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Biomedical subjects

R W Ammann

Publications and source records attributed to R W Ammann.

At least 19 recordsLinked to original sources
PubMed1998

Long-term mebendazole therapy may be parasitocidal in alveolar echinococcosis.

Long-term chemotherapy of human alveolar echinococcosis with benzimidazole compounds (mebendazole, albendazole) has been shown to be primarily parasitostatic, but its curative (parasitocidal) efficacy is debated. This article reports on a 67-year-old male patient with non-resectable alveolar echinococcosis of the liver who had been continuously treated for 13 years with mebendazole (approximately 45-48 mg/kg body weight per day) and who was closely monitored according to a specific protocol. At the age of 80 years the patient died of oesophageal variceal bleeding. During treatment the hepatic lesion had decreased markedly in size in association with progression of perifocal calcification. At autopsy, a well-demarcated, necrotic, partially calcified, parasite-induced lesion of the right liver lobe and secondary biliary cirrhosis were found. Remnants of parasite tissue obtained from the periphery of the lesion showed a small-cystic structure, but it was not viable, as evidenced by transplantation of tissue blocks to rodents. The case is suggestive for a parasitocidal efficacy of mebendazole treatment carried out for 13 years, and is discussed in context with conflicting literature data.

Aged↗
PubMed1998

HLA and alveolar echinococcosis.

Evidence in animal intermediate hosts that susceptibility to larval infection with Echinococcus multilocularis is restricted to individual host factors prompted us to investigate the susceptibility markers in humans. Because antigens of the extracellular parasite E. multilocularis are possibly presented by MHC molecules in a restricted way, we speculated that MHC polymorphism may influence resistance of the host towards infection and course of disease. We studied HLA-A, -B, -DRB1, -DQB1 and -DPB1 polymorphism in 151 patients with alveolar echinococcosis. Patients with an observation period of more than 2 years were grouped according to the clinical follow-up into cured (no recurrence following surgery) patients and patients with regressive or progressive forms of disease during benzimidazole chemotherapy. By comparing phenotypic frequency between patients with alveolar echinococcosis and healthy controls, HLA-DRB1*11 was associated with a reduced risk for disease development (odds ratio=0.55, 95% confidence interval=0.34-0.88; P=0.01). HLA-DQB1*02 was more frequent in patients with progressive disease when compared with patients with regressive disease (54.3% vs 28.3%, P=0.02). The result suggests that HLA-DRB1*11 might confer protection against alveolar echinococcosis and that HLA-DQB1*02 may indicate a risk for progressive disease development. The findings may facilitate the search for immunodominant T-cell epitopes of E. multilocularis.

Animals↗
PubMed1996

Cestodes. Echinococcus.

This article deals with cystic echinococcosis (CE) and alveolar echinococcosis in humans caused by the cestode parasites Echinococcus granulosus and Echinococcus multilocularis. The life cycles of these parasites and their epidemiologic aspects are briefly discussed, and a detailed review is presented on clinical aspects of the diseases, including diagnosis and therapy. Considerable progress has been made in chemotherapy but the results are not yet satisfactory. A new alternative for treatment of CE is puncture of cysts, aspiration of fluid, injection of ethanol, and reaspiration of fluid (PAIR).

Animals↗
PubMed1996

Course of alcoholic chronic pancreatitis: a prospective clinicomorphological long-term study.

BACKGROUND & AIMS: The pathogenesis of alcoholic chronic pancreatitis and its relationship to alcoholic acute pancreatitis are debated. According to our recent clinical long-term study, alcoholic chronic pancreatitis seems to evolve from severe acute pancreatits. The aim of this study was to correlate clinical findings to the pancreatic histopathology at early and advanced stages of the disease. METHODS: Morphological changes (pseudocysts, autodigestive necrosis, calcification, and perilobular and intralobular fibrosis) were recorded in 37 surgical and 46 postmortem pancreas specimens of 73 patients from our long-term series, who progressed from clinically acute to chronic pancreatitis (mean follow-up, 12 years). Pancreatic function was monitored at yearly intervals. RESULTS: Surgical interventions were performed at a mean of 4.1 years from onset. Histologically, focal necrosis (49%) and mild perilobular fibrosis (54%) predominated, Pseudocysts (n = 41, mostly postnecrotic) occurred in 88% within 6 years from onset. Autopsy specimens were obtained at a mean of 12 years. These pancreata often showed severe perilobular and intralobular fibrosis (85%) and calcifications (74%), but rarely necrosis (4%). Fibrosis correlated with progressive pancreatic dysfunction (P < 0.001), particularly in the 10 patients with two histological assessments (mean interval between biopsy and autopsy, 8 years). CONCLUSIONS: The data support an evolution from severe alcoholic acute pancreatitis to chronic pancreatitis.

Acute Disease↗
PubMed1995

Does acute pancreatitis progress to chronic pancreatitis? A microvascular pancreatitis model in the rat.

Ischemia as a causative factor for acute pancreatitis has been discussed for decades but has only recently gained wider acceptance. Chronic pancreatitis, however, has rarely been attributed to ischemic injury. While experimental evidence is available for the ischemic pathogenesis of acute pancreatitis, no studies have been reported about pancreatic ischemia as a single cause of chronic pancreatitis. Also, the progression from acute to chronic pancreatitis has been a very controversial issue. To address both questions we have injected polystyrene microspheres of 20-microns diameter into the pancreatic branches of the splenic artery of 36 rats. Thirteen more rats were sham operated and injected with saline. The animals were killed at 1, 2, 3, and 9 weeks after operation and macroscopically and histologically examined, and serum alpha-amylase and weight gain were determined. For the pancreas the following parameters were assessed using a score from 0 (no change) to 4 (severe change): atrophy, hemorrhage, edema, fat necrosis, acinar necrosis, polymorphonuclear infiltration, mononuclear infiltration, interstitial fibrosis, and ductal changes. While no difference between control and experiment was observed for serum alpha-amylase, weight gain, edema, and hemorrhage, persistent differences were evident for the parameters characteristic of chronic pancreatitis, most significantly for interstitial fibrosis, ductal changes, mononuclear infiltration, acinar necrosis, and atrophy. No spontaneous deaths occurred. The severity of the lesions remained stationary after the first week. Our work shows for the first time that pancreatic ischemia by microvascular hypoperfusion can cause histopathologic changes characteristic of chronic pancreatitis and that these changes follow acute necrotizing pancreatitis.

Acute Disease↗
PubMed1994

Separation and analysis of pig pancreatic zymogen granules with free flow electrophoresis and lectins.

Purified pig pancreatic zymogen granules were subjected to free flow electrophoresis (FFE) in an acetate buffer system (acetic acid/NaOH, pH 5.5) to detect the presence or absence of more than one population or zymogen granules. Pig pancreatic zymogen granules were purified by differential and density gradient centrifugation and subjected to FFE. Fractions were analyzed for protein, alpha-amylase (EC 3.2.1.1) and 5'-nucleotidase (EC 3.1.3.5) as marker enzymes for zymogen granule content and membranes, respectively. Only one distinct peak, with coincident alpha-amylase and 5'-nucleotidase activity, and most protein was detected, which reflects the presence of a single population of intact zymogen granules. This was confirmed by electron microscopy. When the granules were incubated with different lectins before FFE, the one distinct peak representing intact zymogen granules was shifted towards the cathode in the case of concanavalin A (Con A) and Ricinus communis agglutinin 120 (RCA 120). No splitting of the peak occurred. Our results do not support the hypothesis of a coexistence of more than one distinct population of zymogen granules.

Animals↗
PubMed1994

Effect of chemotherapy on the larval mass and the long-term course of alveolar echinococcosis. Swiss Echinococcosis Study Group.

The efficacy of long-term chemotherapy in nonresectable alveolar echinococcosis is debated, particularly because of the difficulty in defining therapeutic success. In this study the effect of chemotherapy on the parasitic mass was evaluated in a series of 37 patients. The patients had larval lesions documented by serial computed tomography studies at least 1.5 yr after chemotherapy (mean = 6.4 yr, range = 1.5 to 10.7 yr). The therapeutic regimen consisted of mebendazole (n = 34) or albendazole (n = 3) as previously described. The maximal areas of the parasitic lesions were assessed morphometrically by means of digital image analysis, utilizing the point-integration method, before and after chemotherapy. Marked regression of larval tissue occurred in 18 patients (group A; 48.6%), stationary lesions were noted in 13 patients (group C; 35.1%) and progression was found in 6 patients (group B; 16.2%). The three groups did not differ significantly with regard to age, plasma drug levels, duration of chemotherapy or initial size and composition of lesions (e.g., cystic cavities, degree of calcification). Despite morphologically successful chemotherapy in moist patients (e.g., 84%; groups A and C), late cholestatic complications after 1.5 to 11 yr of chemotherapy occurred in 10 patients (group A, n = 7; group C, n = 3; 4 of them died) and esophageal variceal bleeding occurred in 3 patients (relieved by sclerotherapy). These late complications were probably mainly due to posttherapy fibrosis of hilar structures. In conclusion, our data support the efficacy of chemotherapy. However, chemotherapy is not curative, and severe late complications were observed in patients with hilar (fibrotic) involvement.

Adult↗
PubMed1994

Progression of alcoholic acute to chronic pancreatitis.

Alcoholic chronic pancreatitis usually progresses from acute attacks to chronic pancreatitis within one to 19 years. The factors responsible for the appreciable variability in progression are unclear. In this study the relation between progression and the incidence and severity of acute episodes in a large cohort of patients with alcoholic chronic pancreatitis was analysed. All patients with at least one documented episode of acute pancreatitis have been studied prospectively over the past 30 years according to our protocol. Patients were classified according to their long term course into (a) calcific (n = 185), (b) non-calcific (n = 30), and (c) non-progressive (n = 39) chronic pancreatitis groups. The yearly incidence of acute attacks of pancreatitis was significantly higher in groups (a) and (b) than in group (c). Furthermore, the progression rate to advanced chronic pancreatitis (groups (a) and (b)) correlated with the incidence of severe pancreatitis (associated with pseudocysts in more than 55%). Pseudocysts were located primarily in the cephalic pancreas in groups (a) and (b) (58-71%) and in the pancreatic tail in group (c) (61%). In conclusion, these data suggest that the progression of acute to chronic pancreatitis is closely related to the incidence and severity of acute attacks. This finding and the primary location of pseudocysts in the cephalic pancreas (groups (a) plus (b)) are compatible with the 'necrosis-fibrosis' pathogenetic hypothesis.

Acute Disease↗
PubMed1994

Alcoholic nonprogressive chronic pancreatitis: prospective long-term study of a large cohort with alcoholic acute pancreatitis (1976-1992).

140 patients with alcoholic acute (recurrent) pancreatitis were enrolled in a prospective long-term study over the last 16 years. Regular control studies regarding progression to advanced chronic pancreatitis were performed. Based on long-term outcome the patients were classified into two groups: group A (n = 109; 77.8%) with progression to advanced chronic pancreatitis (84% with calcification, 95% with exocrine insufficiency) and group B (n = 31; 22.2%) without progression (no calcification, no exocrine insufficiency). The two groups were comparable in age, sex, and mean duration of disease from onset (13.1 +/- 5.2 vs. 13.8 +/- 4.9 years). Surgery for pseudocysts was performed in 47% of group A and in 29% of group B. In group B, no pancreatic duct dilatation occurred (in 86% > 8 years from onset). However, 4 of 7 patients with adequate histology showed unequivocal chronic pancreatitis. Surprisingly, all patients of group B except two got spontaneous lasting pain relief irrespective of alcohol intake or normal pancreatic function. Our findings indicate that a subgroup of alcoholic acute pancreatitis does not progress to advanced chronic pancreatitis. This subgroup may be identical with "small duct" chronic pancreatitis. The factors responsible for progression (group A) or nonprogression (group B) remain to be elucidated.

Adult↗
PubMed1994

Prognosis of chronic pancreatitis: an international multicenter study. International Pancreatitis Study Group.

OBJECTIVES: The aim of this study was to determine which factors predict mortality in a cohort of patients with chronic alcoholic and nonalcoholic pancreatitis. Patients with chronic pancreatitis are known to have a reduced life expectancy, but the quantitative relationship between various clinical features and survival is unclear. METHODS: We evaluated survival among 2015 subjects with chronic pancreatitis treated at seven centers located in six countries. RESULTS: Mean age at diagnosis was 46 +/- 13 yr and mean duration of follow-up was 7.4 +/- 6.2 yr. Overall survival at 10 yr was 70% (95% confidence interval (CI), 68-73%) and at 20 yr was 45% (95% CI, 41-49%). Survival was significantly less than in the background population. There were 559 deaths observed among those with chronic pancreatitis compared with an expected number of 157.4, yielding a standardized mortality ratio (SMR) of 3.6 (95% CI, 3.3-3.9). Older subjects and those with alcoholic pancreatitis had a significant reduction in survival. In a multivariate analysis, mortality of middle-aged and older subjects was 2.3 (95% CI, 1.8-2.8) and 6.3 (95% CI, 4.7-8.3) times greater than subjects less than 40 yr at diagnosis. Smoking (hazard ratio, 1.4; 95% CI, 1.0-1.9), drinking (hazard ratio, 1.6; 95% CI, 1.2-2.2), or development of cirrhosis (hazard ratio, 2.5; 95% CI, 2.0-3.2) increased the risk of death during the observation period, but we observed no survival difference in operated vs. nonoperated patients. CONCLUSIONS: Age at diagnosis, smoking, and drinking are major predictors of mortality in patients with chronic pancreatitis.

Age of Onset↗
PubMed1993

Pancreatitis and the risk of pancreatic cancer. International Pancreatitis Study Group.

BACKGROUND: The results of case-control studies and anecdotal reports suggest that pancreatitis may be a risk factor for pancreatic cancer, but there have been no studies of sufficient size and power to assess the magnitude of the relation between these two diseases. METHODS AND RESULTS: We undertook a multicenter historical cohort study of 2015 subjects with chronic pancreatitis who were recruited from clinical centers in six countries. A total of 56 cancers were identified among these patients during a mean (+/-SD) follow-up of 7.4 +/- 6.2 years. The expected number of cases of cancer calculated from country-specific incidence data and adjusted for age and sex was 2.13, yielding a standardized incidence ratio (the ratio of observed to expected cases) of 26.3 (95 percent confidence interval, 19.9 to 34.2). For subjects with a minimum of two or five years of follow-up, the respective standardized incidence ratios were 16.5 (95 percent confidence interval, 11.1 to 23.7) and 14.4 (95 percent confidence interval, 8.5 to 22.8). The cumulative risk of pancreatic cancer in subjects who were followed for at least 2 years increased steadily, and 10 and 20 years after the diagnosis of pancreatitis, it was 1.8 percent (95 percent confidence interval, 1.0 to 2.6 percent) and 4.0 percent (95 percent confidence interval, 2.0 to 5.9 percent), respectively. CONCLUSIONS: The risk of pancreatic cancer is significantly elevated in subjects with chronic pancreatitis and appears to be independent of sex, country, and type of pancreatitis.

Adult↗
PubMed1992

Element distribution in organelles of pancreatic acinar cells of rat, mouse, and pig investigated by energy-dispersive X-ray microanalysis.

The exocrine pancreas was long thought to be composed of identical subunits, the acinar cells that store the inactive forms of the digestive enzymes in zymogen granules (ZGs). These were generally seen as a homogeneous population of vesicles. This homogeneity was recently questioned: Digestive demands are answered by the release of specific enzymes and immunocytochemical labeling showed distinctive nonidentical populations of ZGs. We have aimed at finding concomitant differences in element contents. We analyzed by energy-dispersive x-ray microanalysis (EDX) the subcellular distribution of elements in acinar cells of resting and stimulated rat, resting mouse, and resting pig pancreas and compared the results with values from the literature. We found large variances in the concentrations of Na, Mg, P, S, Cl, K, and Ca in cytoplasm rich in endoplasmic reticulum (C/E), whereas the concentrations of P, Cl, K, and Ca in mitochondria and ZGs had surprisingly small variations. Na and Mg were detected in measurable amounts only in C/E and mitochondria and Ca was detectable only in ZGs. We could not find any other elements. We have not found clearly distinguishable populations of ZGs. We critically discuss our findings in comparison with the literature. Many discrepancies can be explained by the different preparation procedures. We show that it is questionable to present absolute values of concentration in biological specimens on the basis of EDX. The technique should, in our opinion, be used only for the study of relative concentrations.

Animals↗
PubMed1992

[Acute pancreatitis in the rat following experimental microembolism with cholesterol crystals].

Several case reports exist which demonstrate cholesterol crystals to be the cause of acute pancreatitis in humans. The crystals have been found intravascularly in the pancreas and at least in one case the origin of the crystals was known. We have undertaken to experimentally reproduce this pathogenetic mechanism in the rat. 30 rats were subjected to the following procedures: under anaesthesia the splenic artery was distally ligated and proximally cannulated; 16 control animals were injected via the cannula with saline (8 rats), particle free cholesterol saturated physiologic saline (3 rats) or nothing (5 rats). 14 rats were injected with ca. 400 microliters of a dilute suspension of cholesterol crystals of 5-40 microns diameter in cholesterol saturated physiologic saline. The abdomen was closed and after 24 h all animals were killed. Acute pancreatitis was diagnosed in all animals that received cholesterol microcrystals and in none of the controls. The diagnosis was based on macroscopic and histological findings. Acute pancreatitis was of focal, disseminated, necrotic type with oedema and moderate haemorrhage and fat necrosis. Only those parts of the pancreas were affected which were supplied by branches of the distal splenic artery used for retrograde injections of cholesterol crystals. This model supports the notion that microembolic or microthrombotic events play a pivotal role in the pathogenesis of spontaneous acute pancreatitis.

Acute Disease↗