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Biomedical subjects

B M Wolfe

Publications and source records attributed to B M Wolfe.

At least 55 records · Page 3Linked to original sources
PubMed1997

Cardiopulmonary responses to intravenous infusion of soluble and relatively insoluble gases.

BACKGROUND: Carbon dioxide is the current gas of choice for pneumoperitoneum, but hemodynamic and acid-base effects secondary to its systemic absorption have been reported. Various studies have suggested inert gases as alternatives. METHODS: We studied the cardiopulmonary responses to intravenous infusion of carbon dioxide, nitrous oxide, argon, helium, and nitrogen in anesthetized swine. The gas was infused into the femoral vein at a rate of 0.1 ml . kg-1 . min-1 for 30 min. The changes in end-tidal CO2, mean arterial pressure, hemodynamics, and arterial blood gases were compared to baseline values. RESULTS: No animals died during infusion of the soluble gases (CO2 and N2O). Three of the five pigs infused with nitrogen died suddenly at 20 and 30 min of infusion. The animals in the insoluble gas groups (Ar, He, N2) experienced clinical pulmonary gas embolism and severe acidemia, hypercapnea and tachycardia. CONCLUSIONS: Venous gas embolism is poorly tolerated when the gas is relatively insoluble. Insoluble gases should not be used for pneumoperitoneum when there is any risk of venous gas embolism.

Animals↗
PubMed1997

Uptake of type III hypertriglyceridemic VLDL by macrophages is enhanced by oxidation, especially after remnant formation.

We previously showed that hypertriglyceridemic VLDL (HTG-VLDL, Sf 60 to 400) from subjects with type III (E2/E2) hyperlipoproteinemia do not induce appreciable cholesteryl ester (CE) accumulation in cultured macrophages (J774A.1). In the present study, we examined whether oxidation of type III HTG-VLDL would enhance their uptake by J774A.1 cells. Type III HTG-VLDL were oxidized as measured by both conjugated-diene formation and increased electrophoretic mobility on agarose gels. Both LDL and type III HTG-VLDL undergo oxidation, albeit under different kinetic parameters. From the conjugated-diene curve, type III HTG-VLDL, compared with LDL, were found to have a 6-fold longer lag time, to take 6-fold longer to reach maximal diene production, and to produce a 2-fold greater amount of dienes but at half the rate (all P < .005). Incubation of macrophages with either native type III HTG-VLDL or LDL (50 micrograms lipoprotein cholesterol/mL media for 16 hours) caused small increases (4-fold and 2.7-fold, respectively) in cellular CE levels relative to control cells (both P = .0001). After 24 hours of CuSO4 exposure, we found that oxidized type III HTG-VLDL and LDL caused a 9.4-fold and 10.5-fold increase, respectively, in cellular CE levels (P = .0001). We next examined whether extending the exposure period for type III HTG-VLDL to CuSO4 beyond 24 hours would further enhance its ability to induce macrophage CE accumulation. After 48 hours of CuSO4 exposure, type III HTG-VLDL and LDL caused 21.3-fold and 11.6-fold increases, respectively, in cellular CE levels (P = .0001). The cellular CE loading achieved with 48 hour-oxidized type III HTG-VLDL was significantly higher than either 24 hour-oxidized type III HTG-VLDL (2.3-fold, P = .003) or 48 hour-oxidized LDL (1.8-fold, P = .012). There was no significant difference between the CE loading achieved by incubation of cells with either 24 hour-oxidized type III HTG-VLDL, 24 hour-oxidized LDL, or 48 hour-oxidized LDL (P > or = .518). In this study, we also examined whether partial lipolysis (19% to 50% triglyceride hydrolysis) of type III HTG-VLDL to produce remnants would increase the susceptibility of the lipoprotein to oxidative modification and subsequent cellular CE loading. Forty-eight hour-oxidized type III VLDL-remnants stimulated CE accumulation 30.4-fold over baseline (P = .0001). In contrast, nonoxidized type III VLDL-remnants caused the same very low level of CE loading as did native type III HTG-VLDL (P = .680). The increase in cellular CE levels achieved with 48 hour-oxidized type III VLDL-remnants was significantly higher than that achieved with 48 hour-oxidized type III HTG-VLDL (P = .047). In conclusion, we have shown that oxidized type III HTG-VLDL will induce macrophage CE accumulation well above levels achieved with oxidized LDL. In addition, we also showed that by forming a VLDL-remnant before oxidative modification, we can further enhance macrophage CE accumulation. These results provide a potential mechanism for the atherogenicity of type III HTG-VLDL and their remnants.

Animals↗
PubMed1997

Uptake of hypertriglyceridemic very low density lipoproteins and their remnants by HepG2 cells: the role of lipoprotein lipase, hepatic triglyceride lipase, and cell surface proteoglycans.

Hypertriglyceridemic very low density lipoproteins (HTG-VLDL, S(f) 60-400) are not taken up by HepG2 cells. However, addition of bovine milk lipoprotein lipase (LPL) at physiological concentrations markedly stimulates uptake. In the present study, we determined whether: a) LPL catalytic activity is required for uptake, b) LPL functions as a ligand, and c) cell surface hepatic triglyceride lipase (HL) and/or proteoglycans are involved. Incubation of HepG2 cells with HTG-VLDL plus LPL (8 ng/ml) increased cellular cholesteryl ester (CE) 3.5-fold and triglyceride (TG) 6-fold. Heat-inactivation of LPL abolished the effect. Addition of tetrahydrolipstatin (THL, an LPL active-site inhibitor) to HTG-VLDL + LPL, inhibited the cellular increase in both CE and TG by greater than 90%. Co-incubation of HTG-VLDL + LPL with heparin, heparinase, or heparitinase, blocked CE accumulation by 70%, 48%, and 95%, respectively, but had no effect on the increase in cellular TG. Pre-treatment of cells with 1 mM 4-methylumbelliferyl-beta-D-xyloside, (beta-xyloside) to reduce cell surface proteoglycans inhibited the increase in CE induced by HTG-VLDL + LPL by 78%. HTG-VLDL remnants, prepared in vitro and isolated free of LPL activity, stimulated HepG2 cell CE 2.8-fold in the absence of added LPL, a process inhibited with THL by 66%. Addition of LPL (8 ng/ml) to remnants did not further enhance CE accumulation. HepG2 cell HL activity, released by heparin, was inhibited 95% by THL. The amount of HL activity and immunoreactive mass, released by heparin, was reduced 50-60% in beta-xyloside-treated cells. These results indicate that physiological concentrations of LPL promote HepG2 cell uptake of HTG-VLDL primarily due to remnant formation and that LPL does not play a major role as a ligand. HL activity and cell surface proteoglycans significantly enhance the subsequent uptake of VLDL remnants.

Animals↗
PubMed1996

Lipids and stroke: a paradox resolved.

BACKGROUND: Although dyslipidemia is a well established risk factor for coronary artery disease, its relationship to ischemic cerebrovascular disease has remained unclear, perhaps because of the heterogeneous nature of strokes. METHODS: In a case-control study, we measured the serum concentrations of total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, serum triglycerides, and lipoprotein(a) levels and determined the apolipoprotein E phenotype and serum ferritin level in 90 consecutive systematically investigated patients with stroke or transient ischemic attack of atherothrombotic origin. Ninety age-, sex-, and community-matched subjects served as controls. RESULTS: Plasma total cholesterol (5.99 vs 5.45 mmol/L [232 vs 211 mg/dL], P=.003), low-density lipoprotein cholesterol (3.96 vs 3.45 mmol/L [153 vs 133 mg/dL], P=.004), and serum triglyceride (2.09 vs 1.82 mmol/L [8] vs 70 mg/dL], P=.03) levels were significantly higher among the patients with atherothrombotic strokes and transient ischemic attacks than among the control subjects. The inverse was true for high-density lipoprotein cholesterol (1.07 vs 1.18 mmol/L [41 vs 46 mg/dL], P=.02) levels. No significant differences were found in lipoprotein(a) levels or in the distribution of apolipoprotein E phenotypes or allele frequency. Serum ferritin levels did not differ significantly between patients and control subjects. CONCLUSIONS: Elevated low-density lipoprotein cholesterol and triglyceride levels are significant independent risk factors in patients with proven atherothrombotic cerebrovascular disease manifesting as stroke or transient ischemic attack. The level of stored serum iron, as reflected by serum ferritin levels, does not correlate with the presence of atherothrombotic cerebrovascular or coronary disease.

Aged↗
PubMed1996

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.

Adult↗
PubMed1996

Treatment of familial hypercholesterolemia in children and adolescents: effect of lovastatin. Canadian Lovastatin in Children Study Group.

OBJECTIVE: Familial hypercholesterolemia (FH), an inherited autosomal dominant disorder of lipoprotein metabolism, is associated with premature atherosclerosis. The recommended pediatric therapy consists of dietary intervention and, when necessary, treatment with bile acid-binding resins. However, compliance has been poor in many children. Therefore, our objectives were to determine the efficacy, safety, and tolerance of the short-term use of lovastatin, a 3-hydroxy 3-methylglutaryl coenzyme A reductase inhibitor, in the control of severe FH in a male pediatric population and to evaluate the dose-response relationship. METHODS: Sixty-nine male patients with FH 12.9 +/- 2.4 years of age (mean +/- SD) participated in this multicenter, randomized, double-blind trial. After a 4-week placebo period, the patients were allocated to four treatment groups (lovastatin 10, 20, 30, 40 mg/d) for 8 weeks. Plasma lipid and apolipoprotein (Apo) concentrations were measured every 2 weeks. Clinical and laboratory evidence of adverse events was monitored periodically throughout the study. RESULTS: All lovastatin doses reduced total cholesterol (-17% to -29%), low density lipoprotein cholesterol (-21% to -36%), and ApoB (-19% to -28%) concentrations. A dose-response relationship was seen, and between-group comparisons showed that results were significantly improved up to a dose of 30 mg/d. We observed a 7% increase in high-density lipoprotein cholesterol and a 4% increase in ApoA1 concentrations. The medication was well tolerated by all patients. No serious clinical adverse experience was reported. Lovastatin increased aspartate aminotransferase concentrations, but there was no evidence of a dose-response relationship, and no value exceeded two times the upper limit of normal. No significant change in alanine aminotransferase was observed. Three patients had marked (more than three times the upper limit of normal) asymptomatic elevations in their creatine kinase values, which returned spontaneously to normal, and no action was required regarding the drug.

Adolescent↗
PubMed1995

Effector of hemodynamics during laparoscopy: CO2 absorption or intra-abdominal pressure?

Controversy has been raised about the effects of systemic carbon dioxide accumulation versus the intra-abdominal pressure on hemodynamics during laparoscopy. We compared the acid-base and hemodynamic changes during pneumoperitoneum in a randomized cross-over study between CO2 and nitrogen gases to test the hypothesis that the CO2 absorbed during laparoscopy, rather than the 15 mmHg intra-abdominal pressure created, accounted for these changes. Eight adult pigs were anesthetized and ventilated with a fixed minute ventilation. Metabolic function was measured from analysis of expired flow by a metabolic measurement cart. After baseline periods, animals were randomized into two groups, for 2 hr of either CO2 or nitrogen pneumoperitoneum at 15 mmHg intra-abdominal pressure, followed by 1 hr of recovery. After at least a 48-hr recovery period, the experiment was repeated with the other gas. Metabolic data revealed that there was a significant absorption of CO2 gas across the peritoneal epithelium during CO2 pneumoperitoneum. Animals insufflated with CO2 gas experienced a 75% increase in pulmonary CO2 excretion, with significant acidemia and hypercapnia, whereas there were no acid-base disturbances in those with nitrogen insufflation. Oxygen consumption remained essentially unchanged in both groups, even during pneumoperitoneum. CO2 pneumoperitoneum was also associated with systemic and pulmonary arterial hypertension and a reduction in stroke volume of up to 15%. Pneumoperitoneum alone did not compromise hemodynamics. Pneumoperitoneum using CO2 gas during laparoscopy resulted in systemic CO2 absorption across the peritoneum. This led to acidemia, hypercapnea, and depressed hemodynamics. The intra-abdominal pressure routinely used during laparoscopic surgery did not affect metabolic function, acid-base balance, or hemodynamics in the experimental model.

Acid-Base Equilibrium↗
PubMed1995

Is outpatient laparoscopic cholecystectomy wise?

The authors report a prospective analysis of their experience with 506 consecutive laparoscopic cholecystectomies to examine the appropriateness of outpatient or same-day laparoscopic cholecystectomy. Thirty-eight patients experienced at least one postoperative complication. The complication was clinically evident or suspected in only 4 of these 38 patients within 8 h following surgery. Thirty-nine percent and 76% of complications were clinically detected at 24 and 48 h, respectively. Nausea and vomiting occurred among 32% of all patients on the day of operation and extended into the 1st postoperative day in 10%. Compared to predicted values, forced vital capacity was 61 +/- 5% 1 h postoperatively in 32 patients studied. At 6 and 24 h postoperatively, forced vital capacity was 63 +/- 7% and 66% respectively. Postoperative analgesic medication requirement was determined in 220 patients who were provided with a patient-controlled intravenous morphine analgesia machine with no basal rate. Consumption of morphine was highly variable but substantial on the day of operation: 17 +/- 16 mg. Most complications of laparoscopic cholecystectomy, including life-threatening complications, are not apparent by 8 h postoperatively and may not be apparent at 24 h. The potential for delay in the diagnosis and treatment of complications, variable but substantial analgesic requirements, impaired postoperative ventilation, and postoperative gastrointestinal dysfunction argue for the need to use great caution in selecting patients for outpatient laparoscopic cholecystectomy. Criteria are proposed to identify patients who are safest for outpatient laparoscopic cholecystectomy.

Administration, Oral↗
PubMed1995

Effects of continuous low-dosage hormonal replacement therapy on lipoprotein metabolism in postmenopausal women.

The effects on lipoprotein metabolism of female hormone replacement therapy (HRT) for 7 weeks with combined low dosages of a widely used oral progestin and estrogen combination, medroxyprogesterone acetate ([MPA] 2.5 mg/d) and conjugated equine estrogen ([CEE] 0.625 mg/d), were studied in six postmenopausal women. To investigate the mechanism of the reduction of low-density lipoprotein (LDL) cholesterol by HRT, the kinetics of very-low-density lipoprotein (VLDL) and LDL apolipoprotein (apo) B turnover were studied by injection of autologous 131I-labeled VLDL and 125I-labeled under control conditions and again in the fourth week of HRT. HRT induced (1) a 12% +/- 4% (P < .02) reduction of the cholesterol content of LDL of Sf 0-12, which was attributable to a 15% +/- 5% decrease in the mean ratio of cholesterol to apo B (1.3 +/- 0.1 v 1.5 +/- 0.1, P < .025), and (2) a 13% +/- 4% increase in the mean fractional catabolic rate (FCR) of LDL apo B (0.34 +/- 0.03 v 0.30 +/- 0.02 pools/d, respectively, P +/- .05). However, there were no significant changes in mean values for (1) pool size (42 +/- 4 v 43 +/- 3 mg/kg) or production rate (14 +/- 0.5 v 13 +/- 0.9 mg/kg/d, P > .1) of LDL apo B or (2) pool size (2.5 +/- 0.6 v 2.8 +/- 0.6 mg/kg), FCR (8.0 +/- 2.0 v 8.1 +/- 1.7 pools/d) or production rate (16 +/- 4 v 19 +/- 2 mg/kg/d, P > .4) [corrected] of VLDL apo B. HRT increased high-density lipoprotein (HDL) cholesterol concentration significantly (by 16% to 18%, P < .05), whereas the mean ratio of plasma total cholesterol to HDL cholesterol decreased by 19% +/- 3% (P < .005). HRT favorably influenced the overall plasma lipoprotein lipid vascular risk profile while significantly altering both the composition and fractional catabolism of LDL.

Adult↗
PubMed1995

Identification, molecular characterization, and cellular studies of an apolipoprotein E mutant (E1) in three unrelated families with hyperlipidemia.

Remnants of triglyceride-rich lipoproteins accumulate in plasma of subjects with type III hyperlipoproteinemia (HLP) due to defective clearance by hepatic receptors. Although most subjects with type III HLP are homozygous for apolipoprotein (apo) E2 (arg158-->cys, R158C), a variant that binds defectively to cell surface receptors, some individuals with type III HLP have rare mutations of apo E. We identified six subjects from three families with type III HLP who had either an apo E3/1 or E4/1 phenotype by isoelectric focusing. Using DNA restriction isotyping with HhaI, all six subjects were determined to have only one apo E allele encoding cys158 and the other encoding arg158. Subsequently, digestion of polymerase chain reaction-amplified portions of exon 4 of the apo E gene with endonucleases HaeIII, TaqI, and Sau3AI demonstrated a second DNA variant that encoded a single amino acid substitution (gly127-->asp, G127D) due to a guanosine-to-adenosine nucleotide change resulting in the apo E1 isoform (G127D, R158C), which had arisen from a parent apo E2 allele. This mutation was confirmed with direct DNA sequencing. Incubation of very low density lipoprotein (VLDL) isolated from hyperlipidemic apo E1 subjects with J774 macrophages resulted in a 7- to 12-fold increase in cellular cholesterol ester compared with VLDL from apo E2/2 subjects. Although heterozygosity for apo E1 alone did not impair the interaction of VLDL with cellular receptors in vitro, its presence in subjects with type III HLP suggests that apo E1, perhaps in combination with secondary factors, may be causative for the dyslipidemia.

Adolescent↗
PubMed1995

Potential role of raising dietary protein intake for reducing risk of atherosclerosis.

OBJECTIVE: To ascertain the effect on plasma lipoprotein lipids of substituting moderate amounts of protein for carbohydrate in human diets. DESIGN: Subjects were first stabilized on the desired fat intake for one to two weeks. Using a cross-over design, subjects were randomly allocated to either the high or low protein diet for four to five weeks and then switched to the alternative diet for four to five more weeks. Fasting venous blood was obtained weekly. SETTING: Subjects were studied in tertiary care lipid clinic setting. PATIENTS: Studies in two groups of hypercholesterolemic subjects have been completed: group MH - 10 subjects with moderate hypercholesterolemia (5.8 to 8.0 mmol/L) and group FH - five subjects with familial hypercholesterolemia (more than 8.2 mmol/L prior to treatment with cholestyramine). Preliminary findings in Group NL - six normolipidemic subjects (3.5 to 4.9 mmol/L) are also discussed briefly. INTERVENTIONS: Body weight, intakes of fat, fibre and cholesterol and fat composition were constant. Either 11, 17 or 10% of total energy from protein was exchanged for carbohydrate in groups MH, FH and NL, respectively. MAIN RESULTS: Exchange of dietary protein for carbohydrate: significantly reduced mean plasma low density lipoprotein (LDL) cholesterol 6% in group MH and 9% in group NL (P < 0.02); significantly increased mean fasting plasma high density lipoprotein (HDL) cholesterol by 12% in group MH and by 17% in group FH (P < 0.01); significantly reduced the mean value for the ratio of plasma total cholesterol to HDL cholesterol by 15% in group MH and by 16% in group FH (P < 0.05); and significantly reduced fasting total triglycerides by 23% in groups MH and FH and by 18% in NL (P < 0.05). CONCLUSION: Substitution of dietary protein for carbohydrate favourable alters human blood cholesterol cardiovascular risk profiles.

Coronary Artery Disease↗
PubMed1995

Prospective evaluation of the safety and efficacy of laparoscopic jejunostomy.

We prospectively assessed the safety and efficacy of laparoscopic jejunostomy done by 11 surgeons in 8 medical centers using the T-fastener technique. In all, 23 men and 13 women aged 19 to 84 (mean, 59) years required enteral feeding, but could not undergo gastrostomy and had no contraindication to laparoscopy. Of these patients, 12 had head and neck cancer and 11 had neurologic swallowing dysfunction. The procedure took 25 to 180 minutes (mean, 75). Three (8%) early cases were converted to open jejunostomy because of accidental enterotomies caused by inappropriate techniques that were avoided in later cases. Minor technical problems, such as passing a needle through the back wall of the jejunum, occurred in 7 patients, but they were easily corrected and produced no complications. Feedings were routinely begun within 24 hours of the surgical procedure. All jejunostomy catheters functioned well. This is a safe and effective technique when done by experienced laparoscopic surgeons, and serious complications are rare.

Adult↗
PubMed1995

Novel low-dosage hormonal replacement therapy complements dietary treatment of moderately hypercholesterolemic postmenopausal women.

It is not known whether female hormonal replacement therapy (HRT) influences fasting plasma lipoprotein lipids in diet-treated hypercholesterolemic subjects. Thirteen moderately hypercholesterolemic postmenopausal women were studied during dietary treatment alone with a low fat, low cholesterol diet for the 3 months and during the subsequent 2 y of HRT with dl-norgestrel (0.075 mg daily) and estradiol-17 beta (1 mg, 25 of 28 days) with maintenance of the same diet. Hormonal replacement therapy decreased plasma total cholesterol by 11 +/- 3% (5.7 vs. 6.4 mmol/L, p < 0.005), due to a 17 +/- 3% mean reduction (p < 0.001) in the concentration of plasma low density lipoprotein cholesterol (3.9 vs. 4.7 mmol/L, p < 0.001). The ratio of plasma total cholesterol to high density lipoprotein cholesterol fell significantly by 17 +/- 4% (4.1 vs. 4.9, p < 0.005). Mean fasting plasma concentrations of total triglycerides (1.1 vs. 1.6 mmol/L, p < 0.005) fell by 31 +/- 6%, and very low density lipoprotein triglycerides (0.56 vs. 0.83 mmol/L, p < 0.02) by 33 +/- 9%. Hormonal replacement therapy was well-tolerated, improved mood levels, and increased the mineral content of the vertebral spine significantly, while effectively relieving vasomotor flushing. Hormonal replacement therapy complements the dietary treatment of hypercholesterolemia.

Affect↗
PubMed1994

Desulfoviridin, a multimeric-dissimilatory sulfite reductase from Desulfovibrio vulgaris (Hildenborough). Purification, characterization, kinetics and EPR studies.

Conditions for the rigorous purification of desulfoviridin, the dissimilatory sulfite reductase from the sulfate-reducing bacterium Desulfovibrio vulgaris (Hildenborough) have been established. A final purification by fast protein liquid chromatography yields at least three distinct bands that each exhibit the characteristic absorption spectrum of desulfoviridin. Two of these have been extensively characterized by amino acid analysis, isoelectric focusing, polyacrylamide gel electrophoresis, and formulation of the prosthetic centers. Each contains two pairs of [Fe4S4] and siroheme units. These results stand in marked contrast to recent work claiming significant demetallation of siroheme, excess iron content, and the presence of Fe6S6 clusters. These proposals are critically assessed in light of our results and other published work. Steady-state kinetic parameters have been determined: kcat(SO3(2-) = 0.31 mol SO3(2-).s-1.mol heme-1, Km = 0.06 mM; kcat(NO2-) = 0.038 mol NO2-.s-1.mol heme-1, Km = 0.028 mM; kcat(NH2OH) = 29 mol NH2OH.s-1.mol heme-1, Km = 48 mM. A detailed comparison is made with the Escherichia coli and spinach assimilatory sulfite reductase enzymes and spinach nitrite reductase. Highly purified samples of dissimilatory sulfite reductase display an electron paramagnetic resonance spectrum characteristic of rhombic high spin ferric heme centers, while the fully reduced enzyme shows EPR features typical of [Fe4S4] clusters. The magnetic properties of the prosthetic centers are further characterized by variable temperature experiments and spin quantitation.

Blotting, Western↗
PubMed1994

Hemodynamic effects of argon pneumoperitoneum.

The hemodynamic effects of argon pneumoperitoneum were studied to define its possible role as an alternative gas for intraperitoneal insufflation during minimally invasive surgery. Adult pigs were anesthetized and placed on mechanical ventilation. Parameters measured or determined included mean arterial (MAP), pulmonary arterial (PAP), pulmonary arterial wedge (PAWP), right atrial (CVP), and inferior vena cava venous (IVC) pressures, total excretion of CO2 (VCO2), oxygen consumption (VO2), minute ventilation, and arterial blood gases. Also determined were cardiac output, stroke volume, and systemic vascular resistance all indexed to weight (CI, SVI, SVRI). Data were recorded during a 1-h baseline, 2 h of insufflation with argon gas at a constant pressure of 15 mmHg, and 1 h recovery after desufflation. There was no significant change from baseline in VCO2, VO2, MAP, PAP, PAWP, CVP, PaCO2, or arterial pH. Argon pneumoperitoneum significantly increased systemic vascular resistance index and exerted a depressant effect on stroke volume index and cardiac index by 25% and 30% from baseline values, respectively (P < 0.05). Inferior vena cava pressure increased as a reflection of the intraabdominal pressure. Argon insufflation had no effect on respiratory function. Argon gas may not be physiologically inert, and in patients with cardiovascular disease its effects may be clinically important.

Animals↗
PubMed1994

Early effects of continuous low-dosage all-norgestrel administered alone or with estrogen.

Twenty-six postmenopausal women participated in a double-blind trial involving treatment according to a Latin square design with either (i) dl-norgestrel alone (0.075 mg/day) continuously for two cycles, (ii) estradiol-17 beta alone (1 mg on 25 of 28 days) for two cycles, or (iii) the combined hormones for six cycles. A placebo control cycle followed each hormonal treatment. Plasma triglycerides decreased by an average 22% during treatment with either dl-norgestrel alone (123 +/- 11 vs. 160 +/- 10 mg/dl, n = 25, P < 0.005) or combination therapy (126 +/- 11 vs. 162 +/- 11, n = 25, P < 0.005) as compared with control. Plasma total cholesterol fell by 5% during two cycles of treatment with either dl-norgestrel alone (229 +/- 11 vs. 242 +/- 10 mg/dl, n = 25, P < 0.02) or combination therapy (233 +/- 11 vs. 246 +/- 10, n = 25, P < 0.05) versus placebo. During the fifth and sixth cycles of combination therapy 94% of cycles were free of flushing (vs. 31% for control, P < 0.01), 64% of cycles were free of spotting not requiring protection (control 75%), 96% of cycles were free of vaginal bleeding (control 100%), endometrial biopsy showed inactive endometrium in nine of the 10 subjects re-biopsied, fasting blood pyruvate decreased by 20% (P < 0.05) and diastolic blood pressure fell by 4% compared with control (P < 0.05), whereas glucose tolerance was unchanged. There was a significant reduction in vasomotor flushing beginning with the third to fourth cycles of combination therapy.

Biopsy↗
PubMed1993

Reduced lipolysis of large apo E-poor very-low-density lipoprotein subfractions from type IV hypertriglyceridemic subjects in vitro and in vivo.

Heparin-Sepharose chromatography was used to separate Sf 60-400 very-low-density lipoproteins (VLDL) from type IV hypertriglyceridemic subjects into apolipoprotein (apo) E-poor and apo E-rich subfractions. Since we have previously demonstrated that the apo E-poor fraction accumulates in plasma of type IV subjects, the aim of the present studies was to determine whether it was resistant to lipolysis in comparison to the apo E-rich fraction. The apo E-rich fraction was found to be 30% more effective than the apo E-poor fraction at competing with a glycerol tri[1-14C]oleate emulsion for in vitro lipolysis by normolipidemic human post-heparin plasma (P < .01), when assayed under conditions in which both lipoprotein lipase (LPL) and hepatic triglyceride lipase (HTGL) were active. Similar results were obtained when bovine milk LPL was used as the source of lipolytic activity (P < .025 for apo E-rich relative to apo E-poor VLDL), while neither fraction competed effectively with the synthetic substrate for lipolysis by HTGL only. When equal amounts of triglyceride from VLDL subfractions were incubated with bovine milk LPL, 25% more free fatty acid was released from the apo E-rich fraction than from the apo E-poor fraction (P < .025). The effects of heparin-induced lipolysis in vivo in type IV subjects on the relative amounts and composition of these VLDL subfractions were also assessed. Heparin infusion was associated with a 50% reduction in plasma Sf 60-400 VLDL triglyceride concentration. In addition, heparin-induced lipolysis resulted in a marked decrease in the relative amount of apo E-rich VLDL, while the relative amount of apo E-poor VLDL was increased. These results demonstrate that the apo E-poor VLDL subfraction is resistant to lipolysis by LPL relative to its apo E-rich counterpart, suggesting that reduced lipolytic efficiency may contribute to its observed accumulation in plasma of type IV subjects.

Animals↗