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Biomedical subjects

G H Clowes

Publications and source records attributed to G H Clowes.

At least 37 records · Page 2Linked to original sources

Exchange of amino acids by muscle and liver in sepsis.

The amino acid "central fractional clearance rate" (CFCR), the ratio of the rate of amino acid entry into the extracellular pool to the size of the pool, is a measure of amino acid uptake and clearance by liver and other visceral tissues. In nine normal postabsorptive persons, the mean CFCR was 5%, compared with 21% in 31 seriously infected patients. For comparative purposes, biopsy specimens of liver and muscle were obtained for incubation. In infected patients, the rate of hepatic incorporation of tyrosine into protein was three times that in noninfected patients and correlated well with the CFCR. There was no significant difference in hepatic tyrosine oxidation. In muscle from infected patients, net protein degradation was six times that in noninfected patients. Incubated tissues from rats behaved similarly. Thus, accelerated transfer of amino acid from muscle to viscera for protein synthesis occurs in humans with sepsis, as it does in animals. The CFCR demonstrated the importance to survival of visceral amino acid uptake; it was 35% in surviving patients, and only 19% in those who died.

Amino Acids↗

Effect of nonviable tissue and abscesses on complement depletion and the development of bacteremia.

Complement concentrations and blood cultures were compared in 58 patients within 24 hours of injury and weekly thereafter. Extensive amounts of nonviable tissue (n = 40) were associated with a mean depletion of C4, C3, and C5 by 56%, and minor injuries (n = 18) by 22% of normal concentration within 14 hours after injury. The C4, C3, and C5 concentrations returned to normal or above within a week after minor injuries, but not following major injuries. However, C4, c3, and C5 levels remained depressed after major injuries unless necrotic tissue was removed or abscesses were drained. If complement concentration was below 50% of normal for more than a week all patients developed bacteremia. Following debridement or drainage complement returned to normal in 11 patients and blood cultures became negative in seven. Possible consequences by activation and altered availability of complement for chemotaxis, opsonization, and lysis of bacteria have been analyzed and related to the development of bacteremia.

Abscess↗

The effects of hyperalimentation and infused leucine on the amino acid metabolism in sepsis: an experimental study in vivo.

Liver blood flow and exchange of oxygen, glucose, lactate, and amino acids were measured in pigs at the same time as the peripheral arteriovenous (A-V) difference of these substances was determined. Four groups of animals were studied; they were normal postabsorptive, septic fasted, and septic infused either with complete parenteral nutrition (4.25% mixed amino acid solution with 25% glucose) or an isocaloric solution of 1.8% leucine with glucose. Sepsis in the pig caused a rise in arterial concentration of all essential amino acids except tryptophan and a decrease of most of the others. The liver uptake of the sum of all amino acids rose from nonsignificant values to 26.03 mumol/min/kg at the same time as the peripheral A-V difference changed from +20.4 to -678.0 mumol/l. Hyperalimentation increased arterial amino acid concentration, whereas peripheral A-V difference decreased to -132.3 mumol/l. The total liver uptake of amino acids was 24.80 mumol/min/kg but with a higher proportion of essential amino acids than in the fasted septic state suggesting increased liver protein synthesis. When leucine and glucose were infused the peripheral A-V difference of the sum of all amino acids was only -45.6 mumol/l indicating an almost complete cessation of muscle proteolysis. The arterial plasma concentration of all amino acids except leucine, glutamine, and glutamate were markedly reduced. Although hepatic clearance rate of amino acids fell only slightly, due to the low plasma concentrations, the liver uptake decreased substantially to 7.37 mumol/min/kg suggesting a decreased liver protein synthesis which could be deleterious in the presence of sepsis.

Amino Acids↗

Circulatory isolation of the liver for studying energy metabolism in trauma and sepsis.

An isolated level model was used in 25-30 kg pigs to study the uptake and/or release of various energy substrates across the liver and splanchnic bed during trauma and sepsis. This was accomplished by bypassing the hepatic portion of the inferior vena cava (IVC) using a polytetrafluoroethylene (PTFE) (IMPRA, Inc.) graphite-impregnated graft, from above the renal veins to the right atrial junction. The IVC was then ligated between the distal anastomosis and the liver. Sampling was done from inlying catheters placed in the main portal vein, hepatic vena cava, and an artery. Total hepatic blood flow was determined by the dye dilution technique. Our data showed the same pattern of metabolic derangements in both the traumatized and the septic-starved animals, but differed significantly from the normal fed controls. The correlation between glucogenesis and other energy functions of the liver and the proteolysis in skeletal muscle seen in trauma and sepsis is demonstrated. This model is functional and is applicable to the study of various kinds of shock and/or liver failure.

Amino Acids↗

Platelet function abnormalities in a family with recurrent arterial thrombosis.

Three young family members with recurrent arterial thrombosis underwent investigation for lipid or coagulation abnormalities. Lipoprotein electrophoresis, cholesterol, triglyceride levels, and routine coagulation studies were unremarkable. By contrast, testing of platelet function showed enhanced platelet aggregability to epinephrine and collagen in two of the subjects. In addition, release of 14C-serotonin by adenosine diphosphate and epinephrine was increased over control values in these same two patients. The third subject demonstrated decreased platelet aggregation and lowered 14C-serotonin release, but was symptomatic with rest pain at the time of testing. The ongoing in vivo thrombosis in the third subject may account for hypocoagulable platelets by in vitro testing. These abnormally sensitive platelets identified by platelet function testing may be associated with a familial "hypercoagulability" syndrome. Definition of the hemostatic abnormality in these individuals provided a rational basis for pharmacological therapy with antiplatelet drugs, which appeared to be successful.

Adolescent↗

Total blood washout and exchange. A valuable tool in acute hepatic coma and Reye's syndrome.

Total body washout (TBW) was accomplished thirteen times in twelve patients, with response in five and survival in three. TBW can be done without apparent harm to patients and is less laborious and more rapidly effective than repeated exchange transfusion. Early application of TBW in stage III to stage IV hepatic coma may increase survival and possibly prevent progression of metabolic derangements. Patients with stage III to IV Reye's syndrome probably should have TBW promptly, without time-consuming attempts at exchange transfusion. Based on our experience, further application of TBW is warranted in coma due to acute hepatic failure and stage III to IV Reye's syndrome.

Adolescent↗

A metabolic approach to the evaluation of peripheral vascular disease.

Thirty-five patients with occlusive disease of the arteries underwent metabolic studies. The arteriovenous differences of lactate, glucose and oxygen varied with the severity of the ischemic process, as assessed clinically. Lactate release and glucose extraction were significantly different from control values of patients with rest pain or with ischemic gangrene, while values in patients with claudication were comparable with those in the control group. Percutaneous muscle surface pH measurements, which reflect lactate release, decreased directly with diminished perfusion. Metabolic assessment of arterial occlusive disease may prove to be a useful clinical approach.

Aged↗