Occupational asbestos exposure: how to deal with suspected mesothelioma cases--the Dutch approach.

INTRODUCTION: Patients with asbestos-related diseases, such as malignant mesothelioma (MM), are not uniformly treated in Europe when they apply for compensation. In The Netherlands, the Institute of Asbestos Victims (IAV) acts on behalf of patients with a malignant mesothelioma. In the majority of cases, the diagnosis is clear but in some, uncertainty remains. In these cases a specialist opinion of the Mesothelioma Group of the Dutch Thoracic Society (DTS) is required. The process of data handling and final outcome for these patients is discussed and compared with the situation in other European countries. MATERIALS AND METHODS: Dutch patients with a possible malignant mesothelioma and occupational exposure to asbestos presented their cases to the IAV. In 10% of the cases, pathological confirmation of a malignant mesothelioma could not be obtained. These cases were presented to the Mesothelioma Group to obtain a clinical diagnosis based on clinical reports, occupational history, X-ray examination and other factors. Each case was reviewed by three independent pulmonologists experienced in MM. The majority view was binding for acceptance or rejection of the diagnosis. RESULTS: In the period January 2000 until May 2005, the IAV received 1747 cases for compensation. In 161 cases no definitive diagnosis could be made on pathology and were presented to the Mesothelioma Group. Of these cases, 117 (73%) were considered to be compatible with the clinical diagnosis malignant pleural mesothelioma. Forty-four cases (27%) were rejected. In 75% of the cases (112 of 150), the conclusion of the three independent specialists was unanimous; in 11 cases one specialist refrained from a diagnosis. The median time from request to submission of the report was 34 days (range 1-185 days). CONCLUSIONS: Compared with other European countries, this approach, as determined by the IAV and Mesothelioma Group of the DTS, is an effective and rapid way to investigate claims of patients with a possible occupationally related malignant mesothelioma.

Angiographic assessment of coronary stenoses: a review of the techniques.

This article reviews the fundamental techniques to quantify the physiological severity of (coronary) stenoses. Although a wide survey of different techniques and applications is provided, the focus of this review is on: 1) the assessment of the immediate effect of the stenoses on blood flow (i.e., the hemodynamic severity), and not on the assessment of the pathology of the vessel itself; 2) the flow reserve methods to defining the physiological severity of stenoses; and 3) the determination of blood flow and tissue perfusion by X-ray angiography (a short survey of other imaging modalities is provided as well). Although the practical implementation of the techniques is illustrated by applying them to coronary stenoses, most of the issues involved are of interest in other application areas (using other imaging modalities) as well. This review consists of four parts. The first part deals with the definition of stenoses severity; the second part with tracer kinetic theory necessary to determine flows by imaging; the third part focusses on (cardiac) imaging modalities, with an emphasis on X-ray angiography; and the last part illustrates the practical implementation of the techniques in cardiology.

Digital densitometric determination of relative coronary flow distributions.

In clinical cardiology, stenosis in a coronary artery is measured on the basis of visual assessment. The reading of coronary arteriograms leads, however, to large inter- and intra-observer variability. Image analysis and computer assistance result in a more consistent assessment, but this approach is mainly based upon static geometric parameters, such as diameter reduction of a segment of the stenosed artery. A more functional, physiological measurement is thus desirable. This can be realised by measuring the difference between the normal coronary blood flow and the increased flow under hyperaemic conditions, yielding the so-called coronary flow reserve (CFR). In clinical practice, however, this method is difficult and time-consuming. A less demanding approach is reported, in which relative flow distributions are determined densitometrically from digital angiograms acquired under basal and hyperaemic conditions. The proposition is that, if the relative flow distribution in hyperaemic state differs from that during rest, the functional severity of a stenosis downstream from the bifurcation can be indicated. The new approach is validated by comparing the results of a theoretical model for steady flow with a flow phantom experiment for steady and pulsatile flow. The obtained flow ratios correlate very well, both in steady and pulsatile flow, with correlation coefficients exceeding 0.95.

Ursodeoxycholic acid therapy for primary sclerosing cholangitis: results of a 2-year randomized controlled trial to evaluate single versus multiple daily doses.

BACKGROUND/AIMS: Ursodeoxycholic acid has been reported to be of potential benefit for primary sclerosing cholangitis but little is known about the long-term biochemical, histological and radiological efficacy or the optimum frequency of ursodeoxycholic acid administration. METHODS: A 2-year multicentre randomised controlled trial was initiated to assess the effects of ursodeoxycholic acid (10 mg kg(-1).d(-1), given in either single or multiple daily doses, on symptoms, serum liver tests, cholangiographic and histological findings and the occurrence of treatment failure. Liver biopsies were taken and endoscopic retrograde cholangiography was performed at entry and after 2 years; follow-up examinations were at 3-month intervals. Treatment failure was defined as death, liver transplantation, 4-fold increase in serum bilirubin, variceal bleeding, de novo ascites or cholangitis. Actuarial survival was compared with predicted survival using the revised Mayo natural history model for primary sclerosing cholangitis. RESULTS: Forty-eight patients were enrolled. In one case, ursodeoxycholic acid had to be discontinued because of gastro-intestinal complaints. No other side-effects were observed. After 2 years of follow-up, treatment was not associated with a beneficial effect on either symptoms or liver histology. Serum liver tests (alkaline phosphatase, y-glutamyl transferase, aspartate aminotransferase) improved significantly in both groups, while serum bilirubin (which was near normal at entry) and IgG remained stable. No major changes in radiographic bile duct appearance seemed to be present. After 2 years, actuarial survival was 91% (95 CI 83%-99%), which is comparable to the predicted 97% survival rate. Treatment failure occurred in 15% of cases. No significant differences in any of the study endpoints (symptoms, serum liver tests, cholangiographic findings, histology, disease progression) were found between the two groups. CONCLUSIONS: Ursodeoxycholic acid is well tolerated in primary sclerosing cholangitis. Significant effects on biochemical parameters were found and symptoms, bilirubin and histology did not deteriorate. No advantage of a multiple daily dose over a single dose was observed.

Omeprazole as a diagnostic tool in gastroesophageal reflux disease.

OBJECTIVE: To determine the diagnostic value of empirical treatment with omeprazole in the diagnosis of gastroesophageal reflux disease (GERD). METHODS: Patients with symptoms suggestive of GERD underwent upper gastrointestinal endoscopy and 24-h esophageal pH monitoring. Patients with reflux esophagitis grade 0 or 1 were included in the study and were randomized to double-blind treatment with either 40 mg omeprazole or placebo o.m. The effect of treatment was evaluated after 1 and 2 wk with a symptom questionnaire with a four-grade Likert scale, and symptomatic response outcome was compared with the results of 24-h pH-metry. RESULTS: Ninety-eight patients were included; however, 13 were excluded from the final analysis because of protocol violation. Of the remaining 85 patients, 54 had no signs of esophagitis at endoscopy, and 31 had esophagitis grade 1. The pH registration showed pathological gastroesophageal reflux in 47 patients (55%). Forty-one patients were randomized to treatment with omeprazole and 44 to placebo. There was a significant correlation between the pH registration result and response to omeprazole (p = 0.04, chi2), but not to placebo (p = 0.16). With pH-metry as the gold standard, the omeprazole test had positive and negative predictive values of 68% and 63%, respectively, for the diagnosis of GERD. When the omeprazole test was used as the gold standard, the positive and negative predictive values of pH monitoring were 68 % and 63 %, respectively. Similar sensitivity was found when the pH-metry was compared with presence of esophagitis. CONCLUSION: Determination of the symptomatic response to 40 mg of omeprazole for 14 days is a simple and inexpensive tool for the diagnosis of GERD, with a sensitivity and specificity comparable to 24-h pH monitoring.

Etoposide in malignant pleural mesothelioma: two phase II trials of the EORTC Lung Cancer Cooperative Group.

Intravenous and oral etoposide (VP 16-213) were tested in two sequential phase II trials in chemotherapy-naive patients with malignant pleural mesothelioma. In the first trial, etoposide was given intravenously (i.v.) at a dose of 150 mg/m2 on days 1, 3 and 5 every 3 weeks. The second trial investigated a daily oral dose of 100 mg for 21 days followed by a 2-week treatment-free period, and then recycling. In both trials, the treatment was given until disease progression, intolerable toxicity or patient refusal. In the i.v. trial, 49 patients were included, 2 patients were ineligible. The oral trial recruited 45 patients, 4 patients were not eligible. In both trials, the main side-effects were moderate leucopenia, alopecia, nausea and vomiting. Two partial responses (4%) and three partial responses (7%) were reported in the i.v. and oral trials, respectively. The median survival was 29 weeks and 38 weeks in the i.v. and oral trials, respectively. In conclusion, further investigation of etoposide in malignant mesothelioma is not recommended.

[Boutonneuse fever caught in The Netherlands: a traveling dog as source of Rickettsia conorii]. / Fièvre boutonneuse opgelopen in Nederland: een reizende hond als bron van Rickettsia conorii.

In three patients, women aged 27, 26, and 36 years respectively, boutonneuse fever was suspected, although they had not recently visited an endemic area. Serological investigation confirmed the diagnosis. Treatment with doxycycline was effective. Circumstantial evidence strongly suggested that the infection with Rickettsia conorii had been transmitted through dogs that had stayed in Mediterranean countries and had carried ticks to the Netherlands.

Combination therapy of sucralfate and ranitidine, compared with sucralfate monotherapy, in patients with peptic reflux esophagitis.

A double-blind, multicenter, randomized study was performed in 75 patients with endoscopically documented reflux esophagitis. Patients were randomly given 1 g sucralfate four times a day or the combination of sucralfate three times a day and 300 mg ranitidine after dinnertime. Endoscopy was performed at the beginning of the study, after 8 weeks, and, if, the reflux esophagitis was not healed, after 16 weeks. Four patients had to be excluded from evaluation; 71 patients could therefore be evaluated. Both groups showed symptomatic improvement to similar extents. Endoscopy showed symptomatic improvement in 67% of the patients treated with sucralfate and in 74% of the combination therapy group. Complete healing or Savary-Miller stage 1 was seen in 26.5% and in 31.4%, respectively. We conclude that sucralfate monotherapy in patients with milder forms of reflux esophagitis is comparable with a combination of sucralfate during the day and ranitidine after dinnertime. This study does not support the commonly used combination of sucralfate and H2-receptor antagonists in reflux esophagitis.

Combination therapy of sucralfate and cimetidine, compared with sucralfate monotherapy, in patients with peptic reflux esophagitis.

A double-blind multicenter, randomized study was performed in 70 patients with endoscopically documented reflex esophagitis. Patients were randomly given 1 g sucralfate four times a day or the combination of sucralfate 1 g three times a day and 400 mg cimetidine at night. After healing of the esophagitis, patients were randomly given either sucralfate maintenance 2 g daily or placebo for a period of six months. Endoscopy was performed at the beginning of the study, after eight weeks, and, in cases with no healing, after 16 weeks of therapy. Sixty-three of the 70 patients who initially entered the study could be evaluated after eight weeks. Both groups showed good symptomatic improvement, and no side effects necessitated withdrawal of subjects. Endoscopy showed complete healing in 19.4 percent of the sucralfate group and in 21.9 percent of the combination sucralfate and cimetidine group. Endoscopic improvement was found in 50 percent of the sucralfate group and in 50 percent of the combination group. After 16 weeks, 56 patients could be evaluated. In the sucralfate group, improvement was seen in 78.6 percent, and healing in 31 percent. For the combination group these values were 59.3 percent and 37 percent (not significant). Twenty-six patients entered the maintenance phase of the study; 15 received sucralfate and 11 received placebo. Evaluation of 20 patients after six months showed endoscopic and/or symptomatic relapse of esophagitis in three of 12 patients receiving sucralfate and in two of the eight patients receiving placebo. It is concluded that sucralfate monotherapy in patients with reflux-esophagitis is effective and comparable with a combination of sucralfate during the day and cimetidine at night. No difference was found between sucralfate and placebo in terms of the relapse rate of esophagitis during long-term treatment.

Double-blind comparison of slow-release 5-aminosalicylate and sulfasalazine in remission maintenance in ulcerative colitis.

The results of a clinical trial comparing slow-release 5-aminosalicylic acid tablets (Pentasa) and enteric-coated sulfasalazine tablets (Salazopyrin) with regard to the efficacy of maintaining ulcerative colitis patients in remission for 12 mo and with regard to safety of treatment are reported. Seventy-five patients with ulcerative colitis in remission for between 1 mo and 5 yr were included for analysis. Forty-nine men and 26 women, aged between 18 and 79 yr, received either Pentasa t.i.d. (1500 mg) plus Salazopyrin placebo or Salazopyrin t.i.d. (3 g) plus Pentasa placebo daily. Patients were assessed clinically, endoscopically, and histologically before and 3, 6, 9, and 12 mo after the start of treatment. Life-table analysis showed ongoing remission after 6 and 12 mo for Pentasa to be 63% (26 of 41) and 54% (22 of 41) and for Salazopyrin 72% (22 of 31) and 46% (14 of 31). These differences were not statistically significant. Three patients treated with Salazopyrin were withdrawn because of severe erythrodermia, anxiety and backache, and pregnancy, respectively. One patient on Salazopyrin experienced transient rises in serum urea, creatinine, and lactic dehydrogenase and another patient in this group reported slight reversible loss of hair. In the Pentasa group no side effects were recorded. We conclude that Pentasa is a well-tolerated drug, equally effective as Salazopyrin in maintenance of remission of ulcerative colitis.

99Tcm-labelled HSA-nanocolloid versus 111In oxine-labelled granulocytes in detecting skeletal septic process.

Fifty-seven investigations of the skeletal system were performed on 54 patients, using a 99Tcm-labelled nanometer-sized HSA colloid in a crossover comparison with 111In oxine-labelled granulocytes for the detection of sites of infection. The findings were in agreement in 55 out of 57 investigations (96.5%). Based on 44 studies in which a final clinical diagnosis was obtained, both methods were found to display the same specificity (93%), whilst the sensitivity of 99Tcm nanocolloid scintigraphy (87%) was slightly higher than that obtained with 111In leucocyte scintigraphy (81%). In our opinion, 99Tcm nanocolloid is easier to use and the total duration of the investigation is considerably shorter. The use of 99Tcm is scintigraphically more advantageous and, with the dosage required, the absorbed radiation dose to the red bone marrow is three times lower than with 111In granulocytes. For the detection and therapy monitoring of osteomyelitis, as well as for the investigation of arthroplasties suspected of infective loosening, we consider scintigraphy with 99Tcm nanocolloid to be equivalent to leucocyte scintigraphy. Identical findings were obtained with both tracers in suspected spondylodiscitis.

Scintigraphy of inflammation with nanometer-sized colloidal tracers.

The biodistribution of a nanometer-sized colloid was tested in three groups of rats, one with a turpentine-induced abscess and one with a histamine-induced oedema in the musculature of a hind leg. The third group served as a control. A 99Tcm-labelled colloid with a mean particle size of 30 nm was administered to each group intravenously. The biodistribution of the tracer, studied 1 h after injection, demonstrated that the colloid accumulated to a very limited extent in oedematous tissue, whereas the uptake in inflamed muscle was high. The colloid was subsequently administered to patients with arthritis, osteitis and osteomyelitis. All sites of inflammation accumulated the radiopharmaceutical and could be visualized scintigraphically 45 min after its administration. The results were in agreement with 67Ga-citrate or 111In-leukocyte scintigraphy, and/or other diagnostic modalities. Hyperaemia alone was not sufficient to cause uptake. We conclude that the mechanism of uptake is regional spilling of the tracer into the extravascular space through gaps in the damaged basement membrane, and that nanometer-sized 99Tcm-labelled colloid may constitute a convenient radiopharmaceutical for detecting inflammation in the extremities.

Sucralfate versus cimetidine in reflux esophagitis. A single-blind multicenter study.

A single-blind randomized multicenter study was performed in 42 patients with endoscopically documented reflux esophagitis. Patients were randomly given 400 mg cimetidine q.i.d. or a suspension of 1 g sucralfate q.i.d. for a period of 8 weeks. Forty patients were evaluated after 8 weeks. Symptomatic improvement was good and was comparable in both groups. We saw side-effects in only three patients, two on sucralfate and one on cimetidine, and these did not necessitate withdrawal from the study. Endoscopy showed improvement of esophagitis in 53% and healing in 31% of patients after sucralfate treatment. With cimetidine, improvement was seen in 67% and healing in 14%. One patient on cimetidine developed a stricture during treatment. We conclude that treatment with sucralfate improves symptoms and lessens severity of reflux esophagitis and that the results with sucralfate appear to be comparable to those obtained with cimetidine. Sucralfate is a valid alternative to H2-receptor antagonist therapy.

Endobronchial non-Hodgkin lymphoma: report of two cases.

Two cases of endobronchial localised non-Hodgkin lymphoma are presented. Pathogenesis, clinical history, diagnosis and treatment of this unusual localisation of non-Hodgkin lymphoma are reviewed.

Influence of fasting and refeeding on the elongation step of protein synthesis in rat liver of young (3M) and aging (18M) animals.

The in vitro binding capacity for AA-tRNA of ribosomes, catalysed by EF1 enzyme, was studied in livers of rats, which had been starved for 5 days and re-fed for 3, 9, and 24 hours. The experiments were carried out with 3 and 18-month-old rats. The results were compared to those obtained with normally fed rats of the same ages. For both age groups, there was a similar change in the binding capacity, including a return to normal values after 24 hours of refeeding. When ribosomes of old control animals were treated with different enzymes, we obtained lower binding activities for all the experimental groups than in homologous cell-free systems (ribosomes and EF1 isolated from the same group). The ribosomes of young animals, tested in the presence of different enzymes, display an increased binding capacity, when the enzymes used were those of old (control and re-fed) animals. The recovery of the catalytic activity of EF1 on the binding process was observed after 9 hours in old animals, whereas it was not seen for young re-fed animals at that time of refeeding. EF1 seems to play an important role in the adaptation of older animals to fasting and refeeding.

Modified in vivo behaviour of 99mTc-labelled liver-spleen preparations due to 99Mo/99mTc-generator eluate impurities.

At irregular intervals, a 99mTc-labelled microcolloid for liver and spleen scintigraphy was reported to accumulate in the lungs, in the absence of any pathophysiological condition usually associated with this phenomenon. These findings were in direct contrast to the results obtained during quality control assays performed on the production batches of the kit. The authors tested the hypothesis that the presence of Al3+ ions in the generators eluate used to label the kit caused the formation of larger size aggregates. The experimental results suggest that the 99mTc-pertechnetate solution used for labelling contained far more than 40 micrograms Al3+ per ml, hence a many-fold increase of the maximum level tolerated by the pharmacopoeia. The authors advise caution when interpreting findings of pulmonary activity in the absence of clear evidence of pathological conditions that are sometimes associated with this biodistribution pattern.

Value of colonoscopy in the detection of sigmoid malignancy in patients with diverticular disease.

Sixty patients with diverticular disease, referred because a barium enema examination could not exclude a co-existing malignanty, were studied in a retrospective manner, to find out the contribution of colonoscopy in the diagnosis of sigmoid carcinoma in such patients. All X-ray studies were blindly reviewed and divided in two categories: a) diverticular disease with malignancy or strong suspicion for malignancy and b) diverticular disease without suspicion for malignancy. The accuracy of the endoscopical examination was evaluated by a follow-up study with a range of 3 months-3 years. Colonoscopy appeared to be accurate in more than 3/4 of the referred patients but was not helpful when there was a severe stenoisis and/or the diseases segment could not be reached for biopsy. The incidence diminished when a small calibre fiberendoscope was used, practically always allowing to reach or to pass the stenotic segment. There were no false positive nor false negative endoscopical results in our study. In a substantial number of patients major surgical exploration could be prevented. We consider colonoscopy therefore a valuable adjunct in detecting or eliminating cancer in colonic diverticular disease. The availability of various fiberendoscopic instruments is a prerequisite for reaching an acceptable success rate and diagnostic accuracy.