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Biomedical subjects

M H Humphreys

Publications and source records attributed to M H Humphreys.

At least 91 records · Page 5Linked to original sources
PubMed1981

Factors determining electrolyte excretion and renin secretion after closure of an arteriovenous fistula in the dog.

We studied 12 pentobarbital-anesthetized dogs 8 to 21 days after surgical placement of a femoral AV fistula in order to characterize the renal response to subsequent closure and reopening of the fistula. Closure of the fistula resulted in a significant reduction in cardiac output from 3.3 +/- 0.2 L/min to 2.2 +/- 0.1 (p less than 0.001) and heart rate from 163 +/- 7 beats/min to 150 +/- 7 (p less than 0.005), whereas blood pressure did not change significantly. These changes in systemic hemodynamics were associated with significant increases in GFR, renal vascular resistance, and filtration fraction and a significant decrease in RBF. UNaV (16.4 +/- 3.8 microEq/min to 31.3 +/- 6.5), UKV (27.9 +/- 1.6 microEq/min to 47.5 +/- 3.8), and UHCO3V (6.8 +/- 1.4 mumol/min to 25.0 +/- 2.4) increased significantly (p less than 0.005), whereas UCIV was unchanged. Renal denervation blunted the renal hemodynamic and natriuretic consequences of fistula closure, but other electrolyte excretory responses paralleled those in innervated kidneys. In innervated kidneys RSR fell significantly after fistula closure; RSR was low in denervated kidneys and did not change on fistula closure. Reopening the AV fistula restored systemic hemodynamics toward initial control values but produced no further changes in renal hemodynamics or electrolyte excretion. Overall, an inverse relationship between changes in cation excretion and changes in RSR was observed in innervated kidneys. These results demonstrate involvement of the renal nerves as well as an increase in GFR in the increased cation excretion that occurs after AV fistula closure. However, persistently elevated cation excretion after the reopening of the fistula may be due to other mechanisms.

Animals↗
PubMed1980

Tuberculosis in patients with end-stage renal disease.

Ten patients with proved disease caused by Myocobacterium tuberculosis were identified over a 10 year period in a population of 172 adult patients undergoing long-term dialysis. The incidence of tuberculosis was 12 times greater than that prevailing in the general community during the period of the study and could not be accounted for solely by demographic factors. Diagnosis was obscured because the symptoms were nonspecific and attributable to uremia, intermediate strength (5 TU) tuberculin tests were often negative, the roentgenographic appearance of pulmonary disease was often atypical, and there was more frequent extrapulmonary involvement. Impaired cellular immunity due to advanced renal failure may predispose to the increased incidence of tuberculosis and the greater frequency of extrapulmonary disease observed. Treatment was safe and effective in these patients using 300 mg of isoniazid and 8 to 10 mg/kg of ethambutol daily. Eight patients survived longer than one year following the diagnosis of tuberculosis, and all were clinically cured. No deaths were directly attributed to tuberculosis. A high index of suspicion and aggressive evaluation may be necessary to diminish the significant mortality described previously in association with disseminated disease.

Adult↗
PubMed1980

Anion-stimulated phosphohydrolase activity of intestinal alkaline phosphatase.

Phosphohydrolase activity of a highly enriched commercial preparation of calf intestinal alkaline phosphatase was stimulated in the presence of HCO3. SO4, Cl, SCN, and acetate did not stimulate hydrolysis, whereas SO3 exhibited a bimodal effect, stimulating at low (25mM) concentration but inhibiting at high (100 mM) concentration. The pH optimum of this stimulation by HCO3 or SO3 was 8.5--9.0 and was maximal at a Mg concentration of 0.5 mM. HCO3 increased the Vmax of the reaction without changing the Km for ATP. ATP, GTP, UTP, and xanthosine triphosphate were equally effective as substrates, whereas AMP and p-nitrophenyl phosphate were much less effective. Alkaline phosphatase activity was inhibited by L-cysteine and L-phenylalanine, compounds that also inhibited the HCO3-ATPase activity of the preparation. Passage of the commercial preparation through an anion-exchange column yielded a fraction with enriched alkaline phosphatase and HCO3-ATPase activities; this fraction proved to be a single protein on sodium dodecyl sulfate-polyacrylamide gel electrophoresis, on isoelectric focusing, and by immunologic techniques. These studies strongly suggest that alkaline phosphatase and anion-stimulated phosphohydrolase activities are properties of the same protein in small intestine. It is possible that alkaline phosphatase may function as a HCO3-ATPase involved in intestinal absorption and secretion.

Adenosine Triphosphatases↗
PubMed1980

Renal effects of nitroprusside and hydralazine in patients with congestive heart failure.

The acute effects of nitroprusside infusion and intravenous hydralazine on renal hemodynamics and function were evaluated in nine male patients with severe, low cardiac output, congestive heart failure (CHF). Both drugs resulted in marked systemic hemodynamic improvement. Nitroprusside had a more profound effect on pulmonary artery pressure, while hydralazine produced a greater elevation in cardiac output. Significant decreases in both systemic and pulmonary vascular resistance and pulmonary capillary wedge pressure with increases in stroke volume and stroke work index were noted with both drugs. Total renal resistance decreased and renal blood flow (RBF) significantly increased with both drugs, while the distribution of cardiac output to the kidney remained depressed. Glomerular filtration rate (GFR) did not change significantly with either drug, although increases in GFR were seen in selected patients in whom RBF increased by more than 10% from control. The fraction of plasma filtered decreased toward normal with both drugs and excretion of total cations was significantly increased. These changes all represent improvements in systemic and renal hemodynamic abnormalities occurring in patients with CHF; their maintenance during long-term therapy would facilitate patient management.

Adult↗
PubMed1979

Requirement of Zn to demonstrate HCO3-stimulated ATPase activity of rat small intestinal brush border.

The existence of a membrane-bound HCO3-stimulated ATPase in intestinal mucosa is controversial. A crude brush border fraction of rat small intestinal homogenates contained HCO3-ATPase activity which was inhibited by preincubation with 3 mM EDTA. Alkaline phosphatase activity of this preparation was also inhibited in a parallel, time-dependent fashion by preincubation with EDTA. When 5 mM ZnSO4 accompanied 3 mM EDTA in the preincubation mix, preservation of both enzyme activities occurred, demonstrating a requirement of Zn for the activity of both these phosphatases. These studies support the earlier contention that HCO3-ATPase and alkaline phosphatase activities may be different properties of the same enzyme, and raise the possibility that the ATPase could play a role in intestinal ion transport. The failure to identify a membrane-bound HCO3-ATPase by other workers could be due to the exposure of EDTA which occurred in their tissue preparation.

Adenosine Triphosphatases↗
PubMed1979

Anion-stimulated ATPase activity of brush border from rat small intestine.

Differential centrifugation of rat small intestinal homogenates produced a crude brush border (BB) fraction that was enriched 15-fold for the marker enzymes, alkaline phosphatase and sucrase; contamination with mitochondrial enzymes, monoamine oxidase and succinate dehydrogenase, was minimal. ATP hydrolysis by this BB fraction was stimulated by addition of several anions to the incubation medium: HCO3 and Cl were equally effective in this regard, with NO3, NO2, SO4, and acetate being less stimulatory. SCN and CNO inhibited ATPase activity, whereas the divalent anion SO3 was stimulatory at low concentrations (less than 25 mM) but inhibitory at 100 mM. Maximum anion stimulation was observed at a Mg concentration of 0.5 mM, and pH optimum was 8.5. Kinetic analysis showed that HCO3 increased the Vmax without altering the Km for ATP; the Ka for this effect of HCO3 was 35 mM. This enzyme activity was completely inhibited by 20 mM L-phenylalanine, 10 mM L-cysteine, and 3 mM EDTA, compounds that also inhibited intestinal alkaline phosphatase. These results demonstrate the presence of anion-stimulated ATPase activity in rat small intestinal brush border and suggest that this activity may be related to intestinal alkaline phosphatase. The role of this enzyme in intestinal transport is not known, but could relate to the regulation of intestinal absorption and secretion.

Adenosine Triphosphatases↗
PubMed1979

Peritoneal clearance and total body elimination of vancomycin during chronic intermittent peritoneal dialysis.

Vancomycin is a useful antimicrobial agent in patients undergoing chronic hemodialysis treatment; its efficacy in chronic peritoneal dialysis (CPD) has not been established. Serum (VS) and peritoneal fluid (VPF) vancomycin concentrations were measured in two CPD patients with staphylococcal peritonitis. Half-life of VS agreed with the half-life of VPF in each patient, and the VS/VPF ratio was 1.27 in both patients. Distribution volumes were 37.2 and 58.7 l, values approximating total body water in these patients. VS and VPF persisted in the therapeutic range (greater than 5 microgram/ml) for more than 16 days. In one patient, mean peritoneal clearacne was 9.8 ml/min, and overall drug clearance averaged 2.3 ml/min; in the other patient, overall clearance was 2.1 ml/min. These results indicate that therapeutic vancomycin levels can be maintained for more than 16 days with a single 1 g intravenous dose in patients receiving intermittent CPD, as is the case for hemodialysis patients. Because of this, parenteral vancomycin is useful in the treatment of staphylococcal peritonitis in CPD patients.

Adult↗
PubMed1979

The effect of infusion of mannitol-sodium bicarbonate on the clinical course of myoglobinuria.

Twenty patients who had evidence of myoglobinuria were treated with intravenous infusions of mannitol and sodium bicarbonate. Nine patients (group 1) responded with higher urine output, and continued infusion improved renal function; none required dialysis and all survived. Eleven patients (group 2) did not respond to the infusion, and required an average of 5.3 (range, 0 to 11) dialyses; one patient died. There was no significant difference in initial BUN level, creatinine level, BUN/creatinine ratio, or fractional sodium excretion level between the two groups. However, group 2 patients had a significantly higher creatine phosphokinase (CPK) level, serum phosphate level, and hematocrit reading initially than did group 1, indicative of more severe muscle injury and hemoconcentration. These results demonstrate that some patients with myoglobinuria will respond to infusion of mannitol and sodium bicarbonate. This treatment may be effective in altering the clinical course of myoglobinuric acute renal failure.

Acute Kidney Injury↗
PubMed1978

Nitrogen balance during intermittent dialysis therapy of uremia.

Daily measurements of nitrogen balance were made at two levels of protein intake in five patients undergoing chronic intermittent dialysis therapy. During ingestion of high (1.4 g/kg of body wt) protein intake, nitrogen balance was positive on nondialysis days and negative on dialysis days, so that cumulative balance for the week of study was not different from zero. During ingestion of low (0.5 g/kg) protein intake, nitrogen balance was approximately zero on nondialysis days but was again negative on dialysis days, so that cumulative balance for this period was negative. The negative nitrogen balance observed on dialysis days was associated with a higher rate of urea nitrogen generation (Gu, g/24 hr, determined by a kinetic model of urea nitrogen in dialysis patients) that was most evident in the hours immediately following dialysis. Net protein catabolic rate (PCR, g/24 hr), derived from total nitrogen mass balance equations, correlated very closely with Gu:Gu = 0.154 PCR - 1.7, r = 0.96. This relationship agreed well with previous observations made in nondialyzed uremic patients under more steady-state conditions. These studies demonstrate that nitrogen balance is negative on dialysis days regardless of protein intake, and that Gu is higher on dialysis days. The negative nitrogen balance could result from amino acid loss in dialysate and from increased protein catabolism stimulated by loss of glucose into dialysate.

Adult↗
PubMed1978

Role of hemodynamic changes in the increased cation excretion after acute unilateral nephrectomy in the anesthetized dog.

Studies were carried out in anesthetized dogs to characterize the increase in cation excretion which occurs after acute unilateral nephrectomy (AUN). 60 min after AUN, cation excretion had increased from 31.5+/-2.7 to 66.3+/-12.0 mueq/min (P < 0.005) and fractional cation excretion had increased from 0.56+/-0.05 to 1.03+/-0.14% (P < 0.005), as the glomerular filtration rate was unchanged and renal blood flow fell. The increased cation excretion was accompanied by an increase in fractional phosphate excretion, no change in chloride excretion, and a fall in renin secretion. These alterations in renal function were associated with marked changes in systemic hemodynamics: cardiac output fell from 2.52+/-0.24 to 1.85+/-0.16 liters/min (P < 0.001), as diastolic pressure rose without an overall increase in mean arterial pressure, and heart rate fell. To assess the importance of these hemodynamic changes in the renal response, AUN in a separate group of dogs was accompanied by the simultaneous opening of a surgically created femoral artery-to-vein fistula at flow matching the blood flow to the removed kidney. When this was done, no alterations in systemic or renal hemodynamics were observed, and cation excretion did not differ from control. Subsequent closure of the fistula then caused a fall in cardiac output from 2.15+/-0.25 to 1.77+/-0.20 liters/min (P < 0.05), and an increase in cation excretion from 34.6+/-9.5 to 52.3+/-13.7 mueq/min (P < 0.01), thus mimicking the findings with AUN alone.These results demonstrate that AUN causes hemodynamic changes resembling those seen on closure of a chronic arteriovenous fistula. Prevention of these hemodynamic changes after AUN also prevents the functional adjustment of the remaining kidney, suggesting that they may be important in initiating the renal response. The increased electrolyte excretion after AUN may occur through mechanisms similar to that seen on closure of an arteriovenous fistula.

Animals↗
PubMed1976

Inhibition of NaCl absorption from perfused rat ileum by furosemide.

The effect of furosemide on intestinal absorption of water and electrolytes was studied using segments of rat ileum perfused in vivo. Furosemide (1 mM) in the perfusion fluid reduced absorption of Na, Cl, and water by 50% from a balanced electrolyte solution without changing the transepithelial potential difference (PD). This effect was also observed in the absence of luminal glucose and was largely reversible. Substitution of all Na in perfusion fluid with choline produced secretion of Na and water and abolished Cl absorption; substitution of all Cl with SO4 reduced Na absorption to 20% of control values. Under both these conditions, furosemide had only trivial effects on electrolyte absorption and exerted no effect on PD. Measurements of unidirectional fluxes of Na and Cl showed that furosemide decreased net flux by reducing lumen-to-blood flux of these ions rather than increasing blood-to lumen flux. These results resemble those obtained in this tissue following exposure to acetazolamide, and suggest that furosemide inhibits a coupled, neutral process of NaCl transport from lumen to blood. Although this effect could be a result of carbonic anhydrase inhibition it more likely occurs from a separate action of furosemide on ileal transport.

Animals↗
PubMed1975

Suppression of antidiuretic hormone secretion by clonidine in the anesthetized dog.

Studies were performed to determine the mechanism by which the antihypertensive agent clonidine increases urine flow (V). In 11 anesthetized, hydropenic dogs, i.v. administration of clonidine (30 mug/kg) increased arterial pressure from 128 +/- 4 to 142 +/- 3 mm Hg and slowed heart rate from 138 +/- 7 to 95 +/- 7 beats/min within 30 min of injection; blood pressure then fell to 121 +/- 5 mm Hg 30 to 60 min after injection, and 112 +/- 5 mm Hg in the next 30-min period. V increased from 0.36 +/- 0.09 to 0.93 +/- 0.13 Uosm ml/min and urine osmolality (Uopsm) decreased from 1378 +/- 140 to 488 +/- 82 mOsm/kg of H2O 30 to 60 min following injection (P less than 0.001). These changes were accompanied by a decrease in TcH20. This increased V was not associated with increased glomerular filtration rate (GFR) or solute excretion, and occurred in acutely denervated kidneys and kidneys protected from the initial increase in arterial pressure by constriction of a suprarenal aortic clamp. By contrast, V TcH2O and UOsm were not altered by clonidine administration in seven acutely hypophysectomized dogs receiving a constant infusion of antidiuretic hormone (ADH) (80 muU/kg/min), despite similar hemodynamic changes produced by the drug. The results suggest that clonidine increases V through inhibition of ADH release, possibly via an indirect pathway mediated by the drug's alpha-adrenergic on the circulation.

Animals↗
PubMed1975

The relationship between sodium excretion and renin secretion by the perfused kidney.

The effect of altered tubular sodium reabsorption on renin secretion (RSR) was examined under conditions in which other factors influencing renin release could be controlled or excluded. To do this, isolated canine kidneys were perfused at constant pressure with blood circulating from donor animals. Volume expansion or hemorrhage of the donor dogs produced large changes in the animal's blood pressure, renal function, sodium excretion (UNaV), and RSR, but were without effect on renal hemodynamics, UNaV, or RSR in the perfused kidney. Hemodilution without volume expansion, resulted in hypotension, decreased UNaV and increased RSR in the donor dogs, and increased UNaV and suppressed RSR in the perfused kidney. These effects of hemodilution in the perfused kidney were partially reversed when plasma protein concentration was restored to control levels with hyperoncotic albumin, and, overall, there was a significant inverse relationship between electrolyte excretion and RSR. These results provide new evidence for the hypothesis that the rate at which sodium is delivered to the macula densa is an important determinant of the rate of renin secretion.

Animals↗