Assessing venous thrombus in renal cell carcinoma: preliminary results for unenhanced 3D-SSFP MRI.

AIM: To test the potential of unenhanced cardiac- and respiratory-motion-corrected three-dimensional steady-state free precession (3D-SSFP) magnetic resonance imaging (MRI) for the assessment of inferior vena cava (IVC) thrombus in patients with clear-cell renal cell carcinoma (cRCC), compared to standard contrast-enhanced (CE)-MRI and CE-computed tomography (CT). MATERIALS AND METHODS: Eighteen patients with cRCC and IVC thrombus, who received CE-MRI and 3D-SSFP at 1.5 T between June 2015 and December 2017, were included. The diagnostic performance of 3D-SSFP in determining the level of thrombus extension, contrast-to-noise ratio (CNR), and image quality were compared with standard MRI/CT and validated against intraoperative and histopathology results. RESULTS: There was 100% agreement between 3D-SSFP, 83.3% agreement between CE-MRI, and 71.4% agreement between CE-CT and surgical findings regarding the level of IVC thrombus. In addition, 3D-SSFP showed a slightly superior estimate of pathological IVC volume. 3D-SSFP reached a significantly higher CNR in the supra- and infrarenal IVC compared to the morphological sequence T2-weighted half-Fourier axial single-shot fast spin-echo (T2-HASTE) and all phases of CE-MRI. More specifically, 3D-SSFP showed a significantly higher CNR in the infrarenal IVC (mean CNR of 10.09±5.74 versus 4.21±2.33 in the delayed phase, p≤0.001) and in the suprarenal IVC (mean CNR of 9.22±4.11 versus 4.84±5.74 in the late arterial phase, p=0.015). CE-CT also was significantly inferior to 3D-SSFP (p≤0.01) and slightly inferior to CE-MRI (p>0.05). The thrombus delineation score for 3D-SSFP (4.38±0.67) was higher compared to CE-MRI (3.76±0.56, p=0.005). CONCLUSION: This preliminary study indicates that 3D-SSFP can achieve an accurate assessment of IVC thrombus in cRCC patients without the need for contrast medium administration, being superior to standard MRI and CT.

Implementation of the quality management system improves postoperative pain treatment: a prospective pre-/post-interventional questionnaire study.

BACKGROUND: An organizational approach is proposed as an immediate solution for improving postoperative pain (POP) management. The aim was to evaluate the clinical effectiveness of a quality management system (QMS), based on procedure-specific, multimodal analgesic protocols, modified to meet the individual patients' requirements. METHODS: Patients from the orthopaedic, gynaecological, visceral, and trauma surgery departments of the university hospital were involved in two prospective surveys. Survey 1 was performed at baseline and survey 2 was performed after the implementation of QMS within an interval of 1 year. The patients were asked to report pain intensity on the visual rating scale, incidence of analgesia-related side-effects, and incidence of pain interference with the items of life quality and their satisfaction with the treatment of POP. RESULTS: Patients from Survey 2 (n=251) reported 25-30% less pain than those from Survey 1 (n=269) (P<0.0001). Nausea was reported by 40% of the patients from Survey 1 vs 17% from Survey 2, vomiting by 25 vs 11% and fatigue by 76% in Survey 1 vs 30% in Survey 2 (P<0.0001). Life quality and patients' satisfaction improved in Survey 2 vs Survey 1 (P<0.001). CONCLUSIONS: The implementation of QMS allowed the reduction in POP intensity with a simultaneous decrease in analgesia-related side-effects. This has led to an increased quality of life and patient satisfaction.

Analysis of organo-silica interactions during valve formation in synchronously growing cells of the diatom Navicula pelliculosa.

Biologically formed silica is produced at ambient conditions under the control of molecular and physicochemical processes that are apparently integrated in biosilica morphogenesis, but the mechanisms are not yet fully understood. With the recent identification of small polypeptides and proteins that are encapsulated inside the biosilica and functional in silica polymerization in vitro, it is of importance to determine whether interactions between inorganic silica species and these organic compounds occur in vivo. A time-resolved analysis of valve formation in synchronously growing cells of the diatom species Navicula pelliculosa enabled us to characterize the relevant chemical bonds by attenuated total reflectance Fourier-transformed infrared (ATR-FTIR) spectroscopy. Typically, inorganic bonds of Si-O-Si (bands at 1058, 843 cm(-1)), Si-OH (3689 cm(-1)), and P=O (1239 cm(-1)) and organic bonds of proteinaceous matter (with the amide I and II bands at 1642 and 1543 cm(-1), respectively) were positively identified during one cycle of valve formation. The observed variations in FTIR band intensity and location represented specific interactions between organic and inorganic molecules during the major silicification event, during which stretching of the Si-O bonds was predominantly noticed. The experimentally obtained frequencies (nu) of the major bonds corresponded to those that were obtained by MM+ and PM3 FTIR simulations for organo-silica interactions based on biomolecules that are proposed to be involved in biosilica formation. The results indicated that hydrogen bonds originated from interactions, albeit weak, between organic phosphate or amine groups to the inorganic hydroxyl groups or oxygen atoms from the silicic acid and/or silica. The existence of covalent P-O-Si bonds and electrostatic interactions could not be excluded. These interactions clearly suggest that biomolecules actively contribute to the silica polymerization process during valve formation in N. pelliculosa, and also might act comparably in other diatoms species in which similar biomolecules have been identified.

The German Acromegaly Registry: description of the database and initial results.

UNLABELLED: Patient registries are valuable tools to study long-term morbidity and mortality of rare diseases. Acromegaly is rare (incidence 3-4/mill/year, prevalence 40-70/mill; approx. 300 new patients/yr and up to 5700 patients in Germany). Diagnostic and therapeutic possibilities have considerably improved, but treatment results remain often unsatisfactory. The main cause is residual disease activity after surgery, most importantly due to invasive macroadenomas. The German Acromegaly Registry is an initiative of the Pituitary Study Group of the German Endocrine Society (DGE). Formally established in January 2003 by the Board of the DGE, long-term financial support is guaranteed by an unrestricted grant from Novartis Pharma GmbH to the DGE. The registry cooperates closely with the United Kingdom and the Austrian registries. The aim of the German Acromegaly Registry is to establish a database of sufficient epidemiological strength in order to (1) document co-morbidity and mortality, (2) provide data on diagnostic and therapeutic procedures/effectiveness, (3) enable comparison of procedures in different national centres, (4) provide information for patient support groups/interaction with health care providers, (5) enable comparison with other national registries within Europe. The registry has at present 82 participating centres, and 42 have included patients (20 university clinics, 8 non-university hospitals, 14 centres in private practice). The database aims to include all acromegalic patients in Germany who are cared for and treated at present. Up to December 2005 1543 patients have been entered in a retrospective manner. Data collection is by external monitoring by highly trained study nurses who visit the individual centres. Inclusion is planned to continue at a rate of 500 per year. Starting in 2005 centres are revisited every 3 years at a rate of 500 per year (prospective phase of the registry). Quality of the data has been validated by an independent monitoring team which demonstrated high data concordance. CONCLUSIONS: Initial results of the German Acromegaly Registry show that it was possible to include a large number of patients within 3 years into the registry. Data quality has been validated and shown to be satisfactory. Therefore, the registry will be a useful tool to study long-term morbidity and mortality in a large series of patients.

Replacement therapy with levothyroxine plus triiodothyronine (bioavailable molar ratio 14 : 1) is not superior to thyroxine alone to improve well-being and cognitive performance in hypothyroidism.

OBJECTIVES: There is evidence from recent controlled clinical studies that replacement therapy of hypothyroidism with T4 in combination with a small amount of T3 may improve the well-being of the patients. As the issue is still the subject of controversial discussion, our study was assigned to confirm the superiority of a physiological combination of thyroid hormones (absorbed molar ratio 14 : 1) over T4 alone with regard to mood states and cognitive functioning. DESIGN AND PATIENTS: After a run-in period with the T4 study medication for 4 weeks, a controlled, randomized, double-blind, two-period (each 12 weeks), cross-over study without washout between the treatment periods was performed in 23 hypothyroid patients (three males, 20 females, age 23-69 years, 21 subjects after surgery/radioiodine, two with autoimmune thyroiditis) to compare the effects of the previous individual T4 dose (100-175 micro g) with a treatment in which 5% of the respective T4 dose was substituted by T3. MEASUREMENTS: Standard hormonal characteristics and standardized psychological tests to quantify mood and cognitive performance were measured after the run-in period and at the end of each treatment period. In 12 subjects, the concentration-time profiles of fT3 and fT4 were compared after the last administration of the respective study medication. TSH, fT3 and fT4 were measured with immunological assays. CLINICAL RESULTS: Replacement therapy with T4 and T4/T3 was not different in all steady-state hormonal, metabolic and cardiovascular characteristics except for TSH, which was more suppressed after T4/T3. The efficacy of replacement therapy with the T4/T3 combination was not different from the T4 monotherapy with regard to all psychological test scores describing mood and cognitive functioning of the patients. Mood was even significantly impaired by the T4/T3 combination in eight subjects, with TSH < 0.02 mU/l, compared to patients with normal TSH (Beck Depression Inventory: 8.25 +/- 5.01 vs. 4.07 +/- 5.60, P = 0.026). PHARMACOKINETIC RESULTS: The area under the concentration-time curve (AUC(0-8h)) of fT3 was significantly higher after T4/T3 compared to the T4 monotherapy (42.8 +/- 9.03 pmol x h/l vs. 36.3 +/- 8.50 pmol x h/l, P < 0.05) and was significantly correlated to serum TSH (r(s) = -0.609, P < 0.05). After T4/T3, patients with a history of Graves' disease or autoimmune thyroiditis had significantly higher serum trough levels of fT3 whereas the fT4 concentrations were significantly lower in patients with a nonautoimmune background. CONCLUSION: Replacement therapy of hypothyroidism with T4 plus T3 does not improve mood and cognitive performance compared to the standard T4 monotherapy. There is even a higher risk of signs of subclinical hyperthyroidism associated with impaired well-being of the patients, which is clearly caused by significant fluctuations in the steady-state fT3 serum concentrations.

[Postoperatively recurring instability of the shoulder--a fault analysis in 46 cases]. / Die postoperative Rezidivinstabilität des Schultergelenks--Eine Ursachenanalyse in 46 Fällen.

AIM: The successful operative stabilization of the shoulder joint is a demanding surgical procedure. The causality of shoulder instability is complex with in some cases multiple lesions in different anatomical structures. The surgeon has to understand the complexity of factors causing instability in order to be therapeutically successful. The aim of the study was to document the intraoperative pathology in revision instability surgery. METHOD: 46 patients with recurrent postoperative instability were included (8 female, 38 male, follow-up > 12 months). After diagnostic arthroscopy an open revision surgery was performed in all cases. RESULTS: In 19 cases (40%) an insufficient surgical procedure was performed (inadequate capsular shift with worn out labral tissue). Selection of an incorrect surgical technique was the reason for revision in 12 patients (25%). Anamnestically 5 patients reported a re-injury, whereas objectively only one patient described an adequate trauma. The most frequent finding was an open rotator interval (persisting Foramen Weitbrecht), which was seen in 22 cases (46%). CONCLUSION: A stable range of motion of the shoulder is achieved by a variety of different factors, which leads in most instances to a combination of pathological changes in case of a dislocated shoulder. To understand the contributing factors of an instable shoulder joint is a necessity to carry out a successful surgical procedure.

Possible role of ubiquitin in silica biomineralization in diatoms: identification of a homologue with high silica affinity.

In diatom silicon biomineralization peptides are believed to play a role in silica precipitation and the consequent structure direction of the cell wall. Characterization of such peptides should reveal the nature of this organic-inorganic interaction, knowledge that may eventually well be used to expand the existing range of artificial silicas ("biomimicking"). Biochemical studies on Navicula pelliculosa revealed a set of proteins, which have a high affinity for a solid silica matrix; some were only eluted from the matrix when SDS-denaturation was applied. One of the proteins with an affinity for silica, about 8.5 kDa, is shown to be a homologue of ubiquitin on the basis of its N-terminal amino acid sequence; ubiquitin itself is a highly conserved 8.6 kDa protein that is involved in protein degradation. This finding is in line with a model of silica biomineralization in diatoms that implies the removal of templating polypeptides when pores in the growing cell wall develop. Western blotting with specific anti-ubiquitin antibodies confirmed cross-reactivity. Immunocytochemical localization of ubiquitin indicates that it is present along the diatom cell wall and inside pores during different stages of valve formation.

[Recurrent hemoptysis as initial symptom of a thoracic angiomatosis in an adult patient]. / Rezidivierende Hämoptysen als Erstsymptom einer thorakalen Angiomatose beim Erwachsenen.

HISTORY: A 24-year-old man presented with recurrent hemoptysis and decreased exercise capacity. DIAGNOSTIC FINDINGS: The chest radiograph demonstrated multiple disseminated pulmonary nodules. In addition the patient developed a hematopericardium with tamponade. The further diagnostic approach revealed an extensive thoracic angiomatosis affecting the lung and the heart. TREATMENT AND COURSE: Tumor resection could not be performed. A therapy with Interferon alpha-2a was initiated. After 3 month a significant regression of the pulmonary angiomatosis was documented. On the other hand the cardiac tumor showed no therapeutic response. CONCLUSION: Thoracic angiomatosis should be considered in the differential diagnosis of otherwise unclear hemoptysis or hematopericardium. Diagnosis intra vitamin requires an aggressive and invasive approach. Interferon alpha-2a is effective in palliative treatment of diffuse angiomatous diseases. But not all angiomatous processes respond to that therapy.

[Isolated traumatic rupture of the subscapular muscle tendon as an adolescent injury]. / Die isolierte traumatische Ruptur der Sehne des M. subscapularis als Verletzungsform des Jugendlichen.

INTRODUCTION: Until now no case of a traumatic tear of the subascapularis muscle in children was described in the German speaking literature. Using the example of 2 cases of a 12 and 14 year boys youth history, clinic, diagnostics and therapy will be presented. METHODS: The accident happened in extension and external rotation of the arm without dislocation. Beside the complete tear of the SCP-tendon in one case an accompanying expanded humeral flake fracture at the minor tuberosity was found. Under protection of the epiphysis line the refixation was performed using suture anchors. RESULTS: The post-operative control after 12 months showed a complete tendon healing, no arthritis or delayed bony ingrowth with return to full activity. CONCLUSION: Isolated traumatic SCP-tears can be occur also in young patients. As major consequence, it is necessary to perform a thorough clinical examination with additional apparative diagnostics (Sonography, MRI). This way, this rare but important lesion can be detected early and lead to adequate surgery without any delay.

Prognostic importance of the uPa/PAI-1 complex in breast cancer.

The complex between urokinase-type plasminogen activator (uPA) and its inhibitor PAI-1 (plasminogen activator inhibitor 1) has been prognostically evaluated in patients with breast cancer. The concentrations of uPA antigen, PAI-1 antigen and the uPA/PAI-1 complex were analysed in extracts from breast cancer tumours from 233 patients (median follow-up of patients: 71months). The uPA/PAI-1 complex typically constituted about 5% of the uPA antigen (total uPA). The concentration of complex was found to correlate more strongly to the concentration of PAI-1 (r = 0.72; p < 0.0001) than to the concentration of uPA (r = 0.55: p < 0.0001). Interestingly, in this material the uPA/PAI-1 complex (using an optimised cutoff level of 0.22 ng microg(-1) DNA) had a stronger prognostic value than optimised cut-off valuesfor uPA or PAI-1. The data suggest that activation of prourokinase within the tumour, which is a prerequisite for the formation of the uPA/PAI-1 complex, is of better prognostic value than the production of prourokinase or PAI-1 in the breast cancer tumour.

Duplex scan surveillance during the first year after infrainguinal autologous vein bypass grafting surgery: costs and clinical outcomes compared with other surveillance programs.

PURPOSE: In this study we assessed the costs and clinical outcomes of duplex scan surveillance during the first year after infrainguinal autologous vein bypass grafting surgery and compared duplex scan surveillance, ankle-brachial index surveillance, and clinical follow-up. METHODS: In a clinical study, 293 patients (mean age, 70.1 years; 58.7% men) with peripheral arterial disease were observed in a duplex scan surveillance program after infrainguinal autologous vein bypass grafting surgery. Costs were calculated from the health care perspective for surveillance and subsequent interventions from 30 days to 1 year postoperatively. All costs are presented in 1995 US dollars per patient. In a simulation model, we estimated the costs and amputations of duplex scan surveillance, ankle-brachial index surveillance, and clinical follow-up conditional on the indication for surgery. The main outcome measure was the incremental cost per major amputation per patient avoided during the first postoperative year. RESULTS: Duplex scan surveillance was the least expensive ($2823) and resulted in the fewest major amputations (17 per 1000 patients examined), compared with ankle-brachial index surveillance ($5411 and 77 amputations per 1000 patients) and clinical follow-up ($5072 and 77 amputations per 1000 patients). In patients treated for critical limb ischemia, duplex scan surveillance was the least expensive ($2974) and resulted in the fewest major amputations (19 per 1000 patients). Under all surveillance programs, 13 major amputations per 1000 patients treated for intermittent claudication were performed, and clinical follow-up had the lowest costs ($1577). In a sensitivity analysis that assumed that duplex scan surveillance could have avoided six major amputations per 1000 patients treated for intermittent claudication compared with the other programs, duplex scan surveillance had an incremental cost of $80,708 per major amputation per patient avoided compared with clinical follow-up. CONCLUSION: Duplex scan surveillance is highly effective for patients treated for critical limb ischemia, leading to a reduction of major amputations and consequently to a reduction in costs compared with other surveillance programs. In patients treated for intermittent claudication, the evidence supporting duplex scan surveillance is less firm, but if duplex scan can avoid six major amputations per 1000 patients examined, the incremental costs are justified.

[Diagnostic approaches in pleural effusion]. / Diagnostický postup pri pleurálním výpotku.

It is not easy to discover the underlying cause for pleural effusion. Over a quarter of the pleural effusions remain unexplained by indirect methods of examination such as chemical, cytological or bacterial tests. Thoracoscopy however, shows impressive results and can be conducted under simple conditions. Different statistical collections allow for the assumption that pleural effusions due to cardiac disease and malignant conditions occur equally often. They are followed in frequency by infection diseases and the often misjudged effusion with pulmonary embolism.

Can axillary dissection be avoided by improved molecular biological diagnosis?

Axillary dissection is presently a routine staging procedure in the management of breast cancer. The use of adjuvant systemic treatment is largely based on the diagnosis of axillary metastases. Routine axillary dissection leads to acute and chronic side-effects in a large proportion of patients. The sentinel node technique is presently explored with the aim of decreasing the need for standard axillary dissection. A complementary way forward is to analyse the primary breast cancer for molecular markers with prognostic significance with reference to the risk for metastatic capacity and thereby obtain a 'biological staging' and identify those patients in need of systemic adjuvant therapy. A large number of molecular biological factors have been shown to have prognostic significance in breast cancer e.g. c-erbB-2, p53, uPA, PAI-I and VEGF. This article reviews the expression of these and other factors in the primary breast cancers in relation to the risk for axillary and systemic metastatic disease, with the long-term aim of excluding routine axillary dissection.

Superficially porous silica microspheres for fast high-performance liquid chromatography of macromolecules.

Very fast reversed-phase separations of biomacromolecules are performed using columns made with superficially porous silica microsphere column packings ("Poroshell"). These column packings consist of ultra-pure "biofriendly' silica microspheres composed of solid cores and thin outer shells with uniform pores. The excellent kinetic properties of these new column packings allow stable, high-resolution gradient chromatography of polypeptides, proteins, nucleic acids, DNA fragments, etc. in a fraction of the time required for conventional separations. Contrasted with <2-microm non-porous particles, Poroshell packings can be used optimally with existing equipment and greater sample loading capacities, while retaining kinetic (and separation speed) advantages over conventional totally porous particles.

Malignant Sertoli cell tumor of the ovary metastatic to the lung mimicking neuroendocrine carcinoma: report of a case.

A Sertoli cell carcinoma of the ovary with lung metastases mimicking neuroendocrine carcinoma is presented. Lung metastases frequently occur. Primary and secondary tumors may exhibit similar growth patterns and differentiating primary from secondary tumors may be troublesome. This process may be more difficult when metastases occur from a tumor in which metastases are uncommon and morphologically resemble only a small portion of the primary tumor. We report the case of a 52-year-old woman who underwent resection of a 4,550-g Sertoli cell tumor of the ovary. Histologically, in addition to the characteristic tubular pattern of growth, 5% of the tumor consisted of poorly differentiated areas with tumor cells in sheets, a high mitotic rate, and areas of necrosis. Eleven months after this surgery she presented at a different institution with multiple pulmonary nodules. Microscopic examination of a subsequently resected lung nodule showed histologic findings similar to those of the poorly differentiated areas of the ovarian tumor and initial immunohistochemical studies showed positive staining for cytokeratin, neuron-specific enolase, and focal positivity for synaptophysin. Without knowledge of the ovarian tumor the lung lesion was interpreted as large-cell neuroendocrine carcinoma. On review of the clinical history and comparison with the previous surgical material, however, both tumors showed similar light microscopy and immunohistochemical reactivity, and a final diagnosis of metastatic Sertoli cell tumor was made. Immunohistochemical staining for inhibin revealed weak positivity in the poorly differentiated areas of the ovarian tumor but not in the lung metastasis. This is one of the rare reports of ovarian Sertoli cell tumor metastasizing to the lungs and it emphasizes the importance of complete clinical histories, ancillary studies, appropriate sampling, and review of archival material in such unusual cases.

Predictive value of serum S100B for monitoring patients with metastatic melanoma during chemotherapy and/or immunotherapy.

In the immunohistology of malignant melanoma the use of polyclonal antibodies against protein S100 is well established. Recently, it was shown that S100B, a subunit of the S100 protein family, is detectable in the serum of melanoma patients and correlates with the stage of the disease in patients with metastatic melanoma. In the present study, the first evaluation of a large number of treatment observations (n = 77) in 64 different patients during chemotherapy and/or immunotherapy for advanced metastatic melanoma (stage IV) is presented. All patients received treatment according to standardized protocols comprising 8 weeks of treatment followed by routine staging procedures to evaluate therapeutic outcome. In 13 patients with tumour enlargement after first-line therapy, a second-line treatment was subsequently given. S100B immunoradiometric assay (IRMA) tests were performed before, during and after treatment at scheduled time points. In the interim analysis at 4 weeks 29 of 37 (78%) patients with tumour progression during treatment showed a raised S100B level. In the final analysis at 8 weeks, 31 of these 37 patients (84%) demonstrated rising S100B values (P < 0.001). Patients who responded to treatment (stable or regressing metastatic disease) showed constant or declining S100B levels in 38 of 40 patients (95%) at the interim analysis, at 8 weeks this was further increased to 39 of 40 patients (98%; P < 0.001). Thus, the use of S100B for monitoring treatment is adequate in the majority of cases. Our observations are of great interest for therapeutic trials of adjuvant and palliative therapies as the rise of S100B levels might indicate that re-staging and/or changes in therapy strategies should be chosen.

S100B protein detection in serum is a significant prognostic factor in metastatic melanoma.

The serum detection of S100B, a new melanoma marker, has shown clinical significance in early studies. The aim of our study of 1, 339 serum samples from 412 different melanoma patients and 107 control patients was to prove the prognostic value of serum S100B levels in melanoma patients at different stages of disease and at follow-up (median: 30 months). Using a cutoff level of 0.2 microgram/l S100B, 5 of 286 patients (1.7%) with primary tumors (stage I/II), 14/73 (19.2%) patients with locoregional metastasis (stage III) and 57/84 (67.9%) patients with advanced disease (stage IV) were S100B positive (statistically significant differences for stage I/II vs. III, I/II vs. IV, and III vs. IV, p < 0.001). The estimated overall survival time was significantly longer (p < 0.001) for patients with S100B values below 0.2 microgram/l compared to patients with elevated S100B levels (>/=0.2 microgram/l), which was independent of the stage of disease (I-IV). Regarding prognosis, we were furthermore able to distinguish different subgroups among stage III and IV patients using S100B serum levels (p < 0.01). Patients with different cutaneous non-melanoma diseases served as S100B-negative controls. S100B serum evaluations using the Sangtec(R)100 IRMA are highly specific and sensitive for the detection of metastatic melanoma. S100B has been shown to be a relevant prognostic factor for survival in a study with a large sample size of melanoma patients including close follow-up evaluations.

Cost-effectiveness of dynamic graciloplasty in patients with fecal incontinence.

PURPOSE: This study evaluates the cost-effectiveness of dynamic graciloplasty for intractable fecal incontinence. PATIENTS AND METHODS: The costs and effects of dynamic graciloplasty were measured in a prospective, longitudinal study and in a clinical trial. Forty-three patients with intractable fecal incontinence were evaluated before and after dynamic graciloplasty. Costs were obtained from the hospital information system and from patient-oriented questionnaires. We compared the costs of a dynamic graciloplasty with the costs of a colostomy. Colostomy costs were evaluated using a group of seven patients who had a stoma in place for incontinence for several years. Sensitivity analyses were included. RESULTS: Total direct costs of lifelong dynamic graciloplasty were $31,733 (United States dollars), costs of lifelong conventional treatment were $12,180 (United States), and costs of colostomy, including lifelong stoma care, were $71,576 (United States). The clinical success rate of dynamic graciloplasty was 74 percent. Quality of life after successful dynamic graciloplasty was better than with conventional treatment. CONCLUSION: We found that dynamic graciloplasty was more expensive than conventional treatment but resulted in a significantly higher quality of life. Stoma treatment was the least attractive alternative regarding both costs and effects. The Dutch Health Insurance Executive Board recommended reimbursement for the dynamic graciloplasty procedure.

Interferon- and streptolysin O-induced activation of protein kinases and inhibition of cytochrome P450-dependent monooxygenases in rats.

Immunostimulants known to initiate cytokine production were found to decrease the activity of hepatic microsomal drug oxidative enzymes but to activate protein kinase C (PKC). The present study investigated the effects of immunostimulating doses of rat interferon-gamma (IFN, 670,000 units i.p.) and streptolysin O (SLO, 100 HU/kg i.v. for 5 days) on hepatic soluble, membrane-bound and nuclear PKC, 7-ethylresorufin-O-deethylase (EROD) and 7-pentylresorufin-O-deethylase (PROD) in male Wistar rats. The SLO- and IFN-mediated decrease of EROD and PROD activity was associated with a characteristic activation of the hepatic and spleenic PKC. In SLO- and IFN-treated animals activities of the cytosolic, membrane-bound and nuclear PKC were significantly higher than in respective controls. Our results suggest that a decrease in hepatic cytochrome P450 content as well as the decrease in the EROD and PROD activities are inversely related to the function of PKC.