Richard B. Freeman

Age and prior caffeine use alter the cardiovascular and adrenomedullary responses to oral caffeine

The effects of age and chronic caffeine use (approximately 300 mg/day) on the cardiovascular and humoral responses to 250 mg of oral caffeine (the equivalent of 2 to 3 cups of coffee) were examined. Older subjects had greater increases in blood pressure than younger subjects (p less than 0.03), and caffeine nonusers had greater blood pressure increases than caffeine users, regardless of age (p less than 0.05). Caffeine increased the product of systolic blood pressure and heart rate (an estimate of myocardial oxygen demand) in older caffeine nonusers, but this effect was absent in older caffeine users (p less than 0.01). Cardiovascular effects of caffeine could not be related temporally to changes in plasma epinephrine, which were greater in caffeine nonusers and younger subjects, or to plasma norepinephrine, renin activity or vasopressin, which did not change. Thus, age accentuates and moderate prior caffeine use attenuates the cardiovascular effects of oral caffeine; these effects are not mediated solely through the sympathoadrenal system.

Deficiency of T and B lymphocytes in uremic subjects and partial improvement with maintenance hemodialysis.

Lymphopenia of a group of uremic patients was associated with normal percentages of T cells but reduced percentages of B cells. Lymphocyte counts improved after a period of maintenance hemodialysis, although not to control levels, and B cell percentages returned towards normal. Uremia is therefore associated with depression of total T and B cell numbers, with a relatively more pronounced effect on B cells. A period of maintenance hemodialysis produces increase in numbers of both cell types and depression becomes nonselective.

Toxicity following methoxyflurane anaesthesia

SummarySeven obese and five normal weight patients were studied before, during and after one hour of methoxyflurane-nitrous oxide anaesthesia during peripheral surgical operations and compared with eight patients of normal weight anaesthetized with nitrous oxide-meperidine and d-tubocurare. Estimates were made of renal function, including serum and urinary electrolytes, osmolarity, uric acid, urea and Creatinine. Renal clearances for the latter three substances were also calculated. Serum and urinary inorganic and organic fluoride concentrations were measured, as were renal clearances. This low dose methoxyflurane anaesthesia resulted only in a decrease in uric acid clearance among all the measures, when compared to the meperidine-nitrous oxide controls. The clearance of uric acid remained depressed for longer in the obese patients, but otherwise they did not differ from the normal weight patients. It is possible but not proven that depressed uric acid clearance may be related to the organic fluoride metabolite and an early indicator of methoxyflurane renal toxicity. The previously documented biotransformation of methoxyflurane was seen in this study. A double peak in serum inorganic fluoride was shown in all patients but one. Rather large differences in peak levels of serum inorganic fluoride occurred. The only significant difference between the obese and normal weight patients as far as fluoride metabolism was concerned was a greater variability in the serum inorganic fluoride levels in the obese patients. It would appear that the obese patient metabolizes methoxyflurane in a quantitatively if not qualitatively different fashion than the normal weight patient, perhaps because of fatty infiltration of the liver. Caution is advised in the use of methoxyflurane for more than 90 minutes of low concentration administration in view of the unpredictability of the biotransformation.RésuméDouze patients dont sept obèses et cinq normaux, soumis à une chirurgie extraabdominale, ont été étudiés avant, durant et après une heure et demi d’anesthésie à faible concentration de méthoxyflurane et protoxyde d’azote. Une comparaison a été faite avec huit sujets normaux anesthésiés au N2O, mépéridine et d-tubocurare. Les fonctions rénales ont été estimées y compris les électrolytes sériques et urinaires, l’osmolarité, l’acide urique, l’urée et la Créatinine. Les clearances des trois dernières substances ont été mesurées ainsi que les concentrations sériques et urinaires du fluor inorganique et organique et leur clearance.Parmi toutes les mesures faites, seule la clearance de l’acide urique a diminué avec cette petite concentration de méthoxyflurane par comparaison à celle observée après anesthésie à la mépéridine avec protoxyde d’azote. La clearance de l’acide urique demeure basse plus longtemps chez les obèses. Par ailleurs, ceux-ci ne différent pas des patients normaux. Il est possible, bien que non prouvé, que cette dépression de la clearance d’acide urique soit due à la formation de métabolite du fluor et qu’elle puisse servir comme indice précoce de toxicité rénale du méthoxyflurane.La biotransformation du méthoxyflurane qui a déjà été documentée, a été retrouvée dans cette étude. Le graphique des modifications du fluor inorganique a montré chez tous les patients, sauf un, une courbe à double crête.On a constaté des différences relativement prononcées dans les concentrations de pointe du fluor inorganique. En ce qui concerne le métabolisme du fluor, une grande variabilité dans le taux de fluor inorganique sérique chez les obèses était la seule différence observée entre ceux-ci et les patients normaux.Il semble que le patient obèse metabolise le méthoxyflurane d’une façon quantitativement sinon qualitativement différente du patient normal, peut-être à cause d’une infiltration graisseuse du foie.On recommande la prudence, même lors de l’usage d’une faible concentration de méthoxyflurane pour une anesthésie de durée supérieure ou égale à 90 minutes, en raison d’un taux de biotransformation dont l’importance est difficile à prévoir.

The Influence of Glucocorticoid Dose on Protein Catabolism After Renal Transplantation

Protein catabolic rate (PCR) and protein balance were measured daily by computerized mass balance studies in 20 subjects during hospitalization after renal transplantation. All hospital courses were uncomplicated. Ten subjects received approximately 1 mg/kg/day prednisone, and ten subjects received 3–5 mg/kg/day prednisone on day 1 with a tapering dose to approximately 1 mg/kg/day by discharge. In both groups, PCR rose during the first 3–4 postoperative days then stabilized at an accelerated level. PCR was significantly greater in the higher prednisone group. Despite encouragement most subjects ate less protein than prescribed, and most were in negative protein balance. Mean daily and net protein deficits were more severe in the higher prednisone group. Higher protein intakes improved protein balance. The protein catabolic effects of the two regimens have been defined and a dose dependency demonstrated. In any therapeutic situation the use of the minimum effective dose of steroids seem advised, and high protein intake should be encouraged to improve protein balance. Some steroid morbidity might thus be avoided.

Altered Patterns of Posttransplant Urinary-Tract Infections Associated with Perioperative Antibiotics and Curtailed Catheterization

Postoperative urinary tract infections (UTIs) in renal transplant patients were studied before and after introduction of a protocol requiring single-dose perioperative antibiotics and earlier catheter removal. The overall incidence of UTIs was reduced from 55.4% to 26%. The most dramatic reduction was in nondiabetic males, from 56% to 8.2%. There was a small but statistically insignificant reduction in infection rates in females. There was no change in the rate of infection in diabetics. The incidences of noncoliform and mixed infections, in the group as a whole, were dramatically reduced from 42.9% to 12%, but Escherichia coli infections were totally unaffected. This protocol exposed the special susceptibility of women and diabetics to posttransplant UTIs and the different pathogenesis of E coli versus noncoliform infections. These features need more study.

Toxicity following methoxyflurane anaesthesia. IV. The role of obesity and the effect of low dose anaesthesia on fluoride metabolism and renal function.

SummarySeven obese and five normal weight patients were studied before, during and after one hour of methoxyflurane-nitrous oxide anaesthesia during peripheral surgical operations and compared with eight patients of normal weight anaesthetized with nitrous oxide-meperidine and d-tubocurare. Estimates were made of renal function, including serum and urinary electrolytes, osmolarity, uric acid, urea and Creatinine. Renal clearances for the latter three substances were also calculated. Serum and urinary inorganic and organic fluoride concentrations were measured, as were renal clearances. This low dose methoxyflurane anaesthesia resulted only in a decrease in uric acid clearance among all the measures, when compared to the meperidine-nitrous oxide controls. The clearance of uric acid remained depressed for longer in the obese patients, but otherwise they did not differ from the normal weight patients. It is possible but not proven that depressed uric acid clearance may be related to the organic fluoride metabolite and an early indicator of methoxyflurane renal toxicity. The previously documented biotransformation of methoxyflurane was seen in this study. A double peak in serum inorganic fluoride was shown in all patients but one. Rather large differences in peak levels of serum inorganic fluoride occurred. The only significant difference between the obese and normal weight patients as far as fluoride metabolism was concerned was a greater variability in the serum inorganic fluoride levels in the obese patients. It would appear that the obese patient metabolizes methoxyflurane in a quantitatively if not qualitatively different fashion than the normal weight patient, perhaps because of fatty infiltration of the liver. Caution is advised in the use of methoxyflurane for more than 90 minutes of low concentration administration in view of the unpredictability of the biotransformation.RésuméDouze patients dont sept obèses et cinq normaux, soumis à une chirurgie extraabdominale, ont été étudiés avant, durant et après une heure et demi d’anesthésie à faible concentration de méthoxyflurane et protoxyde d’azote. Une comparaison a été faite avec huit sujets normaux anesthésiés au N2O, mépéridine et d-tubocurare. Les fonctions rénales ont été estimées y compris les électrolytes sériques et urinaires, l’osmolarité, l’acide urique, l’urée et la Créatinine. Les clearances des trois dernières substances ont été mesurées ainsi que les concentrations sériques et urinaires du fluor inorganique et organique et leur clearance.Parmi toutes les mesures faites, seule la clearance de l’acide urique a diminué avec cette petite concentration de méthoxyflurane par comparaison à celle observée après anesthésie à la mépéridine avec protoxyde d’azote. La clearance de l’acide urique demeure basse plus longtemps chez les obèses. Par ailleurs, ceux-ci ne différent pas des patients normaux. Il est possible, bien que non prouvé, que cette dépression de la clearance d’acide urique soit due à la formation de métabolite du fluor et qu’elle puisse servir comme indice précoce de toxicité rénale du méthoxyflurane.La biotransformation du méthoxyflurane qui a déjà été documentée, a été retrouvée dans cette étude. Le graphique des modifications du fluor inorganique a montré chez tous les patients, sauf un, une courbe à double crête.On a constaté des différences relativement prononcées dans les concentrations de pointe du fluor inorganique. En ce qui concerne le métabolisme du fluor, une grande variabilité dans le taux de fluor inorganique sérique chez les obèses était la seule différence observée entre ceux-ci et les patients normaux.Il semble que le patient obèse metabolise le méthoxyflurane d’une façon quantitativement sinon qualitativement différente du patient normal, peut-être à cause d’une infiltration graisseuse du foie.On recommande la prudence, même lors de l’usage d’une faible concentration de méthoxyflurane pour une anesthésie de durée supérieure ou égale à 90 minutes, en raison d’un taux de biotransformation dont l’importance est difficile à prévoir.

Bilateral nephrectomy and splenectomy in renal failure

Abstract Sixty consecutive patients treated by bilateral nephrectomy and splenectomy as a preparation for renal transplantation are reviewed. Only 8 (13.3 per cent) of the patients were totally free of complications related to the procedure. The most frequent complications noted were atelectasis, pneumonia, hypotension, hyperkalemia, pulmonary effusion, hypertension, and gastrointestinal bleeding. There were 7 deaths in the group (11.7 per cent). As a result of this review bilateral nephrectomy in preparation for transplant is recommended to patients only with the following problems: uncontrolled hypertension of the high renin variety; infected, obstructed kidneys or the presence of vesicoureteral reflux; Goodpastures disease or certain cases of rapidly progressive glomerulonephritis, and some patients with polycystic kidney disease. The role of splenectomy is still controversial.

Spontaneous remission of the nephrotic syndrome in diabetic nephropathy

A 28 year old woman, with diabetes since age 18, had the nephrotic syndrome, hypertension and renal insufficiency. The initial renal biopsy specimen revealed diffuse glomerulosclerosis with early nodular changes. After an initial decline in renal function, her creatinine clearance progressively improved and has remained normal. Within 2 years she had a spontaneous remission of the nephrotic syndrome despite the presence of more pronounced nodular glomerular lesions. Although the renal hemodynamic functions were normal, certain tubular functions were impaired. Since we found no etiology for the nephrotic syndrome other than diabetic glomerulopathy, the complete remission of the nephrotic syndrome and improvement in renal function were very unusual events.

Lymphocyte subpopulations in maintenance hemodialysis patients.

Lymphocyte counts and T,B and null cell proportions were analyzed in forty non-splenectomized, non-nephrectomized maintenance hemodialysis patients, and compared with those in controls. The patients were lymphopenic, but had normal T, B and null cell percentages, regardless of tehir primary renal disease. It is postulated that their lymphocyte suppression is non-selective and may be related to the state of controlled azotemia or to the dialysis procedure.

Sony-W sharing of cadaver kidneys for transplantation

Abstract A regional network composed of 12 major medical centers has been organized in southern Ontario, Canada, and upstate New York. During the first four years of experience over 85 cadaver kidneys have been transported to the institution of the waiting recipient. The majority of kidneys were judged to be functioning at thirty days. Simple flushing of the kidney with 500 ml. of Ursol (University of Rochester Solution) is effective in preserving the kidney for fifteen hours.