The impact of primary and modular nursing delivery systems on perceptions of caring behavior

BACKGROUND: The somatostatin analogue octreotide impairs intestinal regeneration and the adaptive response to intestinal resection by inhibition of enterocyte migration and proliferation and increased apoptosis. Epidermal growth factor (EGF) stimulates regeneration and adaptation by increasing proliferation and reducing apoptosis. The aim of this study was to determine the effect of EGF on octreotide-induced enterocyte apoptosis. METHODS: Twenty-four rabbits underwent patch enteroplasty in the distal ileum to stimulate the mucosa. There were four study groups: octreotide 250 microgram/kg/day, EGF 40 microgram/kg/day, EGF plus octreotide, and control. Normal ileal mucosa adjacent to the patch was evaluated at 7 days for villus height, crypt depth, crypt cell production rate (CCPR), and in situ end labeling of DNA fragmentation. RESULTS: Octreotide alone increased apoptosis compared with controls at the villus tip (40 +/- 7% vs 18 +/- 7%, P < 0.05), lateral villus (9 +/- 2% vs 3 +/- 2%, P < 0.05), and crypt (15 +/- 3% vs 10 +/- 3%, P < 0. 05). EGF decreased apoptosis in the crypt (2 +/- 1%) and villus (6 +/- 1% villus tip and 1 +/- 1% lateral villus, P < 0.05) compartments. EGF inhibited octreotide-induced apoptosis in the crypt (5 +/- 2%) but not the villus (31 +/- 5% villus tip and 6 +/- 2% lateral villus, P < 0.05). Mean DNA fragmentation was significantly greater in octreotide-treated animals (P < 0.05). The octreotide-treated animals had reduced crypt depth and villus height but normal CCPR compared with controls. EGF increased CCPR and crypt depth compared with controls. Combining EGF and octreotide resulted in crypt depth and CCPR similar to those of controls but reduced villus height. CONCLUSIONS: EGF inhibits octreotide-induced apoptosis. This effect is greater in crypt than in villus enterocytes. Octreotide appears to have both direct and indirect effects on enterocyte apoptosis.     

Fetal heart rate following coelocentesis

For psychological reasons, coelocentesis was performed in 20 women prior to termination of pregnancy, at 6-11 weeks of gestation. The fetal heart rate (FHR) was measured immediately before the procedure and at 1, 5, and 10 min afterward. There was no significant difference between FHR before coelocentesis compared to the values at 1 min (mean = 158, range 114-178; z = -0.629, P = 0.529), 5 min (mean = 160, range 121-179; z = -0.191, P = 0.848), or 10 min (mean 159, range 117-183; z = -0.214, P = 0.83) after the procedure. These findings suggest that coelocentesis does not have a major effect on the fetal cardiovascular system.     

The effect of acarbose on insulin sensitivity in subjects with impaired glucose tolerance

OBJECTIVE: To study the effect of acarbose, an alpha-glucosidase inhibitor, on postprandial plasma glucose and insulin and insulin sensitivity in subjects with impaired glucose tolerance (IGT). RESEARCH DESIGN AND METHODS: Subjects with IGT were randomly treated in a double-blind fashion with placebo (n = 10) or acarbose (n = 8) at 100 mg t.i.d. for 4 months. All subjects were submitted before randomization and at the end of the study to a standardized breakfast and a 12-h daytime plasma glucose and plasma insulin profile, and insulin sensitivity was measured as steady-state plasma glucose (SSPG) using the insulin suppression test. RESULTS: While placebo had no effect on postprandial plasma glucose and plasma insulin incremental area under the curve (AUC) (3.03 +/- 0.5 vs. 3.76 +/- 0.6 mmol.h-1.l-1, P = NS; 1,488 +/- 229 vs. 1,609 +/- 253 pmol.h-1.l-1, P = NS), acarbose resulted in a significant reduction for both glucose (1.44 +/- 0.3 vs. 4.45 +/- 0.9 mmol.h-1.l-1, P = 0.002) and insulin (626.7 +/- 104.3 vs. 1,338.3 +/- 220.5 pmol.h-1.l-1, P = 0.003). The reduction in 12-h plasma glucose and insulin AUC on acarbose (11.2 +/- 2.1 mmol.h-1.l-1 and 7.5 +/- 0.7 nmol.h-1.l-1) was significantly greater than that on placebo (4.0 +/- 1.6 mmol.h-1.l-1 and 0.8 +/- 0.4 nmol.h-1.l-1) (P = 0.014 and 0.041). While SSPG was not affected by placebo (13.9 +/- 0.4 vs. 13.8 +/- 0.3 mmol/l; P = NS), it was significantly improved by acarbose (10.9 +/- 1.4 vs. 13.1 +/- 1.5 mmol/l, P < 0.004) and was also significantly different from placebo at 4 months (P < 0.02). CONCLUSIONS: It is concluded that in subjects with IGT, acarbose treatment decreases postprandial plasma glucose and insulin and improves insulin sensitivity. Acarbose may therefore be potentially useful to prevent the progression of IGT to NIDDM.     

Von-Voss-Cherstvoy syndrome (DK-Focomelia): description of the first case in Spain and a literature review

Because hypercellularity is an important feature in acute serum sickness (AcSS), we quantified glomerular proliferation with immunoperoxidase staining using anti-proliferating cell nuclear antigen (PCNA Mab) and studied its relationship with lymphocyte infiltration (M108 Mab). AcSS was induced in 31 New Zealand White rabbits; group A (n = 14), with proteinuria, sacrificed 6-8 days after immunization; group B (n = 10), without proteinuria, sacrificed 6-7 days after immunization; group C (n = 7), sacrificed prior to development of AcSS. Four normal rabbits were included as controls. Intraglomerular proliferation (PCNA-positive cells/glomerular cross section) was increased in group A (12.2 +/- SEM, 1.84) but not in groups B (0.93 +/- 0.17) and C (0.37 +/- 0.05), which were similar to controls (0.66 +/- 0.06). Lymphocyte infiltration (lymphs/glomerular cross section) increased with time and was more prominent in rabbits with proteinuria (1.9 +/- 0.21, P < 0.001 vs controls). Lymphocyte infiltration was correlated with proliferative activity (Spearman correlation, r = 0.67, P < 0.0001). There was correlation between the severity of glomerular deposition of IgG and C3 and glomerular proliferation and proteinuria. These studies demonstrate a chronological association between lymphocyte infiltration and proliferative activity in AcSS.     

Early effects of vasectomy on testicular structure and on germ cell and macrophage apoptosis in the hamster

Some patients with early-stage cirrhosis preserve hepatic function, whereas others have little hepatic reserve and rapidly deteriorate. The aim of this study was to use quantitative tests of liver function (QLFTs) to define the degree of functional hepatic impairment in patients with early-stage cirrhosis (Child-Pugh score 5-7) and to determine whether the tests predicted subsequent hepatic decompensation. We recruited 10 cirrhotic (Cr) patients and 10 healthy controls (NI), who were well matched for race, age, weight, and gender. Clearances of caffeine (CF) and antipyrine (AP) after oral administration were measured from timed samples of saliva. The clearance of cholate (CA) was measured from serum samples obtained after simultaneous oral ([2,2,4,4-2H]CA) and intravenous ([24-13C]CA) administration. CA shunt was calculated as (Cl i.v./Clo x 100%). CF elimination rate (Cr v NI, mean +/- SD: 0.03 +/- 0.02 v 0.075 +/- 0.018 h-1, P < .0005) and AP clearance (24 +/- 16 v 40 +/- 7 mL/minute, P < .02) were reduced in Cr patients. CA shunt was increased in Cr patients (43 +/- 18 v 18 +/- 7%, P < .002). Five Cr patients decompensated during follow-up and had the worst CA shunts (76%, 66%, 51%, 48%, and 45%). Three subsequently received successful orthotopic liver transplantation, 1 died of hepatoma, and 1 is on the waiting list for transplantation. In conclusion, QLFTs define the degree of functional impairment in early cirrhosis and may identify Cr patients at greatest risk of decompensation who may require transplantation for survival.     

Correlation of thrombosis with increased platelet turnover in thrombocytosis

There are no readily applicable methods to routinely assess thrombosis risk and treatment response in thrombocytosis. Reticulated platelets (RP) define the most recently released platelets in the circulation, and the RP% has been shown to estimate platelet turnover in thrombocytopenic states. We examined whether increased RP values were associated with thrombotic complications in thrombocytosis. Platelet count, RP%, and absolute RP count were measured at presentation in 83 patients with chronic or transient thrombocytosis, 46 patients with deep vein (DVT) or arterial (ART) thrombosis and normal platelet counts, and 83 healthy controls with normal platelet counts. Chronic thrombocytosis patients presenting with thrombosis (n = 14) had significantly higher RP% (14.7% +/- 10. 1%, mean +/- SD) than asymptomatic chronic thrombocytosis patients (n = 23, RP% = 3.4% +/- 1.8%), healthy controls (3.4% +/- 1.3%), DVT patients (n = 21, 3.8% +/- 2.1%), or ART patients (n = 25, 4.5% +/- 4.1%, P < .05 for all comparisons). Chronic thrombocytosis patients with thrombosis also had significantly higher absolute RP counts than asymptomatic chronic thrombocytosis patients (98 +/- 64 x 10(9)/L [range, 54 to 249 x 10(9)/L] v 30 +/- 13 x 10(9)/L [range, 11 to 51 x 10(9)/L]; P = .0004), whereas healthy controls, DVT, and ART patients had similarly low absolute RP counts (6 +/- 6 x 10(9)/L, 9 +/- 7 x 10(9)/L, and 11 +/- 7 x 10(9)/L, respectively; P > .49). The RP% and absolute RP counts remained significantly higher in chronic thrombocytosis patients with thrombosis when patients were further subdivided into primary myeloproliferative disorders versus secondary thrombocytosis. Similarly elevated RP percentages and absolute counts were also noted in transient thrombocytosis patients with thrombosis (n = 6, 11.5% +/- 4.4% and 90 +/- 46 x 10(9)/L, respectively) when compared with asymptomatic transient thrombocytosis patients (n = 40, 4.5% +/- 2.7% and 35 +/- 16 x 10(9)/L, respectively) and to all control groups (P < .05 for all comparisons). In addition, 7 of 8 thrombocytosis patients who were studied before developing symptoms of thrombosis had elevated absolute RP counts compared with only 1 of 63 thrombocytosis patients who remained asymptomatic. Follow-up studies in seven chronic thrombocytosis patients showed that successful aspirin treatment of symptomatic recurrent thrombosis significantly reduced the RP% from 17.1% +/- 10.9% before therapy to 4.8% +/- 2.0% after therapy; absolute RP counts decreased from 102 +/- 67 x 10(9)/L to 26 +/- 10 x 10(9)/L (P < .01 for both). We conclude that thrombosis in the setting of an elevated platelet count is associated with increased platelet turnover, which is reversed by aspirin therapy. Measurement of reticulated platelets to assess platelet turnover may be useful in evaluating both treatment response and thrombotic risk in thrombocytosis.     

Renal blood flow velocity in acute renal failure following cardiopulmonary bypass surgery

Two lysosomal storage diseases, aspartylglucosaminuria and mannosidosis, are associated with highly elevated serum dolichol concentrations. To elucidate possible mechanisms leading to elevated serum dolichols, we studied the effects of Triton WR 1339 (known to increase serum cholesterol) and orotic acid (known to decrease serum cholesterol) on blood and biliary dolichol and beta-hexosaminidase levels in rats. In Triton WR 1339-treated rats, serum dolichol was markedly increased compared with saline-treated controls 1 (400 +/- 70 ng/mL, n = 7 v 85 +/- 11 ng/mL, n = 8, P < .001), 4 (789 +/- 70 ng/mL, n = 10 v 110 +/- 10 ng/mL, n = 7, P < .0001), and 8 (549 +/- 43 ng/mL, n = 8 v 87 +/- 8 ng/mL, n = 7, P < .001) days after administration of the drug. By contrast, serum dolichol was decreased (64 +/- 5 ng/mL, n = 8 v 119 +/- 7 ng/mL, n = 8, P < .0001) after a 7-day orotic acid feeding compared with controls. Serum beta-hexosaminidase was unaffected by both treatments. Orotic acid also increased biliary dolichol (280 +/- 47 ng/100 g body weight [BW]/h, n = 7 v 83 +/- 15 ng/100 g BW/h, n = 7, P < .01) and beta-hexosaminidase (21 +/- 3 mU/100 g BW/h, n = 7 v 8.3 +/- 2 mU/100 g BW/h, n = 9, P < .01) excretion compared with controls. Thus, both Triton WR 1339 and orotic acid have an effect on dolichol metabolism, and it is conceivable--based on our results--that serum dolichol concentrations are regulated, at least in part, by a mechanism similar to that for serum cholesterol levels.     

Repeated fed-batch operations for microbial detoxification of mercury using wild-type and recombinant mercury-resistant bacteria

A wild-type mercury-resistant strain Pseudomonas aeruginosa PU21 (Rip64), and an Escherichia coli PWS1 strain genetically engineered to harbor mercury resistance were examined for their capacity to detoxify soluble mercuric ions with repeated fed-batch operations. The specific mercury detoxification activity for the two strains at different initial mercury concentrations was determined by resting-cell experiments. The fed-batch operations were conducted with different initial culture volumes (Vo), inoculum sizes (Xo), and different mercury feeding rates (FHg) to investigate the effects of those operation parameters on the performance of mercury detoxification. The results showed that the wild-type and the recombinant strains had an optimal specific activity of 5 x 10(-7) and 8 x 10(-8) micrograms cell-1 h-1, respectively. In fed-batch operation for P. aeruginosa PU21, under the conditions of Vo = 400 ml and Xo = 4.5-4.8 x 10(9) cells ml-1 the overall mercury detoxification efficiency (eta) for FHg = 16.9 mg Hg h-1 was 5.26 mg Hg l-1 h-1, nearly 35% higher than that for a lower FHg (11.7 mg Hg h-1). Among the three initial culture volumes examined in this study, the highest eta (5.60 mg Hg l-1 h-1) was obtained when Vo = 1200 ml and FHg = 16.9 mg Hg h-1. It was also found that an inoculum size higher than 4.0 x 10(9) cells ml-1 enabled a stable fed-batch operation, while as the inoculum was reduced to around 1.6 x 10(9) cells ml-1, the mercury feeding caused severe cell death, leading to an unsuccessful fed-batch operation. In the fed-batch operation for E. coli PWS1 strain with Vo = 1200 ml and FHg = 16.9 mg Hg h-1, the mercury detoxification efficiency was 3.07 mg Hg l-1 h-1, only 54% of that for the wild-type P. aeruginosa PU21 strain under the same operating conditions. It was also noticed that the operation with E. coli PWS1 became less efficient at the second fed-batch cycle due to plasmid instability of the recombinant strain.     

Metabolic assessment of wallaby blastocysts during embryonic diapause and subsequent reactivation

The metabolism of tammar wallaby (Macropus eugenii) blastocysts was analysed by means of quantitative fluorescence microscopy during embryonic diapause and 2, 3, 4, 5, 8 and 10 days after reactivation to determine nutrient preferences during metabolic reactivation of the blastocyst. The surface area of quiescent blastocysts was 0.16 +/- 0.02 mm2 (mean +/- s.e.m.), and increased to 0.44 +/- 0.04 mm2 (P < 0.05) by Day 8 after removal of the sucking stimulus of the pouch young (RPY). Day-10 blastocysts, analysed over two successive breeding seasons, were significantly different in size from each other (Group A, 1992: 4.44 +/- 1.47 mm2; Group B, 1993: 18.87 +/- 4.62 mm2; P < 0.01), and both groups were significantly different in size from diapausing blastocysts (P < 0.01). There was no significant difference in carbohydrate uptake or production by blastocysts during the first five days after RPY. Glucose uptake by blastocysts recovered 8 days after RPY (61.9 +/- 30.0 pmol embryo-1 h-1) was significantly greater than that by Day-0 blastocysts (17.9 +/- 5.5 pmol embryo-1 h-1) and glucose uptake by both groups of Day-10 blastocysts (Group A, 174.0 +/- 28.4 pmol embryo-1 h-1; Group B, 616.0 +/- 239.0 pmol embryo-1 h-1) was significantly different from that by Day-0 blastocysts (P < 0.01). Pyruvate uptake by Day-10 blastocysts (Group A, 46.0 +/- 32.2 pmol embryo-1 h-1; Group B, 250.0 +/- 136.0 pmol embryo-1 h-1; P < 0.01) increased significantly compared with that by Day-0 blastocysts (6.4 +/- 1.6 pmol embryo-1 h-1; P < 0.01). Lactate production by Day-10 blastocysts (Group A, 186.7 +/- 30.3 pmol embryo-1 h-1; Group B, 285 +/- 129 pmol embryo-1 h-1; P > 0.01) was also significantly different from that by quiescent blastocysts (41.20 +/- 9.6 pmol embryo-1 h-1). There was a linear relationship between surface area and glucose uptake and surface area and pyruvate uptake (r2 = 0.965 and r2 = 0.971 respectively). Despite increases in carbohydrate uptake, there was a proportional decrease in lactate production indicating an increase in oxidative metabolism during reactivation. This suggests that there may be a metabolic switch at, or around, Day 5 after RPY.     

In vivo quantification of endotoxin-induced nitric oxide production in pigs from Na15NO3-infusion

1. In this investigation the NO production rate is quantified in the pig during normotensive endotoxin-induced shock with increased cardiac output and during subsequent treatment with the NO synthase inhibitor N omega-monomethy-L-arginine (L-NMMA). NO production rate was derived from the plasma isotope-enrichment of 15N-labelled nitrate (15NO3-). 2. Three groups of animals (control, n = 5; endotoxin, n = 6; endotoxin + L-NMMA, n = 6) were anaesthetized and instrumented for the measurement of systemic and pulmonary haemodynamics. Each animal received a primed-continuous infusion of stable, non-radioactively labelled Na15 NO3 (bolus 30 mg, infusion rate 2.1 mg h-1). Arterial blood samples were taken 5, 10, 15, 30, 60 and 90 min later and every 90 minutes until the end of the experiment. 3. Continuous i.v. infusion of endotoxin was incrementally adjusted until mean pulmonary artery pressure (PAP) reached 50 mmHg and subsequently titrated to keep mean PAP approximately 35 mmHg. Hydroxyethylstarch was administered as required to maintain mean arterial pressure (MAP) > 60 mmHg. Six hours after the start of the endotoxin continuous i.v. L-NMMA (1 mg kg-1 h-1) was administered to the endotoxin + L-NMMA group. Haemodynamic data were measured before as well as 9 h after the start of the endotoxin. 4. After conversion of NO3- to nitro-trimethoxybenzene and gas chromatography-mass spectrometry analysis the total NO3- pool, basal NO3- production rate and the increase per unit time in NO3- production rate were calculated from the time-course of the 15NO3- plasma isotope-enrichment. A two compartment model was assumed for the NO3- kinetics, one being an active pool in which newly generated NO3- appears and from which it is eliminated, the other being an inactive volume of distribution in which only passive exchange takes place with the active compartment. 5. Although MAP did not change during endotoxin infusion alone, cardiac output (CO) increased by 42 +/- 40% (P < 0.05 versus baseline) by the end of the experiment due to a significant (P < 0.05 versus baseline) fall in systemic vascular resistance (SVR) to 65 +/- 25% of the baseline value. L-NMMA given with endotoxin did not change MAP, and both CO and SVR were maintained close to the pre-shock levels. 6. Baseline plasma NO3- concentrations were 43 +/- 13 and 40 +/- 10 mumol l-1 in the control and endotoxin animals, respectively, and did not differ at the end of the experiment (39 +/- 8 and 44 +/- 15 mumol l-1, respectively). The mean NO3- pool and basal NO3- production rate were 1155 +/- 294 mumol and 140 +/- 32 mumol h-1, respectively, without any intergroup difference. Endotoxin significantly increased NO3- production rate (23 +/- 10 mumol h-2, P < 0.05 versus control (6 +/- 7 mumol h-2) and endotoxin + L-NMMA groups). L-NMMA given with endotoxin (-1 +/- 2 mumol h-2, P < 0.05 versus control and endotoxin groups) had no effect. 7. Analysis of the time course of the 15NO3- plasma isotope enrichment during primed-continuous infusion of Na15NO3 allowed us to quantify the endotoxin-induced increase in NO3- production rate independently of total NO3- plasma concentrations. Low-dose L-NMMA blunted the increase in NO3- production rate while maintaining basal NO3- formation.     

Local application of LDL promotes intimal thickening in the collared carotid artery of the rabbit

Oxidized LDL (oxLDL) has been implicated in atherogenesis on the basis of in vitro studies and is present in atherosclerotic lesions. The aim of this study was to investigate the effects of LDL and oxLDL on intimal thickening in vivo. Intimal thickening was evoked by the placement of silicone collars around the carotid arteries of rabbits for 2 weeks. The collars were connected to osmotic minipumps containing LDL (7 micrograms h-1, n = 16 arteries), oxLDL (Cu2+ oxidized, 7 micrograms h-1, n = 16), or phosphate-buffered saline (5 microL h-1, n = 16). Segments proximal to the collars served as controls. Collar placement without lipoprotein application resulted in the appearance of alpha-SMC actin-immunoreactive cells in the intima, thereby increasing the intimal thickness from 5 +/- 1 to 26 +/- 5 microns. The perivascular infusion of LDL or oxLDL within the collar significantly enhanced the development of the intima ninefold and sevenfold, respectively. The large intimas resulting from lipoprotein exposure were infiltrated by macrophages and T lymphocytes, and the intimal collagen area was increased from 5 +/- 2% in the discrete collar-induced intima to approximately 20% in the lipoprotein-evoked lesions. In conclusion, the local vascular application of LDL, oxidized in vitro or possibly in vivo, elicited an inflammatory-fibroproliferative response characteristic of arteriosclerotic lesions, thereby demonstrating an active role for this class of lipoproteins in the disease process.     

Relaxin levels in amniotic fluid, extraembryonic coelomic fluid and maternal serum in early human pregnancy

Separately identified samples of amniotic fluid and extraembryonic coelomic fluid together with maternal serum were collected from 22 women between 8 and 11 weeks of pregnancy and analysed for relaxin by immunoassay. Relaxin levels in maternal serum (median 1085 pg/ml; range 390-1259 pg/ml) were substantially higher than those in extraembryonic coelomic fluid (median 57.5 pg/ml; range 17-145 pg/ml; P < 0.0001; Mann-Whitney U-test). In turn, the levels of relaxin in coelomic fluid were higher than those in amniotic fluid (median 10 pg/ml; range 10-37 pg/ml; P < 0.0001; Mann-Whitney U-test). A linear correlation was found between relaxin levels in maternal serum and coelomic fluid (r = 0.68; P = 0.001) but there was no relation between levels in the other fluid compartments.     

Selective inhibition of syncytium-inducing and nonsyncytium-inducing HIV-1 variants in individuals receiving didanosine or zidovudine, respectively

By studying changes in the clonal composition of HIV-1 populations during the first weeks of zidovudine (ZDV) treatment before the development of ZDV resistance-conferring mutations, we demonstrated previously a selective inhibition of nonsyncytium-inducing (NSI) HIV-1, even when present as coexisting population in individuals also harboring syncytium-inducing (SI) HIV-1. In this study, we observed the opposite in individuals receiving didanosine (ddI) treatment. In these individuals (n = 7) a median -0.98 log change (range -1.55-0.08) in infectious cellular SI load was observed, whereas the coexisting NSI load was only minimally affected (median -0.15 log, range -1.27-0.50; P = 0.03). The virus phenotype-dependent treatment responses were independent of the clonal composition of HIV-1 populations at baseline. Individuals treated with a combination of ZDV and ddI revealed an equal decline of both NSI and SI infectious cellular load (n = 4; NSI: median -1.55 log, range -2.19 to -1.45; SI: median -1.47 log, range -1.81 to -0.86; P = 0.56). To test the hypothesis that the previously reported optimal activation of ZDV and ddI in activated and resting T cells, respectively, in combination with the differential T cell tropism of NSI and SI HIV-1 is the basis for the observed virus phenotype specific efficacy of nucleoside analogs, we studied the effect of treatment with a protease inhibitor that does not require intracellular activation. Individuals receiving ritonavir (n = 4) indeed showed equal declines in NSI and SI infectious cellular load (NSI: median -2.37 log, range -2.59 to -2.16; SI: median -2.82 log, range -3.14 to -2.50; P = 0.25). Our data suggest HIV-1 phenotype as an additional parameter in the design of optimal treatment regimens.     

Comparison of remifentanil in combination with isoflurane or propofol for short-stay surgical procedures

There are few data in the literature that describe the use of remifentanil when administered as a component of an inhalation or total i.v. anaesthetic (TIVA) technique. We studied 251 male and female patients, aged 18-75 years, ASA I-II, undergoing inguinal hernia repair, arthroscopic knee surgery or varicose vein surgery of at least 30 min duration without premedication. Patients were randomized to receive a remifentanil loading dose of 1.0 microgram kg-1 followed by a continuous infusion of 0.5 microgram kg-1 min-1 in combination with isoflurane (end-tidal concentration 0.6%), (Group I, n = 115) or propofol (initial infusion rate 9 mg kg-1 h-1 reduced to 6 mg kg-1 h-1 after 10 min), (Group P, n = 118). The remifentanil infusion rate was reduced by 50%, 5 min after tracheal intubation. Intraoperative stresses were treated with a remifentanil bolus (1 microgram kg-1) followed by an increase in the remifentanil infusion rate. At the insertion of the last suture, the remifentanil infusion and concomitant anaesthetic were switched off simultaneously. Times to spontaneous respiration, adequate respiration and tracheal extubation were significantly shorter in group I compared with group P (6.4 min vs 7.6 min, P < 0.01; 7.6 min vs 9.3, P < 0.003; 7.8 min vs 9.5 min, P < 0.015). Overall mean systolic blood pressures during surgery were greater in group P compared with group I (P < 0.05) but the absolute differences were clinically insignificant (4-5 mm Hg).     

Patterns of expenditures and use of services among older adults with diabetes. Implications for the transition to capitated managed care

BACKGROUND: Rapid quantifiable diagnostic techniques for the diagnosis of cytomegalovirus (CMV) infection may predict patients at risk of CMV pneumonitis and allow preemptive antiviral treatment. METHODS: Using CMV antigenemia as a prospective surveillance technique for CMV infection, we compared the outcome of preemptive treatment (PT) with ganciclovir, 10 mg/kg/day for 21 days directed by "high levels" of CMV antigenemia (PT group, n= 19), with the outcome in a group of historical controls (n=18) treated with ganciclovir when CMV illness occurred. Greater than 50 antigen-positive cells per 2 x 10(5) polymorphonuclear leukocytes was considered to be high-level antigenemia. RESULTS: Nine of the 18 controls developed high-level CMV antigenemia at a median of 33 days (range: 13-65 days) and 5 of the 9 developed CMV disease. Ten of the 19 PT group had high levels of CMV antigenemia detected at a median of 47 days (range: 20-63 days) and were given ganciclovir; none developed CMV disease. There was a significantly lower incidence of CMV disease in the PT group in comparison to controls (0 of 19 vs. 5 of 18: P=0.019). CONCLUSION: We have reduced the incidence of CMV disease using preemptive treatment, and because of a 100% negative predictive value, we omitted unnecessary antiviral prophylaxis for many at-risk patients.     

Influence of ischaemia-reperfusion injury on CD44 expression in rat small intestine

BACKGROUND: CD44 is an adhesion molecule expressed by neutrophils and lymphocytes which is involved in cell-cell and cell-matrix binding. In this study, the effect of ischaemia-reperfusion injury on CD44 messenger RNA (mRNA) and cell surface immunohistochemical expression of CD44 in the rat small intestine was evaluated. METHODS: Wistar rats (n=16) were randomized to either serve as controls (sham surgery) or to be subjected to a standardized ischaemia-reperfusion injury (suprarenal aorta occluded for 1 h followed by 1 h of reperfusion). Standardized segments of jejunum were harvested after ischaemia-reperfusion injury (ischaemic and reperfused samples) to measure the mucosal protein and DNA content, mRNA expression of CD44 and the immunohistochemical expression of CD44. RESULTS: Reperfusion significantly damaged the jejunal mucosa, e.g. mucosal protein content was lower after reperfusion compared with that in the control group (z=-2.31, P=0.02) and the ischaemic samples (z=-2.52, P=001). The expression of cell surface CD44 protein was also significantly decreased after ischaemic injury (z=-1.99, P=0.04); this coincided with a decrease in the amount of cytoplasmic CD44 mRNA within isolated enterocytes (z=-2.31, P=0.02). CONCLUSION: Ischaemia-reperfusion injury decreases the expression of CD44 within the jejunal mucosa. This may contribute to the failure of the gut barrier after such injury.     

Coexisting mental illness and alcohol and other drug dependencies in pregnant and parenting women

1. To determine whether dexfenfluramine is a substrate of cytochrome P450 2D6 (CYP2D6), its disposition has been studied in nine extensive (EM) and eight poor metabolizers (PM) of debrisoquine. 2. Following a 30 mg dose of dexfenfluramine hydrochloride, urine was collected in all subjects for 96 h post-dose and plasma samples were collected in 11 subjects (six EMs and five PMs). Dexfenfluramine and nordexfenfluramine were measured in urine by h.p.l.c. and in plasma by g.c. 3. Urinary recovery of dexfenfluramine was greater in PMs than EMs (4136 +/- 1509 micrograms vs 1986 +/- 792 micrograms; 95% CI of difference 926-3374; P < 0.05) whereas that of nordexfenfluramine was similar in both phenotypes (PM: 1753 +/- 411 micrograms vs 1626 +/- 444 micrograms). 4. Dexfenfluramine AUC was higher in PMs (677 +/- 348 micrograms l-1 h) than EMs 359 +/- 250 micrograms l-1 h). The apparent oral clearance of dexfenfluramine was greater in EMs than PMs (93.6 +/- 42.4 l h-1 vs 45.6 +/- 19.5 l h-1; 95% CI of difference 1.2-94.7; P < 0.05). The renal clearance was similar in both phenotypes (EMs: 5.88 +/- 2.83 l h-1; PMs 6.60 +/- 2.01 l h-1), indicating that the higher urinary recovery of dexfenfluramine in PMs reflects higher plasma concentrations, rather than phenotype differences in the renal handling, of dexfenfluramine. 5. The apparent nonrenal clearance of dexfenfluramine was substantially lower (P < 0.05; 95% CI of difference 3.0-94.1) in PMs (39.0 +/- 19.5 l h-1) than EMs (87.6 +/- 41.2 l h-1). 6. There was a significant inverse correlation (rs = 0.776 95% CI-0.31-0.94; n = 11; p = 0.005) between the debrisoquine metabolic ratio and the apparent nonrenal clearance of dexfenfluramine. 7. PMs had a higher incidence of adverse effects (nausea and vomiting) than EMs. 8. In conclusion, the metabolism of dexfenfluramine is impaired in PMs. Thus CYP2D6, the isoenzyme deficient in poor metabolizers of debrisoquine, must catalyse at least one pathway of dexfenfluramine biotransformation.     

K-RAS-2 gene mutations as predictors of metachronous colorectal adenomas

BACKGROUND: Mutations of K-RAS-2 gene and tumour suppressor genes have been found in both colorectal adenomas and carcinomas. The aim of this study was to investigate the prognostic value of K-RAS-2 gene mutations found in initial colorectal adenomas for predicting the risk of metachronous adenomas. METHODS: Genomic DNA was extracted from formalin-fixed and paraffin-embedded adenomas larger than 5 mm in diameter removed at the initial total colonoscopy between 1980 and 1982. All patients underwent colonoscopic follow-up for at least 10 years. The sequence of exon 1 of the K-RAS-2 oncogene was amplified with the polymerase chain reaction technique and screened for mutation by single-strand conformation polymorphism analysis. All suspected mutations were confirmed by direct DNA sequencing. The predictive value of K-RAS-2 gene mutations for the risk of metachronous adenomas was assessed by chi-square testing and logistic regression analysis. RESULTS: Of 54 patients 39 (72%) were male and 15 (28%) female. At the time the initial adenoma was removed, 31 (57%) patients were younger than 60, whereas 23 (43%) were 60 years or older. Point mutations of the K-RAS-2 oncogene were found in the index adenomas of 15 (27.7%) patients. Mutations were found more frequently in large (> or = 20 mm) adenomas and in adenomas with severe dysplasia (P = 0.0011 and P = 0.0310, respectively). There were no significant associations between K-RAS-2 mutations and anatomic location, histologic type, or number of synchronous initial lesions. Mutations were found predominantly at codon 12 with transversions from GGT to GTT (57%), from GGT to GAT (36%), and from GGT to TTT (one patient). The single mutation found at codon 13 showed a transversion from GGC to GAC. There were significant associations between size (> or = 20 mm) and K-RAS-2 mutation of the initial adenomas and the size (> 5 mm) of metachronous adenomas (P = 0.0259 and P = 0.0265, respectively). However, multivariate analysis showed that K-RAS-2 mutations did not provide a significant additional contribution to the prognostic value of the size of the initial adenoma (odds ratio, 7.62; 95% confidence interval (CI), 1.68-34.48) and the amount of villous structure (odds ratio, 0.22; 95% CI, 0.05-0.90) it contained. CONCLUSIONS: Patients with large (> or = 20 mm) adenomas and adenomas with K-RAS-2 mutations found at the initial examination have a significantly higher risk of developing large (> 5 mm) metachronous adenomas during surveillance. Multivariate analysis of initial adenoma characteristics showed that the risk of metachronous colorectal adenomas can be adequately estimated by the size and the histologic type of the largest initial adenoma and that K-RAS-2 mutations are of secondary importance only. Further studies based on a larger series will have to identify the adenoma characteristics that will help to improve follow-up strategies.     

Increased availability and open probability of single L-type calcium channels from failing compared with nonfailing human ventricle

BACKGROUND: The role of the L-type calcium channel in human heart failure is unclear, on the basis of previous whole-cell recordings. METHODS AND RESULTS: We investigated the properties of L-type calcium channels in left ventricular myocytes isolated from nonfailing donor hearts (n= 16 cells) or failing hearts of transplant recipients with dilated (n=9) or ischemic (n=7) cardiomyopathy. The single-channel recording technique was used (70 mmol/L Ba2+). Peak average currents were significantly enhanced in heart failure (38.2+/-9.3 fA) versus nonfailing control hearts (13.2+/-4.5 fA, P=0.02) because of an elevation of channel availability (55.9+/-6.7% versus 26.4+/-5.3%, P=0.001) and open probability within active sweeps (7.36+/-1.51% versus 3.18+/-1.33%, P=0.04). These differences closely resembled the effects of a cAMP-dependent stimulation with 8-Br-cAMP (n= 11). Kinetic analysis of the slow gating shows that channels from failing hearts remain available for a longer time, suggesting a defect in the dephosphorylation. Indeed, the phosphatase inhibitor okadaic acid was unable to stimulate channel activity in myocytes from failing hearts (n=5). Expression of calcium channel subunits was measured by Northern blot analysis. Expression of alpha1c- and beta-subunits was unaltered. Whole-cell current measurements did not reveal an increase of current density in heart failure. CONCLUSIONS: Individual L-type calcium channels are fundamentally affected in severe human heart failure. This is probably important for the impairment of cardiac excitation-contraction coupling.     

Cyclic food restriction, insulin and mammary cell proliferation in the rat

We reported recently that weight cycling significantly increased the incidence of mammary cancer in virgin female rats that were pretreated with N-methyl-N-nitrosourea. The present study investigated the effect of weight cycling on mammary epithelial cell proliferation and its relationship to changes in plasma insulin, estrogen, progesterone and urinary corticosterone in 30 female virgin Sprague-Dawley rats. Animals were fed a modified AIN-76A diet containing 24.6% corn oil by weight. Weight-cycled (WC) rats were food restricted daily by either 33% or 50% of non-restricted controls for 1 week followed by 3 weeks compensatory refeeding and weight recovery over 18 weeks or 4.5 weight cycles. WC rats consumed 6-10% less food than controls (P = 0.01) but showed a 71-89% greater efficiency of food utilization for growth (P < 0.0001) than controls. There were no differences in total weight gain during treatment. Mammary lobuloalveolar and ductal cell proliferation of WC rats, measured by 5-bromo-2'deoxyuridine labelling, increased in a dose-response fashion, P = 0.03, P = 0.06 respectively in comparison to controls. Energy and substrate utilization measured by indirect calorimetry indicated WC animals expended less energy (P = 0.005) and utilized less glucose (P = 0.0001) and protein (P = 0.006) during restriction, and less lipid during recovery (P = 0.05) than controls. There were no significant differences in hormone levels between groups. Multiple regression analysis with plasma insulin, estrogen, progesterone and urinary corticosterone as independent variables (r = 0.947, r2 = 0.897, P = 0.003) showed that plasma insulin was the only significant predictor (P < 0.01) of mammary cell proliferation. In accord with this observation, tyrosine-phosphorylated activation of insulin receptor substrate-1, detected by immunoprecipitation and Western immunoblot analysis in mammary tumors of WC rats from our previous study, was 3-5 times greater than in non-restricted controls (P < 0.01). Present findings suggest that weight cycling in rats increases risk of breast cancer development via insulin stimulated mammary cell proliferation.