Comparison of robotic-assisted and conventional laparoscopy in the management of adnexal masses.

STUDY OBJECTIVE: To compare the outcome of robotic-assisted laparoscopy vs conventional laparoscopy in the management of ovarian masses. DESIGN: Retrospective cohort (Canadian Task Force classification II-3). SETTING: Academic medical centre in the northeast United States. PATIENTS: Retrospective medical record review of 71 consecutive patients with presumed benign ovarian masses. INTERVENTION: Robotic-assisted laparoscopy in 30 patients with presumed benign ovarian masses was compared with conventional laparoscopy in 41 patients. MEASUREMENTS AND MAIN RESULTS: Operative outcomes including operative time, estimated blood loss, length of hospital stay, and complications were recorded. Standard statistical analysis was used to compare the outcomes in the 2 groups. Mean (SD) operative time in the robotic group was 1.95 (0.63) hours, which was significantly longer than in the conventional laparoscopic group, 1.28 (0.83) hours (p = .04). Estimated blood loss in the robotic group was 74.52 (56.23) mL, which was not significantly different from that in the conventional laparoscopic group, 55.97 (49.18) mL. There were no significant differences in length of hospital stay between the robotic and conventional laparoscopic groups: 1.20 (0.78) days and 1.48 (0.63). Conversion to laparotomy was not necessary in either group of patients. Intraoperative and postoperative complications were similar between the 2 groups. CONCLUSION: Robotic-assisted laparoscopy is a safe and efficient technique for management of various types of ovarian masses. However, conventional laparoscopy is preferred for management of ovarian masses because of shorter operative time. Prospective studies are needed to evaluate the outcomes of robotic-assisted laparoscopic management of benign and malignant ovarian neoplasms.

Regulation of myocardial fatty acid oxidation by substrate supply.

We tested the hypothesis that myocardial substrate supply regulates fatty acid oxidation independent of changes in acetyl-CoA carboxylase (ACC) and 5'-AMP-activated protein kinase (AMPK) activities. Fatty acid oxidation was measured in isolated working rat hearts exposed to different concentrations of exogenous long-chain (0.4 or 1.2 mM palmitate) or medium-chain (0.6 or 2.4 mM octanoate) fatty acids. Fatty acid oxidation was increased with increasing exogenous substrate concentration in both palmitate and octanoate groups. Malonyl-CoA content only rose as acetyl-CoA supply from octanoate oxidation increased. The increases in octanoate oxidation and malonyl-CoA content were independent of changes in ACC and AMPK activity, except that ACC activity increased with very high acetyl-CoA supply levels. Our data suggest that myocardial substrate supply is the primary mechanism responsible for alterations in fatty acid oxidation rates under nonstressful conditions and when substrates are present at physiological concentrations. More extreme variations in substrate supply lead to changes in fatty acid oxidation by the additional involvement of intracellular regulatory pathways.

Contribution of malonyl-CoA decarboxylase to the high fatty acid oxidation rates seen in the diabetic heart.

Myocardial glucose oxidation is markedly reduced in the uncontrolled diabetic. We determined whether this was due to direct biochemical changes in the heart or whether this was due to altered circulating levels of insulin and substrates that can be seen in the diabetic. Isolated working hearts from control or diabetic rats (streptozotocin, 55 mg/kg iv administered 6 wk before study) were aerobically perfused with either 5 mM [(14)C]glucose and 0.4 mM [(3)H]palmitate (low-fat/low-glucose buffer) or 20 mM [(14)C]glucose and 1.2 mM [(3)H]palmitate (high-fat/high-glucose buffer) +/-100 microU/ml insulin. The presence of insulin increased glucose oxidation in control hearts perfused with low-fat/low-glucose buffer from 553 +/- 85 to 1,150 +/- 147 nmol x g dry wt(-1) x min(-1) (P < 0. 05). If control hearts were perfused with high-fat/high-glucose buffer, palmitate oxidation was significantly increased by 112% (P < 0.05), but glucose oxidation decreased to 55% of values seen in the low-fat/low-glucose group (P < 0.05). In diabetic hearts, glucose oxidation was very low in hearts perfused with low-fat/low-glucose buffer (9 +/- 1 nmol x g dry wt(-1) x min(-1)) and was not altered by insulin or high-fat/high-glucose buffer. These results suggest that neither circulating levels of substrates nor insulin was responsible for the reduced glucose oxidation in diabetic hearts. To determine if subcellular changes in the control of fatty acid oxidation contribute to these changes, we measured the activity of three enzymes involved in the control of fatty acid oxidation; AMP-activated protein kinase (AMPK), acetyl-CoA carboxylase (ACC), and malonyl-CoA decarboxylase (MCD). Although AMPK and ACC activity in control and diabetic hearts was not different, MCD activity and expression in all diabetic rat heart perfusion groups were significantly higher than that seen in corresponding control hearts. These results suggest that an increased MCD activity contributes to the high fatty acid oxidation rates and reduced glucose oxidation rates seen in diabetic rat hearts.

Methodology for measuring in vitro/ex vivo cardiac energy metabolism.

The high energy demands of the heart are met primarily by the metabolism of fatty acids and carbohydrates. These energy substrates are efficiently and rapidly metabolized in order to produce the high levels of adenosine triphosphate (ATP) necessary to sustain both contractile activity and other cellular functions. Alterations in energy metabolism contribute to abnormal heart function in many cardiac diseases. As a result, a number of techniques have been developed to directly measure energy metabolism in the heart in order to study energy metabolism. Two important variables that must be considered when making these measurements are energy substrate supply to the heart and the metabolic demand of the heart (i.e. contractile function). The use of the in vitro/ex vivo heart, perfused with relevant energy substrates, is a useful experimental approach that accounts for these variables. This paper overviews a number of the techniques that are used to measure energy substrate metabolism in the isolated perfused heart. Recently developed technology that allows for the direct measurement of energy metabolism in an isolated working mouse heart preparation are also described.

Characterization of cardiac malonyl-CoA decarboxylase and its putative role in regulating fatty acid oxidation.

Malonyl-CoA is a potent inhibitor of fatty acid uptake into the mitochondria. Although the synthesis of malonyl-CoA in the heart by acetyl-CoA carboxylase (ACC) has been well characterized, no information is available as to how malonyl-CoA is degraded. We demonstrate that malonyl-CoA decarboxylase (MCD) activity is present in the heart. Partial purification revealed a protein of approximately 50 kDa. The role of MCD in regulating fatty acid oxidation was also studied using isolated, perfused hearts from newborn rabbits and adult rats. Fatty acid oxidation in rabbit hearts increased dramatically between 1 day and 7 days after birth, which was accompanied by a decrease in both ACC activity and malonyl-CoA levels and a parallel increase in MCD activity. When adult rat hearts were aerobically reperfused after a 30-min period of no-flow ischemia, levels of malonyl-CoA decreased dramatically, which was accompanied by a decrease in ACC activity, a maintained MCD activity, and an increase in fatty acid oxidation rates. Taken together, our data suggest that the heart has an active MCD that has an important role in regulating fatty acid oxidation rates.

Direct measurement of energy metabolism in the isolated working rat heart.

Fatty acids and carbohydrates are the two main energy substrates used by the heart. Studies involving the regulation of these pathways in the heart have historically been hampered by a number of important technical problems. One problem is the need to provide the heart with fatty acids, which, due to their insolubility, must be delivered to the heart either bound to albumin or contained within triacylglycerol-lipoproteins. Another problem is the need to perform experiments at relevant workloads, since the work performed by the heart is a key determinant of ATP production rates. The development of the isolated working heart preparation in the 1960s has been a very powerful tool to study energy metabolism. During this golden era of cardiac energy metabolism research, a number of techniques were developed that successfully overcame these two key problems. In this article, we describe refinements to this original preparation which has allowed for simultaneous measurement of both glycolysis and glucose oxidation, or simultaneous measurements of both lactate oxidation and fatty acid oxidation.

Measurements of fatty acid and carbohydrate metabolism in the isolated working rat heart.

The isolated working rat heart is a useful experimental model which allows contractile function to be measured in hearts perfused at physiologically relevant workloads. To maintain these high workloads the heart is required to generate a tremendous amount of energy. In vivo this energy is derived primarily from the oxidation of fatty acids. In many experimental situations it is desirable to perfuse the isolated working heart in the presence of physiologically relevant concentrations of fatty acids. This is particularly important when studying energy metabolism in the heart, or in determining how fatty acids alter the outcome of myocardial ischemic injury [1, 2]. The other major source of energy for the heart is derived from the oxidation of carbohydrates (glucose and lactate), with a smaller amount of ATP also being derived from glycolysis. Two byproducts of both fatty acid and carbohydrate metabolism are H2O and CO2. By labeling the glucose, lactate, or fatty acids in the perfusate with 3H or 14C the experimenter can quantitatively collect either 3H2O or 14CO2 produced by the heart. By using radioisotopes that are labeled at specific hydrogen or carbon molecules on the various energy substrates, and by knowing the specific activity of the radiolabeled substrate used, it is possible to determine the actual rate of flux through these individual pathways. This paper will describe the experimental protocols for directly measuring fatty acid and carbohydrate metabolism in isolated working rat hearts.

Ranolazine stimulates glucose oxidation in normoxic, ischemic, and reperfused ischemic rat hearts.

BACKGROUND: Ranolazine is a novel antianginal agent that may reduce symptoms without affecting hemodynamics and has shown cardiac antiischemic effects in in vivo and in vitro models. In one study it increased active pyruvate dehydrogenase (PDHa). Other agents that increase PDHa and so increase glucose and decrease fatty acid (FA) oxidation are beneficial in ischemic-reperfused hearts. Effects of ranolazine on glucose and palmitate oxidation and glycolysis were assessed in isolated rat hearts. METHODS AND RESULTS: Working hearts were perfused with Krebs-Henseleit buffer plus 3% albumin under normoxic conditions and on reperfusion after 30-minute no-flow ischemia and under conditions designed to give either low [low (Ca) (1.25 mmol/L), high [FA] (1.2 mmol/L palmitate; with/without insulin] or high (2.5 mmol/L Ca, 0.4 mmol/L palmitate; with/without pacing) glucose oxidation rates; Langendorff-perfused hearts (high Ca, low FA) were subjected to varying degrees of low-flow ischemia. Glycolysis and glucose oxidation were measured with the use of [5-3H/U-14C]-glucose and FA oxidation with the use of [1-14C]- or [9,10-3H]-palmitate. In working hearts, 10 micromol/L ranolazine significantly increased glucose oxidation 1.5-fold to 3-fold under conditions in which the contribution of glucose to overall ATP production was low (low Ca, high FA, with insulin), high (high Ca, low Fa, with pacing), or intermediate. In some cases, reductions in FA oxidation were seen. No substantial changes in glycolysis were noted with/without ranolazine; rates were approximately 10-fold glucose oxidation rates, suggesting that pyruvate supply was not limiting. Insulin increased basal glucose oxidation and glycolysis but did not alter ranolazine responses. In normoxic Langendorff hearts (high Ca, low FA; 15 mL/min), all basal rates were lower compared with working hearts, but 10 micromol/L ranolazine similarly increased glucose oxidation; ranolazine also significantly increased it during flow reduction to 7, 3, and 0.5 mL/min. Ranolazine did not affect baseline contractile or hemodynamic parameters or O2 use. In reperfused ischemic working hearts, ranolazine significantly improved functional outcome, which was associated with significant increases in glucose oxidation, a reversal of the increased FA oxidation seen in control reperfusions (versus preischemic), and a smaller but significant increase in glycolysis. CONCLUSIONS: Beneficial effects of ranolazine in cardiac ischemia/reperfusion may be due, at least in part, to a stimulation of glucose oxidation and a reduction in FA oxidation, allowing improved ATP/O2 and reduction in the buildup of H+, lactate, and harmful fatty acyl intermediates.

High rates of fatty acid oxidation during reperfusion of ischemic hearts are associated with a decrease in malonyl-CoA levels due to an increase in 5'-AMP-activated protein kinase inhibition of acetyl-CoA carboxylase.

We determined whether high fatty acid oxidation rates during aerobic reperfusion of ischemic hearts could be explained by a decrease in malonyl-CoA levels, which would relieve inhibition of carnitine palmitoyl-transferase 1, the rate-limiting enzyme involved in mitochondrial uptake of fatty acids. Isolated working rat hearts perfused with 1.2 mM palmitate were subjected to 30 min of global ischemia, followed by 60 min of aerobic reperfusion. Fatty acid oxidation rates during reperfusion were 136% higher than rates seen in aerobically perfused control hearts, despite the fact that cardiac work recovered to only 16% of pre-ischemic values. Neither the activity of carnitine palmitoyltransferase 1, or the IC50 value of malonyl-CoA for carnitine palmitoyl-transferase 1 were altered in mitochondria isolated from aerobic, ischemic, or reperfused ischemic hearts. Levels of malonyl-CoA were extremely low at the end of reperfusion compared to levels seen in aerobic controls, as was the activity of acetyl-CoA carboxylase, the enzyme which produces malonyl-CoA. The activity of 5'-AMP-activated protein kinase, which has been shown to phosphorylate and inactivate acetyl-CoA carboxylase in other tissues, was significantly increased at the end of ischemia, and remained elevated throughout reperfusion. These results suggest that accumulation of 5'-AMP during ischemia results in an activation of AMP-activated protein kinase, which phosphorylates and inactivates ACC during reperfusion. The subsequent decrease in malonyl-CoA levels wil result in accelerated fatty acid oxidation rates during reperfusion of ischemic hearts.

An imbalance between glycolysis and glucose oxidation is a possible explanation for the detrimental effects of high levels of fatty acids during aerobic reperfusion of ischemic hearts.

High levels of fatty acids can decrease the recovery of previously ischemic hearts by inhibiting myocardial glucose use during reperfusion. We determined if this was due to a decrease in glycolysis or a decrease in glucose oxidation. Isolated working rat hearts were perfused with either 11 mM [2-3H/U-14C] glucose or 11 mM [2-3H/U-14C] glucose and 1.2 mM palmitate. In aerobically perfused hearts, the presence of fatty acids reduced glucose oxidation rates (from 1576 +/- 154 to 228 +/- 28 nmol/min.g dry weight, P < .05), with a nonsignificant reduction in glycolysis (from 3297 +/- 349 to 2798 +/- 343 nmol/min.g dry weight). If fatty acid perfused hearts were subjected to a 30-min period of ischemic function was 36%. Glucose oxidation rates during reperfusion were markedly lower than glycolytic rates (228 +/- 35 and 3096 +/- 576 nmol/min.g dry weight, respectively, P < .05). Dichloroacetate (1 mM) added during reperfusion significantly improved recovery of mechanical function to 96% of preischemic values. In these hearts, Dichloracetate increased glucose oxidation, while actually decreasing glycolytic rates (values during reperfusion were 501 +/- 136 and 1171 +/- 122 nmol/min.g dry weight, respectively). Insulin (500 microU/ml) added at reperfusion resulted in a small increase in glucose oxidation rates and a significant increase in glycolysis (375 +/- 66 and 4769 +/- 955 nmol/g dry weight.min, respectively). However, the presence of insulin at reperfusion did not improve recovery of function (hearts recovered 52% of preischemic function). We demonstrate that the detrimental effects of high concentrations of fatty acids after ischemia are primarily due to an inhibition of glucose oxidation, and not glycolysis, during the reperfusion period. Furthermore, increasing glucose oxidation during reperfusion has a beneficial effect on functional recovery of hearts.

Acute insulin withdrawal from diabetic BB rats decreases myocardial glycolysis during low-flow ischemia.

We have previously demonstrated that withdrawal of insulin treatment from BB diabetic rats for a 24-hour period will increase the failure rate of hearts subjected to low-flow ischemia. The purpose of this study was to determine if this increased severity of ischemia was related to a decrease in glycolytic rates during ischemia. Two groups of insulin-dependent diabetic BB Wistar rats were used; in one group, insulin treatment was withheld from rats 24 hours prior to study (uncontrolled), while in the second group, the daily insulin injection was not withheld (insulin-treated). Isolated working hearts obtained from these animals were perfused with 30 mmol/L (2-3H/U-14C)-glucose and 1.2 mmol/L palmitate, at an 11.5 mm Hg left atrial preload and 80 mm Hg aortic afterload. Hearts were subjected to a 15-minute aerobic perfusion followed by 60 minutes of low-flow ischemia (coronary flow, 0.5 mL/min). Under aerobic conditions, steady-state glucose oxidation rates (measured as 14CO2 production) were decreased in the uncontrolled group compared with the insulin-treated group (85.3 +/- 21.5 v 406.2 +/- 120.1 nmol/min/g dry weight, respectively; P less than .05). Steady-state glycolytic rates (measured as 3H2O production) were also decreased in the uncontrolled group compared with the insulin-treated group (1.73 +/- 0.30 v 5.57 +/- 1.26 mumol/min/g dry weight, respectively; P less than .05). During low-flow ischemia, glucose-oxidation rates markedly decreased in both groups (23.9 +/- 8.7 and 38.3 +/- 25.2 nmol/min/g dry weight in the uncontrolled and insulin-treated diabetic rats, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)

Law and the quality of life.

The use of sophisticated methods of criminological investigation and fact determinations, coupled with advances in forensic sciences and in criminal law and with the extensive procedural safeguards and mechanisms available to prosecutors and defense attorneys alike are, more often than not, taken for granted. Yet, it was not long ago that our legal system functioned on relatively rudimentary procedures, and the tools available to investigate crime and to determine factual matters were little more than very basic scientific principles crudely adapted to the needs of the criminologist. Criminology itself is both a relatively new concept and a distinct branch of forensic sciences. This paper will examine some of the more interesting historical developments in the fields of jurisprudence, criminology, and forensic sciences in order to gain an insight into the contemporary quality of our legal system.

Embossing arabic letters and numbers on new raised-line polyethylene paper: an aid for the blind.

A new polyethylene paper may be marked on a hard surface with an ordinary oversize ball-point pen or dull pencil point. Where the paper is marked, a raised-line imprint appears on the same side of the paper as that used for writing. This imprint may be both felt and seen. Newly blinded and partially sighted persons are able to read ordinary Arabic letters and numerals after a few trials.