Effects of the combinations propofol/alfentanil and midazolam/fentanyl on blood pressure and contact phase system during coronary surgery

Perioperative haemodynamic changes leading to severe circulatory problems during open-heart surgery still represent dreaded complications. The aim of this study was to examine the relationship between the use of applied anaesthetic agents and alterations of the contact phase of the intrinsic blood-clotting system, as changes within the kallikrein-kinin system can lead to a fall in blood pressure. In a randomized study, parameters of the kallikrein-kinin system, coagulation and fibrinolysis were determined for 36 patients with aortocoronary bypass operations. The patients had been given either midazolam/fentanyl or propofol/alfentanil to maintain anaesthesia. Perioperative blood pressure values were registered at seven fixed points. The measured values of the factor XIIa-like activity and the kallikrein-like activity suggested a higher activation of the contact phase, when propofol/alfentanil was given. From the start of the extracorporeal circulation (ECC) to the end of the operation, the kallikrein-like activities in the propofol/alfentanil group were significantly higher than those of the midazolam/fentanyl group. Also, the results of the kallikrein inhibition capacity and the indicators of fibrinolysis (t-PA and D-dimers) indicate a stronger activation of the contact phase--at least at the beginning of recirculation--and as a result of it, a stronger fibrinolysis within the propofol/alfentanil group. In addition, the hypotensive side-effects differed significantly between the two groups. Patients receiving propofol/alfentanil needed the triple amount of antihypotonicum to maintain the mean arterial blood pressure above 75 mmHg. With the results of this study, a correlation between the application of propofol/alfentanil, contact phase activation, with activation of the kallikrein-kinin-bradykinin system and the observed hypotension, can be presumed.     

Evaluation of modified multicompartment models to calculate body composition in healthy males

Body volume was measured by underwater weighing (UWW) or with a skinfold caliper; bone mineral by dual energy X-ray absorptiometry (DXA); and body water by bioelectrical impedance analysis (BIA) in 22 healthy males. The percentage of water and bone mineral in fat-free mass had a significant effect on the calculated amount of fat using a two-compartment model. A three-compartment model based on field-adapted methods (skinfold thickness + BIA) to calculate body fat, correlated significantly with a more complex four-compartment model (UWW + BIA + DXA) (r = 0.95, p < 0.001). The advantages of three- and four-compartment equations are that they reduce the number of assumptions.     

Traversing the menopause: changes in energy expenditure and body composition

The menopause transition is associated with several physiological changes that may impact women's health outcome. Among the changes associated with the loss of ovarian function is an increased risk of metabolic and cardiovascular disease. The present review focuses on changes in energy expenditure, body composition and body fat distribution during the postmenopausal transition. Previous work indicates that the most important component of total daily expenditure, resting metabolic rate, may be reduced by the menopause, independently of the effects of the normal aging process. This effect is mainly attributable to a decrease in fat-free mass. The energy expenditure associated with physical activity is the most variable component of total daily energy expenditure. However, small changes in this component may have a substantial impact on body composition. Longitudinal data from our laboratory indicate that the menopause transition also leads to significant decreases in physical activity energy expenditure. The changes in body composition that accompany the menopause transition have been studied by several groups and, although some studies suggested increases in body mass index or total body fat mass with the menopause, currently available cross-sectional data preclude a firm conclusion. Nevertheless, results from our longitudinal study showed significant increases in fat mass with the menopause. The accumulation of abdominal fat, which may be a better correlate of the comorbidities associated with obesity, has also been shown to be accelerated by the menopause transition. In this regard, it has been shown that treatment with hormone replacement therapy prevents the increase in the rate of abdominal adipose tissue accumulation that was noted with the menopause. Thus, it appears that the loss of ovarian function induces a reduction in resting metabolic rate, physical activity energy expenditure, fat-free mass, and an increase in fat mass and abdominal adipose tissue accumulation. These modifications probably contribute to the increased risk of cardiovascular disease of postmenopausal women.     

The effect of intravenous and oral fluconazole on the pharmacokinetics and pharmacodynamics of intravenous alfentanil

The growth-promoting activity of PDGF-BB was studied on the adult osteoclasts in the present study. The PDGF receptor beta was detected on the osteoclast membrane through immunohistochemistry (LSAB method) and immunomicroscopy. The PDGF-BB was exerted on the osteoclasts that adhered to the bone slice at concentrations of 0, 10, 20, 30, and 40 ng/ml. The volume of Howship's lacuna augmented significantly and the number of resorption pits also increased with its dose (p < 0.01). The activity of both total acid phosphatase (ACP) and tartrate-resistant acid phosphatase (TRAP) increased significantly. These results suggest that PDGF-BB promotes adult osteoclastic bone resorption directly through PDGF receptor beta and is believed to play important roles in the bone healing process and reconstruction.     

Fractionated administration of high-dose cyclophosphamide: influence on dose-dependent changes in pharmacokinetics and metabolism

PURPOSE: The alkylating agent cyclophosphamide (CP) is a prodrug that is metabolized to both cytotoxic and inactive compounds. We have previously shown that following dose escalation from conventional-dose (CD) to high-dose (HD) levels; the fraction of the dose cleared by bioactivation is significantly decreased (66% versus 48.5%) in favor of inactivating elimination pathways when the HD is given as a single 1-h infusion. Based on the concept of bioactivating enzyme saturation with increasing doses, we investigated the influence of fractionated application of HD-CP on dose-dependent changes in metabolism. PATIENTS AND METHODS: Plasma concentrations of CP (measured by high-performance liquid chromatography, HPLC) and urinary concentrations of CP and its major metabolites (quantified by [31P]-nuclear magnetic resonance spectroscopy; [31P]-NMR spectroscopy), were determined in four patients with high-risk primary breast cancer who received adjuvant chemotherapy including both CD-CP (500 mg/ m2 infused over 1 h) and split HD-CP (50 mg/kg infused over 1 h on each of 2 consecutive days (d): d1 and d2. RESULTS: (Data are given as mean values for CD and d1/d2 of HD, respectively). Systemic clearance (CL) of CP was similar during CD and d1 of HD, but significantly increased on d2 of HD (CL: 83 and 78/115 ml/min; P < 0.01 for d1 versus d2). The latter was translated into an increase in formation CL of both active (+ 16.4 ml/min) and inactive metabolites (+ 17.6 ml/ min) and reflects autoinduction of metabolism. As compared with CD-CP, no statistically significant decrease was observed in the relative contribution of bioactivation CL to overall CL during both days of HD (63% versus 57%/53%). Recovery of intact CP in 24-h urine corresponded to 24%, 29%, 22% of the dose (P < 0.05 for d1 versus d2 of HD). CONCLUSIONS: Following dose escalation of CP, dividing the high dose over 2 days instead of one single infusion may favorably impact the metabolism of CP in terms of bioactivation. In addition, on day 2 of a split regimen, renal elimination of CP is decreased, which implies that more drug is available for metabolism.     

Association between insulin and blood pressure in relation to the influence of body mass index

The relationship between plasma insulin level and systolic blood pressure (SBP) was investigated by multiple linear regression procedure in 410 Chinese non-diabetics. The significant positive correlation between SBP and 2-hour plasma insulin (INS 2h) after 75g glucose load was found in the BMI (body mass index) 15.9-27.0 group (n = 287) after the adjustment for age, sex, BMI, smoking and plasma cholesterol (P = 0.01). However, this significant correlation was gradually diminished with the expansion of the BMI range, ie. P = 0.04 in the BMI 15.9-29.0 (n = 356) group, P = 0.07 in the BMI 15.9-31 (n = 389) group, and P = 0.12 in the BMI 15.9-33 (n = 402) group after the same adjustment of variables. Interestingly, the significant inverse correlation between insulin-BMI interaction term (product of BMI and insulin) and SBP was found (P = 0.04) in the presence of the significant positive correlation between 2-hour plasma insulin and SBP (P = 0.02) after adjustment of the above mentioned five factors in the whole group (BMI 15.9-42.2, n = 410). These results indicated that SBP is independently correlated with plasma insulin level in the studied population, and that the severer obesity may interfere the net effects of insulin on the elevating of blood pressure.     

A comparison of different methods to measure body composition in patients

A comparison of different methods to measure body composition in growth hormone deficient patients is presented. The technical limitations of the available methods are discussed. The techniques used to measure body composition and fat free mass has been by total body water, total body potassium, dual energy X-ray absorptiometry, bioelectrical impedance and total body nitrogen.     

The effect of protease inhibitors on weight and body composition in HIV-infected patients

OBJECTIVES: To determine the nutritional changes that occur in HIV-infected patients receiving protease inhibitor (PI) therapy and to determine the effects of PI treatment on physical functioning and health perceptions in patients with HIV infection. DESIGN: Longitudinal data analysis of 38 patients from a large Nutrition and HIV cohort. METHODS: Patients were included if they had started PI therapy after enrollment in the cohort, if they had taken the drug for at least 4 months without interruption and if data on weight, body composition and viral loads were available. RESULTS: Mean person-months of follow-up was 8.1 months before and 12.2 months after PI treatment. Weight (1.54 kg, P < 0.0001), body mass index (0.50 kg/m2, P < 0.0001), physical functioning (8.52 points, P = 0.0006) and current health perception (6.7 points, P = 0.01) increased significantly, and the daily caloric intake increase was close to significance (915.5 kJ/day, P = 0.06), after treatment with PI. Lean body mass did not change. Patients who responded to PI therapy with decreased viral load (n = 28) had significantly greater weight gain per month than non-responders. CONCLUSIONS: PI therapy of HIV infection is associated with weight gain and improvement in quality of life indices. The weight gain is mainly in fat mass, with no change in lean body mass (skeletal muscle). Optimal therapy of HIV-infected patients with weight loss may require highly active antiretroviral therapy combined with an anabolic stimulus such as exercise, anabolic steroids or human growth hormone.     

Serial changes in body composition throughout adulthood and their relationships to changes in lipid and lipoprotein levels. The Fels Longitudinal Study

Few studies have examined the relationships between measures of body composition and lipid and lipoprotein levels in long-term serial data from individuals unselected for cardiovascular disease- or obesity-related variables, and none have considered such extensive serial data as used in the current study. The aim was to examine in such individuals the associations between annual changes in lipid and lipoprotein levels and concurrent changes in total body fat, fat-free mass, percent body fat, and body mass index. Serial data from 1304 examinations of 423 adult white participants in the Fels Longitudinal Study were analyzed sex-specifically in 2 age groups, 18 through 44 years and 45 to 65 years. A regressive analytic approach utilized the long-term (4 to 20 years) serial data of individuals. Annual changes in adiposity, independent of levels of lean tissue changes, before and after age 45 for men and women were significantly correlated with corresponding annual changes in cholesterol and low density lipoprotein cholesterol. In men before age 45, changes in triglycerides and high density lipoprotein cholesterol were also significantly associated with changes in adiposity, with the relationship remaining after age 45 in high density lipoprotein cholesterol. Increases in adiposity in individuals are associated with changes in lipid and lipoprotein levels in the direction of increased risk for cardiovascular disease. Adult levels of total cholesterol and low density lipoprotein cholesterol across age and sex and high density lipoprotein cholesterol in men are responsive to changes in adiposity, independent of initial adiposity or lipid and lipoprotein levels.     

Cationic composition of pancreatic juice and blood plasma during functional changes in the pancreas

In chronic experiments on dogs with Pavlov's fistula, potassium and calcium concentration in the blood plasma was increased after feeding; their pancreatic concentration was lower, respectively, by 0.2 and 0.3 units/ml prior to feeding and 0.3 and 0.6 after the feeding. Sodium concentration in the pancreatic juice corresponded to its concentration in the blood plasma and did not change after feeding. Changes of sodium concentration in the blood plasma or pancreatic juice indicate disturbances in pancreatic function.     

The influence of maternal passive and light active smoking on intrauterine growth and body composition of the newborn

OBJECTIVE: To assess the influence of passive and light active smoking on the reduction of intrauterine growth of the foetus and on modifications in the body composition of the newborn. DESIGN: Random. SETTING: Full term newborn infants at the Department of the Pediatric and Gynaecological Divisions of the City Major Hospital, Chair of Paediatrics, Verona University. SUBJECTS: One hundred and twelve mothers selected after having completed a questionnaire on smoking habits during pregnancy. One hundred and twelve newborn infants were divided into three groups: Group 1: non-smoking and non-exposed mothers; Group 2: non-smoking but exposed mothers; Group 3: light smoking mothers (under 10 cigarettes/d, whether or not also exposed to passive smoking). Examination within 24 h of birth established the anthropometric measurements and estimates of body composition through indices or equations. RESULTS: Newborns of groups 2 and 3 had a statistically significant reduction of fat mass and most anthropometric measurements: fat mass according to Dauncey (P < 0.001), birth-weight (P < 0.013), crownheel length (P < 0.000), upper- and lower-arm length (P < 0.000) and circumference (P < 0.002), triceps skinfold and sum of all skinfolds (P < 0.004). Student t-test, between groups 2 and 3, did not evidence intergroup differences. CONCLUSIONS: Exposure of the foetus to passive and/or light active smoking involves a reduction of most auxiological parameters and not only weight. As regards body composition, smoking appears to reduce fat mass. The prevention of smoking during pregnancy is therefore extremely important, as intrauterine growth seems to be negatively influenced not only by active smoking, but also by passive and light active smoking.     

Comparison of body composition by dual energy X-ray absorptiometry to other estimates of body composition during weight loss in obese patients with rheumatoid arthritis

Body composition was determined by dual energy X-ray absorptiometry (DXA) scanning and classical reference methods (40K, 3H2O, and a combination of these in a four-compartment model) in 19 overweight patients with rheumatoid arthritis who underwent a 12-week weight-reducing regimen. The aim of the study was to investigate whether DXA provides a valid estimate of body composition. The results showed that weight as determined by DXA was highly significantly correlated to weight determined by scales. Furthermore, significant correlations were found in the body components (fat-free mass, fat mass) determined by DXA, 40K, 3H2O and the four-compartment model. Mean values differed slightly but significantly. With respect to changes in body composition, no significant correlations were found between any of the methods, except for the weight loss recorded by DXA and scales, and loss of fat mass (and fat free mass) estimated by 3H2O and the four-compartment model. The sparseness of correlations reflected the small changes in fat-free mass and fat mass (2.6 and 1.7 kg respectively), and the fact that changes were comparable to measurement errors of the various methods. We suggest that DXA scanning is a valid supplement for determination of body composition. Validation of DXA scanning requires new experimental in vitro investigations, which, incidentally, also applies to the classical reference methods.     

Relationships between changes in body composition and changes in cardiovascular risk factors: the SOS Intervention Study. Swedish Obese Subjects

Relationships between 2-year changes in body composition (estimated from computed tomography-validated anthropometry based on sagittal trunk diameter, weight, and height), adipose tissue (AT) distribution, and cardiovascular risk factors (blood pressure, lipids, glucose, insulin, uric acid) were examined in 842 treated adults with severe obesity with weight changes from -95.5 to +30.6 kg. Although the change (delta) of visceral AT mass (expressed in % total AT) for a given change in body mass index (delta BMI) was 6-fold larger in men than in women, delta waist and delta waist/hip were similar in both sexes. In men, risk factor changes were similarly related to delta waist, delta bodyweight, and delta BMI, whereas in women, delta bodyweight seemed to be the single independent variable with the highest explanatory power. In multivariate regressions adjusted for delta BMI and baseline conditions, delta visceral AT mass was more strongly associated with risk factor changes than were delta waist and delta waist/hip. When using a three-compartment model (lean body mass, subcutaneous and visceral AT masses) plus neck and thigh girths (indicators of subcutaneous AT distribution), risk factor changes were related both to delta subcutaneous and delta visceral AT masses but not to delta lean body mass. In agreement with cross-sectional findings, delta neck was positively and delta thigh was negatively related to some risk factor changes. Thus, the use of waist as a single risk factor indicator seems less effective for epidemiological studies than the simple anthropometric measures presented here, which are able to separate the effects of visceral AT mass, subcutaneous AT mass, and subcutaneous AT distribution on metabolic parameters under both cross-sectional and longitudinal conditions.     

Age- and maturity-related changes in body composition during adolescence into adulthood: the Fels longitudinal study

We examined patterns of change in body composition from 8 to 20 yrs of age and the effects of rate of maturation on these patterns using serial data for total body fat (TBF). There is a continual increase, but a declining rate of change with age in TBF. For %BF the same pattern as for TBF exists for females, but for males the pattern of change in percentage body fat (%BF) reflects the concurrent changes in fat free mass (FFM). For FFM, there is an increase in females that slows at older ages, but in males there is a continual rapid increase until young adulthood. There is marked tracking for body composition persisting from childhood to adulthood. At the same age, rapidly maturing children have significantly larger TBF, %BF and FFM than slowly maturing children.     

Effects of dietary carbohydrate, fat and protein on growth, body composition and blood metabolite levels in the dog

Six semipurified canned diets ranging in composition from 0 to 62% of energy from carbohydrate and from 20% to 48% of energy from protein were fed to female beagle dogs for 8 months. Additionally, three commercial-type diets were also fed. The effects of these diets on growth, body composition and selected blood metabolite levels in the dogs were studied. The dogs readily consumed each of the nine diets fed. The level of carbohydrate, fat or protein in the diet did not influence body weight gain during the first 16 weeks nor was nitrogen balance affected by the diets. At the end of the 32-week study, dogs fed the high-carbohydrate (62% of energy) diet contained less body fat but an equal-free mass, than did dogs fed lower-carbohydrate (20--42% of energy) diets with a similar quantity of protein. Consumption of carbohydrate-free diets did not influence postprandial levels of circulating glucose or insulin in the dogs. Plasma cholesterol levels were elevated in dogs consuming in the diets high in fat but plasma triglyceride levels were not influenced by the diets fed. Consumption of high-protein (46--48% of energy) diets elevated plasma urea nitrogen levels but had minimal influence on plasma amino acid levels. The general response of these young dogs was not markedly influenced by consumption of diets ranging from carbohydrate-free to high-carbohydrate and from adequate-protein to high-protein.     

Effect of altitude on body composition during mountaineering expeditions: interrelationships with changes in dietary habits

The concepts involved in the process of managing change successfully in respect of the management of human resources are as complex as they are contentious, with arguments and counter-arguments espoused weekly in the seemingly ever-growing plethora of literature available. The following paper attempts to present a critical analysis of the management of change from the perspective of the human resource and to debate the relative merits pertaining to the imperatives of organizational design and culture, in conjunction with a plea to recognize and respect peoples' needs and feelings, in relation to the impact of internal market reform upon management practice within the context of the contemporary National Health Service (NHS). The paper is predicated upon the dual beliefs that people and organizations are dynamic entities being located both temporally and socially, and that any constructed criterions of success must, therefore, be evaluated not only in terms of the specific individual and/or organizational parameters but also in terms of the relative cultural, moral, philosphical and political ethos, and that as the human race largely survives and operates via organization, which in itself has to be managed, controlled and developed, managers are, therefore, a vital element of any successful organization.     

Effect of (hydroxypropyl)-beta-cyclodextrin on flux of morphine, fentanyl, sufentanil, and alfentanil through the spinal meninges of monkey

Previous studies have demonstrated that (hydroxypropyl)-beta-cyclodextrin behaves as a slow-release reservoir when used as a vehicle for intrathecal administration of opioids. The goal of the current investigation was to determine if (hydroxypropyl)-beta-cyclodextrin might serve as a slow-release vehicle for epidural opioid administration as well. An in vitro diffusion cell model was used to determine the flux of morphine, fentanyl, alfentanil, and sufentanil through the spinal meninges of Macaque nemestrina monkeys in the absence or presence of varying concentrations of (hydroxypropyl)-beta-cyclodextrin. No concentration of cyclodextrin slowed the flux of any of the opioids through the meninges, indicating that (hydroxypropyl)-beta-cyclodextrin will not behave as a slow-release reservoir for these opioids in the epidural space. This finding suggests that the rate-limiting step in opioid transfer was diffusion through the meninges not dissociation of the opioid cyclodextrin complex. However, (hydroxypropyl)-beta-cyclodextrin significantly increased the flux of sufentanil through the meninges. Since sufentanil's hydrophobicity has previously been shown to impede its meningeal flux, this finding suggests that cyclodextrin effectively decreases sufentanil's hydrophobicity by formation of inclusion complexes in the aqueous environments of the spinal meninges.     

The effects of body composition changes to observed improvements in cardiopulmonary parameters after exercise training with cardiac rehabilitation

STUDY OBJECTIVE: To discriminate the effects of body fat reduction on improvements in peak aerobic capacity made following exercise training during cardiac rehabilitation. DESIGN: Observational, prospective study. SETTING: Outpatient cardiovascular health center at regional academic center. PATIENT INTERVENTIONS: Peak oxygen uptake (pkVO2), percent body fat, lean body mass (LBM), and other anthropometric measures were assessed before and after a 3-month program of cardiac rehabilitation and exercise training in 500 consecutive cardiac patients following a major coronary event. Baseline pkVO2 was corrected for LBM (pk/VO2 lean) and compared with posttraining values. RESULTS: Following exercise training, percent body fat decreased 5% from 26.2+/-8.0 to 24.8+/-7.5 (p<0.0001), and LBM increased 1% from 61.3+/-12.5 to 61.7+/-11.8 kg (p=0.02). pk/VO2 increased 16% from 16.0+/-4.1 to 18.5+/-4.8 mL/kg/min (p<0.0001), and pkVO2 lean increased 13% from 21.7+/-5.3 to 24.6+/-6.0 mL/kg/min (p<0.0001). Isolating the effects of reduction in body fat, we discern that these changes contributed to 0.3 of the 2.5 mL/kg/min increase in pkVO2 or 12% of the increase in pkVO2 observed. CONCLUSIONS: Changes in body composition, as a consequence of dietary and exercise modification, contribute to 12% of the "observed" improvement noted in weight-adjusted peak aerobic capacity following cardiac rehabilitation and exercise training. Changes in pkVO2 lean should be used by investigators to assess the singular effects of exercise conditioning alone.     

Evaluation of the influence of placental localization on qualitative estimation of waveforms of blood flow velocity in uterine and arcuate arteries in third trimester physiologic pregnancy

We presented in our study methods and results of blood flow measurements with Doppler ultrasound in uterine and arcuate arteries in relation to localization of placenta in physiological pregnancy. We performed examinations in 154 pregnant women with pregnancy age of 32-42 wk. On the basis of qualitative analysis of blood flow waveforms we discovered the difference in the blood flow in utero-placental compartment in relation to placental localization and we proved that this change takes place in uterine as well an in arcuate arteries.