Hemodynamic physiology and thermoregulation in liposuction

Little is known about the physiology of large-volume liposuction. Patients are exposed to prolonged procedures, general anesthesia, fluid shifts, and infusion of high doses of epinephrine and lidocaine. Consequently, the authors examined the thermoregulatory and cardiovascular responses to liposuction by assessing multiple physiologic factors. The aims of their study were to serially determine hemodynamic parameters perioperatively, to quantify perioperative and postoperative plasma epinephrine levels, and to chronologically document fluctuations in core body temperature. Five female volunteers with American Society of Anesthesiologists' physical status I and II underwent moderate- to large-volume liposuction. Heart rate, blood pressure, mean pulmonary arterial pressure, cardiac index, and central venous pressure were monitored. Serum epinephrine levels and core body temperature were assessed perioperatively. The hemodynamic responses to liposuction were characterized by an increase in cardiac index (57 percent), heart rate (47 percent), and mean pulmonary arterial pressure (44 percent) (p < 0.05). Central venous pressure was not significantly altered. Maximum epinephrine levels were observed 5 to 6 hours after induction. Significant correlations between cardiac index and epinephrine concentrations were shown intraoperatively (r = 0.75). All patients developed intraoperative low body temperatures (mean 35.5 degrees C). An overall enhanced cardiac function was observed in patients subsequent to large-volume liposuction. The etiology of the altered cardiac parameters was multifactorial but may have been attributable in part to the administration of epinephrine, which counters the effects of general anesthesia and operative hypothermia. Additional explanations for raised cardiac output may be hemodilution or emergence from general anesthesia. Elevated mean pulmonary arterial pressure may be a result of subclinical fat embolism demonstrated in previous porcine studies, although fat was not observed in urine. The unchanged central venous pressure levels indicate that young healthy patients with compliant right ventricles can accommodate the fluid loads of large-volume liposuction. Overall hemodynamic parameters remained within safe limits. Within these surgical parameters, patients should be clinically screened for cardiovascular and blood pressure disorders before liposuction is undertaken, and preventative measures should be taken to limit intraoperative hypothermia.     

Electrolyte and plasma enzyme analyses during large-volume liposuction

Substantial fluid shifts occur during liposuction as wetting solution is infiltrated subcutaneously and fat is evacuated, causing potential electrolyte imbalances. In the porcine model for large-volume liposuction, plasma aspartate aminotransferase and alanine transaminase levels were elevated following liposuction. These results raised concerns for possible mechanical injury and/or lidocaine-induced hepatocellular toxicity in a clinical setting. The first objective of this human model study was to explore the effect of the liposuction procedure on electrolyte balance. The second objective was to determine whether elevated plasma aminotransferase levels were observed subsequent to large-volume liposuction. Five female volunteers underwent three-stage, ultrasound-assisted liposuction. Blood samples were collected perioperatively. Plasma levels of sodium, potassium, venous carbon dioxide, blood urea nitrogen, chloride, and creatinine were determined. Liver function analyte levels were measured, including albumin, total protein, aspartate aminotransferase, and alanine transaminase, alkaline phosphatase, gamma-glutamyl transpeptidase, and total bilirubin. To further define intracellular enzyme release, creatine kinase levels were measured. Mild hyponatremia was evident postoperatively (134 to 136 mmol/liter) in four patients. Hypokalemia was evident intraoperatively in all subjects (mean +/- SEM; 3.3 +/- 0.16 mmol/liter; range, 3.0 to 3.4 mmol/liter). Hypoalbuminemia and hypoproteinemia were observed throughout the study (baseline: 2.9 +/- 0.2 g/dl; range, 2.6 to 3.5 g/dl), decreasing to 10 to 40 percent 24 hours postoperatively (2.0 +/- 0.2 g/dl; range, 1.7 to 2.1 g/dl). Aspartate aminotransferase, alanine transaminase, and creatine kinase levels were significantly elevated after the procedure (190 +/- 47.1 U/liter, 50 +/- 7.7 U/liter, and 11,219 +/- 2556.7 U/liter, respectively) (p < 0.01). Release of antidiuretic hormone and even mildly hypotonic intravenous fluid infiltration have long been known to cause hyponatremia postoperatively. Intraoperative hypokalemia is associated with hypocarbia and respiratory alkalosis and the elevated epinephrine levels observed in the concurrent study. Factors having the greatest initial impact on diminished serum albumin and protein levels postoperatively are redistribution and hemodilution. Subsequent diminished viscosity may significantly affect postoperative hemodynamics. Elevated aspartate aminotransferase, alanine transaminase, and creatine kinase levels are associated with skeletal muscle injury, adipocyte lysis, and/or hepatic damage. Therefore, tissue injury is associated with large-volume liposuction as observed in several cellularly released enzymes. Future clinical studies are required to determine the degree of injury and specific tissues that are damaged or sensitive to mechanical trauma and/or drugs used in large-volume liposuction.     

Application of a multiplex PCR for the detection of protozoan pathogens of the eastern oyster Crassostrea virginica in field samples

Populations of eastern oysters Crassostrea virginica along the east coast of North America have repeatedly experienced epizootic mass mortality due to infections by protozoan parasites, and molecular diagnostic methodologies are fast becoming more widely available for the diagnosis of protozoan diseases of oysters. In this study we applied a modified version of an existing multiplex polymerase chain reaction (PCR) for detection of the eastern oyster parasites Haplosporidium nelsoni, H. costale and Perkinsus marinus from field-collected samples. We incorporated primers for DNA quality control based on the large subunit ribosomal RNA (LSU rRNA) gene of C. virginica. The multiplex PCR (MPCR) simultaneously amplified genomic DNA of C. virginica, and cloned DNA of H. nelsoni, P. marinus and H. costale. In field trial applications, we compared the performance of the MPCR to that of the conventional diagnostic techniques of histopathological tissue examination and the Ray/Mackin fluid thioglycollate medium (RMFT) assay. A total of 530 oysters were sampled from 18 sites at 12 locations along the east coast of the United States from the Gulf of Mexico to southern New England. The modified MPCR detected 21% oysters with H. nelsoni, 2% oysters with H. costale, and 40% oysters with P. marinus infections. In comparison, histopathological examination detected H. nelsoni and H. costale infections in 6 and 0.8% oysters, respectively, and the RMFT assay detected P. marinus infection in 31% oysters. The MPCR is a more sensitive diagnostic assay for detection of H. nelsoni, H. costale, and P. marinus, and incorporation of an oyster quality control product limits false negative results.     

The neural representation of time

This review summarizes recent investigations of temporal processing. We focus on motor and perceptual tasks in which crucial events span hundreds of milliseconds. One key question concerns whether the representation of temporal information is dependent on a specialized system, distributed across a network of neural regions, or computed in a local task-dependent manner. Consistent with the specialized system framework, the cerebellum is associated with various tasks that require precise timing. Computational models of timing mechanisms within the cerebellar cortex are beginning to motivate physiological studies. Emphasis has also been placed on the basal ganglia as a specialized timing system, particularly for longer intervals. We outline an alternative hypothesis in which this structure is associated with decision processes.     

Glycoforms obtained by expression in Pichia pastoris improve cancer targeting potential of a recombinant antibody-enzyme fusion protein

MFE-CP is a recombinant antibody-enzyme fusion protein used for antibody-mediated delivery of an enzyme to cancer deposits. After clearance from normal tissues, the tumor-targeted enzyme is used to activate a subsequently administered prodrug to give a potent cytotoxic in the tumor. MFE-CP localizes to cancer deposits in vivo, but we propose that its therapeutic potential could be improved by N-glycosylation, obtained by expression in Pichia pastoris. Glycosylation could enhance clearance from healthy tissue and result in better tumor:normal tissue ratios. To test this, glycosylated MFE-CP was expressed and purified from P. pastoris. The resultant MFE-CP fusion protein was enzymatically active and showed enhanced clearance from normal tissues in vivo. Furthermore, it showed effective tumor localization. This favorable glycosylation pattern was analyzed by tandem mass spectrometry. High-resolution, high-detection sensitivity collision-induced dissociation experiments proved essential for this task. Results showed that of the three potential N-glycosylation sites only two were consistently occupied with oligomannose structures. Asn-442 appeared the most heterogeneously populated with oligomannose carbohydrates extending from 5 to 13 units in length. Asn-484 was found only in its nonglycosylated form. There was less heterogeneity at Asn-492, which was glycosylated with oligosaccharide structures ranging from 8 to 10 mannose units. Nonglycosylated forms of Asn-442 and Asn-492 were not observed.     

Penicillin-derived inhibitors that simultaneously target both metallo- and serine-beta-lactamases

The synthesis and beta-lactamase inhibitory activity of four 6-(mercaptomethyl)penicillinates and the four corresponding 6-(hydroxymethyl)penicillinates are described. These penicillins include both C6 stereoisomers as well as the sulfide and sulfone oxidation states of the penam thiazolidine sulfur. All compounds were evaluated as inhibitors of representative metallo- and serine-beta-lactamases enzymes. Selected (mercaptomethyl)penicillinates are shown to inactivate both metallo- and serine-beta-lactamases and to display synergism with piperacillin against beta-lactamase producing strains.     

An ordinary differential equation model for the multistep transformation to cancer

Cancer is viewed as a multistep process whereby a normal cell is transformed into a cancer cell through the acquisition of mutations. We reduce the complexities of cancer progression to a simple set of underlying rules that govern the transformation of normal cells to malignant cells. In doing so, we derive an ordinary differential equation model that explores how the balance of angiogenesis, cell death rates, genetic instability, and replication rates give rise to different kinetics in the development of cancer. The key predictions of the model are that cancer develops fastest through a particular ordering of mutations and that mutations in genes that maintain genomic integrity would be the most deleterious type of mutations to inherit. In addition, we perform a sensitivity analysis on the parameters included in the model to determine the probable contribution of each. This paper presents a novel approach to viewing the genetic basis of cancer from a systems biology perspective and provides the groundwork for other models that can be directly tied to clinical and molecular data.     

Predicting mating patterns from pollination syndromes: the case of "sapromyiophily" in Tacca chantrieri (Taccaceae)

Tacca, a genus of tropical herbs, possesses near black flowers, conspicuous involucral bracts and whisker-like filiform bracteoles. These features have been assumed to function as a "deceit syndrome" in which reproductive structures resemble decaying organic material attracting flies that facilitate cross-pollination (sapromyiophily). We investigated pollination and mating in Tacca chantrieri populations from SW China to evaluate this assumption. Contrary to this expectation, populations were highly selfing. Pollinator visitation was infrequent and bagged flowers set abundant seed. Pollen loads on stigmas indicated autonomous self-pollination, some of which occurred prior to flower opening. The seed set of inflorescences with bracts and bracteoles removed was not significantly different from unmanipulated inflorescences, suggesting that these structures play a limited role in pollinator attraction, at least at our study sites. Pollen : ovule ratios averaged 49, a value expected in a highly selfing species. Selfing rates estimated in four populations using allozyme markers averaged 0.86 (range 0.76-0.94), thus corroborating this inference. Our results indicate that despite considerable investment in extravagant display, populations of T. chantrieri are highly selfing. We propose several hypotheses to resolve this paradox and argue that future studies of pollination syndromes would benefit by investigation of both pollination and mating biology.     

Molar enamel thickness in the chacma baboon, Papio ursinus (Kerr 1792)

Modern humans exhibit increasing relative enamel thickness from M1 to M3. Some biomechanical (basic lever) models predict that the more distal molars in humans encounter higher occlusal forces, and it has been postulated that this provides a functional explanation for the observed gradient in relative enamel thickness. However, constrained three-dimensional models and experimental observations suggest that there is a reduction in bite force potential from M1 to M3, which would be consistent with the tendency for humans to reduce the size of the distal molars. In this regard, it has been postulated that the distal increase in enamel thickness is a consequence of crown size reduction; thus, it is unnecessary to invoke functional scenarios to explain this phenomenon. We assess these competing proposals by examining relative enamel thickness in a catarrhine primate (Papio ursinus) that exhibits crown size increase from M1 to M3. The molar row of P. ursinus is positioned relatively far forward of the temporomandibular joint, which results in the baboon being able to exert relatively greater muscle forces during posterior biting in comparison to modern humans. Thus, a significant distalward gradient of increasing enamel thickness would be expected in P. ursinus according to the hypothesis that posits it to be functionally related to bite force. The present study reveals no significant difference in relative enamel thickness along the molar row in P. ursinus. This finding lends support to the notion that the relatively thicker enamel of human distal molars is related primarily to their reduction in size. This carries potential implications for the interpretation of enamel thickness in phylogenetic reconstructions: the relatively thick molar enamel shared by modern humans and some of our fossil relatives may not be strictly homologous, in that it may result from different underlying developmental mechanisms.