Isotopic evaluation of the metabolism of pyruvate and related substrates in normal adult volunteers and severely burned children: effect of dichloroacetate and glucose infusion

In this study we have assessed the hypothesis that there is a postreceptor defect in glucose metabolism that makes the severely burned patient unable to oxidize glucose efficiently as an energy source. The intracellular pyruvate pool was labeled by the infusion of 3-13C-lactate, and expired CO2 production and isotopic enrichment of both pyruvate and CO2 were determined to calculate the rate of pyruvate production and oxidation. 6,6-d2-Glucose and 15N-alanine were infused simultaneously to relate pyruvate kinetics and oxidation to glucose and alanine kinetics. Five normal volunteers and 10 severely burned patients (mean of 80% +/- 5% body surface burned) were studied in the basal state and during continuous (unlabeled) glucose infusion. Also, the effect of dichloroacetate, which normally stimulates pyruvate dehydrogenase activity, was assessed in both volunteers and patients. The burned patients had many of the classic metabolic responses to severe injury, including significant increases in resting energy expenditure, glucose production, and alanine release from protein breakdown. However, rather than being inhibited, the rate of pyruvate oxidation was increased approximately 300% in burned patients. Although the patients had an elevated mean concentration of lactate, stemming from increased lactate production, no deficit in pyruvate dehydrogenase activity was evident. Rather, the high rate of lactate production was apparently a consequence of the high rate of glycolysis. On the other hand, the direct pathway for synthesis of glycogen from infused glucose appeared to be impaired in burned patients. In both volunteers and patients, dichloroacetate stimulated the percent of pyruvate directed to oxidation, thereby reducing the conversion of pyruvate to other fates, including lactate. However, because there was no deficit in pyruvate dehydrogenase activity in the patients compared with normal volunteers before dichloroacetate treatment, no unique effect of dichloroacetate on glucose or protein kinetics was observed in burned patients. From these results we conclude that if there is a postreceptor defect in glucose metabolism in burned patients, it involves the pathway of direct glycogen synthesis and not the pathway of oxidation.     

Femorodistal vein bypass graft stenoses

Eighty femorodistal in situ vein bypass grafts have been evaluated at 3-monthly intervals clinically, with ankle:brachial pressure indices (ABI), by intravenous digital subtraction angiography (IV DSA) and by Duplex scanning. Five grafts (6 per cent) failed in the perioperative period. Nineteen (25 per cent) of the remaining 75 grafts subsequently developed stenoses on IV DSA during the first 12 months. All angiographic stenoses were detected by Duplex scanning using velocity ratio criteria before the development of symptoms or a measurable decline in ABI, i.e. while non-haemodynamically significant. This technique involves scanning the entire length of the graft but allows even minor stenoses to be detected and progression of stenoses can be determined. At a mean follow-up of 12 months (3-18 months), four (7 per cent) of the fifty-six grafts without stenoses occluded. Eight (42 per cent) of the nineteen stenosed grafts either occluded or developed symptoms. None of the occluded grafts in this series could be salvaged. Non-haemodynamically significant vein stenoses can be detected non-invasively, occur frequently and are associated with graft failure.     

The impact of laparoscopic cholecystectomy on the treatment of symptomatic cholelithiasis

Background: There has been a debate about the cost-effectiveness of laparoscopic cholecystectomy (LC), as well as a concern regarding its possible overutilization and changes in the indication for surgery. Methods: A retrospective analysis of all cholecystectomies performed at UCDMC from 1988 to 1994 was done. The annual rate of cholecystectomy increased by 50% in 1990 when LC was introduced but has since stabilized at a rate 11% higher than the rate before LC. The disease status and severity did not change. Results: The incidence of nonelective surgery remained stable at 31.2% to 37.5%. Elective cholecystectomy had lower mortality (0.16% vs 1.8%, P=0.029), morbidity (2.6% vs 11.2%, P=0.0001), and conversion rate (2.6% vs 16%, P=0.0001) and a shorter length of stay (2.1 days vs 5.4 days), compared with nonelective procedure. Conclusions: The indication for surgery in cholelithiasis has not changed since the introduction of LC. In patients with symptomatic gallstones, early elective surgery is recommended and may be more cost-effective.Presented at the annual meeting of the Society of American Gastrointestinal Endoscopic Surgeons (SAGES), Orlando, FL, March 12–14, 1995     

Acetyladenylate plays a role in controlling the direction of flagellar rotation.

Cells of Escherichia coli deleted for genes that code for the transducers and all the known cytoplasmic Che proteins except CheY responded reversibly to the addition of acetate by spinning their flagellar motors clockwise. By varying growth conditions and using metabolic inhibitors and mutants deficient in acetate metabolism, this effect was shown to require acetate-CoA synthetase [acetate:CoA ligase (AMP-forming); EC 6.2.1.1], an enzyme that catalyzes the formation of acetyl-CoA from acetate by an acetyladenylate intermediate. A mutant deficient in this enzyme but retaining the chemotaxis genes was deficient for chemotaxis. Thus, acetyladenylate appears to play a role in generating clockwise rotation at the level of CheY or the motor.     

Metabolic intervention in surgical patients. An assessment of the effect of somatostatin, ranitidine, naloxone, diclophenac, dipyridamole, or salbutamol infusion on energy and protein kinetics in surgical patients using stable and radioisotopes.

We have assessed the effect of a variety of forms of metabolic intervention on both energy and protein metabolism in 44 severely ill surgical patients. The patients were studied either in the basal state or while receiving total parenteral nutrition (TPN), and the metabolic effects were assessed using the primed-constant infusion of a combination of stable isotopes and radioisotopes. Somatostatin infusion, either in the basal state or in the TPN, did not change glucose kinetics, but there was a significant decrease in the rate of net protein catabolism (NPC). In the basal studies the rate of NPC decreased from 3.4 +/- 0.7 g/kg/d to 2.9 +/- 0.7 g/kg/d (p less than 0.002), while in the TPN patients the corresponding values were 1.48 +/- 0.61 g/kg/d and 1.10 +/- 0.50 g/kg/d, respectively (p less than 0.005). Histamine type 2 blockade with ranitidine did not significantly alter glucose kinetics, but in both the TPN patients and in the basal state ranitidine was associated with a significant decrease in the rate of NPC. In the basal state rate of NPC was 2.44 +/- 0.53 g/kg/d and during ranitidine infusion the value was 2.08 +/- 0.42 g/kg/d (p less than 0.04). Naloxone infusion did not alter glucose kinetics, but there was a significant decrease in the rate of NPC from a basal value of 2.6 +/- 0.6 g/kg/d to 2.3 +/- 0.5 g/kg/d (p less than 0.04). The infusion of the prostaglandin antagonists diclofenac or dipyridamole resulted in increases in the plasma insulin level, and as a result glucose turnover decreased in both groups. In the diclofenac group the rate of glucose turnover decreased from 14.4 +/- 1.7 mumol/kg/min to 12.6 +/- 1.3 mumol/kg/min (p less than 0.02). Neither prostaglandin antagonist resulted in any significant change in the rate of NPC. Beta-adrenergic stimulation with salbutamol resulted in a significant increase in glucose turnover from 12.1 +/- 1.1 mumol/kg/min to 13.4 +/- 0.9 mumol/kg/min (p less than 0.02), and the rates of appearance (Ra) of both alanine and free fatty acids (FFAs) also increased. Alanine Ra increased from 11.7 +/- 2.5 mumol/kg/min to 12.8 +/- 3.0 mumol/kg/min, and the corresponding values for FFA turnover were 7.6 +/- 1.1 mumol/kg/min and 10.3 +/- 2.1 mumol/kg/min (p less than 0.03), respectively. Salbutamol infusion did not result in any significant change in the rate of NPC.(ABSTRACT TRUNCATED AT 400 WORDS)     

The uptake and costs of guidelines for stroke in a district of southern England.

STUDY OBJECTIVE: To assess the impact of guidelines for stroke management on the utilisation of services by patients and the cost consequences of implementation. DESIGN: Prospective audit. SETTING: District health authority in southern England. PATIENTS: A total of 468 live non-comatose stroke patients registered between November 1991 and May 1993. MAIN OUTCOME MEASURES: A comparison between the three, six month periods for investigations performed and rehabilitation received and their associated costs. RESULTS: The appropriateness of the use of investigations improved over time to between 88 and 92% except for computed tomography (CT) (24%). Younger, more severely impaired patients in a medical bed were more likely to have CT. Overall levels of rehabilitation were low. There was no change in use of physiotherapy (61% to 63%), a significant increase in occupational therapy (26% to 39%) and a non significant change in speech therapy (34% to 25%) over time. Guideline introduction caused a modest 23 Pounds increase in costs per patient in the 2nd six months and 41 Pounds in the 3rd six months but this sum could rise to 430 Pounds per patient if full implementation of the guidelines occurred which is still only around 13% of the costs of nursing care while in hospital. CONCLUSIONS: This 18 month aduit shows only modest changes in practice compared with guidelines, and overall levels of rehabilitation were low. The costs of full implementation seem considerable, but in fact constitute only a small proportion of nursing care costs.     

Recovery and Utilization of Deceased Donor Kidneys from Small Pediatric Donors

The optimal use of kidneys from small pediatric deceased donors remains undetermined. Using data from the Scientific Registry of Transplant Recipients, 2886 small (< 21 kg) pediatric donors between 1993 and 2002 were identified. Donor factors predictive of kidney recovery and transplantation (1343 en bloc; 1600 single) were identified by logistic regression. Multivariable Cox regression was used to assess the risk of graft loss. The rate of kidney recovery from small pediatric donors was significantly higher with increasing age, weight and height. The odds of transplant of recovered small donor kidneys were significantly higher with increasing age, weight, height and en bloc recovery (adjusted odds ratio = 65.8 vs. single; p < 0.0001), and significantly lower with increasing creatinine. Compared to en bloc, solitary transplants had a 78% higher risk of graft loss (p < 0.0001). En bloc transplants had a similar graft survival to ideal donors (p = 0.45) while solitary transplants had an increased risk of graft loss (p < 0.0001). En bloc recovery of kidneys from small pediatric donors may result in the highest probability of transplantation. Although limited by the retrospective nature of the study, kidneys transplanted en bloc had a similar graft survival to ideal donors but may not maximize the number of successfully transplanted recipients.     

Treatment of post-traumatic orbital deformities

Correction of post-traumatic orbital deformities requires adequate exposure, often through coronal and intraoral approaches; adequate dissection, at times circumferential and to within 1 cm of the optic foramen; repositioning of displaced bone segments; refabrication of an orbital framework with autogenous materials; and reattachment of soft-tissue adnexae--all of which are basic maneuvers in craniofacial surgery.