Serum phospholipase A2 in intensive care patients with peritonitis,multiple injury,and necrotizing pancreatitis

Summary To study the source and role of circulating phospholipase A₂ (PLA₂) catalytic activity we monitored the serum from patients with necrotizing pancreatitis (n=8), diffuse peritonitis (n=6), and multiple injuries (n=11). Immunoreactive PLA₂ serum protein concentration was analysed using a fluoroimmunoassay based on an antibody against human pancreatic PLA₂. Serum PLA₂ catalytic activity was analysed using a radiochemical method based on a substrate with tritiated palmitic acid in beta position. In necrotizing pancreatitis immunoreactive PLA₂ and PLA₂ catalytic activity both increased. Obviously, in necrotizing pancreatitis the major part of serum catalytic activity stems from the pancreas. In patients with diffuse peritonitis and multiple injuries, as a rule, immunoreactive phospholipase A₂ serum concentration appears to be within the normal range. In contrast, in these patients we demonstrated high serum catalytic PLA₂ activity comparable to that in necrotizing pancreatitis. The source of catalytic PLA₂ activity in peritonitis and multiple injuries seems not to be the pancreas. There was a correlation between pulmonary insufficiency and serum PLA₂ catalytic activity in patients with necrotizing pancreatitis, peritonitis, and multiple injuries.     

The relationship between moisture or mould observations in houses and the state of health of their occupants.

This work was conducted in order to study how the health of adults is affected by the presence of moisture or mould in the home. A random sample of 310 houses in Finland was studied during the years 1993-1994. The houses were investigated for visual signs of moisture by a surveyor, and observations of mould were reported by the occupants. A moisture problem was observed in 52% and a mould problem in 27% of the houses. Health data was collected by means of a postal questionnaire from 699 adults. Exposure to moisture was significantly associated with sinusitis, acute bronchitis, nocturnal cough, nocturnal dyspnoea and sore throat, and the exposed inhabitants had significantly more episodes of common cold and tonsillitis. Exposure to mould was significantly associated with common cold, cough without phlegm, nocturnal cough, sore throat, rhinitis, fatigue and difficulties in concentration. Building-related moisture or mould increased the risk of upper and lower respiratory infections and symptoms as well as of nonrespiratory symptoms.     

S-Ketamine Anesthesia Increases Cerebral Blood Flow in Excess of the Metabolic Needs in Humans

Background: Animal studies have demonstrated neuroprotective properties of S-ketamine, but its effects on cerebral blood flow (CBF), metabolic rate of oxygen (CMRO2), and glucose metabolic rate (GMR) have not been comprehensively studied in humans.

Methods: Positron emission tomography was used to quantify CBF and CMRO2 in eight healthy male volunteers awake and during S-ketamine infusion targeted to subanesthetic (150 ng/ml) and anesthetic (1,500-2,000 ng/ml) concentrations. In addition, subjects' GMRs were assessed awake and during anesthesia. Whole brain estimates for cerebral blood volume were obtained using kinetic modeling.

Results: The mean +/- SD serum S-ketamine concentration was 159 +/- 21 ng/ml at the subanesthetic and 1,959 +/- 442 ng/ml at the anesthetic levels. The total S-ketamine dose was 10.4 mg/kg. S-ketamine increased heart rate (maximally by 43.5%) and mean blood pressure (maximally by 27.0%) in a concentration-dependent manner (P = 0.001 for both). Subanesthetic S-ketamine increased whole brain CBF by 13.7% (P = 0.035). The greatest regional CBF increase was detected in the anterior cingulate (31.6%; P = 0.010). No changes were detected in CMRO2. Anesthetic S-ketamine increased whole brain CBF by 36.4% (P = 0.006) but had no effect on whole brain CMRO2 or GMR. Regionally, CBF was increased in nearly all brain structures studied (greatest increase in the insula 86.5%; P < 0.001), whereas CMRO2 increased only in the frontal cortex (by 15.7%; P = 0.007) and GMR increased only in the thalamus (by 11.7%; P = 0.010). Cerebral blood volume was increased by 51.9% (P = 0.011) during anesthesia.     

Knowledge expectations of patients on dialysis treatment

In order to be empowered in different situations related to dialysis care, patients need knowledge. This study describes the knowledge expectations of patients on dialysis treatment (n = 47) and selected background variables. The results indicated that patients expressed moderate knowledge expectations. Most important were the biophysiological, functional, and ethical dimensions of knowledge. The least important were the social and experiential dimensions of knowledge. Patients' age, employment status, dialysis modality, and length of dialysis were positively correlated with knowledge expectations.     

Site dependent bioavailability and metabolism of levosimendan in dogs.

Site specific bioavailability and metabolism of levosimendan was studied in ten dogs by placing intestinal access port catheters in different parts of the gastrointestinal tract. 14C-labelled levosimendan (0.1 mg/kg) was administered intravenously, by gastric tube and directly through catheters that were placed in the duodenum, jejunum and ileum. Plasma samples were collected and radioactivity in the different organs and tissues was measured. The results of the present study showed that bioavailability of levosimendan was high varying from 71 to 86% after extravascular administration. Metabolite OR-1855 concentrations in the plasma were about 3-4 times higher after administration to the ileum compared to the other administration routes. It can be concluded that the bioavailability of levosimendan is not affected by site specific administration. The bacteria or enzymes responsible for the metabolism of levosimendan are located in the lower parts of the gastrointestinal tract.     

Single doses of FK506 and OKT3 reduce severity in early experimental acute pancreatitis.

OBJECTIVE: To find out if two immunomodulatory drugs used in organ transplantation (FK506 (tacrolimus) and OKT3 (Orthoclone) would reduce early inflammatory complications in experimental acute pancreatitis. DESIGN: Laboratory study. SETTING: University hospital, Germany. ANIMALS: 36 Balb/c mice. INTERVENTIONS: Pancreatitis induced by 7 intraperitoneal injections of cerulein 50 microg/kg at hourly intervals followed by FK506 0.32 mg/kg, OKT3 0.6 mg/kg, or 0.9% sodium chloride (controls) (n = 12 in each group). 12 hours after induction of pancreatitis the animals were killed. MAIN OUTCOME MEASURES: Serum amylase activity and interleukin-6 (IL-6) concentrations; histological damage to pancreas and lungs, apoptotic cells in pancreas; and myeloperoxidase activity in lungs. RESULTS: No animal died during the experiment. At 12h serum amylase activity and IL-6 concentrations were increased in all 3 groups, but highest in the OKT3 group. The pancreatic histological score, apoptosis, and inflammatory infiltration were lower in the two experimental groups than controls, but the degree of vacuolisation of acinar cells was similar. Packed cell volume was higher in the control than the experimental groups, and pulmonary damage and myeloperoxidase activity were less in the experimental groups than the controls. CONCLUSION: Single therapeutic doses of FK506 and OKT3 reduced the early severity of pancreatitis, pulmonary damage, and haemoconcentration in mice. Single doses of FK506 or OKT3 may therefore be effective in preventing the early complications of pancreatitis.     

Diagnostic value of immunoreactive phospholipase A2 in acute pancreatitis

Summary In a prospective clinical trial 85 patients with acute pancreatitis were analysed for serum total amylase, pancreatic amylase, pancreatic lipase, trypsin, elastase 1, and immunoreactive phospholipase A₂ (IR-PLA₂). The diagnostic sensitivity of serum IR-PLA₂ was comparable to that of serum total amylase, pancreatic amylase, and trypsin. The specificity of IR-PLA₂ is superior to that of serum total amylase determination due to the fact that the IR-PLA₂ determination is based on an antibody against human pancreatic PLA₂.     

DNA ploidy in pancreatic neuroendocrine tumors

The nuclear DNA content of 17 pancreatic neuroendocrine tumors was measured from paraffin-embedded tissue with flow cytometry. The tumors were classified by immunostaining with antisera for synaptophysin, insulin, gastrin, glucagon, pancreatic polypeptide, somatostatin, and vasoactive intestinal polypeptide. Eight (47%) of the 17 tumors were aneuploid, and two (12%) were multiploid (had two aneuploid stemlines of cells). Seven of the eight insulinomas, one of the four gastrinomas, and two of the four nonspecified neuroendocrine tumors had an abnormal nuclear DNA content. The DNA indices of the aneuploid and multiploid cases ranged from 1.13 to 1.93, and three cases had a DNA index greater than 1.50. During the follow-up for up to 16 years (mean, 7 years), one patient with diploid nonspecified tumor died of the disease, another patient with a multiploid gastrinoma had metastatic disease develop, and a third patient with a multiploid nonspecified tumor was alive with the disease. The authors conclude that many neuroendocrine tumors of the pancreas have an abnormal nuclear DNA content as measured by DNA flow cytometry. DNA multiploid pancreatic neuroendocrine tumors may be associated with a less favorable clinical course, but this needs to be confirmed in additional studies.     

The role of genetics and environment in lifting force and isometric trunk extensor endurance

BACKGROUND AND PURPOSE: Our understanding of what different back performance tests are measuring is limited. The purpose of this study was to investigate the relative contributions of genetics and unique and common environmental factors for 3 tests of back muscle performance in a classic twin analysis. SUBJECTS: The subjects were a population-based sample of 122 monozygotic and 131 dizygotic male twin pairs aged 35 to 69 years (mean=49.9, SD=7.7). METHODS: Variance component analysis was applied to estimate genetic and environmental influences on isokinetic and psychophysical lifting and isometric trunk extensor endurance test performance. The Cholesky decomposition genetic factor model was used to estimate genetic and environmental correlations of these variables. Path analysis was applied to study determinants of isokinetic and psychophysical lifting and isometric trunk extensor endurance test performance. RESULTS: Genetic effects accounted for 60%, 33%, and 5% of the total variance of isokinetic and psychophysical lifting forces and isometric trunk extensor endurance, respectively, and unique environmental factors accounted for 35%, 49%, and 61% of the variance. DISCUSSION AND CONCLUSION: Genetics had a dominant role in isokinetic lifting and unique environmental factors in isometric trunk extensor endurance. The relatively high role of genetics in lifting force suggests the potential to increase and sustain changes in back muscle force in the general population may be particularly challenging.     

Novel spectral indexes of heart rate variability as predictors of sudden and non-sudden cardiac death after an acute myocardial infarction

BACKGROUND: Various indexes of 24-hour heart rate variability (HRV) have been able to predict all-cause mortality after an acute myocardial infarction (AMI), but their value in predicting specific modes of cardiac death has been limited. AIM: The aim of this study was to assess the role of two novel spectral indexes of HRV as predictors of either sudden (SCD) or non-sudden cardiac death after an AMI. Method. We used two novel methods of spectral analysis of HRV: 1) the high-frequency (HF) spectral component, V(index), calculated as an average HF power from the most linear portion of HF power versus the R-R interval regression curve, and 2) the prevalent low-frequency oscillation of heart rate (PLF). V(index), conventional HRV measures, and PLF were analyzed from 24-hour Holter recordings of 590 patients with a recent AMI. RESULTS: During the mean follow-up of 39+/-14 months, SCD occurred in 3% (n = 17) and non-sudden cardiac death in 5% (n = 28) of the patients. In univariate analysis, V(index) was the most potent predictor of SCD (RR: 6.0, 95% CI: 1.7-20.7, P<0.01), also remaining the most powerful predictor of SCD after adjustment for clinical variables and ejection fraction (RR: 4.2, 95% CI: 1.2-15.2, P<0.05). PLF was a potent predictor of non-sudden cardiac death (RR: 13.9, 95% CI: 5.9-32.5, P<0.001), but it did not predict SCD. CONCLUSIONS: Novel spectral HRV analysis methods, V(index) and PLF, provide significant information of the risk of the specific mode of death after an AMI.