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Biomedical subjects

D C Brooks

Publications and source records attributed to D C Brooks.

At least 55 records · Page 3Linked to original sources

Insulin stimulates branched chain amino acid uptake and diminishes nitrogen flux from skeletal muscle of injured patients.

Resistance to insulin-mediated glucose disposal occurs in uninjured skeletal muscle of trauma patients but the effect of insulin on the accelerated proteolysis of trauma is unknown. We examined the influence of insulin on forearm amino acid and substrate exchange in five normals and four trauma patients using the hyperinsulinemic glucose clamp technique. Forearm substrate and amino acid flux (Q, nM/100 ml tissue/min), the product of blood flow and arterial deep venous concentration difference, was calculated before and during insulin infusion. Total nitrogen release (NQ, nM/100 ml tissue/min) was calculated as the algebraic sum of all nitrogen groups contained in the amino acids released. Among normal subjects, total nitrogen release from the forearm did not change (581 +/- 197 nM/100 ml tissue/min to 1167 +/- 455) during insulin infusion nor did total branched chain amino acid flux (0 +/- 30 nM/100 ml/min to 106 +/- 36). Under conditions of hyperinsulinemia, neither glutamine nor alanine changed in control subjects. In trauma patients, total nitrogen release (3843 +/- 1383 nM/100 ml/min) was inhibited during insulin administration (819 +/- 314, P less than 0.05). Total branched chain amino acid flux went from a net release of 460 +/- 134 nM/100 ml/min to a net uptake of 10 +/- 82 (P less than 0.05). In patients, statistically significant (P less than 0.05) differences were seen in individual amino acids as well. Forearm nitrogen flux was directly related to total branched chain amino acid flux in patients (r2 = 0.89). Additional studies in normals (n = 4) at higher insulin infusion rates confirmed that these effects were unique to injured subjects and not an effect of the insulin dose. Insulin attenuates the accelerated release of skeletal muscle amino acid in trauma patients. This effect may be mediated in part by facilitated branched chain amino acid uptake. The manipulation of both insulin and branched chain amino acid concentrations may provide a method to reduce post-traumatic protein catabolism.

Adult↗

Hypothermic anesthesia attenuates postoperative proteolysis.

The catabolic response that commonly occurs after major operation is characterized by net skeletal muscle proteolysis and accelerated nitrogen excretion. This response was absent in patients undergoing cardiac surgical procedures associated with the combination of cardiopulmonary bypass, narcotic anesthesia, neuromuscular blockade, and hypothermia. Forearm nitrogen release was 422 +/- 492 nmol/100 ml X min on the first postoperative day, approximately 25% of preoperative values (1677 +/- 411, p less than 0.05). Nitrogen excretion and the degree of negative nitrogen balance were comparable to levels observed in nonstressed, fasting subjects. The potential role of hypothermia, high-dose fentanyl anesthesia, and neuromuscular blockade in modifying the catabolic response to laparotomy and retroperitoneal dissection was further evaluated in animal studies. Six hours after operation, amino acid nitrogen release from the hindquarter was 84% less than control values (p less than 0.05). Nitrogen excretion and urea production were also reduced compared to normothermic controls. It is concluded that the combination of hypothermia, narcotic anesthesia, and neuromuscular blockade attenuates the catabolic response to injury and thus may be useful in the care of critically ill surgical patients.

Amino Acids↗

Intramural gastrointestinal hemorrhage.

Intramural gastrointestinal hemorrhage should be suspected in patients taking anticoagulants who develop acute abdominal symptoms with clotting parameters out of the therapeutic range. Likewise, patients with inherent bleeding disorders may present with intramural hemorrhage. Characteristic features are seen on radiological examination; ultrasonography or computed tomography may be valuable noninvasive diagnostic approaches. The diagnosis may be supported by abdominal paracentesis. Surgical intervention is not necessary as conservative treatment, with replacement of clotting factors leading to rapid recovery.

Adult↗

New dimensions in board-CEO relations.

Hospitals can vary greatly in the development of board-CEO relations. This article, based on a 1985 American Hospital Association survey of hospital governing boards, examines those differences in four key areas: CEO tenure, performance evaluation, incentive compensation plans, and CEO contracts.

Contract Services↗

Surgery for thyroid carcinoma.

The cases of thyroid carcinoma treated at this hospital during the period 1948 to 1981 were reviewed retrospectively. Nine hundred eighty-six patients with thyroid nodules were operated on. One hundred fifty-two were thyroid carcinoma (59 papillary, 36 mixed papillary-follicular, 30 follicular, 20 anaplastic, 5 medullary, and 2 Hurthle cell tumors). There was a 92% follow-up for a mean of 10 years. In the last decade, patients presented at a younger age, the female predominance was diminished, and 15% had had previous neck irradiation. Surgery consisted of total (27) or subtotal thyroidectomy (89), lobectomy or nodulectomy (24), and biopsy (12). Total thyroidectomy had an incidence of postoperative complications that was 20 times higher than that with partial thyroidectomy (P less than 0.001). Disease-related death, recurrence, and survivor status were discussed. There was no significant difference between total versus subtotal thyroidectomy. This study reaffirms the usefulness of subtotal resection and the avoidance of morbidity of more radical total thyroidectomy surgery.

Adenocarcinoma↗

Patterns of failure after surgical cure of large liver tumors. A change in the proximate cause of death and a need for effective systemic adjuvant therapy.

During a period of 7 years, we have aggressively treated liver tumors whether primary or metastatic. Our experience after 43 curative major liver resections has shown an excellent overall survival: 34 of 43 patients still alive a median of 12 months after liver resection (patient ages ranged from 21 to 85 years, median 57 years). Nineteen patients underwent right hepatic lobectomy, 9 trisegmentectomy, 5 left hepatic lobectomy, 5 extended left hepatic lobectomy, 4 right lobectomy plus left lobe wedge resection, and 1 patient underwent a major hilar wedge resection. Two patients died from sepsis and hepatic failure on or before the 60th postoperative day. One patient with no evidence of recurrent colorectal cancer was lost to follow-up after 2.5 years. One patient died without cancer 12 months after left hepatic lobectomy for colon cancer metastases. Cumulative survival for the entire series and for patients after resection of colorectal cancer metastases was the same: 1 year survival 90 percent; 2 year survival 75 percent, and 3 year survival 65 percent. Seventeen of 30 patients remain disease-free after resection of liver metastases. Of the 13 who had recurrence, 8 are still alive. Ten recurrences were outside of the residual liver (predominantly multiple pulmonary metastases). One recurrence was in the right hemidiaphragm, and only three were in the residual or regenerated liver. Serial carcinoembryonic antigen analysis was the best indicator of recurrence in these 13 patients, 12 of whom were asymptomatic. These data confirm that major liver resection can be performed with minimum postoperative mortality (4.7 percent in this series). More importantly, the majority of patients were cured of their liver metastases. The next goal should be the initiation of adjuvant systemic therapy trials after liver resection in such patients.

Adult↗

Post-traumatic insulin resistance in uninjured forearm tissue.

Insulin resistance is a hallmark of post-traumatic metabolism. The mechanism and site of this resistance, however, have not been elucidated. To further define the site of this abnormality, glucose uptake across the uninjured forearm was measured in conjunction with hyperinsulinemic glucose clamp studies in 21 normals and 5 patients with multiple trauma. Under these conditions, glucose infused approximates whole body glucose disposal (M, milligrams/kilogram/min). Forearm glucose flux (Q, milligrams/100 ml tissue/min) is the product of blood flow and arterial-deep venous glucose difference (A-DV). In the basal, unperturbed state forearm glucose uptake (Q) was significantly lower in the patients (0.01 +/- 0.04 mg/100 ml/min) than in the normals (0.06 +/- 0.02) and not significantly different from zero. Basal serum insulin in patients (17 +/- 3 microU/ml) was significantly greater than controls (11 +/- 1). During steady-state conditions of euglycemia and hyperinsulinemia, forearm glucose uptake in the patients (0.36 +/- 0.18 mg/100 ml/min was not significantly different from the basal value. At comparable serum insulin levels in controls, forearm glucose uptake was approximately three times that of the injured patients. This is the first in vivo confirmation of the hypothesis that post-traumatic insulin resistance occurs in uninjured forearm tissue, primarily skeletal muscle. Diminished forearm glucose uptake is present in the resting basal state and cannot be overcome by increasing insulin concentrations.

Adult↗

Epinephrine acutely mediates skeletal muscle insulin resistance.

Alterations in carbohydrate metabolism and insulin resistance are major features of the metabolic response to injury. The mediators of these changes are not defined. In this study we investigated the influence of epinephrine on insulin-mediated glucose uptake by peripheral tissue. Forearm blood flow and substrate exchange were determined during insulin clamp studies with and without epinephrine infusion in normal persons. During control studies insulin concentration was raised to 103 +/- 5 microU/ml. Whole body glucose disposal was 9.23 +/- 1.01 mg/kg . min. At a comparable level of hyperinsulinemia (93 +/- 4 microU/ml), epinephrine reduced glucose disposal to 4.54 +/- 0.39 mg/kg . min (P less than 0.01). Forearm glucose uptake was reduced from 0.66 +/- 0.08 to 0.18 +/- 0.13 mg/100 ml . min (P less than 0.05) despite a doubling of forearm blood flow. Epinephrine reduces whole body glucose disposal in part by reducing glucose uptake in peripheral tissue, primarily muscle. Epinephrine-induced skeletal muscle insulin resistance may play a major role in insulin-resistant states and may contribute to accelerated protein catabolism seen following injury.

Adult↗

Mechanisms of insulin resistance following injury.

To assess the mechanisms of insulin resistance following injury, we examined the relationship between insulin levels and glucose disposal in nine nonseptic, multiple trauma patients (average age 32 years, Injury Severity Score 22) five to 13 days postinjury. Fourteen age-matched normals served as controls. Using a modification of the euglycemic insulin clamp technique, insulin was infused in 35 two-hour studies using at least one of four infusions rates (0.5, 1.0, 2.0 or 5.0 mU/kg min). Basal glucose levels were maintained by a variable infusion of 20% dextrose using bedside glucose monitoring and a servo-control algorithm. The amount of glucose infused reflected glucose disposal (M, mg/kg.min). Tracer doses of (6,6,2D2) glucose were administered in selected subjects to determine endogenous glucose production. At plasma insulin concentrations less than 100 microU/ml, responses in both groups were similar. However, maximal glucose disposal rates were significantly less in the patients than in the controls (9.17 +/- 0.87 mg/kg . min vs. 14.3 +/- 0.78, mean +/- SEM, p less than 0.01). Insulin clearance rates in the patients were almost twice that seen in controls. To further characterize this decrease in insulin responsiveness, we studied six additional patients and 12 controls following the acute elevation of glucose 125 mg/dl above basal (hyperglycemic glucose clamp). In spite of exaggerated endogenous insulin production in the patients (80-200 microU/ml vs. 30--70 in controls), M was significantly lower (6.23 +/- 0.59 vs. 9.46 +/- 0.79, p less than 0.02). In conclusion, this study demonstrated that (1) the maximal rate of glucose disposal is reduced in trauma patients; (2) the metabolic clearance rate of insulin in the injured patients is almost twice normal and; (3) insulin resistance following injury appears to occur in peripheral tissues, probably skeletal muscle, and is consistent with a postreceptor defect.

Adult↗

Evaluation of palliative procedures for pancreatic cancer.

In a retrospective review of 51 patients undergoing palliative procedures for carcinoma of the pancreas from 1974 to 1979, cholecystoenterostomy was as effective as choledochoenterostomy. Patients with loops had the same incidence of cholangitis as those with Roux-Y limbs. Prophylactic gastroenterostomy was not performed routinely. Few patients needed a later gastroenterostomy for progressive cancer.

Aged↗

A sampling of medical staff cost containment projects.

Medical staffs are implementing and participating in a variety of programs designed to lower health care costs in their institutions and communities. This article details a number of these programs ranging from cost awareness to procedural changes within the hospital. These projects are representative of a large selection of projects soon to be published in digest form.

Cost Control↗

Amine repletion in the reserpinized cat: effect upon PGO waves and REM sleep.

Selective repletion of 5-HT and catecholamines in the reserpinized cat was used to study the role of these biogenic amines in the regulation of PGO wave activity and sleep. The results include: 1. Repletion of 5-HT, following injections of D, L and L-5-HTP, suppressed PGORes in the pons and visual system. A consistent relationship between drug dose and duration of suppression was established. D-5-HTP failed to influence PGORes. L and D, L-5-HTP also induced a state closely resembling slow wave sleep and this change corresponded, temporally, with the period of wave suppression. 2. Repletion of catecholamined, following injections of L-DOPA, often caused behavioral arousal and a conversion from PGORes to PGOW. The molar dose of L-DOPA required to block PGORes was 10-20 times greater than that of L-5-HTP required for a comparable effect. In some cases, L-DOPA failed to arouse the cat, and in each of these instances, it failed to suppress PGORes. 3. L-DOPA consistently failed to induce a premature return of REM sleep in the reserpinized animal. These results suggest that 2 neuronal systems, one employing 5-HT and the other catecholamines, play a part in the regulation of PGORes, and presumably, PGOrem. The 5-HT system may be primarily responsible for suppressing PGOrem during slow wave sleep, with the catecholamine system playing a comparable part during wakefulness. Earlier reports that L-DOPA induces REM sleep in the reserpinized animal were not confirmed, indicating that the postulated role of catecholamines in the induction of this state should be reevaluated.

5-Hydroxytryptophan↗

Biosynthetic events of hydrid regeneration. II. Patterns and profiles of RNA synthesis during distal morphogenesis.

The pattern of RNA synthesis during the first 48 h of distal regeneration in Hydra oligactis has been investigated. In addition the RNA synthetic profiles during selected time periods have been studied. RNA synthesis was found to increase five-fold during the first 3 h of regeneration and remained high throughout the rest of the 48 h period. An additional increase was observed 27-30 h following subhypostomal excision, immediately preceding the appearance of the first tentacle pair. The RNA synthetic level then returned to that found at 3 h of regeneration. This pattern was similar to that reported previously for DNA synthesis. Profiles of radioactively labeled RNA remained constant during most of the times studied, showing the presence of newly synthesized 28S, 18S, 5S, and 4S RNA. During two time periods, 28-32 h and 36-40, a novel 8S RNA species was observed. The occurrence of this species coincided with times of increased overall RNA synthesis and immediately preceded tentacle elaboration.

Animals↗