[Use of positron-emission tomography in oncology].
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Biomedical subjects
Publications and source records attributed to T Sauerbruch.
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As the host's immune response may determine the course of hepatitis C virus (HCV) infection, we studied the humoral and cellular immune responses to HCV-related antigens in subjects with different outcomes of HCV infection. Lymphoproliferative responses and circulating antibodies to a panel of HCV core- and E1-related 25-mer peptides were examined in 10 healthy anti-HCV-seropositive blood donors (group A) and in 29 patients with chronic hepatitis C (group B). In addition, cellular recognition of recombinant HCV proteins (core, NS3, NS4A, NS5A, NS5B) were investigated. In group A, stronger T-cell responses were detected against both HCV proteins (core, P = .03; NS4, P = .005; NS5B, P = .03) and peptides. Proliferation was induced by the same peptides in each group, defining at least five distinctive epitopes within core (amino acids [aa] of 20-44, aa 39-63, aa 79-103, aa 118-152 and aa 148-172) and three regions within E1(aa 198-252, aa 308-372, and aa 368-392). Subjects with strong T-cell responses had low or no detectable levels of peptide-specific antibodies, and vice versa. In particular, T-cell responses were more common in group A; B-cell responses were more common in group B. From our data, we conclude that a benign course of HCV infection may be the consequence of the effective activation of T-helper lymphocytes.
OBJECTIVE: To ascertain the prevalence of Helicobacter pylori infection in Germany and to identify risk factors associated with H. pylori seroconversion. METHODS: Two hundred and sixty blood donors (169 men, 91 women; median age 29 years, range 18-61 years, 92% with German parents, all white) were studied. None had previously been treated for H. pylori infection. Their serum samples were analysed for H. pylori immunoglobulin (lg) G antibodies with a validated enzyme-linked immunosorbent assay (ELISA). All subjects completed a complex questionnaire under supervision. Special attention was paid to their present and childhood (at the age of 8 years) living conditions. To identify independent risk factors for seropositivity, a multivariate, stepwise forward, unconditional, logistic regression analysis was performed. RESULTS: In total, 102 participants (39.2%) were seropositive for H. pylori. Seroprevalence increased significantly with age (21.1% aged 21 or younger compared with 60.0% over 51 years of age). According to the multivariate analysis of the unclassified data [odds ratio (95% confidence interval)], variables such as age [1.04 (1.01-1.07) per year], persons per room in household in childhood [2.14 (1.07-4.26)] and number of children (< 8 years) in household at present [1.79 (1.01-3.16) per child] were significantly and independently associated with H. pylori seroprevalence. CONCLUSION: Crowded living conditions in childhood affect current H. pylori status. In addition, the number of children in the present household increases the risk of infection for the adult family members. This suggests that children are an additional source of infection, probably due to close and frequent physical contact outside the immediate family.
BACKGROUND: The rapid urease test is the most widely used standard procedure for the detection of Helicobacter pylori infection. This is because it is a simple, reliable and inexpensive test, which provides results rapidly. AIM: The aim of the present study was the evaluation of a modified rapid urease test (HUT-test) in comparison with the standard CLO-test. In addition, it was questioned whether the performance of the rapid urease test in two biopsy samples from antrum and gastric body would increase the sensitivity of the test. METHODS: One hundred and fifteen consecutive patients undergoing oesophagogastroduodenoscopy were studied. Diagnosis of H. pylori infection was based on histological examination of biopsy samples from antrum and gastric body. The HUT-test was performed in two biopsy specimens from antrum and body, respectively, and the CLO-test in one antral biopsy sample. The time to positivity and the stability of the HUT-test kit at different storage temperatures were previously optimized by adapting the type and concentration of buffer and indicators. RESULTS: Sixty patients (52%) were diagnosed as being infected with H. pylori. Sensitivity of the rapid urease tests in biopsy samples from the antrum was 90% for the HUT-test and 88% for the CLO-test, with a specificity of 100% for both tests. Combining biopsies from the antrum and corpus increased the diagnostic sensitivity of the HUT-test to 93%, but the specificity decreased to 98%. In patients with H. pylori infection, the HUT-test gave positive results more rapidly than the CLO-test (104 +/- 21 min compared with 195 +/- 49 min, respectively, P < 0.02). CONCLUSION: Application of the HUT-test to a simple biopsy from the antrum can establish the diagnosis of H. pylori infection with high accuracy, similar to that of the standard CLO-test. Compared with the CLO-test, the HUT-test has a significantly faster reaction time, which is an obvious clinical advantage. An additional biopsy from the distal gastric body did not add to the diagnostic efficacy in untreated patients, but may be needed in specific circumstances, such as following treatment.
Tuberculous splenic abscesses do virtually not occur in immunocompetent patients. Tuberculous abscesses have been reported only from areas, where the prevalence of both HIV infection and tuberculosis is very high such as Central Africa. In our institution two of seven patients with AIDS and disseminated tuberculosis who were treated during the year 1994 developed tuberculous splenic abscesses. Both patients were resident in Central Europe and had fever and weight loss prior to admission. Multiple hypoechoic lesions up to 1.5 cm in diameter developed in the spleen of both patients on day 11 and 16 after admission, respectively. Initially no symptoms related to the splenic involvement and no leucocytosis were seen in both patients. One patient developed leucocytosis and left sided flank pain caused by a subtotal splenic abscess because the diagnosis and therapy of tuberculosis was delayed. Both patients responded promptly to triple drug antituberculous therapy without surgical intervention. We conclude that also in European patients multiple hypoechoic/hypodense lesions in the spleen of HIV positive patients are highly suggestive of disseminated tuberculosis. Follow-up by ultrasound may help to establish the correct diagnosis and may further prevent unnecessary complications in these patients.
Infection with the hepatitis C virus (HCV) commonly causes persistent disease, which may lead to cirrhosis and hepatocellular carcinoma. The pathogenesis of HCV infection is not well understood. It is most likely that both viral and host factors contribute to HCV persistence. This review focuses on the host's immune response to HCV in an attempt to present the current knowledge and concepts of the interactions between the virus and the host during HCV infection. Expansion of B lymphocytes and antibody production to virtually any HCV protein can be detected in most infected patients. However, observations in HCV-infected humans as well as experimental infections in chimpanzees suggest that natural HCV infection does not induce protective immunity, and reinfection can readily be demonstrated after inoculation with homologous or independent strains in HCV-seroconverted animals. Nevertheless, the immune system may gain partial control over HCV even in patients with chronic infection, as HCV infection in severely immunocompromised patients runs a particular cholestatic course which may rapidly lead to death from liver failure. Cytotoxic CD8+ T lymphocyte responses to HCV proteins have been characterized in peripheral blood and liver tissue and were found to be remarkably polyclonal and multispecific. Epitopes were identified on all of the putative HCV proteins, although only few major histocompatibility complex molecules were considered restriction elements. Immunoregulation may be particularly important in HCV infection. The HCV core and NS4 proteins appear to be most immunogenic for peripheral blood lymphocytes, and NS4 specific CD4+ lymphocytes are preferentially compartmentalized to the liver. However, there is an inverse relationship between CD4+ lymphocyte responses and antibody levels in infected patients. Furthermore, a strong cellular response to the HCV core protein apparently favors a benign course of infection. This unusual T-B cell relationship may be the consequence of an altered cytokine release during HCV infection. Alternatively, this virus may have found devices that can disturb immunoregulation in infected patients. A better understanding of these immunological mechanisms induced by HCV infection should make it possible to develop more effective strategies for the prevention and treatment of this insidious disease.
BACKGROUND: Detection of Helicobacter pylori infection in clinical routine is based either on the direct visualization of the bacterium in gastric biopsies by histology or microbiology or on the demonstration of urease activity in gastric biopsies and by the labelled-urea breath test (UBT). Omeprazole has a strong inhibitory effect on H. pylori urease activity in vitro, but its effect in vivo and thus its influence on urease-based diagnostic procedures has not been investigated systematically. AIM: To investigate whether omeprazole is able to inhibit H. pylori urease activity in vivo and, if so, at which doses. PATIENTS: Eighteen patients with H. pylori associated chronic gastritis were studied. METHODS: H pylori diagnosis was based on histology, rapid urease test and culture from antral biopsies. Following a positive H. pylori diagnosis patients received omeprazole 20mg (n = 6), 40mg (n = 6) and 80mg (n = 6) once daily for 5 days and 13C-UBT was performed on day 1, 3 and 5, 30min after each omeprazole administration. The 13C-UBT was performed with 200ml 0.1 N citric acid as test drink and 75mg 13C-urea. Breath samples were collected before and 30 min after 13C-urea administration. RESULTS: A significant inhibition of urease activity was observed only under high dose omeprazole administration (80 mg/day), and the 13C-UBT turned negative in three (50%) of these patients after 5 days therapy. CONCLUSION: Short-term omeprazole administration reduces H. pylori urease activity only at doses as high as 80 mg/day. A direct inhibition of enzyme activity as well as a reduction in the number of viable H. pylori bacteria may be responsible for this omeprazole-mediated reduction in urease activity. Urease-based diagnostic procedures for H. pylori are not suitable for patients under omeprazole therapy depending on the dose and duration of therapy.
OBJECTIVE: The aim of this study was to examine the interaction between HIV and hepatitis C virus (HCV) in hemophiliacs coinfected with the viruses and to investigate the possible relationship between immunosuppression and liver failure. METHODS: To identify risk factors for impending liver failure in hemophiliacs coinfected with HIV and HCV, we analyzed clinical and laboratory parameters, including CD4 count, aminotransferases (ALT, AST), cholinesterase, alkaline phosphatase, bilirubin, and gamma-glutamyltransferase, during 3 yr of follow-up (1990-1993) in four groups of patients: hemophiliacs with progressive immunodeficiency who were coinfected with HCV and HIV (group A, n = 49); hemophiliacs with stable immune function who were seropositive for HIV and HCV (group B, n = 95); hemophiliacs who were infected with HCV but not HIV (group C, n = 72); and homosexuals with progressive immunodeficiency who were infected with HIV but not HCV (group D, n = 24). RESULTS: Univariate analysis of data for group A showed a significant rise in gamma-glutamyltransferase and alkaline phosphatase (p < 0.01) that was not seen in groups B, C, and D. In a multivariate Cox regression analysis, age (odds ratio, 1.054 per yr; 95% confidence interval, 1.014-1.096 per yr), decline in CD4 count (odds ratio, 1.063 per cell/microl; 95% confidence interval, 1.037-1.091 per cell/microl), and alkaline phosphatase level (odds ratio, 1.012 per U/L; 95% confidence interval, 1.002-1.021 per U/L) emerged as independent determinants of death. CONCLUSIONS: Our data suggest that progressive immune dysfunction in hemophiliacs coinfected with HIV and HCV may influence progression of liver failure. In these patients cholestasis is an additional prognostic marker for survival that may reflect both exhausted immunity and impaired liver function.
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A 22-year-old Libyan patient suffering from chronic diarrhea presented with an alpha-heavy chain paraprotein and a lympho-plasmacellular lymphoma infiltration of the duodenal mucosa. These findings supported the diagnosis of "immunoproliferative small intestinal disease" (IPSID). In this disease, that occurs almost solely in countries with low socioeconomic status, a diffuse infiltration of small intestinal mucosa by neoplastic lymphoid cells causes chronic malabsorption. About 65% of patients exhibit a paraprotein in serum, urine or jejunal juice that consists of the heavy chain of immunoglobulin A (alpha-heavy chain). In advanced stages, IPSID resembles histologically and clinically high grade lymphoma: some patients develop masses in the gut wall, an abdominal lymphadenopathy and involvement of other organs including bone marrow. The disease is believed to be triggered by a chronic infectious antigenic stimulus. Thus, in early stages in some patients cure may be achieved by antibiotic therapy alone. In advanced disease, chemotherapy including anthracyclins is necessary.
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To determine the rate and characteristics of gallstone recurrence after direct contact dissolution with methyl tert-butyl ether, 60 consecutive patients were followed for up to 4.5 years (median 2.2 years) after complete disappearance of all stone residues and debris and cessation of adjuvant bile acid therapy. Initial gallstones had been multiple in all but four patients. Twenty-eight of the 60 patients developed recurrent gallstones. The cumulative risk of gallstone recurrence (actuarial analysis) was 23 +/- 6%, 34 +/- 7%, 55 +/- 8%, and 70 +/- 9% at one, two, three, and four years, respectively. The recurrent stones were usually multiple and small (6 +/- 4 mm). Gallstone recurrence was associated with recurrent biliary pain in two patients, one of whom developed acute cholecystitis. Recurrent stones were cleared completely by bile acid medication with or without shock-wave lithotripsy in 61 +/- 15% of patients at one year (actuarial analysis). In conclusion, gallstone recurrence after successful contact dissolution of multiple stones with methyl tert-butyl ether has to be expected in a high percentage of patients. Most patients, however, remain free of biliary pain during long-term follow-up.
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BACKGROUND AND STUDY AIMS: Endoscopic extraction of bile duct stones may be complicated by impaction of the Dormia basket with captured stones, or rupture of the traction wire of the basket during mechanical lithotripsy. In an attempt to release impacted baskets by nonoperative means, we studied the efficacy of extracorporeal shock-wave lithotripsy in this dangerous clinical situation. PATIENTS AND METHODS: Fourteen extracorporeal shock-wave treatments were performed in 12 consecutive patients (eight women and four men; mean age 73.2 +/- 13.2 years, range 46-86 years) with an electrohydraulic shock-wave lithotriptor, using fluoroscopy (n = 13) or ultrasound (n = 1) for targeting. A total of 1845 +/- 334 (mean +/- SD) shock-wave discharges at a voltage of 22 +/- 4 kV were delivered per treatment. Nine treatment sessions (64%) were performed while patients were under general anesthesia. An attempt to extract the Dormia basket was made after disintegration of the captured stone had been confirmed by fluoroscopy. RESULTS: It was possible to remove the Dormia basket by nonsurgical means in 11 of the 12 patients (92%) after one treatment session, and after three treatment sessions in the remaining patient. Thus, disintegration of the stones allowed extraction of the Dormia basket in all patients. None of the patients needed surgical intervention. All patients were rendered free of bile duct stones after extracorporeal shock-wave lithotripsy and subsequent endoscopic removal of the fragments. No adverse effects of shock-wave therapy with subsequent extraction of the Dormia baskets were observed. CONCLUSION: Shock-wave therapy represents a primary nonsurgical therapeutic option in patients with either impacted Dormia baskets or broken devices which cannot be extracted by endoscopic means.
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