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Biomedical subjects

M Classen

Publications and source records attributed to M Classen.

At least 37 records · Page 2Linked to original sources

Reduced incidence of radiocontrast-induced nephropathy in ICU patients under theophylline prophylaxis: a prospective comparison to series of patients at similar risk.

OBJECTIVE: To investigate whether the adenosine-antagonist theophylline reduces the incidence of contrast-induced nephropathy (CIN). DESIGN AND SETTING: Prospective, comparison to series of patients at similar risk of CIN in a university hospital medical ICU. PATIENTS: 78 ICU patients with at least one risk factor for CIN undergoing 150 consecutive contrast examinations. INTERVENTIONS: Administration of 200 mg theophylline/70 kg BW intravenously 30 min before that of 100 ml or more low-osmolarity contrast medium (CM). MEASUREMENTS AND RESULTS: Concentrations of serum creatinine and blood urea nitrogen (BUN), urine volume, fluid balance, and the incidence of CIN [increase in creatinine > or =20.5 mg/dl (= 44.2 micromol/l) within 48 h] were monitored for 48 h. Despite the large number of risk factors (6.8 per patient) including a high dose of CM (169.4 ml), impaired renal function (51%), diabetes (38%), aminoglycosides (61%), vancomycin (53%), catecholamines (52%), creatinine concentrations were not increased 24 h (1.40+/-0.92 mg/dl) or 48 h (1.38+/-0.88 mg/dl) after CM [1.47+/-1.0 mg/dl (= 130+/-88 micromol/l)] vs. baseline. The fluid balance was not different before (+3 ml/h) and after CM (-9 ml/h). The urine volume slightly increased after CM and theophylline (184 ml/h vs. 164 ml/h). Only three patients (2%) developed CIN. The incidence was significantly lower than that of 14% (78/565) in the control series with patients at comparable risk of CIN (p < 0.0001). CONCLUSIONS: Using a theophylline prophylaxis the incidence of CIN in patients with increased risk of CIN is as low as 2%.

Adenosine↗

A new system for rapid large-caliber percutaneous transhepatic drainage in patients with obstructive jaundice: a prospective randomized trial.

UNLABELLED: BACKGROUND AND STUDY, AIMS: Percutaneous access to the biliary tract is an important diagnostic and therapeutic tool in the management of biliary diseases. It is usually chosen when the endoscopic approach via endoscopic retrograde cholangiopancreatography (ERCP) fails, or is not possible. Once established, the percutaneous tract is then used for the treatment of biliary stones and strictures. To establish a percutaneous tract with a caliber large enough for cholangioscopy to be performed, or for a large-bore permanent drainage tube to be inserted, stepwise dilation up to 14 Fr or 16 Fr is usually required. We present here a new method of rapid dilation using specially designed materials, including a stiffenable guide wire and specially adapted bougies. PATIENTS AND METHODS: Consecutive patients undergoing percutaneous drainage for biliary diseases were included in this prospective study, over a 19-month period. After establishment of a 10-Fr transpapillary drain, the patients were randomly assigned to either conventional percutaneous transhepatic biliary drainage (PTBD) or stepwise dilation using the new method, aiming at a need for only one further session, using a specially designed stiffenable metal guide wire of 6.6 Fr and plastic bougies. The details of the procedure (duration, materials used, technical ease), initial and later complications, assessment by the patients, and procedural costs were compared between the two groups. RESULTS: Of the 60 patients included, 29 were randomly assigned to group I (the new method) and 31 to group II (the conventional approach); there were no significant differences between the two groups in terms of clinical data or biliary pathology. The clinical efficacy of PTBD was similar in the two groups, although three patients in group II were switched to the new procedure because of failure of dilation using the conventional approach. The rates of major complications (four of 29 in group I, five of 31 in group II) and patient tolerance were also similar. However, the new procedure led to a significant reduction in the cumulative procedure duration (20.1 minutes vs 30.1 minutes), mean number of sessions (1.1 vs. 1.7), and mean number of hospital days (2.0 vs 5.5), and was therefore also cost-effective, reducing costs from a mean of 5813 to 2581 German marks (DM) per patient. CONCLUSIONS: The new system for rapid establishment of large-caliber PTBD offers significant advantages in terms of saving hospital resources while maintaining clinical efficacy.

Adult↗

Treatment of achalasia: botulinum toxin injection vs. pneumatic balloon dilation. A prospective study with long-term follow-Up.

BACKGROUND AND STUDY AIMS: In patients with achalasia, intrasphincteric injection of botulinum toxin (BTX) has been suggested as an alternative regimen to balloon dilation and has been shown to be superior to placebo injection. The aim of the present study was to test the effectiveness, the long-term outcome and the cumulative costs of BTX injection in consecutive patients with symptomatic achalasia in comparison with pneumatic balloon dilation. PATIENTS AND METHODS: 37 patients, who presented with symptomatic achalasia between January 1994 and December 1996 were treated with either BTX injection (n = 23) or pneumatic dilation (n = 14). Patients with short-term or long-term symptomatic failures of the initial procedure were treated again, either with the same or with the alternative method, depending on the initial response and on the patient's wish. Symptoms were assessed using a global symptom score (0 - 10) which was evaluated before treatment and 1 week, 1 month and then every 6 months after the treatment. In addition, body weight and recurrence of symptoms were noted and manometry was carried out before and after treatment. The patients were regularly contacted for the long-term follow-up. RESULTS: There were significant improvements in the global symptom scores of all patients treated, in both the BTX injection group (before 8.2 +/- 1.3, after 3.0 +/- 1.6) and the dilation group (before 8.3 +/- 1.1, after 2.3 +/- 1.9). There was also a significant decrease of lower esophageal sphincter pressure after treatment in the BTX group and the dilation group. There were no significant differences with regard to overall treatment failure and long-term outcome between patients who had or had not received previous treatment. No major complications were encountered in either group. An actuarial analysis over 48 months comparing patients receiving BTX injection or balloon dilation demonstrated that after 12 months neither therapy was significantly superior. After 24 months a single pneumatic dilation was superior to a single BTX injection, and after 48 months all patients treated by BTX injection had experienced a symptomatic relapse. In contrast, 35 % of all patients treated by dilation and 45 % of patients treated successfully by dilation were still symptom-free in an intention-to-treat analysis after 48 months. When the overall costs of treatment and further treatment after recurrence were compared, dilation and BTX injection showed a similar cost-effectiveness (costs per symptom-free day) after 48 months. CONCLUSIONS: BTX injection, which can be performed in an outpatient setting, is as safe and cost-effective as balloon dilation in symptomatic achalasia. Taking into account the lower long-term efficacy of BTX injection therapy, however, it is an alternative only in a minority of older or high-risk patients.

Actuarial Analysis↗

Current concepts on pathophysiology, diagnosis and treatment of diffuse oesophageal spasm.

Diffuse oesophageal spasm is a functional oesophageal motility disorder of unknown aetiology, which appears to be due to a disturbance of the normal pharmacological timing of propulsive contraction occurring in the oesophageal body after swallowing. The lack of pathophysiological understanding may be due to the fact that there is more than one pathophysiological pathway causing symptoms of diffuse oesophageal spasm. Barium studies, oesophageal scintigraphy and fiberoptic examination can be helpful in finding the correct diagnosis, but manometry is still the gold standard of diagnostic procedures. Similar to other spastic oesophageal motility disorders, pharmacological treatment of diffuse oesophageal spasm includes nitrates, calcium antagonists, anticholinergics and antidepressants with varying beneficial effects. Botulinum toxin, which provides sufficient treatment as measured by symptom score and manometric patterns in patients with achalasia, was recently evaluated for the treatment of diffuse oesophageal spasm in small patient selections with promising results.

Biofeedback, Psychology↗

Treatment of symptomatic diffuse esophageal spasm by endoscopic injections of botulinum toxin: a prospective study with long-term follow-up.

BACKGROUND: Diffuse esophageal spasm is a rare esophageal motility disorder for which there are no satisfactory pharmacologic alternatives for treatment. The aim of this study was to investigate whether botulinum toxin (BTX) injection is an effective short- and long-term treatment for patients with symptoms caused by diffuse esophageal spasm. Whether recurrence of clinical symptoms can be successfully retreated by BTX injection was also studied. METHODS: Nine symptomatic patients (6 women, 3 men; 57-86 years) with manometrically proven diffuse esophageal spasm underwent BTX injection. One hundred IU BTX were diluted in l0 mL of saline solution and injected endoscopically at multiple sites along the esophageal wall beginning in the region of the lower esophageal sphincter and moving proximally in 1- to 1.5-cm intervals, and into endoscopically visible contraction rings. Symptom scores based on an analogue scale for dysphagia, regurgitation, and noncardiac chest pain were assessed before and after therapy, 1 day thereafter, and at 1 and 6 months. RESULTS: Symptoms improved immediately in 7 (78%) patients after 1 injection session. After 4 weeks 8 (89%) patients were in remission with a decrease in total symptom score. The total symptom score decreased from a median 8.0 (interquartile range: 6.75; 9.0) before treatment to 2.0 (1.5; 3.75) after 1 day (p < 0.01) and to 2.0 (interquartile range: 0.75; 3.0) after 1 month (p < 0.01). After 6 months all 8 patients with a response at 1 month still had a symptom score of 3 or less without further treatment. Subsequently 4 patients required reinjection 8, 12, 15, or 24 months after the initial treatment with similarly good results. No serious adverse effects were observed. CONCLUSIONS: BTX injection at several levels of the tubular esophagus is an effective treatment for patients with symptoms caused by diffuse esophageal spasm. Symptom relapse can be effectively treated by repeated BTX injection.

Aged↗

IL-1beta-induced apoptosis in rat gastric enterochromaffin-like cells is mediated by iNOS, NF-kappaB, and Bax protein.

BACKGROUND & AIMS: Enterochromaffin-like (ECL) cells are histamine-containing endocrine cells in the gastric mucosa. Previous studies have shown that the proinflammatory cytokine interleukin (IL)-1beta present during chronic gastritis inhibits histamine synthesis in ECL cells and leads to sustained functional impairment. This study investigated the effects of IL-1beta on ECL cell apoptosis and the related signal-transduction mechanisms. METHODS: ECL cells were isolated by pronase digestion and a combination of elutriation, gradient centrifugation, and 48-hour culture (purity >/=90%). Apoptosis was measured by terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling reaction and cell death detection enzyme-linked immunosorbent assay. RESULTS: IL-1beta (100 pg/mL) increased the rate of programmed cell death 2-3 fold in ECL cells after 24 hours of incubation (total of 12%-14%). This effect was completely inhibited by the NF-kappaB inhibitor, proteasome inhibitor I, and the nitric oxide synthase inhibitor (iNOS) N(G)-monomethyl-L-arginine (10(-4) mol/L), but not by the caspase 3 inhibitor, Asp-Glu-Val-Asp-CHO. Western blot analysis, reverse-transcription polymerase chain reaction (PCR), and in situ PCR showed that IL-1beta induced gene expression (after 2-4 hours) and protein synthesis (6-18 hours) of the iNOS isoform in ECL cells. Bax protein expression was increased in response to IL-1beta. In contrast, bcl-2 gene expression was increased in response to basic fibroblast growth factor, which has been shown to counteract IL-1beta- induced apoptosis. CONCLUSIONS: These data suggest that IL-1beta induces programmed cell death in isolated rat ECL cells via activation of NF-kappaB, iNOS, and the Bax protein.

Animals↗

Mutations in the gene encoding the serine protease inhibitor, Kazal type 1 are associated with chronic pancreatitis.

Chronic pancreatitis (CP) is a continuing or relapsing inflammatory disease of the pancreas. In approximately one-third of all cases, no aetiological factor can be found, and these patients are classified as having idiopathic disease. Pathophysiologically, autodigestion and inflammation may be caused by either increased proteolytic activity or decreased protease inhibition. Several studies have demonstrated mutations in the cationic trypsinogen gene (PRSS1) in patients with hereditary or idiopathic CP. It is thought that these mutations result in increased trypsin activity within the pancreatic parenchyma. Most patients with idiopathic or hereditary CP, however, do not have mutations in PRSS1 (ref. 4). Here we analysed 96 unrelated children and adolescents with CP for mutations in the gene encoding the serine protease inhibitor, Kazal type 1 (SPINK1), a pancreatic trypsin inhibitor. We found mutations in 23% of the patients. In 18 patients, 6 of whom were homozygous, we detected a missense mutation of codon 34 (N34S). We also found four other sequence variants. Our results indicate that mutations in SPINK1 are associated with chronic pancreatitis.

Adolescent↗

Long-term outcome in patients with advanced hilar bile duct tumors undergoing palliative endoscopic or percutaneous drainage.

OBJECTIVE: Advanced tumors of the hepatic duct bifurcation (Klatskin tumors) present problems to the endoscopist in deciding which procedure to use for palliative treatment of the resulting cholestasis--endoscopic retrograde cholangiopancreatography (ERCP) or percutaneous transhepatic biliary drainage (PTBD), or both. There are technical difficulties with all forms of treatment for stenoses in the hilar region and intrahepatic bile ducts, and there are as yet no clear data on which type of drainage is feasible or preferable. SUBJECTS: 59 consecutive patients (30 men, 29 women; mean age 71 years) underwent palliative treatment for malignant hilar bile duct tumors of Bismuth stages II-IV during a three-year period (1992-94). METHOD: A retrospective analysis was carried out, and long-term follow-up data were obtained from telephone interviews with the patients, relatives, or referring physicians. RESULTS: The 59 patients were treated using ERCP (n = 20) or PTBD (n = 39). Three died within 30 days, and six were lost to follow-up. Clinically adequate drainage was achieved in 78% (n = 46) of the total patient group. Patient survival was a median of six months (range 0.5-38), and was slightly longer when the primary drainage procedure was successful (7.5 months). Initial complications occurred in 11% after ERCP and in 33% after PTBD, with a 30-day mortality of 5%. After the initial intervention, five patients who received ERCP treatment had to be switched to PTBD during the longer-term course. Three of these five patients died within 30 days of the PTBD insertion. CONCLUSIONS: Palliative treatment in patients with advanced Klatskin tumors is still suboptimal, even when combined endoscopic and percutaneous techniques are used in the same institution, allowing treatment to be tailored to the individual patient's needs. There is therefore a need for improvements in existing forms of treatment, as well as for the development of new forms of treatment.

Adult↗

Endohyperthermia--experimental evaluation of a new therapeutic approach for treatment of biliary carcinoma.

BACKGROUND AND STUDY AIMS: To improve the prognosis of patients with unresectable, locally advanced bile duct carcinoma, new treatment strategies need to be evaluated. Hyperthermia has been successfully applied as part of multimodal therapy in esophageal and rectal carcinoma. We performed in-vitro and in-vivo experiments with a new intraluminal hyperthermia system in the biliary tract. METHODS: A radiofrequency system (13.56 MHz, Endoradiotherm XERT-200A; Olympus Optical Co., Tokyo, Japan) was used with a special intraluminal microelectrode (diameter 4.5 mm, length 40 mm) covered by a silicone balloon with cooling water and a large counter electrode for focusing the electromagnetic field around the electrode. The heating capacity of the endohyperthermia unit was examined in vitro in a muscle-equivalent phantom (agar 4 %), in isolated livers of pigs and cows, as well as in vivo in anesthetized sheep. Continuous thermometry was done with thermosensors at the applicator surface, and with multichannel thermocouple probes in the environment of the applicator. RESULTS: Endohyperthermia induced a homogeneous heating of the phantom and the isolated liver bile duct preparation to a temperature > or = 40 degrees C in an area at least 10 mm in depth. After placement of the applicator into the common bile duct of anesthetized sheep, endohyperthermia led to a consistent and repeatable heating of the surrounding tissue to 40.5 +/- 0.5 degrees C at 1 cm distance, and 39.9 +/- 0.7 degrees C at 2 cm distance. Blood pressure, heart rate, and systemic temperature did not change in vivo. Histological examination of the bile duct showed superficial mucosal necrosis (depth 100-200 microm), microvascular damage with petechiae, congestion and edema of the bile duct wall and adventitia after hyperthermia treatment in vivo. CONCLUSIONS: The intraluminal endohyperthermia system produces consistent and repeatable heating of the surrounding tissue. Since effective thermal power can reach a depth of up to 2 cm, tumors may also be heated adequately.

Animals↗

Fecal bacterial activity in symptomatic carbohydrate malabsorption: effect on the fecal short-chain fatty acid ratio.

BACKGROUND: It is still not clear why only some patients with carbohydrate malabsorption experience symptoms. In a previous study on healthy fructose malabsorbers an increased degradation of fructose in anaerobic fecal cultures from symptomatic malabsorbers was found, indicating increased bacterial activity. In the present study, the same investigation was repeated in patients with nonspecific abdominal complaints and fructose malabsorption. Moreover fecal short-chain fatty acids (SCFA), products of colonic bacterial fermentation of carbohydrates were measured. PATIENTS AND METHODS: A standard quantity of fructose (500 mg) was added to anaerobic fecal cultures from 25 patients (nine men, 16 women; median of age 53 years, range 36-69 years). The fructose degradation rate was assessed using photometry, and interpreted as representing bacterial activity in the colon. In 14 of the patients, SCFA levels were also measured using chromatography on a capillary column. RESULTS: 10 of the 25 patients had a history of symptoms after ingesting fructose-containing foods, and also showed symptoms during the test; 6 patients had symptoms either in their history or during the test; and the remaining 9 were free of symptoms. There were no differences in the H2 increase. The fructose degradation rate was higher in symptomatic malabsorbers (255 mg vs. 217 mg), but the difference was not significant. However, there was a strong inverse correlation between this bacterial activity and the acetate level, with r = -0.822 (P = 0.000) and r = -0.868 (P = 0.000) in the rank correlation. The correlation for propionate was r = 0.479 (P = 0.083), and that for butyrate was r = 0.599 (P = 0.024). CONCLUSIONS: This study failed to confirm a significant correlation between fecal bacterial activity and the occurrence of symptoms in patients with fructose malabsorption. However, the interesting correlation with the SCFA raises questions regarding possible connections between colonic bacteria, carbohydrate malabsorption, and the beneficial effect of this pattern of SCFA in several colonic diseases.

Adult↗

Endoscopic ultrasound criteria for vascular invasion in the staging of cancer of the head of the pancreas: a blind reevaluation of videotapes.

BACKGROUND: It has been claimed in several prospective studies that endoscopic ultrasonography (EUS) is highly accurate in the locoregional staging of pancreatic cancer. However, the value of the EUS criteria for the diagnosis of vascular involvement is less well established. To totally exclude potential bias introduced by the availability of prior information, a completely blinded analysis of videotapes of patients with cancer of the pancreatic head was therefore conducted. METHODS: Videotape sequences of 75 patients with cancer of the head of the pancreas with surgical confirmation or unequivocally positive angiography demonstrating vascular invasion were reevaluated without any clinical data or information from other imaging studies. Involvement of the vascular system (portal vein with confluence, superior mesenteric vein, celiac axis) was assessed on EUS with special emphasis on EUS parameters of the tumor-vessel relationship. RESULTS: The overall sensitivity and specificity of EUS in the diagnosis of venous invasion were 43% and 91%, respectively, when using predetermined parameters (visualization of tumor in the lumen, complete obstruction, or collateral vessels). If the parameter "irregular tumor-vessel relationship" had been added to these criteria, the sensitivity would have risen to 62%, but the specificity would have fallen to 79%. The only vascular system that could be properly visualized by EUS was the portal vein/confluence area. The positive and negative predictive values for the single parameters chosen to diagnose portal venous involvement were as follows: 42% and 33% for irregular tumor-vessel relationship, 36% and 34% for visualization of tumor in the vascular lumen, 80% and 28% for complete vascular obstruction, and 88% and 18% for collateral vessels. CONCLUSIONS: In a completely blinded evaluation of the EUS diagnosis of vascular invasion by cancer of the head of the pancreas it was not possible to find suitable morphologic parameters with clinically useful sensitivity and specificity values (over 80%).

Adult↗

Modern imaging methods versus clinical assessment in the evaluation of hospital in-patients with suspected pancreatic disease.

OBJECTIVE: Various modern imaging procedures such as endoscopic retrograde cholangiopancreatography (ERCP), computed tomography (CT), and endoscopic ultrasonography (EUS) have been shown to be highly accurate in the diagnosis of specific disorders of the pancreas. However, prior information often causes bias in the interpretation of these results. Little information is available concerning the value of these examinations in the primary and differential diagnosis of suspected pancreatic disease-particularly in comparison with clinical evaluation, including laboratory tests and transabdominal ultrasound (TUS). METHODS: Clinical and imaging information (EUS, ERCP, and CT) was collected for 184 inpatients who were referred over a 5-yr period for evaluation of suspected pancreatic disease. On the basis of patient history, laboratory tests, and the results of routine TUS, one gastroenterologist, who was unaware of any of the other procedures or the final diagnosis, made a presumptive clinical diagnosis. CT and ERCP images and EUS videotapes were then analyzed by three different and independent examiners, who had the same clinical information except for the TUS results, but were completely blinded to the results of the other examinations and the patients' diagnoses. The final diagnoses were obtained by surgery, histology, and cytology, plus a follow-up of at least 1 yr (mean 35 months) in all noncancer cases. RESULTS: The final diagnoses were: normal pancreas (n = 36), chronic pancreatitis without a focal inflammatory mass (n = 53) or with a focal inflammatory mass (n = 18), and pancreatic malignancy (n = 77). Clinical evaluation, including ultrasonography, achieved a sensitivity for pancreatic disease of 94% but a specificity of only 35%. The figures for the sensitivity and specificity of the three imaging procedures were 93% and 94%, respectively, for EUS; 89% and 92% for ERCP; and 91% and 78% for CT (p < 0.05 for the specificity of clinical assessment vs all three imaging tests, p > 0.05 for comparison of the three imaging procedures). In the differential diagnosis between cancer and chronic pancreatitis as well as between malignant and inflammatory tumors, there was no difference among clinical assessment and the three imaging tests. CONCLUSIONS: In a group of patients with a high suspicion of pancreatic disease, little additional sensitivity in the diagnosis of pancreatic disease is provided by sophisticated imaging procedures such as EUS, ERCP, and CT, in comparison with clinical assessment including laboratory values and TUS. However, the specificity can be substantially improved. To confirm the diagnosis, one of the three examinations is needed, depending on the suspected disease and local expertise. The imaging procedures should be performed in a stepwise fashion for specific purposes, such as exclusion of pancreatic disease and the planning of treatment in chronic pancreatitis and pancreatic cancer.

Adolescent↗