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K Truninger

Publications and source records attributed to K Truninger.

17 recordsLinked to original sources
PubMed2005

Impact of etiology on the painful early stage of chronic pancreatitis: a long-term prospective study.

BACKGROUND AND AIM: This prospective study aimed to investigate the impact of etiology on the pain profile in relation to alterations of function and morphology from early to advanced chronic pancreatitis (CP). METHODS: Our mixed medico-surgical cohort comprised 265 patients with alcoholic (ACP), 21 with idiopathic "juvenile" (IJCP), 46 with idiopathic "senile" (ISCP) and 11 with hereditary CP (HPCP). The patients were followed regularly from onset of disease according to the protocol published previously. RESULTS: Males predominated in ACP, IJCP, ISCP (> 71%) but not in HP (46%). Age at onset (median) was 10, 23, 36 and 62 years in HP, IJCP, ACP and ISCP, respectively. Follow-up from disease onset ranged from 14 to 36 years. The progression to late-stage CP, documented by exocrine insufficiency (86-100%) and calcification (80-91%) lasted 2 to 5-fold longer in HP/IJCP compared to ACP. Early stage CP, characterized by recurrent pancreatitis prevailed in > or = 90% of patients, except for those with ISCP (48%), and lasted up to 5-fold longer in HP/IJCP compared to ACP. Surgery for severe pain was required for ACP/IJCP in 57% of the patients compared to < 27% in HP/ISCP. Permanent pain relief regularly occurred in late-stage CP irrespective of etiology and surgery. CONCLUSION: The clinical profile of the 4 "etiological" subgroups is predictably different in the painful early (precalcific) CP stage.

Adolescent↗
PubMed2005

Exon 3 beta-catenin mutations are specifically associated with colorectal carcinomas in hereditary non-polyposis colorectal cancer syndrome.

BACKGROUND AND AIMS: Activating beta-catenin mutations in exon 3 have been implicated in colorectal tumorigenesis. Although reports to the contrary exist, it has been suggested that beta-catenin mutations occur more often in microsatellite unstable (MSI+) colorectal carcinomas, including hereditary non-polyposis colorectal cancer (HNPCC), as a consequence of defective DNA mismatch repair. We have analysed 337 colorectal carcinomas and adenomas, from both sporadic cases and HNPCC families, to provide an accurate assessment of beta-catenin mutation frequency in each tumour type. METHODS: Direct sequencing of exon 3 of beta-catenin. RESULTS: Mutations were rare in sporadic (1/83, 1.2%) and HNPCC adenomas (1/37, 2.7%). Most of the sporadic adenomas analysed (80%) were small (<1 cm), and our data therefore differ from a previous report of a much higher mutation frequency in small adenomas. No oncogenic beta-catenin mutations were identified in 34 MSI+ and 78 microsatellite stable (MSI-) sporadic colorectal cancers but a raised mutation frequency (8/44, 18.2%) was found in HNPCC cancers; this frequency was significantly higher than that in HNPCC adenomas (p=0.035) and in both MSI- (p<0.0001) and MSI+ (p=0.008) sporadic cancers. Mutations were more common in higher stage (Dukes' stages C and D) cancers (p=0.001). CONCLUSION: Exon 3 beta-catenin mutations are associated specifically with malignant colorectal tumours in HNPCC; mutations appear not to result directly from deficient mismatch repair. Our data provide evidence that the genetic pathways of sporadic MSI+ and HNPCC cancers may be divergent, and indicate that mutations in the HNPCC pathway of colorectal tumorigenesis may be determined by selection, not simply by hypermutation.

Adenoma↗
PubMed2005

Polymorphisms of UDP-glucuronosyltransferase 1A7 are not involved in pancreatic diseases.

BACKGROUND: Xenobiotic mediated cellular injury is thought to play a major role in the pathogenesis of pancreatic diseases. Genetic variations that reduce the expression or activity of detoxifying phase II biotransformation enzymes such as the UDP-glucuronosyltransferases might be important in this respect. Recently, a UGT1A7 low detoxification activity allele, UGT1A7*3, has been linked to pancreatic cancer and alcoholic chronic pancreatitis. OBJECTIVE: To investigate whether UGT1A7 polymorphisms contribute to the risk of pancreatitis and pancreatic cancer. METHODS: Genetic polymorphisms in the UGT1A7 gene were assessed in a large cohort of patients with different types of pancreatitis and pancreatic cancer originating from the Czech Republic (n = 93), Germany (n = 638), Netherlands (n = 136), and Switzerland (n = 106), and in healthy (n = 1409) and alcoholic (n = 123) controls from the same populations. Polymorphisms were determined by melting curve analysis using fluorescence resonance energy transfer probes. In addition, 229 Dutch subjects were analysed by restriction fragment length polymorphism. RESULTS: The frequencies of UGT1A7 genotypes did not differ between patients with acute or chronic pancreatitis or pancreatic adenocarcinoma and alcoholic and healthy controls. CONCLUSIONS: The data suggest that, in contrast to earlier studies, UGT1A7 polymorphisms do not predispose patients to the development of pancreatic cancer and pancreatitis.

Adenocarcinoma↗
PubMed2001

Genetic aspects of chronic pancreatitis: insights into aetiopathogenesis and clinical implications.

The recent genetic discoveries in CP support the hypothesis that inappropriate intrapancreatic activation of zymogens by trypsin results in autodigestion and pancreatitis. Two different protective mechanisms prevent activation of the pancreatic digestive enzyme cascade. First, SPINK1 inhibits up to 20% of potential trypsin activity and, second, trypsin itself activates trypsin-like enzymes readily degrading trypsinogen and other zymogens. Pancreatitis may therefore be the result of an imbalance between proteases and their inhibitors within the pancreatic parenchyma. The discovery of PRSS1 mutations in families with CP was the first breakthrough in the understanding of the underlying genetic mechanisms. Enhanced trypsinogen activation may be the common initiating step in pancreatitis caused by these mutations. The discovery of SPINK1 mutations underlines the importance of the protease inhibitor system in the pathogenesis of CP. Thus, gain-of-function in the cationic trypsinogen resulting in an enhanced autoactivation, or loss-of-function mutations in SPINK1 leading to decreased inhibitory capacity, may similarly disturb the delicate intrapancreatic balance of proteases and their inhibitors. The recent findings of SPINK1, CFTR, and PRSS1 mutations in CP patients without a family history have challenged the concept of idiopathic CP as a non-genetic disorder and the differentiation between HP and ICP. There is a clear mode of autosomal dominant inheritance for some mutations (R122H, N291, possibly MIT), whereas the inheritance pattern (autosomal recessive, complex, or modifying) of other mutations (A16V, N34S) is controverted or unknown. The lack of mutations in the above-mentioned genes in many patients suggests that CP may also be caused by genetic alterations in yet unidentified genes. Evaluation of CP patients without an obvious predisposing factor, e.g. alcohol abuse, should include genetic testing even in the absence of a family history of pancreatitis. Finally, identification of further disease-causing genes will create a better understanding of pathogenesis and may help to develop specific preventive and therapeutic strategies.

Chronic Disease↗
PubMed2001

Lack of MSH2 and MSH6 characterizes endometrial but not colon carcinomas in hereditary nonpolyposis colorectal cancer.

Hereditary nonpolyposis colorectal cancer syndrome is associated with an inherited predisposition to primarily colorectal cancer (CRC) and endometrial cancer (EC); however, the biological basis of the organ involvement remains unknown. As an attempt to explore whether the expression levels of MLH1, MSH2, and MSH6 may play a role, we used immunohistochemistry to study 42 ECs and 35 CRCs from patients carrying the same predisposing mutations. Among MSH2 mutation carriers, MLH1 was expressed in both tumor types, whereas MSH2 and, in many cases, also MSH6, were absent. Remarkably, among MLH1 mutation carriers, 54% of ECs (21 of 39), but none of the CRCs (0 of 32), lacked the MSH2 and/or MSH6 protein in addition to lacking MLH1 protein expression. These results demonstrate a marked difference between hereditary nonpolyposis colorectal cancer-related CRCs and ECs and suggest that the development of the latter tumors is selectively associated with the MSH2/MSH6 protein complex deficiency.

Adaptor Proteins, Signal Transducing↗
PubMed2001

Trypsinogen gene mutations in patients with chronic or recurrent acute pancreatitis.

Three-point mutations (R117H, N211, A16V) within the cationic trypsinogen gene have been identified in patients with hereditary pancreatitis (HP). A genetic background has also been discussed for idiopathic juvenile chronic pancreatitis (IJCP), which closely mimicks the clinical pattern of HP, and alcoholic chronic pancreatitis because only a small number of heavy drinkers develop pancreatitis. This prompted us to screen 104 patients in our well-defined pancreatitis cohort for the currently known cationic trypsinogen gene mutations. The R117H mutation was detected in seven patients (six patients of two clinically classified HP families, one patient with clinically classified IJCP) and the A16V mutation in one IJCP patient. No cationic trypsinogen gene mutations were found in the remaining 96 patients with chronic and recurrent acute pancreatitis of various etiologies. Our results demonstrate the need for genetic testing to exclude HP, particularly in the presence of an atypical or unknown family history. In addition, cationic trypsinogen gene mutations are no predisposing factor in patients with chronic and recurrent acute pancreatitis of different etiologies.

Acute Disease↗
PubMed2001

Mutations of the cystic fibrosis gene in patients with chronic pancreatitis.

OBJECTIVE: Several studies have reported an increased frequency of cystic fibrosis gene mutations in idiopathic but not in alcoholic chronic pancreatitis. The impact of cystic fibrosis gene mutations on the long-term course of chronic pancreatitis has not been analyzed. The aim of our study was to determine the frequency of cystic fibrosis gene mutations in patients with chronic pancreatitis with long-term follow-up and to see whether patients with mutations have a clinically different natural course compared to those without mutations. METHODS: Eighty two patients with chronic pancreatitis and 11 patients with recurrent acute pancreatitis of our well defined pancreatitis cohort were screened for the 31 most common cystic fibrosis gene mutations. The impact of cystic fibrosis gene mutations on the long-term course of chronic pancreatitis was assessed. RESULTS: A cystic fibrosis gene mutation was detected in five of 49 patients with alcoholic chronic pancreatitis (10.2%; 2.3 times the expected frequency) and in three of 14 patients with idiopathic-juvenile chronic pancreatitis (21.4%; 4.8 times the expected frequency). No mutations were found in the remaining patients with chronic pancreatitis of rare causes, hereditary pancreatitis, and recurrent acute pancreatitis. The frequency of pancreatic calcifications was significantly higher in patients with alcoholic chronic pancreatitis without mutations. This result was not confirmed in patients with idiopathic-juvenile chronic pancreatitis. The duration of pain and the frequency of exocrine and endocrine insufficiency was comparable in both subgroups irrespective of the mutation status. CONCLUSION: Our data indicate a significantly increased frequency of cystic fibrosis gene mutations both in patients with alcoholic and idiopathic-juvenile chronic pancreatitis. The natural course was similar in patients with mutations compared to those without mutations.

Adult↗
PubMed2000

[Risk groups for pancreatic and bile duct carcinomas].

Biliopancreatic carcinoma has a poor prognosis since the diagnosis of the tumor occurs late when advanced disease is present. The identification of potential causes and earlier diagnosis are needed to prevent the disease or identify it early enough to improve survival. The main risk factors for pancreatic cancer include advanced age, cigarette smoking, high-fat diet, diabetes mellitus, chronic pancreatitis (especially hereditary pancreatitis) and a positive family history of pancreatic cancer. The most important etiologic factor for the development of gallbladder cancer is gallstone disease. Patients with anatomic abnormalities and chronic inflammatory conditions (primary sclerosing cholangitis, infections with parasites) have an increased incidence of bile duct cancers. Several new and promising imaging techniques have recently become available and our understanding of the mechanisms of carcinogenesis are growing rapidly. However, there is currently no effective screening strategy applicable and it is unknown when to begin screening. For pancreatic cancer, reduction of risk is likely to occur with avoidance of smoking and promotion of healthful diets. Cholecystectomy rates have increased since the introduction of new laparoscopic techniques and will eventually reduce the incidence of gallbladder cancer. Improved imaging techniques, the identification of new genes and a better definition of genetic alterations that characterize preinvasive lesions will hopefully allow to develop sensitive and specific technologies to screen and to detect early biliopancreatic cancer for even premalignant lesions to improve the mostly fatal prognosis if this tumor.

Aged↗
PubMed2000

[Screening for prevention and early detection of colorectal carcinoma].

Colorectal Cancer (CRC) fulfills all the criteria for a successful screening: i) it is a frequent tumor associated with serious morbidity and mortality; ii) recognition and treatment of premalignant lesions or early tumor stages improves prognosis and lowers its incidence, respectively. During recent years, our understanding of the biology, diagnosis and therapy of adenomas and CRCs led to the identification of risk factors. Based on these, screening strategies differ for individuals with average risk (age > or = 50 years, no risk factors) and individuals with increased risk for CRC development (positive personal history [CRC, colorectal adenomas, inflammatory bowel disease]; positive family history [CRC, colorectal adenomas, hereditary syndromes]). The currently available strategies aimed at prevention and early detection of CRCs (past history, family history, rectal digital examination, fecal occult blood testing, endoscopy) are discussed and recommendations for their implementation are formulated.

Adult↗
PubMed1999

[Methotrexate pneumonitis].

A 72 year old female with rheumatoid arthritis was treated with methotrexate for nine months. Four days before admission she complained of dyspnea NYHA III. Chest-X-ray revealed diffuse interstitial pneumopathy. Pulmonary infection was excluded by several microbiological samples. A pulmonary manifestation of rheumatoid arthritis is usually more chronic. Methotrexate-induced pneumonitis remained the most probable diagnosis. We halted methotrexate and initiated therapy with glucocorticoids. This treatment led to rapid clinical improvement and complete resolution of radiological changes.

Aged↗
PubMed1999

Bronchiolitis obliterans organizing pneumonia associated with polymyalgia rheumatica.

The association of bronchiolitis obliterans organizing pneumonia (BOOP) with polymyalgia rheumatica is rare, and only one case has previously been described. This study reports on the case of an 80 yr-old male who presented with malaise, nonproductive cough and exertional dyspnoea for several weeks, along with a history of bilateral shoulder and pelvic girdle pain of several months' duration. The chest radiograph revealed a pneumonic infiltrate in the right lower lobe, which was unresponsive to antibiotics. Bronchoscopy, bronchoalveolar lavage and a transbronchial lung biopsy established the diagnosis of BOOP. The patient improved consistently on steroids. As in other connective diseases, organizing pneumonia may be one of the early manifestations of polymyalgia rheumatica.

Aged↗
PubMed1999

Long term follow up of prosthetic valve endocarditis: what characteristics identify patients who were treated successfully with antibiotics alone?

OBJECTIVE: To identify predictors for the safe use of antibiotic treatment without reoperation in patients with prosthetic valve endocarditis. SETTING: Retrospective study in a tertiary care centre. SUBJECTS AND DESIGN: All 49 episodes of definite prosthetic valve endocarditis (Duke criteria) diagnosed at one institution between 1980 to 1997 were analysed. Ten episodes (20%) were treated with antibiotics only (antibiotic group) and 39 episodes (80%) with combined antibiotic and surgical treatment (surgery group). The analysis included detailed study of hospital records and data on long term follow up which were obtained in all patients by a questionnaire or telephone contact with physician or patient. The length of follow up (mean (SD)) was 41 (32) months in the antibiotic group and 45 (24) months in the surgery group (NS). Long term survival was estimated by the Kaplan-Meier method and compared by the log-rank test. RESULTS: There was no significant difference in age, history of previous endocarditis, number of previous heart operations, vegetations, emboli, type of prosthesis, or percentage of early prosthetic valve endocarditis and positive blood cultures between the two groups. In the antibiotic group, there were more enterococcal (50%; p = 0.005) and in the surgery group more staphylococcal infections (55%; p = 0.048). Annular abscesses (p < 0. 0001) and aortoventricular dehiscence (p = 0.02) were more common in the surgery group. No patient in the antibiotic group had heart failure. Long term follow up showed no significant difference between the surgery and antibiotic groups regarding late mortality (14% v 18%) and five year rates of recurrent endocarditis (14% v 16%), event related mortality (14% v 3%, log-rank test), and the need for reoperation (14% v 19%; log-rank test). The only patient with conservatively treated staphylococcal prosthetic valve endocarditis died after reoperation for recurrence. CONCLUSIONS: Haemodynamically stable patients with non-staphylococcal prosthetic valve endocarditis who are carefully supervised can be treated with antibiotics alone without an increased rate of reinfection, reoperation, or death.

Adolescent↗
PubMed1996

[Fever and headache].

A 30-year-old male patient was admitted to our outpatient clinic because of fever, headache and cerebellar symptoms. Clinically he presented with a slight meningism. After exclusion of a focal intracerebral process by head scanning, a first diagnosis of an aseptic meningitis was made by the analysis of the cerebrospinal fluid. With the hint of repeated tick bites, the diagnosis of an early-summer meningoencephalitis was confirmed. The patient recovered without neurological residua within two months. The clinical course, dates of new epidemiologic studies and problems of vaccination are discussed.

Adult↗
PubMed1996

[Febrile state and pleural effusion].

A 42 year old patient was admitted for evaluation of a febrile state and left thoracic pain. Chest-X-ray revealed a left-sided pleural effusion nonresponsive to a trial antibiotic treatment. The subsequent punction yielded sterile exudate without microorganisms or malignant cells. Tuberculostatic treatment for suspected tuberculosis lead to exacerbation and hospitalization. Antibodies against native DNA first became detectable during the further course. Together with anamnestic information about fatigue, hair loss and the family history revealing two sisters touched by the disease, the diagnosis of systemic lupus erythematodes was made. Corticosteroids led to rapid improvement with complete resolution of the pleural effusion.

Adult↗