Safe laparoscopic cholecystectomy in a community setting, N = 762.

Laparoscopic cholecystectomy (LC) can be introduced into a community with morbidity and mortality rates equal to that of open cholecystectomy. The entire general surgical community of Greensboro, NC, learned the technique of LC on animal models prior to offering this innovation to the community. Over the ensuing 12 months, they served as surgeons or assistant surgeons to each other on 762 LCs with morbidity and mortality rates comparable to open cholecystectomy. This retrospective study examined the first 1 year of experience beginning 8/13/90. This work represents all of the LCs performed in Greensboro, and all of the surgeons participated in this review. All of the surgeries were done with an electrocautery and utilized a 0 degree forward-viewing scope. Cases were performed at two hospitals with a surgeon as both operator and assistant, and no effort was made to exclude high-risk or elderly patients from this procedure. Patients averaged 50 years of age and ranged from 14 to 96 years. Static cholangiograms were performed in 27% of patients. Conversion to open cholecystectomy was seen in 4.8%. There were two cardiac deaths (0.26%) and significant complications were seen in 3.4%. Seven patients required reoperations. There were no major common bile duct injuries. This retrospective review indicates that this new procedure can be introduced into a community setting by novice laparoscopic surgeons acting both as operators and assistant with a morbidity and mortality rate comparable to that reported for open cholecystectomy.

Extrapancreatic effects of L-leucine infusion in leucine-sensitive and control subjects.

We studied the extrapancreatic effects of L-leucine infusion (2.5 mumol/kg/min) in six controls (three females, three males) and three members of a family with leucine-sensitive hypoglycemia (LSH). Total glucose disposal and endogenous glucose production (EGP) rates were assessed after an overnight fast (12 to 14 hour) during somatostatin (SRIF) infusion (500 micrograms/h) with insulin replacement (0.2 mU/kg/min), combined with D-(3-3H)-glucose infusion. Additional studies of forearm arterial-venous (A-V) balances of amino acids, glucose, and other substrates, combined with L-(1-14C)-leucine kinetics, were done in these two groups. L-leucine infusion resulted in a 15% decrease in whole-body total glucose utilization in controls (P less than .05) during SRIF-insulin infusion, but did not affect glucose utilization in LSH subjects. EGP was not affected by L-leucine infusion in either group. Control subjects demonstrated a significant reduction in forearm glucose uptake and greater lactate release during L-leucine infusion, compared to the basal state. In contrast, subjects with LSH showed a slight increase in forearm glucose uptake and significantly less lactate release during L-leucine infusion. Subjects with LSH demonstrated significantly lower forearm leucine uptake, and lower rates of appearance and oxidation of L-(1-14C)-leucine during leucine infusion, compared to controls. Our data suggest that members of this LSH kindred have a defect in intracellular leucine metabolism in skeletal muscle, resulting in a lack of leucine-induced inhibition of glucose utilization. This may contribution to the development of hypoglycemia in these subjects.

alpha-Ketoisocaproate is superior to leucine in sparing glucose utilization in humans.

The present study was designed to examine the glucose-sparing effect of leucine and its keto acid alpha-ketoisocaproate (KIC) in vivo. Two groups of overnight-fasted normal volunteers were studied. In the first group, eight subjects received an intravenous infusion of leucine and six subjects received KIC (2.3 mumol X kg-1 X min-1) for 3 h; on another occasion, all subjects received saline and acted as their own controls. In the second group, 11 subjects received an infusion of 1 mU X kg-1 X min-1 for 3 h with a variable glucose infusion to maintain euglycemia. On another occasion, five subjects received an additional infusion of leucine and six subjects received KIC each at 2.3 mumol X kg-1 X min-1 for 3 h. The amount of exogenous glucose required to maintain euglycemia (M, mg X kg-1 X min-1) was used as an index of total body glucose utilization. Forearm exchange of leucine, KIC, glucose, and lactate was determined in both groups. Both leucine and KIC infusions alone decreased glucose uptake (42 and 40%) and increased lactate release (37 and 116%, respectively). Hyperinsulinemia (6-fold basal) and euglycemia resulted in a fivefold increase in glucose uptake across the human forearm. The amount of exogenous glucose required to maintain euglycemia averaged 7.4 +/- 0.5 mg X kg-1 X min-1. The combination of leucine and insulin infusions did not alter the stimulated forearm glucose uptake nor did it change M (7.25 +/- 0.6 mg X kg-1 X min-1, P = NS).(ABSTRACT TRUNCATED AT 250 WORDS)

Role of glutamine in adaptations in nitrogen metabolism during fasting.

The present study examines the effect of glutamine infusion on the interorgan fluxes of glutamine, alanine, urea, and ammonia with progressive fasting. Experiments were carried out in two groups of conscious dogs with catheters previously implanted in an artery and in the hepatic, portal, and renal veins. Group I (n = 12) was fasted for 24 h, and group II (n = 10) was fasted for 96 h. On the day of the study, seven animals of group I and five of group II received a constant infusion of glutamine (3.0 mumol . kg-1 . min-1) for 1 h, and the rest (controls) received saline. Four-day fasting produced ketosis with a compensated metabolic acidosis. The demand for glutamine by the kidneys and gut increased, and the liver switched from net glutamine utilization to that of net production. The kidneys (33%) and gut (230%) increased their production of ammonia, while their release of alanine decreased. The estimated efflux of glutamine by skeletal muscle, however, did not change. All of the infused glutamine was cleared by the splanchnic and renal tissues. In group I, there was increased gut production of alanine, which was matched by increased hepatic alanine uptake and urea production. No such changes were observed in Group II. There was, however, an increase in hepatic uptake of ammonia. Finally, glutamine infusion did not alter glutamine or alanine output by skeletal muscle in group I, while it decreased efflux of alanine but not that of glutamine in group II. The data emphasize the complex interdependence of the liver, gut, kidneys, and skeletal muscle in nitrogen sparing.(ABSTRACT TRUNCATED AT 250 WORDS)

A new model to study quantitative effects of laser angioplasty on human atherosclerotic plaque.

A new model for analyzing the major effects of the use of any laser angioplasty system is described. Changes in any of the six major determinants of effect (energy, duration, wavelength, medium, absorption, geometry) can be evaluated. In this report a neodymium: yttrium aluminum garnet (Nd:YAG) laser was used to make 408 laser exposures in vitro on segments of human cadaveric atherosclerotic aorta. Energy, medium (air, human blood, perfluorochemical and saline), geometry and duration were varied. The depth and width of the resultant plaque craters were measured. A large amount of exposure to exposure variability was found in all groups of experiments, even when conditions were held as constant as possible in this rigidly controlled laboratory setting. This variability is attributable to differences in energy absorption by the plaque. Changes in media and fiber optic tip to plaque distance also markedly altered exposure outcome. For example, the average depth of the hole created by a 15 W, 2 second blast with the fiber tip adjacent to the plaque in blood was 1.7 +/- 0.1 mm (n = 27), but the range was between 0.5 and 2.7 mm. Under the same conditions, except with the fiber tip 1 mm away from the plaque, the average hole depth was 0.4 +/- 0.1 mm (n = 12) and the range was 0.0 to 1.7 mm. The use of this model to analyze the major determinants of lasing effects in different laser angioplasty systems should help to select the best conditions for lasing and allow assessment of the variability of outcome.

Glutamine blocks lipolysis and ketogenesis of fasting.

Several in vivo studies have indirectly suggested a relationship between blood glutamine and ketonemia. The present study was designed to characterize the role glutamine plays in regulating lipolysis and ketogenesis during fasting in vivo. Twelve dogs had catheters implanted in the hepatic and portal veins (V) and in the femoral artery (A) 17-21 days before study. The animals were fasted for 4 days. After a 120-min rest and 40-min basal periods, 6 dogs received an infusion of L-glutamine at 6 mumol X kg-1 X min-1 and 6 received saline and acted as controls. Hepatic and splanchnic balances (mumol X kg-1 X min-1) were estimated by A-V differences multiplied by blood flow determined by indocyanine green. Fasting was associated with a compensated (no change in pH) mild metabolic acidosis but no change in plasma insulin and glucagon or blood glutamine. L-Glutamine infusion increased blood glutamine by 20% but decreased arterial free fatty acids (FFA, from 1,054 +/- 47 to 850 +/- 43 mumol/l, P less than 0.01), beta-hydroxybutyrate (beta-OHB, from 136 +/- 15 to 66 +/- 8 mumol/l, P less than 0.01), acetoacetate (AcAc, from 168 +/- 26 to 86 +/- 21 mumol/l, P less than 0.01), and glycerol (from 90 +/- 4 to 65 +/- 5 mumol/l, P less than 0.01). It also decreased hepatic uptake of glycerol (from 2.5 +/- 0.5 to 0.8 +/- 0.3 mumol X kg-1 X min-1, P less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Insulin's effect on Leucine turnover changes during early fasting in the conscious dog.

To study the effects of insulin on leucine turnover during fasting, acute insulin deficiency was induced by the simultaneous infusion of somatostatin and glucagon in conscious dogs fasted 18 h (N = 10) and 48 h (N = 11). Insulin levels during the basal period (before hormone perturbation) were similar in both groups of dogs (12 +/- 3 versus 10 +/- 3 microU/ml, respectively). Glucagon levels were similar in the two groups (94 +/- 9 versus 106 +/- 19 pg/ml). Leucine levels rose from 118 +/- 9 mumol/L to 155 +/- 12 mumol/L as fasting progressed (P less than 0.005). Its rate of appearance also increased by 30% (P less than 0.005) from 3.4 +/- 0.3 to 4.3 +/- 0.4 mumol/kg/min (P less than 0.005), while its clearance remained unchanged. Acute insulin deficiency caused an increase in leucine levels in both 18-h and 48-h-fasted dogs by 55% (to 181 +/- 10 mumol/L) and 45% (to 225 +/- 20 mumol/L), respectively (P less than 0.005). However, while the rate of appearance of leucine remained unchanged in dogs fasted overnight, it rose to 5.1 +/- 0.3 mumol/kg/min (P less than 0.01) in those fasted 48 h. The metabolic clearance rate fell in both groups, although this drop was twice as great in the 18-h group (from 28 +/- 3 to 17 +/- 3 ml/kg/min, P less than 0.005) as in the 48-h group (from 28 +/- 3 to 23 +/- 2 ml/kg/min, P less than 0.005). We conclude that insulin has disparate effects on protein turnover as fasting becomes more prolonged.(ABSTRACT TRUNCATED AT 250 WORDS)

Leupeptin's effect on organ weight, RNA, DNA, and protein content after long bone fracture in the rat.

Long bone fracture in the rat is accompanied by enhanced urinary nitrogen loss reflecting changes in protein synthesis and breakdown. The effects of leupeptin, an inhibitor of lysosomal proteases, were assessed on organ weights, RNA, DNA, and protein content after injury in the rat. Two groups of 8-week-old rats were studied: The first group received left femoral fracture. Half of these received leupeptin (25 mumole ip/day), and the remainder received saline. The second group served as uninjured pair-fed controls, with half receiving leupeptin and half receiving saline. On Days 0, 1, 2, 4, and 7 after injury, animals were sacrificed and organs were removed for determination of weight, RNA, DNA, and protein content. All injured rats lost weight, with maximum loss occurring on Day 4. Food intake was also reduced. Pair-fed rats lost the same amount of weight as injured ones, and leupeptin could not prevent whole body weight loss. Expressed as percentage of total body weight, livers from leupeptin-treated injured rats weighed 10% greater than saline-treated ones on Days 2, 4, and 7 after injury (P less than 0.05). No differences occurred in RNA, DNA, or protein contents. Diaphragms similarly weighed 10, 20, and 30% greater on Days 2, 4, and 7 after injury, respectively, in leupeptin-treated rats (P less than 0.05). In addition, the RNA and DNA contents of diaphragms were 96 and 88% greater, respectively, in treated rats than in controls (P less than 0.05) on Day 4. It is concluded that leupeptin causes a relative increase in the weights of livers and diaphragms after injury, and causes a marked increase in the RNA and DNA contents of diaphragms.