Late onset interstitial nephritis associated with mesalazine treatment.
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Biomedical subjects
Publications and source records attributed to P Stevens.
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BACKGROUND: Ultrasound catheter probe-assisted endosonography is a relatively new technique. The aim of this prospective multicenter study was to determine its potential clinical impact by assessing changes in diagnostic and therapeutic management affected by catheter probes compared with ultrasound endoscopes. METHODS: Endosonographers at three centers selected theoretic diagnostic and therapeutic plans that would be followed if neither catheter probes nor ultrasound endoscopes were available. Patients with suitable lesions underwent endosonography with catheter probes followed by an ultrasound endoscope. Diagnostic and therapeutic plans were noted after each examination. RESULTS: Sixty-six patients, of whom 15 had a stenotic esophageal cancer, 39 had a mucosal or submucosal lesion, and 12 had a stricture of the pancreaticobiliary system or the gastrointestinal tract, were enrolled. If neither form of endosonography were available, invasive or surgical diagnostic procedures would have been performed on 23 (35%) patients and surgical therapy would have been planned in 31 (47%) patients. Catheter probe-assisted ultrasonography and endoscopic ultrasonography led to a less invasive diagnostic plan in 11 (16%) and 12 (18%) patients and a less invasive therapeutic plan in 10 (15%) and 14 (21%) patients, respectively (p > 0.1 for differences). CONCLUSIONS: Catheter probe-assisted endosonography has a modest effect on diagnostic and therapeutic management, comparable with endoscopic ultrasonography in the same patients. The vast majority of effected changes are toward less invasive management.
Bacterial infections that may be related to impaired phagocyte function often develop in patients infected with human immunodeficiency virus (HIV). We examined the oxidative capacity of circulating phagocytes in 78 HIV+ patients and 31 control subjects by measuring chemiluminescence with a whole blood assay. Phagocytes were stimulated with zymosan opsonized with human complement (hC-OPZ) or immunoglobulin (hI-OPZ) with or without exogenous primers. Patients with CD4+ < 500/microL showed reduced whole blood chemiluminescence at maximal opsonin receptor (MOR) activity after priming in response to hC-OPZ relative to control subjects, and the difference was significant for patients with CD4+ < 100/microL. Patients had lower absolute phagocyte counts; however, the chemiluminescence activity calculated per phagocyte count was significantly depressed in advanced HIV infection, indicating the impairment of phagocytic cell function and a reduction in number. Data were similar when hI-OPZ was used as a stimulus. The chemiluminescence of unprimed phagocytes at circulating opsonin receptor (COR) activity relative to maximally primed phagocytes (COR/MOR ratio) was significantly higher for HIV+ patients as compared with control subjects and indicates a defect in phagocyte priming. Alternatively, the phagocytes do not increase chemiluminescence with priming because they have already been primed or activated in vivo. In late-stage disease, decreased opsonin receptor-dependent respiratory burst activity contributes to the risk of secondary bacterial infections.
A role of neutrophils in the host response against Mycobacterium avium (MAC) has recently been suggested. To investigate this matter further, we determined the effect of granulocyte colony-stimulating factor (G-CSF) on the outcome of MAC infection in mice. C57BL/6bg+/bg- black mice were intravenously infected with 1 x 10(7) MAC and then divided into four experimental groups to receive G-CSF as follows: (i) 10 micrograms/kg/day; (ii) 50 micrograms/kg/day; (iii) 100 micrograms/kg/day; (iv) placebo control. Mice were killed at 2 and 4 weeks of treatment to determine the bacterial load of liver and spleen. Treatment with G-CSF at both 10 and 50 micrograms/kg/day doses significantly decreased the number of viable bacteria in liver and spleen after 2 weeks (approximately 70.5% and 69.0%, respectively), and after 4 weeks (approximately 53% and 52%, respectively, P < 0.05 compared with placebo control). Treatment with 100 micrograms/kg/day did not result in decrease of bacterial colony-forming units in the liver and spleen after 4 weeks. Administration of G-CSF induced interleukin-10 (IL-10) and IL-12 production by splenocytes. To examine if the protective effect of G-CSF was accompanied by the activation of phagocytic cells, blood neutrophils and splenic macrophages were purified from mice receiving G-CSF and their ability to kill MAC was examined ex vivo. Neutrophils and macrophages from G-CSF-treated mice were able to inhibit the growth of or to kill MAC ex vivo, while phagocytic cells from untreated control mice had no anti-MAC effect. These results suggest that activation of neutrophils appears to induce an effective non-specific host defence against MAC, and further studies should aim for better understanding of the mechanisms of protection.
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The alkenyl-acyl subclass of phosphatidylethanolamine (PtdEtn) and phosphatidylcholine (plasmalogens) are minor components of alveolar surfactant. Plasmalogens promote and stabilize hexagonal structures of phospholipids. In another study (W.R. Perkins, R.B. Dause, R.A. Parente, S.R. Michey, K.C. Neuman, S.M. Gruner, T.F. Taraschi, and A.S. Janoff. Science 273: 330-332, 1996), it was shown that polymorphic phase behavior may have an important role in the effective functioning of pulmonary surfactant. Therefore, we hypothesized that surface properties of phospholipid mixtures that contain plasmalogens are superior to plasmalogen-free mixtures. The effect of plasmalogens on surface tension of surfactant-like phospholipid mixtures (70 mol% dipalmitoyl phosphatidylcholine, 10 mol% phosphatidylglycerol, and 20 mol% PtdEtn) was measured. Using the pulsating bubble surfactometer, we show that an increasing amount of ethanolamine plasmalogens [plasmenylethanolamine (PlsEtn) results in reduction of surface tension (0 mol% PlsEtn 44.7 +/- 1.7, 2 mol% 33.5 +/- 1.7, 4 mol% 36 +/- 3.1, 6 mol% 26.2 +/- 2.9, and 8 mol% 22.2 +/- 0.3 mN/m). By means of the captive bubble surfactometer, minimal surface tension reached with 8 mol% PlsEtn was even lower (3.8 +/- 0.7 mN/m). With regard to morphological studies (B. Fringes, K. Gorgas, and A. Reith. Eur. J. Cell Biol. 46: 136-143, 1988), clofibrate treatment of rats might increase the plasmalogen content of alveolar surfactant. However, in the present study, we could not show that synthesis and secretion of plasmalogens are affected by clofibrate treatment.
GHRH plays a critical role in pituitary somatotroph development and function, actions which are mediated by a G-protein coupled receptor (GHRHr) that has been recently cloned. PCR amplification of rat pituitary mRNA using primers that span the GHRHr coding region resulted in two distinct products. When sequenced, the two isoforms were identical through bp 1278 of the GHRH coding region. However, the novel variant, which we have termed GHRHrbeta, contains a 131 bp deletion (1279-1408) and resumes at bp 1409 in the 3'UTR of the previously identified transcript (GHRHralpha). The identical isoforms were present in pituitaries from dwarf (dw) rats. The predicted amino acid sequence for the alternate receptor isoform differs from the published amino acid sequence at the extreme carboxyl terminus, with the last 5 amino acids of the published sequence replaced and an additional 17 amino acids added to the sequence. When translated in vitro or expressed as an epitope-tagged construct in non-GHRHr containing cell lines, the GHRHrbeta mRNA produces a 42 kDa protein product, appropriately larger than the 40 kDa product of GHRHralpha mRNA. Furthermore, GHRHrbeta retains the ability to promote cAMP generation in response to GHRH when expressed in non-GHRHr containing cell lines. These results indicate the presence of a splice variant of rat GHRHr mRNA present in normal and dw rat pituitary that codes for a functional receptor protein with an alternate carboxyl terminal domain. These findings raise the possibilities of target cell regulation of GHRH response, modulation of response through receptor isoform interactions and the involvement of multiple intracellular signaling pathways.
BACKGROUND: Both four-site skinfold anthropometry (FSA) and bioelectrical impedance analysis (BIA) claim to be useful in routine clinical practice of maintenance dialysis as easy methods to assess nutritional status. The purpose of this study was to investigate which of these two methods is to be preferred. METHODS: Both before and after dialysis nutritional and hydration status were evaluated by BIA in 20 stable hemodialysis patients. Variables of nutritional status as lean body mass (LBM) and body fat (BF) were assessed by four-site skinfold anthropometry (LBM-FSA and BF-FSA) and BIA (LBM-BIA and BF-BIA). Variables of hydration status were total body water (TBW), its distribution into intracellular and extracellular compartments (ICW and ECW, respectively) and ICW/ECW. RESULTS: Weight loss during dialysis correlated with a change of LBM-FSA (r = 0.75, p <0.005) and also with that of LBM-BIA (r = 0.69, p < 0.005). To promote reliability of follow-up measurements in intervention studies it is warranted to evaluate nutritional status in an unchanged hydration status. The highly significant correlation (r = 0.93, p < 0.005) between the two techniques and the comparability between means and SD indicate that both techniques were almost equivalent to each other, although, compared to LBM-BIA, LBM-FSA was less affected by changes in fluid status. The sam held true for BF-BIA and BF-FSA. BF-FSA correlated significantly with BF-BIA (r = 0.65, p <0.005), whereas no difference of mean +/- SD was found between BF-FSA and BF-BIA. CONCLUSION: FSA and BIA are almost comparable techniques to assess both LBM and BF, although FSA is less affected by changes in fluid status. However, assessing LBM in normohydration is mandatory. Compared with FSA, BIA is able to establish hydration status and lacks depency on operator interpretation. Therefore, in routine patient care the BIA technique is the one to be preferred.
BACKGROUND: Vena cava diameter (VCD) measurement is an accepted method to evaluate hydration status in patients on hemodialysis. Bioelectrical impedance analysis (BIA) is a less laborious method to assess hydration variables and more suitable for routine patient care. However, BIA has not yet been validated in dialysis patients. We investigated whether BIA can replace VCD in patients on hemodialysis. METHODS: In 20 stable hemodialysis patients [age (+/-SD): 47+/-17 yrs, dialysis duration (+/-SD): 76+/-59 months] hydration status was evaluated by VCD. Impedance variables such as resistance, reactance and phase angle were provided by BIA. They were used to calculate intracellular water (ICW), extracellular water (ECW) and total body water (TBW). RESULTS: VCD did not correlate with TBW-BIA, but correlated with ECW/TBW (r = 0.46; p<0.025), ECW/m2 (r = 0.42; p<0.005) and ICW/ECW (r = -0.49; p<0.005). Hemodialysis decreased TBW with 2.7+/-1.91. The difference in ECW before and after dialysis (8.9+/-1.3 and 7.4+/-1.41, respectively) was significant (p = 0.001). The same did not hold true for ICW (13.3+/-1.4 and 13.1+/-1.41). Major underhydration (n = 9; VCD <6.5 mm/m2) revealed sharp limits for ICW/ECW (>1.80) and ECW/TBW (<0.35), whereas these BIA-variables were significantly (p<0.005) different from those in minor underhydration (n = 8; 6.6 < VCD <8.0 mm/m2), normohydration (n = 15; 8 11.5 mm/m2). CONCLUSION: BIA can replace VCD only in major underhydration (VCD < 6.5 mm/m2). Fluid loss during hemodialysis is caused by a decrease of ECW, compatible with the postulation that excess fluid volume is carried by the extracellular compartment.
OBJECTIVE: To prospectively test the hypothesis that a diagnosis of deep vein thrombosis can be excluded in outpatients who present with clinical indications of deep vein thrombosis and whose results of D-dimer testing and impedance plethysmographic examination on the day of presentation are normal. DESIGN: Prospective cohort study. SETTING: Four university-affiliated hospitals. METHODS: Three hundred ninety-eight consecutive patients with clinical indications of deep vein thrombosis were included in the final analysis. All patients underwent an assessment of pretest probability, bedside D-dimer testing, and impedance plethysmographic examination. In most patients, if the results of D-dimer testing and impedance plethysmographic examination were negative for deep vein thrombosis, anticoagulants were withheld and patients were followed up for 3 months. If the results of one or both tests were abnormal, an examination using venous compression ultrasonography or phlebography was performed. RESULTS: In the majority of patients (69%), the results of D-dimer testing and impedance plethysmographic examination were normal. This combination had a negative predictive value of 98.5% (95% confidence interval, 96.3-99.6) for deep vein thrombosis. CONCLUSION: The results of the D-dimer assay and impedance plethysmographic examination on the day of presentation can be used to treat the majority of outpatients who present with clinical indications of deep vein thrombosis without further testing.
BACKGROUND: An initial multicenter study using a 21 mm flanged esophageal Z stent demonstrated excellent palliation but an 11% immediate complication rate at placement and a 27% migration rate at 1 month. This North American multicenter trial prospectively studied a 25 mm flanged Z stent to define its palliative ability and whether the increased diameter affected placement or migration problems. METHODS: Fifty patients who had esophageal Z stents at seven university or regional referral hospitals were prospectively studied. Indications for prosthesis placement, previous therapy, patient demographics, incidence of concomitant tracheoesophageal fistula, and degree of dysphagia were defined, as were procedural and subsequent stent-related problems, survival times, the ability to occlude a tracheoesophageal fistula, and subsequent degree of dysphagia. RESULTS: Twenty-four patients had infiltrating malignancy (16 exophytic and 10 extrinsic), 9 of whom had concomitant tracheoesophageal fistulas. Ten patients (20%) had misplaced stents requiring retrieval and replacement, 12 patients (24%) had subsequent stent-related problems including exsanguination (2), aspiration (3), tumor overgrowth (3), and postplacement migration (4) (8%). There was statistically significant improvement in prestent versus poststent dysphagia and two thirds of patients had complete occlusion of their tracheoesophageal fistula. CONCLUSIONS: Redesign of the esophageal Z stent has decreased the migration rate without increasing placement or subsequent erosion problems. Its efficacy appears comparable to the currently marketed Z stent for the palliation of malignant dysphagia and occlusion of tracheoesophageal fistula.
The aim of the present multicenter study was to assess quality of life of Dutch dialysis patients 3 months after the start of chronic dialysis treatment. The quality of life was compared with the quality of life of a general population sample, and the impact of demographic, clinical, renal function, and dialysis characteristics on patients' quality of life was studied. New end-stage renal disease (ESRD) patients who were started on chronic hemodialysis or peritoneal dialysis in 13 dialysis centers in The Netherlands were consecutively included. Patients' self-assessment of quality of life was measured by the SF-36, a 36-item Short Form Health Survey Questionnaire encompassing eight dimensions: physical functioning, social functioning, role-functioning physical, role-functioning emotional, mental health, vitality, bodily pain, and general health perceptions. One hundred twenty hemodialysis and 106 peritoneal dialysis patients completed the SF-36. Quality of life of hemodialysis and peritoneal dialysis patients was substantially impaired in comparison to the general population sample, particularly with respect to role-functioning physical and general health perceptions. Mean role-functioning physical and general health perceptions scores of the hemodialysis patients corresponded with the lowest scoring 8% and 12%, respectively, of the reference group. Mean role-functioning physical and general health perceptions scores of the peritoneal dialysis patients corresponded with the lowest scoring 10% and 12%, respectively, of the reference group. Hemodialysis patients showed lower levels of quality of life than peritoneal dialysis patients on physical functioning, role-functioning emotional, mental health, and pain. However, on the multivariate level, we could only demonstrate an impact of dialysis modality on mental health. A higher number of comorbid conditions, a lower hemoglobin level, and a lower residual renal function were independently related to poorer quality of life. The variability of the SF-36 scores explained by selected demographic, clinical, renal function, and dialysis characteristics was highest for physical functioning (29.7%). Explained variability of the other SF-36 dimensions ranged from 6.9% for general health perceptions to 15.4% for vitality. We conclude that quality of life of new ESRD patients is substantially impaired. Comorbid conditions, hemoglobin, and residual renal function could explain poor quality of life only to a limited extent. Further research exploring determinants and indices of quality of life in ESRD patients is warranted. From a clinical perspective, we may conclude that quality of life should be considered in the monitoring of dialysis patients.
We reviewed the results of Pemberton pericapsular osteotomy in nineteen hips (fifteen patients) that were subluxated (fifteen hips) or dislocated (two hips) or had severe acetabular dysplasia (two hips) secondary to spastic cerebral palsy. At least one concomitant procedure was performed in fifteen hips. These procedures included an intertrochanteric osteotomy to correct excessive femoral anteversion or valgus deformity of the neck-shaft angle (thirteen hips), a soft-tissue release (nine hips), and an open reduction (three hips). Four hips had no concomitant procedure. Five of the nineteen hips were painful preoperatively. The average age of the patients at the time of the index operation was seven years and nine months (range, three years and five months to twelve years and three months). The average duration of follow-up was ten years and nine months (range, three years and one month to nineteen years and nine months). All osteotomy sites healed without complications. At the latest follow-up examination, all of the hips were pain-free and satisfactorily reduced and none of the patients had deterioration in function. The average center-edge angle was -5 degrees (range, -45 to 18 degrees) preoperatively and 38 degrees (range, 17 to 53 degrees) at the latest follow-up examination. The average migration index of Reimers was 55 per cent (range, 30 to 100 per cent) preoperatively compared with 12 per cent (range, 0 to 46 per cent) at the latest follow-up examination. Sixteen of the nineteen hips were followed until closure of the triradiate cartilage. There were no instances of posterior uncovering or osteonecrosis of the femoral head or premature closure of the triradiate physeal cartilage leading to deficient acetabular coverage. Our results suggest that good clinical and radiographic results can be achieved with the Pemberton pericapsular osteotomy, with simultaneous intertrochanteric osteotomy and soft-tissue release when indicated, as treatment for subluxation or dislocation of the hip or acetabular dysplasia in cerebral palsy.
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The purpose of the present study was to investigate whether total body bioelectrical impedance analysis (BIA) could be appropriate to assess normohydration (i.e. dry weight) in hemodialysis patients. This study is warranted, because the simultaneous assessment of both hydration and nutritional status by BIA requires the presence of a situation of normohydration in order to guarantee valid conclusions about the nutritional analysis. Segmental bioelectrical impedance was performed to classify patients according to their hydration status. BIA measurements revealed significant differences in TBW, ECW and ICW/ECW between three hydration subgroups (under-, normo-, and overhydration), whereas ICW was similar. Therefore, TBW, ECW and ICW/ECW appear appropriate variables to assess hydration status in patients on hemodialysis. Hemodialysis diminished ECW significantly, whereas ICW did not change, suggesting that a decrease of ECW explains the fluid loss during hemodialysis.
Neutrophil (PMNL) function defects occur as a consequence of HIV infection. This study examined PMNL apoptosis in patients with the acquired immunodeficiency syndrome (AIDS) to determine if accelerated apoptosis contributes to impaired function. PMNL were isolated from 10 HIV-infected patients with CD4+ lymphocyte counts < 200/mm3 without signs of active infection and 7 healthy volunteers. PMNL were stained with acridine orange and ethidium bromide after 0, 3, 6, and 18 h in culture, and examined for the morphologic changes of apoptosis and viability by fluorescent microscopy. Apoptosis was also demonstrated by electron microscopy, flow cytometry, and DNA gel electrophoresis. Apoptosis was minimal at 0 h, but PMNL from AIDS patients exhibited significantly greater apoptosis than controls at 3 h (22.5+/-11.5 vs. 8.9+/-6.9%, P = 0.015), 6 h (38.1+/-14.2 vs. 18.1+/-4.5%, P = 0.003), and 18 h (71.3+/-19.0 vs. 38.8+/-16.7%, P = 0.002). Viabilities were > or = 88.0% for both groups from 0-6 h, but by 18 h viability was significantly decreased for the HIV group (58.8+/-12.4 vs. 83.5+/-10.4%, P = 0.001) due to an increase in non-viable apoptotic cells. Incubation with serum from AIDS patients had no effect on control PMNL, and incubation with control serum did not reduce the rate of apoptosis of PMNL from AIDS patients. Incubation with granulocyte colony-stimulating factor (G-CSF) in vitro significantly decreased apoptosis for PMNL from AIDS patients. PMNL from patients with AIDS exhibit markedly accelerated apoptosis ex vivo. In vivo, apoptosis and functional impairment of PMNL may contribute to the risk of secondary infections, and cytokine therapy may be of potential clinical benefit in this circumstance.
BACKGROUND: Conventional esophageal prosthesis placement has been associated with a 6% to 8% perforation rate and numerous postplacement complications. Expandable esophageal stents have been developed to preclude the above but there are few studies that have prospectively defined clinical results and subsequent stent-related complications. METHODS: All patients who underwent esophageal Z-stent placement at nine university or referral hospitals were prospectively assessed. Data collected included patient demographics, acute and subacute placement problems, the ability to occlude airway fistulas, prestent and poststent dysphagia scores, and patient survival. RESULTS: Fifty-four of 56 patients (96%) with refractory dysphagia or malignant esophagoairway fistulae had 73 Z-stents successfully inserted. Initial distal deployment occurred in 13% of the patients and an additional 17% required balloon dilation to achieve maximal diameter. Acute placement complications occurred in 11% of patients and included severe pain (3), bleeding from necrotic tumor (2), and hiatal hernia intussusception (1). No perforations occurred. Eight of 11 patients (73%) had complete tracheoesophageal fistula occlusion and mean dysphagia score (+/- SD) improved from 2.6 (0.7) to 1.1 (1.2) (p < 0.01). Fifteen stents (27%) had delayed migration at a mean of 1 month and 3 required surgery for retrieval. Three patients had ultimate stent erosion resulting in bleeding in 2 (exsanguination 1) or fistula (treated with a conventional stent). CONCLUSIONS: The authors conclude that esophageal Z-stents can be placed safely and successfully in the majority of patients. The tendency of distal deployment during placement and subsequent migration problems at a time distant from placement in a patient subset deserve attention and are currently being addressed.
BACKGROUND: Despite increased clinical use of endoscopic ultrasound (EUS), there are little data regarding complications of EUS or its impact on patient management. METHODS: A prospective multicenter study was completed to evaluate clinical outcomes of EUS. Before each EUS examination the endosonographer recorded further theoretical patient management plans as if EUS was unavailable. After the EUS, endosonographers recorded actual management plans based on EUS results. The actual management plan after EUS was compared to the theoretical management before EUS. Complications were assessed in short-term follow-up. RESULTS: Four hundred twenty-eight subjects were enrolled. Of subjects able to be evaluated, EUS changed the treatment plan in 74%. Management changes of major importance occurred in 120 patients (31% of subjects able to be evaluated) and included decisions regarding surgery (62 patients), decisions regarding nonsurgical invasive management (36 patients), and decisions regarding further follow-up (22 patients). When there was a change in management, the change was to less costly, risky, or invasive management in 55%, to more costly/risky/invasive in 37%, and to equally costly/risky/invasive in 8%. Short-term follow-up was completed in 81% of subjects, with six complications identified (1.7%). Three complications were mild, two were moderate, one severe, and none fatal. CONCLUSIONS: (1) Changes in management plan may occur in the majority of patients based on EUS results. (2) The management changes are often of major importance with regard to health care costs and safety, and are more often in the direction of less costly, risky, and invasive management. (3) EUS is safe in experienced hands.