simple, ready-to-use tools have increased specificity of both diagnosis and treatment. This patient series includes over 700 severely constipated patients with over 70 percent overall therapeutic success. Cinedefecography, pelvic floor electromyography, and determination of rectoanal inhibitory reflex were performed with simple and readily available equipment to document outlet anatomy and dynamics. Colonic transit time was examined in patients whose defecography and electromyography results were nondiagnostic and/or whose response to medical management was suboptimal, using a commercially available marker capsule, followed by abdominal x-rays. Retention of markers throughout the colon suggested colonic hypomotility or "inertia"; rectosigmoid retention confirmed functional outlet obstruction. With careful history, physical examination, and exclusion of organic causes, orderly application of readily available techniques can afford rapid, objective, and anatomically specific evidence upon which treatment of disordered defecation may be based.

Cineradiography↗

Sodium-proton exchange in human ileal brush-border membrane vesicles.

This study examines the characteristics of Na+ and H+ transport as well as Na+-H+ exchange in human ileal brush-border membrane vesicles from organ donor intestine. 22Na+ uptake into vesicles and the fluorescence quenching of Acridine orange were employed to measure Na+ and H+ transport, respectively. Concentrative uptake of 22Na+ (4-fold overshoot above equilibrium) was observed under conditions of an outward proton gradient (pHi 5.5; pHo 7.5). Voltage-clamping (Ki+ = Ko+ + valinomycin) reduced the uptake of 22Na+ by 40-50% indicating the presence of Na+ conductance. Dissipation of the Acridine orange fluorescence quench in ileal vesicles with a preformed pH gradient (pHi 5.5; pHo 7.5) was accelerated by either external Na+ or voltage-clamping in the absence of Na+. The effects of Na+ and voltage-clamping were additive under the above conditions. In the absence of a pH gradient, Acridine orange quenching was induced by intravesicular Na+ as well as an interior negative K+ diffusion potential. In voltage-clamped BBMV, pH-driven Na+ uptake was inhibited by amiloride (Ki = 140 microM). The initial rate of pH-driven Na+ uptake was saturable and conformed to Michaelis-Menten kinetics with apparent Km and Vmax values of 27 +/- 1 mM and 47 +/- 1 nmol.(mg protein)-1.(3 s)-1, respectively. Li+ and NH4+, but not Cs+, K+, Rb+ or choline+ inhibited pH gradient-driven 22Na+ uptake. The results demonstrate in human ileal brush-border membrane vesicles the presence of an Na+/H+ exchanger and conductive transport pathways for Na+ and H+.

Amiloride↗

Induction of neurally mediated NaHCO3 secretion by luminal distension in rat ileum.

Distension induces secretion in the intact intestine, but the mechanism of this secretory process remains unresolved. We sought to characterize the effect of intraluminal pressures below 20 cmH2O on water and electrolyte movements in the rat ileum and the subsequent effects of two cholinergic antagonists, hexamethonium and atropine. An increase in intraluminal pressure from 3.0 to 12.5 cmH2O led to inhibition of net H2O and Na absorption and stimulation of HCO3 secretion. However, there was no significant change in Cl absorption. Secretion occurred in the absence of changes in tissue wet weight, intercellular fluid accumulation, villus tip erosions, or mannitol flux. Alterations in fluid and electrolyte absorption were prevented by the intra-arterial administration of hexamethonium (10 mg/kg). Atropine (0.5 mg/kg) had no effect. Our studies demonstrate that distension induces the secretion of Na and HCO3 by the intact ileum. This secretory process may represent a neurally rather than passively mediated mechanism.

Animals↗

Relationship between distention and absorption in rat intestine. I. Effect of luminal volume on the morphology of the absorbing surface.

Previous studies in vivo have suggested that distention of the intestinal lumen may enhance intestinal absorption by augmenting absorptive surface area. The precise anatomic mechanism for this increase in surface area, however, has not been explored in detail. We developed methods for rapidly freezing and fixing intestinal segments in situ in the nondistended or distended state. Distention led to a reduction in villus height (309.2 +/- 9.9 to 230.7 +/- 11.8 micron) and a marked increase in the width of intervillus space in both the transverse (50.4 +/- 4.8 to 298.0 +/- 24.8 micron) and longitudinal (15.2 +/- 3.4 to 76.0 +/- 10.6 micron) dimensions. There was, however, no absolute change in total mucosal surface area. The changes in morphology occurred instantaneously, were entirely reversible, and were demonstrated at pressures that occur spontaneously in the mammalian intestine. These studies demonstrate that luminal distention results in marked alterations in intestinal histology that promote increased access of luminal contents to intervillus transport sites in the intestine in vivo. The resulting alterations could lead to an increase in functional rather than absolute absorptive surface area.

Animals↗

Relationship between distention and absorption in rat intestine. II. Effects of volume and flow rate on transport.

Studies in intact animals have shown that intestinal solute absorption may be enhanced with increasing intraluminal volume and flow rate, perhaps because of increases in functional absorptive surface area or perturbation of unstirred layers. We used single-pass perfusions of rat ileum, performed by simultaneously infusing and withdrawing at equal rates, to determine the separate effects of volume and flow rate on solute absorption at pressures between 3.0 and 12.5 cmH2O. Distention enhanced the absorption of passive probes (3H2O, urea), had no effect on the absorption of solutes transported by carrier mechanisms (D-glucose, L-alanine), and led to decreases in the net absorption of sodium and water whenever intraluminal pressure exceeded 10 cmH2O. Increasing flow rate enhanced the absorption of both glucose and 3H2O. However, the effects of increasing flow rate and distention on 3H2O were not additive. In the presence of higher filling volume, faster flow rate led to no further increases in 3H2O absorption; vice versa, at faster flow rate, no further increases in 3H2O absorption were noted when luminal volume was increased. We conclude that increased intraluminal volume enhances the absorption of solutes transported by passive but not carrier-mediated mechanisms, perhaps via augmentation of functional absorptive surface area. Increased flow rate and volume may increase the absorption of passively absorbed probes, in part, by a similar mechanism.

Animals↗

Rectal reservoir reduction procedures for internal rectal prolapse.

Forty-four patients presenting with painful outlet constipation had internal rectal intussusception documented by cinedefecography. Rectal reservoir reduction by multiple elastic ligation or staple excision of redundant mucosa effectively improved bowel function and outlet symptoms in the majority of patients. Rectal reduction procedures were performed under intravenous sedation with antibiotic coverage, no postoperative sepsis, and a single case of significant postoperative bleeding. Associated abnormalities on defecography were unaffected.

Adult↗

Augmentation of neutral sodium chloride absorption by increased flow rate in rat ileum in vivo.

Studies in intact animals have shown that intestinal solute absorption is enhanced with increasing flow rates; the mechanism of this phenomenon has not been explored in detail. We used single pass perfusions of rat ileum to study the effect of higher flow rate on electrolyte absorption. Augmenting perfusion rate from 0.5 to 5.0 ml/min resulted in increased rates of sodium (11.0 +/- 0.9 vs. 23.5 +/- 2.7 mueq/min X g) and chloride (12.1 +/- 0.8 vs. 25.0 +/- 2.2 mueq/min X g) absorption, reduction in the estimated unstirred layer thickness (668 +/- 31 vs. 433 +/- 28 micron), minimal changes in intraluminal pressure and transmural potential difference, and a small, though significant, increase in intraluminal volume (19.4 +/- 8.4%). Removal of sodium from the perfusion medium abolished the effect of increased flow rate on chloride absorption as did removal of chloride on sodium absorption; addition of furosemide or acetazolamide to Ringer's solution also inhibited this effect. In separate experiments, stepwise increases in intraluminal volume were induced by elevating the outflow tubing; no effect on electrolyte transport was observed. These studies demonstrate that neutral sodium chloride absorption is enhanced in rat ileum at higher flow rates, perhaps as a result of a decrease in the thickness of unstirred layers.

Animals↗

Planning a statewide genetic screening program: defining program functions to achieve desired outcomes.

When responsibility for administering the Genetic Screening Program in Georgia was transferred from an academic institution to state authority in 1982, the need was identified to reassess program planning. Accordingly, a cooperative effort was initiated between the Director of the Genetic Screening Program and representatives of the Centers for Disease Control to define desired program outcomes and the functions that should be performed to achieve these outcomes. This cooperative effort resulted in the development of specific and measurable outcomes for Georgia's Genetic Screening Program. These desired outcomes indicate the degree of reduction in morbidity and mortality associated with genetic diseases the Program is expected to achieve within a specified period of time. The major actions that should be taken to achieve these outcomes were also identified and delineated in sequence using flowchart format. These explicit descriptions of desired program outcomes and the functions necessary to achieve these outcomes provide the Genetic Screening Program Director with a valuable resource to use in planning program activities and assessing the extent to which the Program is successful in achieving its overall goal of reducing morbidity and mortality associated with genetic diseases.

Anemia, Sickle Cell↗

Preparation and release characteristics of potassium chloride microcapsules.

The release characteristics of potassium chloride was studied when it was coated with a selection of polymers; from the results obtained, a suitable batch was microencapsulated using a gelatin-gum arabic coacervate system. The microencapsulated product offers better controlled release for this drug when compared to standard table and powder forms.

Capsules↗

The induction of cellular DNA synthesis in G1-arrested BKH21 cell infected with adenovirus type 2.

G1-arrested BHK21 cells infected with adenovirus type 2 were studied to determine the effect of infection on host DNA synthesis in a productive cycle of infection. At various intervals following infection, analysis of the intracellular DNA was carried out by zonal sedimentation centrifugation through alkaline sucrose gradients. In addition to material which sedimented to the position of the virus markers (34S), a class of high mol. wt. DNA (40 to 100S) was found to be synthesized beginning approx. 13 h p.i. and continuing up to about 35 h p.i. DNA--DNA hybridization studies on this newly synthesized DNA showed it to be cellular DNA. When this material was density labelled with 5-bromodeoxyuridine and centrifuged to equilibrium through alkaline CsCl gradients, it was found to be the product of semi-conservation replication and not of repair synthesis.

Adenoviruses, Human↗

Relationship between the plasma glucose level and glucose uptake in the conscious dog.

In the absence of a change in the pancreatic hormonal milieu, elevations in the normal fasting plasma glucose level have little effect on glucose clearance. In view of these data, and the previously established responsiveness of M to hormones, glucose clearance can be considered to represent a useful index of hormone action on glucose uptake in vivo. Care should be taken, however, when interpreting clearance data obtained under hypoglycemic conditions, since there is a possibility that clearance may spontaneously increase at very low plasma glucose levels.

Animals↗

Virus-like particles and double stranded RNA from killer and non-killer strains of Saccharomyces cerevisiae.

Virus-like particles and DsRNA found in extracts of killer, non-killer and suppressive non-killer strains were co-precipitated from cell extracts using an antibody prepared against purified virus-like particles isolated from a non-killer strain having only the higher molecular weight L dsRNA. The relative amount of virus-like particles correlated roughly with the amount of dsRNA: those strains with high concentrations of dsRNA had the most particles. When a preparation of particles was subjected to sucrose gradient velocity centrifugation, particles containing the S and M dsRNA could be separated from those containing the L dsRNA. These experiments taken together suggest that the L, M and S dsRNAs are separately encapsulated by the same protein coat.

Capsid↗