Normal saline versus a balanced crystalloid for goal-directed perioperative fluid therapy in major abdominal surgery: a double-blind randomised controlled study.

BACKGROUND: This double-blind randomised controlled trial investigated whether normal saline or a balanced crystalloid has distinct effects on vasopressor use in patients undergoing major abdominal surgery. METHODS: Patients received either normal saline 0.9% or an acetate-buffered crystalloid for intraoperative volume replacement in a goal-directed fashion. The primary outcome was need for vasopressors; the secondary outcomes were the total dose of catecholamines, total perioperative fluid, and unplanned intensive care admissions. RESULTS: This study was terminated early for safety reasons. A total of 60 out of the planned 240 patients were randomized. Thirty patients received normal saline and 30 patients received the balanced crystalloid, with a total volume of 3427 (2732-4130) ml and 3144 (1673-4926), respectively. The normal-saline group developed hyperchloraemic metabolic acidosis. More patients needed vasopressors for circulatory support in the normal-saline group compared with the buffered crystalloid group (97% vs 67%, respectively; P=0.033). The median weight and anaesthesia duration-adjusted dose of norepinephrine were 0.11 (0.00-0.45) ng kg-1 min-1 and 0.00 (0.00-0.00) kg-1 min-1 in the normal-saline and balanced-crystalloid groups, respectively (P=0.003). Cox regression revealed that the need for vasopressors was related to a high volume of administered fluid, normal-saline resuscitation, and lower mean arterial blood pressure. There was no difference between the groups in total perioperative fluid and unplanned intensive-care-unit admissions. Between-group differences in the duration of anaesthesia did not influence the necessity for a vasopressor. CONCLUSIONS: Compared with patients receiving a balanced crystalloid, normal saline in patients undergoing major abdominal surgery was associated with an increased need for vasopressor support. This should be interpreted in view of the large volume of fluid resuscitation and the small sample size because of the preliminary termination of the study. CLINICAL TRIAL REGISTRATION: EudraCT 2014-004867-19, NCT 02414555.

[Mobile laboratories for rapid deployment and their contribution to the containment of emerging diseases in Sub-Saharan Africa, illustrated by the example of Ebola virus disease]. / Laboratoires mobiles et leur contribution dans l'endiguement de pathologies émergentes en Afrique subsaharienne illustrée par l'exemple de la maladie à virus Ebola.

The Ebola virus, which became a global health concern in 2014, is an example of an emerging pathogen. Ebola virus disease can only be diagnosed in biosafety level 3 and 4 laboratories, which provide the security required to avoid exposure of both the staff and the environment to the pathogen. These laboratories are often far from the site of outbreaks, which may occur in rural areas or border regions (when the disease is imported from a neighboring country). Rapidly deployable laboratory units can bring the diagnosis closer to the outbreak site and thus significantly shorten the time to delivery of results, thus facilitating epidemic containment. Here we report our experience from the first months of implementation in Mali of a mobile laboratory unit of the same type as the European mobile labs and we describe the workflow in the laboratory as well as the training of its Malian staff. Based on our experience and the reports of other projects, we propose a framework in which these mobile laboratory units can strengthen epidemiological surveillance and contribute to containing outbreaks of emerging diseases in sub-Saharan Africa.

Effects of supplemental oxygen and dexamethasone on surgical site infection: a factorial randomized trial‡.

BACKGROUND: Tissue oxygenation is a strong predictor of surgical site infection. Improving tissue oxygenation should thus reduce wound infection risk. Supplemental inspired oxygen can improve tissue oxygenation, but whether it reduces infection risk remains controversial. Low-dose dexamethasone is often given to reduce the risk of postoperative nausea and vomiting, but steroid-induced immunosuppression can increase infection risk. We therefore tested the hypotheses that supplemental perioperative oxygen reduces infection risk and that dexamethasone increases it. METHODS: Using a factorial design, patients having colorectal resections expected to last ≥2 h were randomly assigned to 30% (n=270) or 80% (n=285) inspired oxygen during and for 1 h after surgery, and to 4 mg intraoperative dexamethasone (n=283) or placebo (n=272). Physicians blinded to group assignments evaluated wounds postoperatively, using US Centers for Disease Control criteria. RESULTS: Subject and surgical characteristics were similar among study groups. Surgical site infection incidence was similar among groups: 30% oxygen 15.6%, 80% oxygen 15.8% (P=1.00); dexamethasone 15.9%, placebo 15.4%, (P=0.91). CONCLUSIONS: Supplemental oxygen did not reduce surgical site infection risk. The preponderance of clinical evidence suggests that administration of 80% supplemental inspired oxygen does not reduce infection risk. We did not observe an increased risk of surgical site infection with the use of a single low dose of dexamethasone, indicating that it can be used for nausea and vomiting prophylaxis without promoting wound infections. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov number: NCT00273377.

Plasma thrombospondin 1 as a predictor of postoperative liver dysfunction.

BACKGROUND: Liver regeneration following liver resection involves a complex interplay of growth factors and their antagonists. Thrombospondin 1 has recently been identified as a critical inhibitor of liver regeneration by the activation of transforming growth factor ß1 in mice, and preliminary data seem to confirm its relevance in humans. This study aimed to confirm these observations in an independent validation cohort. METHODS: Perioperative circulating levels of thrombospondin 1 were measured in patients undergoing liver resection between January 2012 and September 2013. Postoperative liver dysfunction was defined according to the International Study Group of Liver Surgery and classification of morbidity was based on the criteria by Dindo et al. RESULTS: In 85 patients (44 major and 41 minor liver resections), plasma levels of thrombospondin 1 increased 1 day after liver resection (mean 51·6 ng/ml before surgery and 68·3 ng/ml on postoperative day 1; P = 0·001). Circulating thrombospondin 1 concentration on the first postoperative day specifically predicted liver dysfunction (area under the receiver operating characteristic (ROC) curve 0·818, P = 0·003) and was confirmed as a significant predictor in multivariable analysis (Exp(B) 1·020, 95 per cent c.i. 1·005 to 1·035; P = 0·009). Patients with a high thrombospondin 1 concentration (over 80 ng/ml) on postoperative day 1 more frequently had postoperative liver dysfunction than those with a lower level (28 versus 2 per cent) and severe morbidity (44 versus 15 per cent), and their length of hospital stay was more than doubled (19·7 versus 9·9 days). CONCLUSION: Thrombospondin 1 may prove a helpful clinical marker to predict postoperative liver dysfunction as early as postoperative day 1.

Ultrasound-guided peripheral regional anaesthesia: a feasibility study in obese versus normal-weight women.

BACKGROUND AND OBJECTIVES: In particular, obese patients may profit from peripheral regional anaesthesia due to avoidance of general anaesthesia. Currently, ultrasound (US) guidance is described as the golden standard in regional anaesthesia, but no studies have so far evaluated the US behaviour of peripheral nerve structures in obese versus normal-weight patients. To be able to perform such studies, it is necessary to develop new and more objective methods to quantify nerve visibility by US. We therefore designed a prospective, observational, comparative and blinded study to investigate the visibility of peripheral nerves in obese versus normal-weight patients by using a novel method based on histogram grey-scale values. METHODS: We scanned the median and sciatic nerves in 40 obese and normal-weight female patients and calculated differences of histogram grey-scale values between nerves and surrounding tissues. RESULTS: Histogram value analysis showed less US visibility of sciatic nerves in obese versus normal-weight study patients, which is caused by higher surrounding tissue histogram values. No differences could be detected for median nerves. CONCLUSIONS: The novel technique of comparing histogram grey-scale values to determine the visibility of the peripheral nerve in different patient categories was found feasible. Median nerves are appropriately visible by US in both normal and obese subjects, whereas sciatic nerves are less visible in obese as compared with normal-weight women. Our results serve as the rationale behind difficulties in peripheral regional anaesthesia in obese patients.

Hypercapnia and surgical site infection: a randomized trial.

BACKGROUND: Tissue oxygenation is a strong predictor of surgical site infection (SSI). Mild intraoperative hypercapnia increases peripheral, gastrointestinal, and splanchnic tissue oxygenation and perfusion. Hypercapnia also has anti-inflammatory effects. However, it is unknown whether hypercapnia reduces SSI risk. We tested the hypothesis that mild intraoperative hypercapnia reduces the risk of SSI in patients having colon resection surgery. METHODS: With institutional review board approval and subject consent, patients having elective colon resection (e.g. hemicolectomy and low-anterior resection) expected to last >2 h were randomly assigned to intraoperative normocapnia (PE'CO2 ≈ 35 mm Hg; n=623) or hypercapnia ( PE'CO2 ≈ 50 mm Hg; n=592). Investigators blinded to group assignment evaluated perioperative SSI (Center for Disease Control criteria) for 30 postoperative days. SSI rates were compared. RESULTS: Patient and surgical characteristics were comparable among the groups. The SSI rate for normocapnia was 13.3%, and for hypercapnia, it was 11.2% (P=0.29). The Executive Committee stopped the trial after the first a priori determined statistical assessment point because of much smaller actual effect compared with the projected. However, because the actual difference found in the SSI rates (15-16%) were within the 95% confidence intervals (CIs) of the projected relative difference of 33% (95% CI -43 to +24%), our results cannot be considered as 'no difference', and cannot exclude a Type II error. Time to first bowel movement was half-a-day shorter in the hypercapnia group. CONCLUSIONS: Mild hypercapnia appears to have little or-possibly-no ability to prevent SSI after colon resection. Other strategies for reducing SSI risk should thus take priority.

Effect of preoperative fever-range whole-body hyperthermia on immunological markers in patients undergoing colorectal cancer surgery.

BACKGROUND: Previous studies have demonstrated beneficial immunological effects of fever-range whole-body hyperthermia (FR-WBH) as an adjunct to non-surgical cancer therapy. We conducted a study of preoperative FR-WBH in patients undergoing colorectal cancer surgery to evaluate perioperative, hyperthermia-induced immunomodulation. METHODS: The trial was conducted as a subject-blinded, controlled, randomized study. Subjects in the FR-WBH group (n=9) were treated with FR-WBH before operation under propofol sedation; the target core temperature was 39 (0.5)°C with 1 h warming and 2 h plateau phase. Subjects in the control group (n=9) were treated with propofol sedation only. Blood samples were acquired before and after treatment, after operation, and 24, 48 h, and 5 days after the end of surgery. The following parameters were measured: lipopolysaccharide (LPS)-induced tumour necrosis factor (TNF)-α, procalcitonin (PCT), interleukin (IL)-6/10, heat shock proteins (HSPs) 60, 70, and 90, human leucocyte antigen-DR (HLA-DR), and LPS-binding protein (LBP). RESULTS: HSPs were increased in the FR-WBH group after treatment [HSP60, 48 h postop: 143 (41)% vs 89 (42)%, P=0.04; HSP90, postop: 111 (33)% vs 64 (31)%, P=0.04; HSP70: P=0.40; FR-WBH vs control, P-values for area under the level/time curve]. TNF-α levels were elevated after surgery in the control group and remained near baseline in the FR-WBH group [24 h postop: 73 (68)% vs 151 (72)%, P=0.04]. PCT increased in both groups 24 h after surgery; in the control group, this increase was significantly higher (P=0.02). There were no significant differences for IL, HLA-DR, or LBP. CONCLUSIONS: The immune system to react to surgical stress, as measured by a panel of laboratory indicators, might be improved by preoperative FR-WBH.

Epidemiological, clinical, and diagnostic data on intestinal infections with Entamoeba histolytica and Entamoeba dispar among returning travelers.

BACKGROUND: Among travelers returning from the tropics, Entamoeba spp. are among the most frequently detected intestinal parasites, mainly the presumable apathogenic E. dispar and the pathogenic E. histolytica. METHODS: Among 5,378 travelers seeking diagnosis and treatment for intestinal infections at the travel clinic of the University of Munich between 2005 and 2009, 103 laboratory-confirmed amebiasis cases were detected. The study compares the results of various diagnostic tests among these patients, analyzes data on co-infections and clinical symptoms, and determines the risk for acquiring amebiasis. RESULTS: Initial screening tests (stool microscopy, coproantigen enzyme-linked immunosorbent assay [ELISA]) were positive in 82.5 and 93.9%, respectively. Fecal samples from patients with positive screening test results were subjected to polymerase chain reaction (PCR), which detected E. histolytica in 9.7% and E. dispar in 88.3% of the cases. The majority of E. histolytica cases and more than half of the E. dispar cases had intestinal symptoms typical for amebiasis. In 53.4% of the cases, intestinal co-infections were found, mostly Blastocystis hominis (39.8%), Giardia lamblia (10.7%), Campylobacter spp. (4.9%), and Salmonella typhi (2.9%). The risk for travelers to be infected with E. histolytica or E. dispar was highest for destinations in West Africa, East Africa, and South and South-East Asia. CONCLUSION: Stool microscopy and coproantigen ELISA are appropriate screening tests for intestinal Entamoeba infections among travelers, but intestinal co-infections are common. PCR is highly recommended as the diagnostic method of choice for the differentiation of Entamoeba spp. The presumable apathogenic E. dispar seems to provoke intestinal symptoms.

Controlled study on enteropathogens in travellers returning from the tropics with and without diarrhoea.

Diarrhoea is the most frequent health problem among travellers in the tropics. However, data on the spectrum and relevance of enteropathogens in international travellers with and without diarrhoea are limited. Stool samples from 114 cases of diarrhoea in travellers returning from the tropics were collected for microbiological examination and PCR for norovirus genogroups I and II, enteroaggregative Escherichia coli (EAEC), and enterotoxigenic E. coli (ETEC) producing heat-labile toxin (LT) and heat-stable toxin (ST). Travel and laboratory data of cases were compared with those of 56 travellers without diarrhoea. Among cases, EAEC was found in 45% of stool samples, followed by LT-ETEC (20%), ST-ETEC (16%), Blastocystis hominis (15%), Campylobacter jejuni (12%), norovirus (11%), Giardia lamblia (6%), Shigella spp. (6%), and Salmonella spp., Cryptosporidium spp., and Cyclospora cayetanensis (3% each). However, only for EAEC, ST-ETEC, Blastocystis and Campylobacter was the prevalence significantly higher among cases than among controls. Co-infections were common: 61% for cases and 13% for controls. The most common travel destination was Asia (54%), followed by Africa (35%) and Latin America (9%). The highest relative risk for diarrhoea was calculated for travellers to West Africa, East Africa, and South Asia. In this study, EAEC, LT-ETEC and ST-ETEC were detected most frequently in cases of travellers' diarrhoea. Although enteric infections with EAEC, ST-ETEC and Campylobacter often cause diarrhoea, the pathogenetic relevance remains unclear for most of the other enteropathogens, because of significant prevalence rates also being seen in controls without diarrhoea and the high frequency of co-infections.

Lateral ultrasound-guided paravertebral blockade: an anatomical-based description of a new technique.

BACKGROUND: Paravertebral blockade (PVB) is a regional anaesthetic technique with a large number of indications. PVB is usually performed with landmark-based techniques or methods that rely on pressure differences between the extra- and intraparavertebral space. This consecutive case series was designed to describe the ultrasound appearance of the lateral thoracic paravertebral space (PVS) and develop an ultrasound-guided method for PVB. METHODS: The PVS of 20 women undergoing breast cancer surgery was investigated with a high-frequency linear ultrasound transducer in the sitting position. After identification of the transverse process, internal intercostal membrane (IIM), and pleura at the T3 and T6 levels, the depths of the IIM and pleura, and the sagittal diameter of the PVS were determined. An out-of-plane needle guidance technique was used to perform the PVB with ropivacaine 0.75% (12 ml) at both levels. Successful blockade was determined by the ability to perform surgery under light general anaesthesia without opioids. RESULTS: Appropriate ultrasound identification of the IIM, transverse processes, and pleura was possible in all cases. Correct placement of the tip of the needle in the PVS resulted in successful PVB. No correlations of morphometric data with ultrasound measurements of the PVS were detected. CONCLUSIONS: After ultrasound identification of the boundaries of the lateral PVS, an out-of-plane needle guidance technique facilitated successful PVB. There were no clinically relevant correlations between morphometric data and ultrasound measurements.

Evaluation of stroke volume variation obtained by arterial pulse contour analysis to predict fluid responsiveness intraoperatively.

BACKGROUND: Fluid management guided by oesophageal Doppler monitor has been reported to improve perioperative outcome. Stroke volume variation (SVV) is considered a reliable clinical predictor of fluid responsiveness. Consequently, the aim of the present trial was to evaluate the accuracy of SVV determined by arterial pulse contour (APCO) analysis, using the FloTrac/Vigileo system, to predict fluid responsiveness as measured by the oesophageal Doppler. METHODS: Patients undergoing major abdominal surgery received intraoperative fluid management guided by oesophageal Doppler monitoring. Fluid boluses of 250 ml each were administered in case of a decrease in corrected flow time (FTc) to <350 ms. Patients were connected to a monitoring device, obtaining SVV by APCO. Haemodynamic variables were recorded before and after fluid bolus application. Fluid responsiveness was defined as an increase in stroke volume index >10%. The ability of SVV to predict fluid responsiveness was assessed by calculation of the area under the receiver operating characteristic (ROC) curve. RESULTS: Twenty patients received 67 fluid boluses. Fifty-two of the 67 fluid boluses administered resulted in fluid responsiveness. SVV achieved an area under the ROC curve of 0.512 [confidence interval (CI) 0.32-0.70]. A cut-off point for fluid responsiveness was found for SVV > or =8.5% (sensitivity: 77%; specificity: 43%; positive predictive value: 84%; and negative predictive value: 33%). CONCLUSIONS: This prospective, interventional observer-blinded study demonstrates that SVV obtained by APCO, using the FloTrac/Vigileo system, is not a reliable predictor of fluid responsiveness in the setting of major abdominal surgery.

Effects of continuous remifentanil administration on intra-operative subcutaneous tissue oxygen tension.

Surgical stress response markedly increases sympathetic nerve activity and catecholamine concentrations. This may contribute to peripheral vasoconstriction, reduced wound perfusion and subsequent tissue hypoxia. Opioids are known to depress the hypothalamic-adrenal response to surgery in a dose-dependent manner. We tested the hypothesis that continuous remifentanil administration produces improved subcutaneous tissue oxygen tension compared to fentanyl bolus administration. Forty-six patients undergoing major abdominal surgery were randomly assigned to receive either fentanyl bolus administration or continuous remifentanil infusion. Mean subcutaneous tissue oxygen values over the entire intra-operative period were significantly higher in the remifentanil group, when compared to the fentanyl group: 8 (2) kPa vs 6.7 (1.5) kPa, % CI difference: - 2.3 kPa to - 0.3 kPa, p = 0.013. Continuous intra-operative opioid administration may blunt vasoconstriction caused by surgical stress and adrenergic responses more than an equi-effective anaesthetic regimen based on smaller-dose bolus opioid administration.

[Acute febrile disease with splenomegaly and pancytopenia. A 66-year-old Greek patient with a prosthetic mitral valve]. / Akute fieberhafte Erkrankung mit Splenomegalie und Panzytopenie. 66-jähriger griechischer Patient mit Mitralklappenprothese.

We report on a 66-year-old patient originating from Greece and living in Germany with a prosthetic mitral valve because of a combined vitium following juvenile rheumatic fever. The patient fell ill with acute fever, splenomegaly, and pancytopenia. After unsuccessful antibiotic therapy because of presumed endocarditis or sepsis with unknown focus, visceral leishmaniasis was suspected because of recent travel to Greece. Subsequently, this diagnosis was confirmed by serology. Considering thrombocytopenia and concurrent anticoagulation after prosthetic mitral valve replacement, we avoided a bone marrow biopsy usually required for definite proof of leishmania infection. Instead, infection with Leishmania infantum was diagnosed by PCR of a peripheral blood sample. After treatment with liposomal amphotericin B the patient recovered fully.

Laparoscopic surgery impairs tissue oxygen tension more than open surgery.

BACKGROUND: Wound infection remains a common and serious complication after colonic surgery. Although many colonic operations are performed laparoscopically, it remains unclear whether this has any impact on the incidence of wound infection. Subcutaneous tissue oxygenation is an excellent predictor of surgical wound infection. The impact of open and laparoscopic colonic surgery on tissue oxygenation was compared. METHODS: Fifty-two patients undergoing elective open and laparoscopic left-sided colonic resections were evaluated in a prospective observational study. Anaesthesia management was standardized and intraoperative arterial partial pressure of oxygen was kept at 150 mmHg in both groups. Oxygen tension was measured in the subcutaneous tissue of the right upper arm. RESULTS: At the start of surgery subcutaneous tissue oxygen tension (PsqO(2)) was similar in both groups (mean(s.d.) 65.8(17.2) and 63.7(23.6) mmHg for open and laparoscopic operations respectively; P = 0.714). Tissue oxygen remained stable in the open group, but dropped significantly in the laparoscopic group during the course of surgery (PsqO(2) after operation 53.4(12.9) and 45.5(11.6) mmHg, respectively; P = 0.012). CONCLUSION: Laparoscopic colonic surgery significantly decreases PsqO(2), an effect that occurs early in the course of surgery. As tissue oxygen tension is a predictor of wound infection, these results may explain why the risk of wound infection after laparoscopic surgery remains higher than expected.

Selective resection of colorectal liver metastases.

AIMS: Safety of liver surgery for colorectal cancer liver metastases after neoadjuvant chemotherapy has to be re-evaluated. PATIENTS AND METHODS: Two hundred Patients were prospectively analyzed after surgery for colorectal cancer liver metastases between 2001 and 2004 at our institution. Special emphasis was given to perioperative morbidity and mortality under modern perioperative care. RESULTS: There was no in-hospital mortality and the perioperative morbidity was 10% (20/200). Four patients had to be reoperated due to bile leak or intraabdominal abscess. The remainder either had infectious complications or pleural effusion and/or ascites requiring tapping. Variables strongly associated with decreased survival were T, N, G and UICC (International Union against cancer) classification of the primary, hepatic lesions>5 cm and elevated tumour markers. Short disease free interval and neoadjuvant chemotherapy without response predicted impaired recurrence free survival (RFS). Multivariate analysis revealed lymph node status and differentiation of the primary, presence of extrahepatic tumour and gender as factors associated with decreased survival. Administration of neoadjuvant chemotherapy was not associated with higher postoperative morbidity or prolonged hospital stay. CONCLUSIONS: Modern dissection techniques and improved perioperative care contributed to a very low rate of surgery-related morbidity (10%) and a zero percent mortality which was also observed in patients pretreated with neoadjuvant chemotherapy prior to resection. Liver resection in experienced hands has become a safe part in the potentially curative attempt of treating patients with metastatic colorectal cancer.

External quality assurance for the laboratory diagnosis of Buruli ulcer disease in Ghana.

OBJECTIVE: To assure the quality of the laboratory diagnosis of Buruli ulcer disease; microscopy and PCR were subjected to external quality assurance (EQA). METHODS: Slides were read by test laboratory staff, followed by blinded re-reading by the controller. Parallel testing of PCR specimens was carried out at the local and external reference laboratory. Slides and PCR specimens with discordant results were subjected to a second reading/testing by the controller to determine the final result. For training purposes, slides and PCR specimens with discrepant results were subsequently re-read/re-tested under supervision at the test laboratory. RESULTS: Microscopy. First reading: concordance rate 82.9%, discordance rate 17.1%, percentage false negatives 27.1% (sensitivity 72.9%), percentage false positives 10.1% (specificity 89.9%). Second reading: concordance rate 97.9%, discordance rate 2.1%, percentage false negatives 4.2% (sensitivity 95.8%), percentage false positives 0.6% (specificity 99.4%). PCR. First testing: concordance rate 87.9%, discordance rate 12.1%, percentage false negatives 8.2% (sensitivity 91.8%), percentage false positives 19.1% (specificity 80.9%). Second testing: concordance rate 96.2%, discordance rate 3.8%, percentage false negatives 4.7% (sensitivity 95.3%), percentage false-positives 2.1% (specificity 97.9%). CONCLUSIONS: EQA identified deficiencies in the laboratory performance. Corrective action consisted in on-site training and reduced the number of false-negative and false-positive microscopy and PCR results.

Impaired basal NO activity in patients with glomerular disease and the influence of oxidative stress.

Endothelial dysfunction has been found to be linked to and predictive of cardiovascular events. Whether endothelial function of the renal vasculature is impaired in patients with chronic glomerular disease and whether oxidative stress is of importance in this setting has not yet been determined. In this study, endothelial function of the renal vasculature was investigated in 25 patients with chronic glomerular disease and 50 control subjects matched for age and blood pressure. Renal plasma flow (RPF) and glomerular filtration rate were measured by constant infusion input clearance technique at baseline and following infusions of the nitric oxide synthase (NOS) inhibitor N(G)-monomethyl-L-arginine (L-NMMA, 4.25 mg/kg), the substrate of NOS L-arginine (100 mg/kg) and the antioxidant vitamin C (3 g co-infused with L-arginine 100 mg/kg). At baseline, RPF was similar in the two groups. The reduction in RPF in response to L-NMMA was less pronounced in patients with chronic glomerular disease compared to control subjects (-4.6+/-12 vs -9.8+/-9%; P=0.040), indicating reduced basal nitric oxide (NO) activity in chronic glomerular disease. Co-infusion of the antioxidant vitamin C on top of L-arginine induced a more pronounced increase in RPF in patients with chronic glomerular disease than in control subjects (21.7+/-17 vs 10.9+/-22%; P=0.036). Our findings suggest that basal NO activity of the renal vasculature is reduced in patients with chronic glomerular disease compared to age- and blood pressure-matched control subjects. This might be in part related to increased oxidative stress.

The effect of statins on angiotensin II-induced hemodynamic changes in young, mildly hypercholesterolemic men.

BACKGROUND: Angiotensin II type 1 (AT(1)) receptors are well known to mediate angiotensin II (Ang II)-induced pro-atherosclerotic effects. It has been found that hypercholesterolemia influences the expression of AT(1) receptors on vascular smooth muscle cells and that increased density of AT(1) receptors exaggerates the hemodynamic response to Ang II. We analyzed to what extent statins and AT(1) receptor antagonists diminish the vasoconstrictive response to Ang II infusion in hypercholesterolemic patients. METHODS: A total of 24 male patients with LDL cholesterol levels >130 mg/dL were enrolled in a randomized, cross-over study. After baseline evaluation, 12 patients received first cerivastatin (0.3 mg/day) and the other 12 patients initially received candesartan (8 mg/day) for 3 weeks, with subsequent cross-over of the medication for the second 3-week drug period. The vascular response was analyzed by the increase in mean arterial pressure (MAP) and total peripheral resistance (TPR) during infusion of increasing doses of Ang II at baseline and the end of each treatment period. Hemodynamic changes were also compared with those in 24 normocholesterolemic subjects without any therapy. RESULTS: At baseline, Ang II provoked a similar increase of MAP and TPR in patients and control subjects. Treatment with cerivastatin did not affect the response to Ang II compared with baseline. By contrast, treatment with candesartan attenuated significantly the response to Ang II compared with baseline and cerivastatin. CONCLUSIONS: Our hemodynamic data indicate the hypothesis that statins do not reduce the responsiveness to Ang II in resistance arteries of young, mildly hypercholesterolemic patients.

Nitrous oxide increases the incidence of bowel distension in patients undergoing elective colon resection.

BACKGROUND: Nitrous oxide rapidly inflates gas-filled spaces such as the intestines; but whether the resulting bowel distension is clinically important remains unclear. We therefore tested the hypothesis that nitrous oxide produces clinically important bowel distension. METHODS: Patients scheduled for colon resection were anesthetized with isoflurane and 35% oxygen and randomly assigned to 65% nitrous oxide (n = 175) or 65% nitrogen in air (n = 169). At the end of surgery, blinded surgeons rated the degree of bowel distension as none, mild, moderate, or severe. Patients reported pain, and nausea and vomiting (PONV) 2 h after surgery. Data are reported as means (SD). P < 0.05 was statistically significant. RESULTS: Morphometric and demographic data were similar in the groups. The duration of surgery was 3.0 (1.2) h in the nitrous oxide group and 3.4 (1.5) h in the air group (P = 0.017). Postoperative self-reported pain scores (visual analog scale, 0-100 mm) were greater in the nitrous oxide group (43 [30] mm) than in the air group (35 [31] mm, P = 0.018). Although the incidence of PONV was similar in the groups, VAS scores for nausea were significantly greater in the nitrous oxide group (P = 0.040). Moderate-to-severe bowel distension was observed in 23% of nitrous oxide patients, but in only 9% of patients in the air group (P < 0.001). The number-needed-to-harm for moderate or severe bowel distension from nitrous oxide was thus seven. CONCLUSIONS: Our results suggest that avoiding nitrous oxide administration during prolonged bowel operations will minimize bowel distension and possibly reduce postoperative pain related to it.

Intensive training of patients with hypertension is effective in modifying lifestyle risk factors.

The burden of insufficiently treated arterial hypertension is still underestimated. In addition to pharmacological therapy, patient training is a valuable therapeutic option. During 1998-1999, the Institute for Preventive Medicine conducted an intensive training programme in cooperation with regional practitioners. The goal of this programme was to educate patients about their disease and motivate them to comply with the therapy. To evaluate the effectivity of this programme, 126 patients with arterial hypertension were trained. They received eight training sessions of 90 min each. In 90 patients blood pressure measurements before and 6 months after training were available. In addition, data concerning health status and lifestyle risk factors were analysed with standardised questionnaires. There was a marked reduction in blood pressure after 6 months (152+/-6/89+/-10 vs. 145+/-12/85+/-8 mmHg, P<0.001). In parallel, mean body weight declined by 0.9 +/- 2.9 kg (P<0.001) and body mass index (BMI) by 0.33+/-1.04 kg/m2 (P<0.001). Further analysis revealed that weight loss was more marked in obese patients (P< 0.01) than in lean subjects. Similarly, the decline of blood pressure was also greater in obese patients, but did not reach statistical significance. The activity score for physical exercise increased overall from 2.1+/-0.4 to 2.8+/-3.1 h/week (P<0.01). Moreover, knowledge about hypertension increased as well (P<0.01). Of all the quality life measurements, the vitality index improved from 53+/-19 to 59+/-19 (P<0.05) according to the patients' self-estimation. In conclusion, training of hypertensive patients has a profound effect on blood pressure control. It motivates patients to change lifestyle risk factors, namely to lose weight, and increases the patients' physical activity level, thereby decreasing the patients' blood pressure. Thus, intensive training programmes are effective and should be used on a widespread basis.