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Biomedical subjects

R H Didlake

Publications and source records attributed to R H Didlake.

17 recordsLinked to original sources

Metabolic responses to fructose-1,6-diphosphate in healthy subjects.

Fructose-1,6-diphosphate (FDP) is an important naturally occurring intracellular metabolite with a direct regulatory role in many metabolic pathways. The most important and widely studied of the FDP effects has been its regulation of glycolysis, particularly the enzyme that synthesizes FDP--phosphofructokinase (PFK). Since it was observed experimentally that FDP does indeed modulate carbohydrate metabolism, we investigated whether FDP would similarly enhance carbohydrate utilization in man. The study used indirect calorimetry and was open to healthy adults (N = 45) of either sex and above legal age. After a steady metabolic state was obtained, 5 g of FDP (10%) was infused into a brachial vein. In 10 subjects, glucose (5 g) or FDP (5 g) was sequentially infused. The rapid intravenous infusion of FDP produced a slight but significant decrease in heart and respiration rates (P < .05). A significant increase in the serum concentration of inorganic phosphate (P < .0001) and the intraerythrocytic concentration of adenosine triphosphate (ATP) (P < .01) was also observed. The FDP infusion produced a decrease in plasma cholesterol and triglycerides (P < .001 and P < .01, respectively). The indirect calorimetric data indicate that the infusion produced a highly significant increase in the respiratory quotient ([RQ] P < .0001) and the energy derived from carbohydrates (P < .0001) and a significant decrease in the energy derived from lipids (P < .0001). Glucose infusion did not cause changes in any of the parameters. These data indicate that carbohydrate metabolism is stimulated by FDP.

Calorimetry, Indirect↗

Atrial natriuretic peptide and sodium homeostasis in compensated heart failure.

The purpose of this study was to determine whether high plasma levels of atrial natriuretic peptide (ANP) in compensated heart failure are important in the maintenance of sodium balance. This was achieved by subjecting eight dogs to bilateral atrial appendectomy (APX) to blunt the ANP response to pacing-induced heart failure. Five intact dogs served as controls. In controls, 14 days of left ventricular pacing at 240 beats/min produced a sustained fall in cardiac output and mean arterial pressure of approximately 40 and 20%, respectively; compared with cardiac output, reductions in renal blood flow (up to approximately 25%) were less pronounced and even smaller decrements in GFR occurred (up to 9%). Despite these changes and a threefold elevation in plasma norepinephrine concentration, plasma renin activity (PRA) did not increase and sodium balance was achieved during the second week of pacing in association with a six- to eightfold rise in plasma levels of ANP. Similar responses occurred in four dogs in which APX was relatively ineffective in blunting the ANP response to pacing. In marked contrast, there were substantial increments in PRA and in plasma norepinephrine concentration, and marked sodium and water retention during the last week of pacing in four dogs with APX and severely deficient ANP. These results indicate that ANP plays a critical role in promoting sodium excretion in the early stages of cardiac dysfunction.

Adaptation, Physiological↗

Peripherally-placed central venous access ports: clinical and laboratory observations.

The P.A.S. Port system is a totally implantable central venous access device consisting of a miniature titanium portal and a 5.8 French catheter that is specifically designed for implantation in the forearm. The configuration of this system combined with its unique placement technology provides a simplified alternative to conventional chest-placed systems. Our group has placed a total of 61 P.A.S. Port devices in 56 patients whose ages ranged from 9 months to 85 years and who were followed for a median of 672 days. Over this period of follow-up, these devices have demonstrated a low overall complication rate (13.1%), an infection rate of 6.6%, median event-free patency of 278 days, and exceptional patient acceptance. Placement of the P.A.S. Port system is easily performed as an outpatient procedure under local anesthesia and requires neither fluoroscopy nor a conventional operating room setting. In vitro measurement of infusion pressure across a P.A.S. Port and a conventional catheter system revealed much higher resistance in the peripherally placed device, but this was found to be of no clinical significance because infusion pressures generated by flow rates up to 750 mL/hr were well within the limits of clinically available infusion pumps. We recommend the P.A.S. Port system as a safe, durable, and effective alternative for patients in whom a chest-placed device is inappropriate or undesired.

Adolescent↗

Changing clinical picture of mammary hamartoma.

During a 6-year period, we identified 12 patients (age range: 16 to 72 years) with a histologic or mammographic diagnosis of mammary hamartoma. The lesion was found in 9 of 441 open breast biopsy specimens (2%) and was identified radiographically in 5 of 8,122 mammographic examinations (less than 1%). Two groups of patients were identified. Three patients under 30 years of age underwent the excision of small palpable lesions found on pathologic examination to be mammary hamartomas (group I). In nine patients over age 30, masses were identified or confirmed on mammography (group II). Five lesions showed the classic mammographic appearance of a mammary hamartoma (a circumscribed tumor of mixed soft tissue and fatty density), and the other four were indeterminate. Presentation in these older women who had a relatively high incidence of atypical mammographic findings mandates that biopsy be performed.

Adolescent↗

Role of pressure natriuresis in long-term control of renal electrolyte excretion.

If pressure natriuresis is to play an important role in arterial pressure control, renal perfusion pressure must have a long-term effect on urinary sodium excretion. The aim of this study was to quantitate the importance of renal perfusion pressure per se in controlling renal hemodynamics and electrolyte excretion chronically. Female mongrel dogs (n = 6) were instrumented with bilateral renal artery catheters for measurement of renal perfusion pressure and occluders on both renal arteries for servo-control of renal perfusion pressure at different levels; the urinary bladder was split for determination of renal clearances and electrolyte excretion from each kidney separately. Because both kidneys were exposed to the same neurohumoral influences, any changes in renal function could be attributed to differences in renal perfusion pressure between the two kidneys. After 5 days of control, renal perfusion pressure to one kidney was reduced from 86.7 +/- 0.2 to 74.2 +/- 0.6 mm Hg for 12 days, and pressure in the contralateral kidney increased to 91.5 +/- 0.4 mm Hg. Sodium excretion decreased from 41 +/- 2 to 25 +/- 1 mmol/d in the servo-controlled kidney and increased from 41 +/- 1 to 55 +/- 1 mmol/d in the contralateral kidney during 12 days of servo-control. Urine volume, chloride excretion, and potassium excretion exhibited similar patterns during servo-control. In addition, autoregulation of effective renal plasma flow and glomerular filtration rate was relatively well maintained; however, in the low-pressure kidney, glomerular filtration rate was slightly but significantly lower (approximately 8%) than in the contralateral kidney.(ABSTRACT TRUNCATED AT 250 WORDS)

Analysis of Variance↗

Increasing survival of dogs subjected to hemorrhagic shock by administration of fructose 1-6 diphosphate.

Previous reports from this laboratory described animal experiments in which intravenous administration of fructose 1-6 diphosphate (FDP) at the onset of hypovolemia, toxemia, and trauma effected improvement in hemodynamic and metabolic parameters, attenuation of tissue damage, and a significant increase in survival. The obvious question remained: Would this agent be as effective if administered after the onset of the shock syndrome? Thus 72 anesthetized dogs were subjected to normotensive hemorrhagic shock and were subsequently treated with FDP at 30 minutes, 1 hour, 90 minutes, and 2 hours after exsanguination. Analysis of the results (as compared with vehicle-treated controls) revealed evidence of improved cardiac output and arterial pressure (p less than 0.02), conservation of effective circulatory volume, better oxygen utilization, and a significant increase in survival (p less than 0.0001). These results, in conjunction with earlier experimental and recent clinical data, indicate that the therapeutic effect of FDP in ischemic and hypoperfusion states is in part metabolically mediated by the augmentation of carbohydrate utilization. Prevention of tissue injury is in part due to the inhibition of generation of oxygen-derived free radicals by neutrophils.

Animals↗

Cortisone, vitamin A, and wound healing: the importance of measuring wound surface area.

Traditional methods of measuring wound strength have often ignored one of the most important variables, i.e., wound surface area. Using a readily reproducible method of determining wound surface area, the effect of topical vitamin A on steroid-treated rats was studied. Findings revealed a significant (P less than 0.001) increase in wound strength with topical vitamin A application. No difference could be detected between steroid-treated and saline-treated rats when wound surface area was taken into account. Measurement of wound surface area is essential for meaningful results in wound healing studies.

Administration, Topical↗

Giant inguinal hernia.

We have presented a case of massive scrotal hernia containing the entire mesenteric small bowel and the entire colon. Review of the literature reveals that such extensive hernias are rare and that their surgical repair is often difficult because of loss of domain.

Abscess↗

Epidermoid cyst of the spleen manifested as an abdominal abscess.

We have reported a case of epidermoid cyst of the spleen, an uncommon congenital anomaly that usually occurs as an asymptomatic abdominal mass. The diagnosis of splenic cyst may be established by ultrasonography. Uncomplicated cysts should be resected, while infected cysts should be drained and resected after resolution of the infection. Splenic salvage should be achieved when possible.

Abdomen↗

Experimental small bowel transplantation utilizing cyclosporine.

Cyclosporine prolonged the survival of ectopic small bowel allografts in a canine model. A 9-fold increase in mean survival as compared with controls was obtained. Addition of prednisone to cyclosporine did not result in further graft prolongation, but improved the gross and histological appearance of the allograft. Monitoring the motility and histology of the allograft appears to be useful in predicting approaching rejection. Xylose absorption was not helpful in this regard. A new technique for measuring fat absorption in the transplant is described. Following allografting, fat absorption is resumed by 14 days posttransplantation.

Animals↗