Hospital as a temple.

The present concept of hospital health care has exhausted its purpose. In a personal view as well as experience the idea "Hospital as a temple" was studied in an attempt to reconcile modern and technical with older form of health care, the latter often labelled as alternative or complementary. Both from a historical perspective as well as nowadays situation this vision is pursued.

Relation between functional dysphagia and vocal cord palsy after transhiatal oesophagectomy.

OBJECTIVE: To assess the incidence, natural course, and possible pathogenesis of dysphagia that is not caused by anastomotic stricture, after transhiatal oesophagectomy and gastric tube reconstruction. DESIGN: Prospective study. SETTING: District teaching hospital, The Netherlands. SUBJECTS: 22 patients who had transhiatal oesophagectomy and gastric tube reconstruction for cancer. MAIN OUTCOME MEASURES: Incidence of dysphagia that is not caused by anastomotic stricture one week after operation, and presence of this functional dysphagia and correlation with vocal cord palsy at 4, 8, 12, and 16 weeks postoperatively. RESULTS: The incidence of functional dysphagia was 7 out of 22 (32%); it was self-limiting in 5 out of 7 (71%) of the cases and associated with the incidence of vocal cord palsy (p = 0.0006). CONCLUSION: Functional dysphagia after transhiatal oesophagectomy occurs frequently, but is self-limiting in most patients. Injury to branches of the recurrent laryngeal nerve is a likely cause.

[Frequency of postoperative wound infections: an unsuitable parameter for comparison of hospitals]. / De frequentie van postoperatieve wondinfecties: een ongeschikte parameter om ziekenhuizen te vergelijken.

OBJECTIVE: To evaluate the reliability of registration of wound infections and their contribution to total postoperative morbidity. DESIGN: Prospective. METHOD: During the period from 1 July 1997 through 30 June 1998 of all patients treated in the department of Surgery of the Diaconessen Hospital, Utrecht, the treatment-related complications were recorded during the hospital stay as well as at the first outpatient follow-up. The clinical registration forms were checked and supplemented after discharge, during the transfer and by the hospital hygienist. The precision of registration, the implications of the registered wound infections, and the share of this complication in overall postoperative morbidity were studied. RESULTS: There were 2172 admissions (2004 patients): 996 males and 1176 females (mean age at admission 55 years). The response of registration was 100% during hospital stay and 59.5% in the outpatient department. Postoperative course was complicated in 506 patients (23% of the admissions). Of the 735 registered complications 583 (79%) were recorded during clinical stay. Airway and wound infections were the most frequently registered complications (in 4.4% and 4.3% of the admissions respectively). Of the wound infections 45% were recorded after discharge and 88% fully recovered by conservative means. Both the frequency of wound infections in relation to other postoperative complications and the severity of the registered wound infections varied with the reason of admission. CONCLUSION: The incidence of postoperative wound infections was not reliably measured as a result of low response of registration after hospital discharge. The contribution of wound infections to overall postoperative morbidity and the severity of these infections varied with the reason of admission.

Influence of peroperative lavage solutions on peritoneal defence mechanisms in vitro.

OBJECTIVE: To find out the in vitro reaction of mesothelial cells and polymorphonuclear leucocytes (PMN) to incubation with seven commonly-used lavage solutions. DESIGN: Experimental study. SETTING: Laboratories, The Netherlands. MATERIAL: Cultured human peritoneal mesothelial cells and isolated PMN. INTERVENTION: Incubation of cells with clinically used lavage solutions (sodium chloride, Hartmann's solution, povidone-iodine, Dakin's solution, taurolidine, chlorhexidine, and hydrogen peroxide). MAIN OUTCOME MEASURES: Activation of monolayers of mesothelial cells and PMN measured by release of oxygen free radicals (chemiluminescence) and interleukin (IL)-8 concentrations and toxic effects measured by morphology, release of lactate dehydrogenase, failure of the restriction of the passage of inulin, and incorporation of propidium iodide. RESULTS: All solutions activated and killed mesothelial cells and PMN to some extent; the more concentrated the solution the greater the effect on these cells. CONCLUSION: Lavage solutions both poison and stimulate mesothelial cells and neutrophils, and some solutions are more potent than others.

Perioperative lavage promotes intraperitoneal adhesion in the rat.

This study was designed to study the effect of peritoneal lavage solutions on postsurgical adhesion formation in rats undergoing laparotomy and standardized ischemic injury to the lateral peritoneum with sutures. This reproducible model enabled semiquantitative scoring of adhesion formation. Adhesions were induced in 33 adult female Wistar rats. The solutions RPMI medium, NaCl (0.9%), Viaspan(R) and both povidone-iodine (1%) and chlorhexidine (0.02%) in dilution were evaluated. In the control group that was operated upon (without peritoneal lavage), a mean adhesion percentage of 22.5% was scored. All solutions used for abdominal lavage in this rat model induced significantly (p = 0. 0001) more adhesions (40.6-70.8%). Not all solutions induced an equal effect. The results found in the present in vivo study correlate with observations in previous in vitro experiments i.e. exposure of peritoneal areas to lavage solutions enhances peritoneal activation and thus promotes intra-abdominal adhesion formation.

Chlamydia trachomatis infection of human mesothelial cells alters proinflammatory, procoagulant, and fibrinolytic responses.

In this study we demonstrate the capability of Chlamydia trachomatis to infect cultured human mesothelial cell (MC) monolayers and to induce the production of the proinflammatory cytokines interleukin 1beta (IL-1beta) and IL-8. Seventy-two hours after initial infection, both the procoagulant activity of MC and the activity of the fibrinolytic inhibitor (plasminogen activator inhibitor 1) in the supernatants were enhanced. These findings support the hypothesis that provoked proinflammatory responses contribute to the development of complications after chlamydial infection.

[Clostridium difficile outbreak in surgical wards]. / Een Clostridium difficile-uitbraak op chirurgische afdelingen.

OBJECTIVE: To evaluate the clinical consequences of a hospital outbreak of Clostridium difficile infections in the Netherlands. DESIGN: Descriptive. SETTING: Diakonessen Hospital Utrecht, the Netherlands. METHODS: In the period from 1 August 1995 to 1 September 1996 C. difficile infections were recorded (gastrointestinal symptoms after use of antibiotics and findings at C. difficile toxin assay in faeces, or sigmoidoscopy). The monthly incidence of infections increased to 5 patients in December 1995; at that time strict hygienic measures were implemented and perioperative antimicrobial prophylaxis was adjusted. Data on the clinical course were collected retrospectively from the records of the patients involved. RESULTS: In 20 patients, admitted for various reasons to the surgical wards, hospital stay was complicated by a C. difficile infection. The mean age was 70 years. Eleven patients presented with diarrhoea, eight patients had nausea and vomiting as well. Diagnosis was confirmed by C. difficile toxin determination in most patients (n = 15). Despite antibiotic treatment in 19 patients, recurrences were seen in five patients (25%) and five patients died (25%). The monthly incidence declined to 0-1 per month. CONCLUSION: C. difficile infections in surgical patients carry a significant morbidity and mortality. Preventive hygienic measures are important to control spread of the infection.

Peritoneal interleukin-8 in acute appendicitis.

Interleukin-8 (IL-8) is a chemoattractant that is highly selective for neutrophils. This study was designed to investigate the presence of IL-8 in peritoneal fluid of patients with acute appendicitis. The clinical circumstances underlying the secretion of IL-8 by mesothelium and its mechanism of activation have not been defined. In an in vitro model for bacterial peritonitis the role of bacteria in activating human mesothelial cells to secrete IL-8 was studied. Cultured human mesothelium was incubated with various species of pathogenic bacteria, isolated from peritoneal exudate fluids of patients with appendicitis. The amount of IL-8 secreted by the cultured mesothelial cells was determined in an IL-8 ELISA, as IL-8 was present in the original peritoneal fluid of these patients. Peritoneal fluids from patients with a perforated appendix were found to contain a significantly higher concentration of IL-8 compared to peritoneal fluids from patients with nonperforating appendicitis (121.6 (57.8) ng/ml versus 0.2 (0.07) ng/ml, respectively; mean (SEM), P < or = 0.01). Species of Bacteroïdes and Fusobacterium necrophorum induced IL-8 secretion from cultured mesothelial monolayers to levels comparable to those found in peritoneal fluids in vivo. Heat-killed bacteria and bacterial supernatant were also able to stimulate mesothelium to secrete IL-8. The results suggest that in the early phase of bacterial peritonitis the influx of PMN is regulated by bacteria-induced IL-8 secretion by the mesothelium lining the peritoneal cavity.

Neutrophil adherence to and migration across monolayers of human peritoneal mesothelial cells. The role of mesothelium in the influx of neutrophils during peritonitis.

Increased adherence to and subsequent migration of leukocytes across cultured human peritoneal mesothelial cell monolayers takes place after pretreatment of the mesothelial cells with interleukin-1beta. The contribution of the leukocyte beta2 integrins (CD11/CD18) and the mesothelial adhesion protein intercellular adhesion molecule-1 (ICAM-1) and the role of the cytokines interleukin-8, platelet-activating factor (PAF), and transforming growth factor-beta (TGF-beta) were studied in a three-dimensional model system for neutrophil-mesothelial monolayer interaction. Polymorphonuclear leukocytes (PMNs) showed minimal adherence to and migration across unactivated mesothelial monolayers, despite an extensive amount of ICAM-1 on the mesothelial membrane. Pretreatment of the monolayers with rIL-1beta induced enhanced PMN adherence to the mesothelial monolayer together with a further increase in ICAM-1 expression on the mesothelial membrane. PMN migration was observed across rIL-1beta-activated mesothelial cell (MC) monolayers whenever cytokines secreted by the MCs were present during migration. Monoclonal antibody (mAb) R6.5 against ICAM-1 and mAb CLB-LFA1/1 against CD18 both reduced the migration of PMNs across mesothelial monolayers with a predominant inhibitory effect of CLB-LFA1/1, indicating a significant role of the beta(2) integrins of PMNs in this process. Interleukin-8 was the major cytokine synthesized by the MCs to stimulate the migration of PMNs; both PAF and TGF-beta had a more modest role in our system. Adherence of PMNs to MC monolayers was not dependent on these latter cytokines. Neuraminidase did not have any effect, indicating that selectins were not involved in the adherence process. rIL-1beta-pretreated MCs induced a rapid increase in intracellular Ca2+ in PMNs; actinomycin D blocked this effect and was also able to prevent adhesion of neutrophils to activated MC monolayers. Neutrophil migration across activated cultured MCs is thus a cascade of events in which the MCs are actively involved.

Limited influence of the mesothelium on the influx of monocytes into the peritoneal cavity.

We have investigated the role of human mesothelium in an in vitro model of peritonitis on the monocyte adherence to and migration across monolayers of peritoneal mesothelial cells. Monocytes adhere avidly to non-activated mesothelial cell monolayers; however, migration in this situation was minimal. Prestimulation of the monolayers with II-1 beta did not alter these results. Anti-CD18 and anti-VLA-4 mAbs used in combination had an additive inhibitory effect on monocytes adherence to resting or IL-1 beta-pretreated mesothelial cells. MCP-1 and TGF-beta are secreted by mesothelial cells. Both have a modest role in mesothelium-induced monocyte chemotaxis: mAbs against these cytokines had an additive inhibitory effect on the chemotaxis induced by supernatant from 24-h prestimulated mesothelial cells. Our results indicate that the mesothelium itself has a limited role in the influx of monocytes into the peritoneal cavity during the onset of peritonitis.

[Acute appendicitis: a serious disease in the elderly]. / Appendicitis acuta: een ernstige aandoening bij oudere patiënten.

OBJECTIVE: To determine the differences between acute appendicitis in younger and in older patients. DESIGN: Retrospective study. SETTING: Utrecht University Hospital and Diakonessen Hospital Utrecht, the Netherlands. METHOD: All patients operated in the period 1989-1991 because acute appendicitis was suspected were included in this study. The patients were divided into two groups, one fifty years of age or older, one younger. Duration of symptoms, histology, closure or non-closure of the incision, complications and hospital stay were examined. RESULTS: About ten percent of the patients were over fifty years of age (35/366). The duration of symptoms in this group was significantly longer. Appendix sana occurred less often in the elderly, perforated appendix more often. The wound was left open more often in the elderly, but they did not have more complications. Their hospital stay, however, was significantly longer. CONCLUSION: The longer duration of symptoms and the higher rate of perforation justify a higher place of acute appendicitis in the differential diagnosis of acute abdomen in the elderly. The more serious course of the disease appears from the longer hospital stay.

Polarized secretion of interleukin-8 by human mesothelial cells: a role in neutrophil migration.

We investigated the role of human mesothelium in an in vitro model of peritonitis with emphasis on the secretion of the neutrophil chemoattractant interleukin-8 (IL-8) and the migration of polymorphonuclear leucocytes (PMN) across monolayers of peritoneal mesothelial cells. PMN showed minimal migration across non-activated mesothelial monolayers (< 2%). However, migration was induced after mesothelial cell activation by IL-1 beta (24%) and this induced migration was significantly blocked by antibodies against IL-8 (63% inhibition; P < or = 0.01). IL-1 beta-activated mesothelial monolayers were shown to secrete IL-8 in a polarized way, which was preferentially oriented towards the apical side of the monolayer. Our results indicate that the influx of PMN into the peritoneal cavity is, at least in part, controlled by the mesothelial cell layer of the peritoneal membrane.

The value of ultrasound in the evaluation of palpable breast tumours: a prospective study of 400 cases.

In a prospective study, 400 palpable breast tumours were examined to establish the value of ultrasound. 174 Carcinomas were diagnosed by histological examination. The sensitivity of ultrasound examination in detecting malignancy was 96.6%, the specificity 94.2%. Ultrasound examination of a palpable breast tumour is reliable in differentiating between benign and malignant tumours.

CA 125 secretion by peritoneal mesothelial cells.

AIMS: To investigate the secretion of the tumour marker CA 125 by cultured human mesothelial cells; to determine if secretion of CA 125 could be observed by activating the mesothelial monolayers with different cytokines. METHODS: Mesothelial cells were isolated from human omentum and cultured to confluent monolayers on perforated polycarbonate membranes (pore size 0.4 micron). The mesothelial monolayers were activated and the apical and basolateral secretion of CA 125 compared. To investigate the influence of cytokines, mesothelial cells were cultured and activated with recombinant interleukin-1 beta (rIL-1 beta), tumour necrosis factor-alpha (TNF-alpha) or lipopolysaccharide from Escherichia coli. The secretion of CA 125 was tested using a microparticle enzyme immunoassay. RESULTS: Mesothelial monolayers secreted CA 125 in a polarised manner with preference for the apical side. Apical polarisation occurred irrespective of the side of the inducing stimulus (p < or = 0.05). Non-activated cultured mesothelial monolayers secreted significant quantities of CA 125, indicating constitutive production of this protein. However, CA 125 production was significantly enhanced if mesothelial cells were incubated with rIL-1 beta (p < or = 0.05), TNF-alpha (p < or = 0.05), and E coli LPS (p < or = 0.01). CONCLUSIONS: Human mesothelial monolayers secrete CA 125 preferentially from their apical surfaces. The secretion of CA 125 can be enhanced by the inflammatory cytokines Il-1 beta, TNF-alpha, and by E coli LPS.

[Perforation rate and diagnostic accuracy in acute appendicitis]. / Perforatie-ratio en diagnostische accuratesse bij appendicitis acuta.

OBJECTIVE: To determine perforation rate and diagnostic accuracy in acute appendicitis. DESIGN: Retrospective study. SETTING: Deaconesses' hospital Utrecht. METHOD: Data on 235 acute appendectomies performed between 1989 and 1991 were collected: duration of symptoms, doctor or patient delay, pathology, septic complications, and objective data such as body temperature, leukocyte count and sedimentation rate. RESULTS: Symptoms lasted on average 1.68 days and in 12.3% of the cases there was doctor delay, while an accurate diagnosis was made in 80%. The perforation rate was 18.3% and tended to be higher in young children and adults over 50. Septic complications ensued in 25% of the perforations. Perforation was associated with symptoms existing for longer than 48 hours. The number of negative appendectomies was 5 times higher in women than in men. The objective data were of limited diagnostic value. According to literature of the last 15 years, the mean value for perforation rate is 17% and for diagnostic accuracy 79%. CONCLUSION: In children and elderly appendicectomy should be considered earlier. For sexually mature women additional laparoscopy can be of help in decreasing the number of negative appendectomies. It is recommended not to observe patients too long.

Mesothelial cell adherence to vascular prostheses and their subsequent growth in vitro.

Cell seeding may decrease the thrombogenicity of implanted vascular grafts, but its application is hampered by the limited availability of autologous endothelial cells. Human peritoneal mesothelial cells have blood flow supporting qualities and are readily available. This study investigated the adherence of mesothelial cells to vascular prostheses and their subsequent growth in vitro. Circular pieces of various vascular prosthetic materials were seeded with 51Chromium-labeled mesothelial and endothelial cells and left for either 5, 15, 30, 60, and 120 minutes. The unattached cells were removed and the degree of cell attachment was measured. The number of mesothelial cells to Dacron increased during the first 60 min up to 35.2% of the seeded inoculum whereafter a plateau was reached. Scanning electron microscopy showed spread mesothelial cells adherent to the Dacron fibers. A significant increase in adherence was observed after preincubation of Dacron with 10 micrograms/mL fibronectin, but no improvement was found after preincubation with human serum albumin or gelatin. Mesothelial cells adhered better to Gel-coated than to Gel-sealed or plain Dacron. The adherence of mesothelial cells to ePTFE (Teflon) was significantly poorer. No significant differences in adherence were found between mesothelial and endothelial cells. Mesothelial cell growth on Dacron resulted in a modest increase in the number of viable cells during 27 days, which implies biocompatibility of Dacron and mesothelial cells in vitro.

Comparison of the cardiovascular effects of intravenous, epidural and intrathecal sufentanil analgesia as a supplement to general anaesthesia for abdominal aortic aneurysm surgery.

Sixty ASA Grade II-III patients, without clinical symptoms of ventricular dysfunction and scheduled for elective bifemoral grafting for abdominal aneurysms, were allocated randomly to three equal groups to receive 150 micrograms sufentanil intravenously, epidurally or intrathecally. All patients received midazolam, vecuronium and nitrous oxide. Except for right ventricular stroke work index and pulmonary vascular resistance, all haemodynamic measurements decreased after sufentanil injection, but to the greatest extent after intravenous injection. Response to abdominal incision reversed the haemodynamic changes, although this was not accompanied by an increase in heart rate and coronary perfusion pressure after intrathecal injection. Four patients given intravenous, and four patients given epidural sufentanil required additional sufentanil after abdominal incision. Despite the changes in systemic vascular resistance and the concordant alterations in cardiac index after aortic cross-clamping and revascularization, intrathecal sufentanil provided more stability in heart rate than intravenous or epidural sufentanil. In conclusion, intrathecal sufentanil produced the most stable heart rate. Two patients in the intrathecal group developed spinal headaches post-operatively.

A cobblestone cell isolated from the human omentum: the mesothelial cell; isolation, identification, and growth characteristics.

Normal human mesothelial cells (NHMC) were isolated from pieces of human omentum. The cell yield was approximately one million cells per square centimeter omentum. The mesothelial cells were identified by their positive staining with monoclonal antibodies against cytokeratins 6 and 18. Transmission electronmicroscopy of cultured NHMC revealed many microvilli on the apical surface and many mitochondria and pinocytotic vesicles in the cytoplasm, indicating active transmembrane transport. Growth of NHMC was directly related to the concentration of human serum or of fetal bovine serum in the growth medium. Addition of epidermal growth factor with or without hydrocortisone resulted in a significant increase of NHMC growth; when endothelial cell growth factor, insulin, or hydrocortisone were added no such increase was observed. Seeding NHMC at densities less than 3000/cm2 did not result in monolayer formation. The mesothelial cells were serially passed in growth medium M199 with added 10% fetal bovine serum up to 7 passages. However, after Passage 4 the cells changed into giant cells with an irregular pattern, and a lack of intracellular cytokeratin expression was observed for most of the cells.

Thrombogenicity and procoagulant activity of human mesothelial cells.

Cell seeding may decrease the thrombogenicity of implanted vascular grafts, but its application is hampered by the limited availability of autologous endothelial cells. We studied the interaction of alternate cells, human peritoneal mesothelial cells, with whole blood in a flow chamber. When citrated blood was perfused over mesothelial cells, platelet adhesion was seen on the intercellular matrix but not on the cells themselves. Perfusions with blood anticoagulated with low-molecular-weight heparin resulted in fibrin formation at the surface of mesothelial cells but not at the surface of human umbilical venous endothelial cells. At shear rates of 200 sec-1 fibrin deposition on the mesothelial cell surface increased during the first 5 minutes to 5.7 +/- 1.06 micrograms fibrin per square centimeter, whereafter these values stabilized. The procoagulant activity of cultured mesothelial cells was higher than that of peritoneal membrane studied ex vivo. However, cultured mesothelial cells incubated with polyclonal antibodies against tissue factor showed a significant decrease in procoagulant activity. We conclude that human peritoneal mesothelial cells may be used for cell seeding procedures, provided that their tissue factor expression can be controlled.