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Biomedical subjects

H A Bruining

Publications and source records attributed to H A Bruining.

At least 73 records · Page 4Linked to original sources

Pulmonary hypertension and reduced cardiac output during inhibition of nitric oxide synthesis in human septic shock.

It has been suggested that inhibitors of nitric oxide synthesis are of value in the treatment of hypotension during sepsis. In this pilot study, we examined the effects of inhibition of nitric oxide synthesis by continuous infusion of N(omega)-nitro-L-arginine methyl ester (L-NAME) at 1.5 mg/kg/h in a patient with severe septic shock. L-NAME produced a rise in mean arterial blood pressure and systemic vascular resistance; catecholamine infusion could be reduced. Parallel to these findings, there was a 50% reduction in cardiac output and a 5-fold rise in pulmonary vascular resistance, which resulted in severe pulmonary hypertension after 3 h of L-NAME infusion, for which the infusion had to be stopped. Following the termination of L-NAME infusion, pulmonary artery pressure and blood pressure returned to baseline values, although pulmonary and systemic vascular resistance remained elevated for several hours. We conclude that nitric oxide appears to play a role in the cardiovascular derangements during human sepsis. Inhibition of nitric oxide synthesis with L-NAME can increase blood pressure and systemic vascular resistance. However, reduced cardiac output and pulmonary hypertension are possible side effects of continuous NO synthase inhibition. These side effects necessitate careful monitoring and may hinder the clinical application of NO synthase inhibitors.

Aged↗

Upper gastrointestinal endoscopy at four intensive care units in one hospital: frequency and indication.

OBJECTIVE: To investigate the frequency, indication and results of upper gastrointestinal endoscopy (UGIE) at four different intensive care units (ICUs) in one hospital. DESIGN: Retrospective analysis. SETTING: Rotterdam Erasmus University Hospital, The Netherlands. PARTICIPANTS: One hundred and ninety-nine male and 102 female patients; mean age, 58.3 years (range, 14-91 years). INTERVENTIONS: Four hundred and eleven UGIEs. MAIN OUTCOME MEASURES AND RESULTS: UGIE was primarily diagnostic and therapeutic in 55% and 45% of patients, respectively. Seventy-three per cent of the diagnostic UGIEs were performed for localization of a haemorrhage and 70% of the therapeutic UGIEs for placement of feeding tubes. The causes of haemorrhage were varices, duodenal ulcer and oesophagitis in 26, 22 and 14% of cases, respectively. As co-incidental findings, oesophagitis, gastritis and gastric ulcer were seen in, respectively, 18, 8 and 7% of cases. The vast majority of UGIEs (81%) were performed at the surgical and medical ICUs. At the medical ICU, upper gastrointestinal haemorrhage (UGIH) usually was the ICU admission diagnosis, and usually concerned varices (56%). At the surgical ICU, UGIH was usually not the ICU admission diagnosis but a postoperative complication, and usually concerned oesophagitis (25%) or a duodenal or gastric ulcer (25 and 13%, respectively). Of all ICU patients, surgical patients were most prone to have co-incidental abnormalities of the digestive tract at UGIE (63%). CONCLUSIONS: UGIE is a frequent diagnostic and therapeutic procedure in patients admitted to the ICU, particularly at the surgical and medical ICU. Diagnostic and therapeutic endoscopy are most frequently performed for assessment of bleeding and placement of feeding tubes, respectively. Oesophagitis is a surprisingly common finding, both as a co-incidental diagnosis as well as the cause of bleeding, especially after surgery.

Adolescent↗

Effect of L-NAME, an inhibitor of nitric oxide synthesis, on cardiopulmonary function in human septic shock.

STUDY OBJECTIVES: We tested the effects of continuous infusion of N(G)-nitro-L-arginine methyl ester (L-NAME), an inhibitor of nitric oxide (NO) synthesis, on cardiovascular performance and pulmonary gas exchange in patients with hyperdynamic septic shock. DESIGN: Prospective clinical study. SETTING: ICU of a university hospital. PATIENTS: Eleven critically ill patients with severe refractory septic shock. INTERVENTIONS: Standard hemodynamic measurements were made and blood samples taken before, during, and after 12 h of continuous infusion of 1 mg/kg/h of L-NAME. MEASUREMENTS AND RESULTS: Continuous infusion of L-NAME increased mean arterial pressure (MAP) from 65+/-3 (SEM) to 93+/-4 mm Hg and systemic vascular resistance (SVR) from 962+/-121 to 1,563+/-173 dyne x s x cm(-5)/m2. Parallel to this, cardiac index (CI) decreased from 4.8+/-0.4 to 3.9+/-0.4 L/min/m2 and myocardial stroke volume (SV) was reduced from 43+/-3 to 34+/-3 mL/m2. Left ventricular stroke work was increased in the first hour of L-NAME infusion from 31+/-3 to 43+/-4 g x m/m2 (all p<0.01 compared with baseline). Heart rate, cardiac filling pressures, and right ventricular stroke work did not change significantly (p>0.05). L-NAME increased the ratio of arterial PO2 to the fraction of inspired O2 from 167+/-23 to 212+/-27 mm Hg (p<0.05). Venous admixture (QVA/QT) was reduced from 19.4+/-2.6% to 14.2+/-2.1% (p<0.05) and oxygen extraction ratio increased from 21.1+/-2.4% to 25.3+/-2.7% (p<0.05). Oxygen delivery (DO2) was reduced following L-NAME, whereas oxygen uptake and arterial lactate and pH were unchanged. CONCLUSIONS: Prolonged inhibition of NO synthesis with L-NAME can restore MAP and SVR in patients with severe septic shock. Myocardial SV and CI decrease, probably as a result of increased afterload, since heart rate and stroke work were not reduced. L-NAME can improve pulmonary gas exchange with a concomitant reduction in QVA/QT. L-NAME did not promote anaerobe metabolism despite a reduction in DO2.

Enzyme Inhibitors↗

p55 Tumor necrosis factor receptor fusion protein in the treatment of patients with severe sepsis and septic shock. A randomized controlled multicenter trial. Ro 45-2081 Study Group.

OBJECTIVE: To evaluate the safety and efficacy of p55 tumor necrosis factor receptor fusion protein, a recombinant chimeric protein of human p55 (type I) tumor necrosis factor receptor (CD120a) extracellular domain and IgG1 sequences (referred to as p55-IgG), in the treatment of patients with severe sepsis or septic shock. DESIGN: Randomized, prospective, multicenter, double-blind, placebo-controlled clinical trial. SETTING: Forty-four community and university-affiliated hospitals in the United States and Europe. PATIENTS: There were 498 patients enrolled in this clinical trial. INTERVENTION: Patients prospectively stratified within each site into refractory shock or severe sepsis groups were randomized to receive a single infusion of p55-IgG, 0.083 mg/kg, 0.042 mg/kg, or 0.008 mg/kg, or placebo. Patients received standard aggressive medical/surgical care during the 28-day postinfusion period. OUTCOME MEASURE: Twenty-eight-day all-cause mortality. RESULTS: The distribution of variables describing demographics, organ system dysfunction or failure, infecting microorganisms, predicted mortality, plasma interleukin 6 levels, and plasma tumor necrosis factor alpha (TNF-alpha) levels were similar among patients in the p55-IgG and placebo treatment arms. A planned interim analysis was performed after 201 patients were enrolled. Because a statistically nonsignificant trend toward increased mortality was present in patients who had received 0.008 mg/kg, this treatment arm was discontinued, and the study continued with 3 arms. Among all infused patients, there was a statistically nonsignificant trend toward reduced 28-day all-cause mortality in those who received p55-IgG compared with placebo-treated patients (5% reduction, 0.042 mg/kg vs placebo; 15% reduction, 0.083 mg/kg vs placebo; P=.30). However, in patients with severe sepsis and early septic shock (n=247), therapy with p55-IgG, 0.083 mg/kg, was associated with a 36% reduction in 28-day all-cause mortality compared with placebo (P=.07): 20 (23%) of 87 patients died among those treated with p55-IgG, 0.083 mg/kg; 30 (37%) of 82 among those treated with p55-IgG, 0.042 mg/kg; and 28 (36%) of 78 in the placebo group. A prospectively planned logistic regression analysis to assess treatment effect on 28-day all-cause mortality by means of predicted mortality and serum interleukin 6 levels as continuous covariates demonstrated a significant improvement in outcome for the patients with severe sepsis treated with p55-IgG, 0.083 mg/kg, compared with placebo (P=.01). Serious adverse events, including death and the development of new organ system dysfunction, were reported in 65% of patients infused with placebo, with no increased frequency (56%) present in the 2 p55-IgG treatment arms. There were no reports of immediate hypersensitivity reactions caused by p55-IgG. CONCLUSIONS: In this dose-finding study, there was no decrease in mortality between placebo and p55-IgG in all infused patients. In the prospectively defined population of patients with severe sepsis who received p55-IgG, 0.083 mg/kg, there was a trend toward reduced mortality at day 28 that became significant when predicted mortality and plasma interleukin 6 levels were included in a logistic regression analysis.

APACHE↗

[Endoscopic retroperitoneal adrenalectomy: a surgical improvement].

OBJECTIVE: Evaluation of endoscopic retroperitoneal adrenalectomy in patients with adrenal tumours less than 6 cm in diameter. DESIGN: Retrospective analysis. SETTING: University Hospital Rotterdam-Dijkzigt, Department of General Surgery, Rotterdam, the Netherlands. METHOD: Analysis of per- and postoperative data on 19 patients subjected to endoscopic retroperitoneal adrenalectomy; 3 patients had bilateral surgery. RESULTS: Twenty adrenal tumours in 17 patients were successfully removed endoscopically. Conversion to lumbotomy was necessary in the two other cases. Median operative time was 85 min (range: 50-120). Median blood loss was 50 ml (10-400). Median postoperative hospital stay was 4 days (2-14). CONCLUSION: Endoscopic retroperitoneal adrenalectomy is associated with minimal morbidity and therefore valuable in patients with adrenal tumours smaller than 6 cm in diameter.

Adrenal Gland Neoplasms↗

Intraoperative nuclear guidance in benign hyperparathyroidism and parathyroid cancer.

The success of parathyroid surgery is determined by the identification and removal of all hyperactive parathyroid tissue. Ectopic location of parathyroid tumours and fibrosis due to previous operations can cause failure of parathyroidectomy. Parathyroid tumours accumulate and retain 2-methoxyisobutylisonitrile (MIBI) labelled with technetium-99m. This study assesses the value of intra-operative localization of parathyroid tumours using a hand-held gamma detector in patients with hyperparathyroidism and parathyroid cancer. Twenty patients undergoing their first operations for hyperparathyroidism, 15 patients undergoing reoperations for either persistent or recurrent hyperparathyroidism and two patients with parathyroid cancer were studied. Radioactivity in the neck and the mediastinum was recorded by a gamma detector after administration of 370 MBq 99m Tc-MIBI. Surgical findings and postoperative serum levels of calcium were documented. The sensitivity of the gamma detector in identifying parathyroid tumours was 90.5% in first parathyroidectomies, 88.9% in reoperations for either persistent or recurrent hyperparathyroidism and 100% in parathyroid cancer. One false-positive result was due to a thyroid nodule. Hypercalcaemia ceased in all but one patient postoperatively. It is concluded that employment of the gamma detector is to be advocated in first parathyroidectomies when a parathyroid tumour cannot be discovered, in reoperations for either persistent or recurrent hyperparathyroidism and in surgery for parathyroid cancer.

Evaluation Studies as Topic↗

Laparoscopic splenectomy and nephrectomy in a rat model. Description of a new technique.

BACKGROUND: In experimental studies on the effects of laparoscopic procedures on tumor biology, a localized tumor model is desirable. The spleen and the kidney are preferable, because these organs are amenable to tumor placement and subsequent removal. This study describes the technique of laparoscopic splenectomy and nephrectomy in the rat model. METHODS: Pneumoperitoneum was established by CO2 insufflation. Laparoscopic splenectomy involved two-handed dissection, intracorporeal ligation, and division of gastrosplenic attachments and hilar and short gastric vessels. Laparoscopic nephrectomy was done by intracorporeal ligation and division of the renal vessels and the ureter after mobilization of the kidney. RESULTS: Laparoscopic splenectomy was performed in six rats; laparoscopic nephrectomy was done in six rats. Operative time ranged from 45 to 90 min for splenectomy and from 40 to 65 min for nephrectomy. Postoperatively, two rats died from hemorrhage. Necropsy of the rats after 10 days revealed adhesion in three rats after splenectomy and in four rats after nephrectomy. Inflammatory processes were found around the silk ligatures in all rats after splenectomy; in two rats wound infections occurred at the port sites. CONCLUSIONS: Laparoscopic splenectomy and nephrectomy in the rat proved technically feasible and may provide new localized tumor models suitable to be used in further studies on the oncological effects of laparoscopic surgery.

Animals↗

(Semi-)quantitative analysis of reduced nicotinamide adenine dinucleotide fluorescence images of blood-perfused rat heart.

In vivo analysis of the metabolic state of tissue by means of reduced nicotinamide adenine dinucleotide (NADH) fluorimetry is disturbed by tissue movements and by hemodynamic and oximetric effects. These factors cause changes in the absorption of ultraviolet (UV) excitation light by the tissue. Many different methods have been used in the literature to compensate measured NADH fluorescence intensities for these effects. In this paper we show on theoretical grounds that the ratio of NADH fluorescence intensity and UV diffuse reflectance intensity provides a (semi-)quantitative measure of tissue NADH concentrations. This result is corroborated by experiments with tissue phantoms in which absorption and back-scattering properties were varied. Furthermore, we have verified the validity of this compensation method in isolated Langendorff-perfused rat heart preparations. In this preparation oximetric effects (of blood and tissue) are the major determinants of the metabolism-dependent UV diffuse reflectance change. Hemodynamic effects accompanying compensatory vasodilation are negligible. Movement artifacts were eliminated by simultaneously recording fluorescence and reflectance images, using a CCD camera with a biprism configuration. The results show that the NADH fluorescence/UV reflectance ratio can be used to monitor the mitochondrial redox state of the surface of intact blood-perfused myocardium.

Animals↗

Nitric oxide causes dysfunction of coronary autoregulation in endotoxemic rats.

OBJECTIVE: This study tested the hypothesis that overproduction of endogenous nitric oxide (NO) during endotoxemia may modulate coronary autoregulation and myocardial reactive hyperemia. METHODS: Hearts of endotoxin-pretreated rats and controls were isolated and arranged for perfusion in a Langendorff preparation. Autoregulation was studied by examining flow-pressure relations during stepwise changes in perfusion pressure. The contribution of nitric oxide was examined by perfusion with N omega-nitro-L-arginine (NNLA), an inhibitor of nitric oxide synthesis and methylene blue (MB), an inhibitor of soluble guanylate-cyclase. RESULTS: Endotoxin-treated hearts showed massive coronary vasodilatation and autoregulatory function was impaired at perfusion pressures from 20 to 60 mmHg. Both NNLA and MB reduced coronary flow, improved autoregulation and eliminated differences in coronary flow and autoregulation between the control and endotoxin-treated group. Vasoconstriction with vasopressin, a direct smooth muscle constrictor, could not eliminate differences in autoregulation between groups. Reactive hyperemia following coronary occlusion in endotoxin-treated hearts showed decreased duration, flow repayment and repayment ratio. In the presence of NNLA or MB, however, no significant differences in reactive hyperemic flow patterns were present. CONCLUSIONS: These observations suggest that massive coronary vasodilatation due to increased myocardial NO synthesis can result in autoregulatory dysfunction and altered myocardial reactive hyperemia during endotoxemia.

Animals↗

Differential prognosis of gram-negative versus gram-positive infected and sterile pancreatic necrosis: results of a randomized trial in patients with severe acute pancreatitis treated with adjuvant selective decontamination.

Results of a previous randomized multicenter trial involving 102 patients with severe acute pancreatitis treated with or without adjuvant selective decontamination (SD) were analyzed additionally with regard to the bacteriologic status of (peri)pancreatic necrosis. The incidence of gram-negative pancreatic infection was significantly reduced in patients treated with SD (P = .004). Once such an infection develops, mortality increases 15-fold (P < .001) in comparison with that for patients with sterile necrosis. Among patients in whom only gram-positive infection of pancreatic necrosis was found, there was no significant increase in mortality. These results were similar in both treatment groups. In addition, the hospital stay was significantly longer in cases of gram-negative infected necrosis. The incidence of gram-positive infected necrosis in patients treated with SD did not increase. Gram-negative pancreatic infection can be prevented with adjuvant SD, thereby reducing mortality among patients with severe acute pancreatitis.

Acute Disease↗

A silicon bidirectional flow sensor for measuring respiratory flow.

We describe a solid-state, silicon integrated, bidirectional flow sensor for respiratory applications. The sensor is a thermal vector sensor. The electronic circuitry for obtaining bidirectional sensitivity is presented together with actual application to a healthy volunteer put on mechanical ventilation. The sensor's input flow range is from -60 to +60 L/min, and its rise-time is < or = 40 ms and fall-time is < or = 60 ms. The effect of changes in gas composition as used in mechanically ventilated patients on the sensor output signal are estimated to be less than 2%. The temperature sensitivity is about -1.5% per degree Celsius.

Equipment Design↗

Impact of continuous hemofiltration on cytokines and cytokine inhibitors in oliguric patients suffering from systemic inflammatory response syndrome.

The impact of continuous hemofiltration (CHF) using a polyacrylonitrile membrane on the kinetics of tumor necrosis factor alpha (TNF alpha), interleukin-1 beta (IL-1 beta), and their inhibitors (soluble TNF receptors [sTNFrI, sTNFrII], interleukin-1 receptor antagonist [IL-1Ra]) was assessed in nine oliguric patients suffering from systemic inflammatory response syndrome. Blood and plasma flow (Qb, Qp), sieving coefficient (SC), plasma and ultrafiltrate clearances (Kp, Kuf), and plasma extraction rates (ERp) were calculated at different time points using standard formulas. No significant improvement of hemodynamics or gas exchange was noted following HF but a significant increase in serum bicarbonate occurred after 24 h (P < 0.05). TNF alpha was detected in plasma from all patients (153 +/- 2.3 pg/mL [mean +/- SEM]). None of the patients had detectable IL-1 beta levels. High levels of the TNF receptors (sTNFrI 20.338 +/- 2.431 pg/mL; sTNFrII 17.839 +/- 2.630 pg/mL) and IL-1Ra (19.775 +/- 3.943 pg/mL) were found in all patients. Upon initiation of hemofiltration (HF), the mean individual sTNFrI/TNF alpha ratio amounted to 269 +/- 84.6 and the sTNFrII/TNF alpha ratio to 249 +/- 91.8. Mean ultrafiltrate volume (Vuf) was 11.8 +/- 0.4 L/day. Appreciable sieving of IL-1Ra (SC 0.45 +/- 0.10), but not of the other cytokines, was noted (SC TNF alpha, sTNFrI, sTNFrII < 0.09). Despite minimal Kuf of TNF alpha, sTNFrI, and STNFrII (Kuf < 0.8 mL/min), appreciable Kp was noted, suggesting that membrane adsorption occurs (Kp approximately 8 mL/min). There was a nonsignificant increase of the ratios between both TNF receptors and TNF alpha across the filter (sTNFrI/TNF alpha ratio [pre] 231 +/- 37.9 versus [post] 312 +/- 75.3); sTNFrII/TNF alpha ratio [pre] 211 +/- 42.1 versus [post] 291 +/- 79.3). Appreciable Kp of IL-1Ra was noted (Kp 17.3 +/- 1.61 mL/min), which was only in part due to Kuf (4.0 +/- 0.86 mL/min). There was a significant decrease of IL-1Ra levels across the membrane, both overall ([pre] 20.223 +/- 2.282 versus [post] 16.637 +/- 2.039 pg/mL; P < 0.01) and at different time points (P < 0.01). Only for IL-1Ra was significant extraction from plasma noted (ERp 26 +/- 6.0%). Plasma levels of TNF alpha, sTNFrI, sTNFrII, and IL-1Ra were not altered by 24 h of CHF. In conclusion, both cytokines and cytokine inhibitors can be removed from the circulation, either by convective transport or by membrane adsorption. Using low-volume HF (Vuf approximately 12 L/day), no impact on cytokine plasma levels nor the patients hemodynamics or gas exchange was noted. The appreciable SC of IL-1Ra (0.45), however, suggests that HF with high(er) UF volumes (> 50 L/day) may be able to achieve reductions in plasma levels of some peptide (anti)mediators. However, whether this aspecific elimination of both mediators and antimediators may alter the clinical course in critically ill patients remains to be investigated.

Acrylic Resins↗

Single radionuclide scintigraphy with 99mtechnetium-sestamibi and ultrasonography in hyperparathyroidism.

OBJECTIVE: Assessment of 99mTechnetium-sestamibi scintigraphy and ultrasonography as methods of locating enlarged parathyroid glands before operation. DESIGN: Retrospective analysis. SETTING: University hospital, The Netherlands. SUBJECTS: 21 patients with primary hyperparathyroidism and 6 patients with persistent or recurrent hyperparathyroidism. INTERVENTIONS: Single radionuclide scintigraphy with 99mTc-sestamibi, ultrasonography of the neck, and parathyroidectomy. MAIN OUTCOME MEASURES: Operative findings, postoperative serum calcium concentrations. RESULTS: 99mTc-sestamibi scintigraphy correctly identified 17 of 21 parathyroid tumours in patients who were about to undergo their first parathyroidectomy (sensitivity = 81%) with a positive predictive value of 94% and all 6 in patients with persistent or recurrent hyperparathyroidism. Ultrasonography correctly identified 13 parathyroid tumours in 18 patients about to undergo their first parathyroidectomy (sensitivity = 72%) with a positive predictive value of 93%, but only 3 among the 6 patients with persistent or recurrent hyperparathyroidism. CONCLUSION: Single radionuclide scintigraphy with 99mTc-sestamibi seems to identify the sites of parathyroid tumours accurately in patients with persistent or recurrent hyperparathyroidism but is not recommended for patients with primary hyperparathyroidism. Combining scintigraphy with ultrasonography does not improve the accuracy.

Adult↗

Comparison of three techniques for adrenalectomy.

BACKGROUND: Conventional open adrenal surgery requires relatively large incisions and is associated with postoperative wound pain, intercostal neuralgia and pulmonary complications. Introduction of laparoscopic techniques has enabled development of minimally invasive adrenalectomy. METHODS: A case-control study of nine open, nine transperitoneal laparoscopic and 12 retroperitoneal endoscopic adrenalectomies was done in patients who were matched for Quetelet index, adrenal disorder and size of adrenal lesion; all tumours were less than 6 cm in diameter. RESULTS: Conversion to open adrenalectomy was necessary in two patients having transperitoneal laparoscopic adrenalectomy and in one having retroperitoneal endoscopic adrenalectomy. Operative time was longest in transperitoneal laparoscopic adrenalectomy (P = 0.004 and P = 0.005 versus open and retroperitoneal endoscopic adrenalectomy respectively). Blood loss was least in retroperitoneal endoscopic adrenalectomy (P = 0.01 versus both other groups). End-tidal carbon dioxide increase was greater in transperitoneal laparoscopic and retroperitoneal endoscopic than in open adrenalectomy (P = 0.014 and P = 0.01 respectively). After retroperitoneal endoscopic adrenalectomy, use of analgesia was least (P = 0.0003 versus other groups). Postoperative hospital stay was shortest after retroperitoneal endoscopic adrenalectomy (P = 0.024 and P = 0.027 versus open and transperitoneal laparoscopic procedures respectively). CONCLUSION: Retroperitoneal endoscopic adrenalectomy was optimal in patients with small adrenal tumours.

Adrenal Gland Neoplasms↗

How should multiple organ dysfunction syndrome be assessed? A review of the variations in current scoring systems.

There are many scores for evaluating multiple organ dysfunction (MODS) which differ appreciably, and this makes it difficult to compare results from different research groups. In addition the variables used to describe organ dysfunction are not always as organ-specific as they should be. In this review we have studied 20 MODS scoring systems to illustrate the variety in variables used to assess organ dysfunction.

Heart Function Tests↗