Evidence of impaired carbohydrate assimilation in euthyroid patients with Hashimoto's thyroiditis.

BACKGROUND/OBJECTIVES: Hashimoto's thyroiditis (HT) represents a wide-spread autoimmune disease. In euthyroid patients with HT, an impaired assimilation of common carbohydrates has been observed. Our objectives were to compare the frequency of (1) fructose (FM), lactose (LM) and sorbitol malassimilation (SM), (2) gastrointestinal symptoms (GS) following carbohydrate ingestion and (3) recurrent GS relevant to the participants' daily lives. SUBJECTS/METHODS: We conducted a prospective case-control study of 45 ambulatory patients with HT and 38 healthy volunteers, matched with regard to age, gender and area of origin. Hydrogen breath tests with fructose, lactose, sorbitol and glucose were performed, the lactose testing additionally comprising measurements of capillary blood glucose (cBG). GS during the tests and recurrent GS concerning the participants' daily lives were assessed. A food-frequency questionnaire was administered. RESULTS: FM was diagnosed in 48.9% of patients compared with 26.3% of the control group (P=0.035). In all, 42.2% of patients with HT and 21.1% of healthy controls showed LM (P=0.04). FM and/or LM was present in 73.3% of the patients and in 42.1% of healthy controls (P=0.004). GS after the ingestion of fructose (P=0.003) or lactose (P=0.025) and recurrent GS were significantly more prevalent in the case group. The consumption of free fructose, lactose or sorbitol did not differ. CONCLUSIONS: Carbohydrate malassimilation and gastrointestinal complaints are frequent in euthyroid patients with HT, leading to novel clinical and pathophysiological considerations and concepts.

[Acute mesenteric ischemia]. / Akute Mesenterialischämie.

BACKGROUND: Acute vascular occlusion within the mesenteric circulation leads to ischemic damage of the corresponding bowel segment, which starts on the mucosal level and progresses transmurally. OBJECTIVES: Report on pathogenesis, clinical picture and treatment of various forms of intestinal ischemia. MATERIALS AND METHODS: Analysis of the available literature taking into consideration our own experience. RESULTS: Frequently, predisposing diseases and risk factors are present (e.g., cardiac diseases, hypercoagulability, status post cardiac surgery, circulatory failure, or administration of vasoconstrictive drugs). Acute small bowel ischemia-caused by either mesenteric embolism, mesenteric artery thrombosis, nonocclusive mesenteric ischemia (NOMI) or mesenteric venous thrombosis-represents an acute emergency. If this condition is suspected clinically, the diagnosis must be established immediately by computed tomography of the abdomen with intravenous administration of contrast medium in order to prevent irreversible damage to the small bowel. Medical treatment is supportive. If possible, occluded vessels may be re-opened either by radiologic intervention or surgically. Irreversibly damaged bowel segments must be surgically removed. Ischemic colitis has a benign course in most cases if limited to reversible mucosal damage. The diagnosis is based mainly on colonoscopy and computed tomography findings, and treatment is symptom oriented. Rarely, severe manifestations with a worse prognosis due to considerable comorbidities occur. In such cases, surgical removal of the ischemic bowel is frequently required. CONCLUSION: Even today, acute mesenteric ischemia is associated with a poor prognosis. To improve survival and to reduce long-term morbidity, a rapid and systematic diagnostic workup is mandatory.

[Long-term use of proton pump inhibitors: who needs prophylaxis?]. / Langzeitbehandlung mit Protonenpumpenhemmern: Wer braucht die Prophylaxe tatsächlich?

Proton pump inhibitors (PPI) are among the most frequently prescribed drugs worldwide. Recently, several side effects of chronic PPI therapy have been identified. Reduced intestinal absorption of vitamin B12 or calcium, an increased rate of bone fractures, an interference with the metabolism of other drugs (e.g., clopidogrel), and an increased incidence of Clostridium difficile-associated colitis are discussed. So far, data on such side effects of PPI are mainly supported by retrospective and/or uncontrolled studies. Therefore, a definitive estimation of the real risk of long-term PPI medication is not yet possible. However, since chronic treatment with PPI may lead to severe side effects, it is necessary to keep the established indications for these drugs (peptic ulcer therapy, gastro-esophageal reflux disease, prophylaxis of mucosal lesions by potentially ulcerogenic drugs) in mind. PPI therapy as stress ulcer prophylaxis should be confined to risk groups and risk situations. Long-term treatment with PPI requires repeated confirmation of a persisting indication, choice of the lowest effective dose, and-if applicable-an interval or "on demand" treatment.

[Managing psychiatric side effects of antiviral therapy in chronic hepatitis C]. / Management psychiatrischer Nebenwirkungen im Rahmen der antiviralen Therapie der chronischen Hepatitis-C-Virusinfektion.

The efficacy of antiviral therapy in patients with chronic hepatitis C virus (HCV) infection has largely improved over the last years. Rates of long-term therapy success (sustained virological response, SVR) clearly exceed 50% in the population of all antivirally treated HCV patients, even when including the less favourable virus genotypes 1 and 4. From recent research, it is well-known that adherence to current standard combination therapy (peginterferon alfa plus ribavirin) is crucial for the achievement of sustained response. Psychiatric adverse events, however, are subjectively very burdening and are among the most frequent reasons for premature discontinuation of antiviral therapy in HCV patients and therefore endanger therapy success. Therefore, effective side effect management regarding this branch of symptoms (e.g. depression, anger-hostility, anxiety) is to be considered crucial for the achievement of SVR. This review presents a current overview of the most relevant IFN-associated psychiatric side effects in antivirally treated patients with chronic hepatitis C infection. Moreover, various strategies for the management of these undesired conditions are reported: In particular, we address the issues of diagnostics and pretherapeutic screening for risk factors for the subsequent development of IFN-associated psychiatric symptoms. Moreover, we provide an overview of suitable instruments for the psychiatric monitoring of patients on antiviral therapy. We further discuss appropriate treatment strategies (e.g. prophylactic medication vs. medication only after the occurrence of symptoms) as well as indications for immediate therapy discontinuation due to serious psychiatric adverse events. In many cases, premature therapy discontinuation can be prevented by individual and adequate side effect management, provided that it is started in a timely manner. The continuing clinical relevance of psychiatric side effect management in this context is further backed up by the fact that also novel treatment strategies comprising protease or polymerase inhibitors will still include pegylated interferon alfa and ribavirin.

[Newly recognized side-effects of proton pump inhibitors. Arguments in favour of fundoplication for GERD?]. / Neu erkannte Nebenwirkungen von Protonenpumpeninhibitoren. Argumente Pro Fundoplicatio bei GERD?

Among other indications proton pump inhibitors (PPIs) are used as medical treatment of gastroesophageal reflux disease (GERD) and are the most frequently prescribed and most frequently used drugs in gastroenterology. Until recently PPIs were regarded as very safe and associated with very few side-effects. However, during recent years study results have revealed many severe adverse events associated especially with long-term PPI use. We review the currently available evidence, regarding the side-effects of PPIs and discuss the potential impact on treatment strategies for GERD (conservative treatment vs. antireflux surgery). Currently available data suggest that PPIs are associated with osteoporosis-related fractures, Clostridium difficile associated diarrhea (CDAD), community and hospital-acquired pneumonia, pharmacologic interaction with clopidogrel and acetylsalicylic acid with subsequent increased rate of cardiovascular events, refractory hypomagnesemia and rebound reflux symptoms etc. The risk-benefit ratio of PPIs is increasingly recognized as being less favourable. This leads to a more critical viewpoint and raises the question whether the side-effects of PPIs may outweigh the benefits, especially with long-term use. The side-effects of PPIs seem to make a strong argument in favour of laparoscopic fundoplication in the treatment of GERD.

Therapy of interferon-induced depression in chronic hepatitis C with citalopram: a randomised, double-blind, placebo-controlled study.

BACKGROUND: Interferon-induced depression represents a major complication in antiviral treatment of chronic hepatitis C virus (HCV) infection. AIM: To evaluate in a placebo-controlled study the efficacy of a selective serotonin reuptake inhibitor (SSRI) in HCV patients on antiviral therapy with interferon-associated depression. METHODS: 100 HCV outpatients were included in a randomised, double-blind, placebo-controlled study. During interferon therapy (peginterferon alpha-2b plus ribavirin), depression was monitored using the Hospital Anxiety and Depression Scale (HADS). Patients with clinically relevant interferon-induced depression (HADS >or=9) were randomly assigned to placebo or citalopram (SSRI, 20 mg/day). RESULTS: In 28 patients (28%), HADS scores increased to >8 during interferon therapy. They were treated with placebo (n = 14) or SSRI (n = 14). HADS scores declined significantly in SSRI patients within four weeks of therapy (p<0.001) but not in placebo patients. This difference between subgroups was statistically significant (p = 0.032). Unblinding became necessary in five placebo patients as a result of intolerable depression. Rescue medication (20 mg citalopram) led to a significant decrease in HADS scores (p = 0.008). All citalopram patients were able to complete interferon therapy as planned. As an interim analysis showed a significant superiority of SSRI over placebo, the study was terminated prematurely. Three patients, who became depressed afterwards, were treated in an unblinded fashion with citalopram. CONCLUSIONS: The findings demonstrate clearly that citalopram treatment is highly effective in HCV patients on interferon therapy, when initiated after the onset of clinically relevant depressive symptoms. This suggests that a general SSRI prophylaxis is not necessary in these patients.

[The role of the diet in the prevention of gastrointestinal tumors]. / Ernährungstipps zur Prävention gastrointestinaler Tumoren. Obst und Gemüse sind die Favoriten.

Second only to cardiovascular diseases, malignant tumors are the most common fatal disease, with malignant neoplasms in the gastrointestinal tract playing an important role. Underlying the most numerous of these malignancies is a complex interaction between genetic and environmental factors. The data relating to the role of environmental factors (for the most part dietary factors) in the development of gastrointestinal tumors derive mainly from, epidemiological research. The current evidence is "convincin" with regard to complex lifestyle patterns, but at most "plausible" when the chemically defined individual substances are considered. Summarizing the potential protective value of dietary factors reveals that the risk of contracting the majority of the gastrointestinal tumors can be reduced by increasing the intake of fruit and vegetables. An additional protective effect is associated with a balanced diet, physical activity, preservation of normal weight, avoidance of smoking, and moderation in the amount of alcohol consumed.

[Phlegmonous gastritis in a 44-year-old woman on immunosuppressive therapy]. / Phlegmonöse Gastritis bei einer 44-jährigen Patientin unter immunsuppressiver Therapie.

HISTORY AND ADMISSION FINDINGS: A 44-year-old woman was on long-term immunosuppressive therapy with leflunomide and adalimumab for rheumatoid arthritis. She was admitted to the emergency room with diffuse abdominal pain of sudden onset. On physical examination she had rebound tenderness in all four abdominal quadrants. INVESTIGATIONS: The white blood cell count was 3300/l, C-reactive protein 25 mg/dl and serum lactate 10 mmol/l. Abdominal computed tomography revealed a diffusely thickened gastric wall and ascites. At explorative laparotomy 1000 ml of a cloudy peritoneal fluid were aspirated and found to be negative for bacteria. But a culture of a mesenterial smear grew streptococci group A. Intra-operative endoscopy showed extensive hemorrhagic gastritis. Because there was no perforation or transmural necrosis gastric resection was not performed. DIAGNOSIS, TREATMENT AND COURSE: Diffuse thickening of the gastric wall, extended mucosal necrosis and the peritoneal finding of streptococci in an immunocompromised patient suggested the diagnosis of phlegmonous gastritis. On treatment with antibiotics and proton pump inhibitor the patient made a slow recovery over the following eight weeks. Nine months after the event an asymptomatic antral stricture was noticed at follow-up gastroscopy. CONCLUSION: Phlegmonous gastritis is a rare but life-threatening complication in immunosuppressed patients.

Giant fold gastritis with consecutive gastric carcinoma in a patient with peutz-jeghers syndrome.

We describe the case of a 36-year-old patient with Peutz-Jeghers syndrome and a very unusual gastric morphology resembling giant fold gastritis. The latter lacked additional features of Menetrier's syndrome, was not influenced by eradication of Helicobacter pylori and persisted for more than ten years under regular endoscopic surveillance. Histologically, foveolar hyperplasia was found in the enlarged folds. Endoscopic ultrasound documented a hyperechoic widening of the gastric mucosa without involvement of the deeper layers. However, despite annual control gastroscopies, an adenocarcinoma developed between the folds and was in an already advanced stage at diagnosis (UICC III). We suggest that a variant of Peutz-Jeghers syndrome may be characterised by marked foveolar hyperplasia similar to Menetrier disease, and that not conventional endoscopy alone, but rather endoscopic ultrasound may be considered in such patients.

Sexual dysfunction in males with chronic hepatitis C and antiviral therapy: interferon-induced functional androgen deficiency or depression?

Decrease of libido and erectile dysfunction are reported by male patients during antiviral therapy of chronic hepatitis C, but therapy-associated underlying factors for sexual dysfunction are not well defined. To assess putative contributions of interferon-induced sex hormone changes to sexual dysfunction, we prospectively investigated changes in free testosterone, total testosterone, dehydroepiandrosterone sulfate, prolactin, sex hormone-binding globulin, FSH and LH levels and psychometric self-assessment scores in 34 male patients treated with interferon alfa-2b (5 MIU three times weekly) (n=19)+ ribavirin (n=15) for 6-12 months. Depression was measured by the Hospital Anxiety and Depression Scale. Sexual dysfunction was evaluated by the Symptom Checklist 90 Item Revised and a five-point rating scale assessing sexual arousal disorder. Free and total testosterone decreased significantly during antiviral therapy in close correlation with libido/sexual function. Depression scores increased during therapy and were also significantly associated with sexual dysfunction. However, androgen levels displayed no significant correlation with depression. These results suggest that interferon-induced decrease in sexual function is associated - but not causally related -with both androgen reduction and increased depressive symptoms. These findings may affect care for male hepatitis C patients during interferon therapy.

Prophylactic SSRI during interferon alpha re-therapy in patients with chronic hepatitis C and a history of interferon-induced depression.

Only limited data are available on selective serotonin re-uptake inhibitor (SSRI) prophylaxis for antiviral re-treatment in hepatitis C patients with previous interferon-induced major depressive episodes. Therefore, we investigated the efficacy and safety of secondary SSRI prophylaxis in these patients. In a prospective and longitudinal study, repeated psychometric testing (Hospital Anxiety and Depression Scale) was performed before, during, and after antiviral re-treatment. Chronic hepatitis C virus (HCV)-infected patients, who had been psychometrically monitored during an unsuccessful previous antiviral therapy, and had developed major depression were included. Interferon re-therapy with SSRI prophylaxis was started (n = 8). The reference group was comprised of HCV patients without a history of interferon-associated depression and also a group who were previously unsuccessfully treated with interferon and were re-treated without SSRI prophylaxis (n = 9). All patients receiving SSRI prophylaxis were able to complete interferon re-therapy as scheduled. As in the first therapeutic course, depression scores were significantly elevated during re-treatment also (P < 0.001). Depression scores were significantly lower (P =0.036) during interferon re-therapy with SSRI prophylaxis. Reference group subjects showed similar depression scores during first therapy and re-therapy (P > 0.05). In conclusion, hepatitis C patients with a history of interferon-induced major depression can be successfully re-treated with peginterferon/ribavirin and concomitant SSRI prophylaxis. In these patients, SSRI prophylaxis is safe and efficacious and should be considered, if antiviral re-therapy is indicated.

[Diagnosis and treatment of intrahepatic cholestasis syndrome]. / Diagnostik und Therapie der intrahepatischen Cholestasesyndrome. Lassen Sie es nicht zur biliären Zirrhose kommen.

Prompted by the histomorphological aspect of ductopenia, chronic intrahepatic liver diseases are increasingly being subsumed under the term vanishing bile duct syndrome. Classification by cholestasis syndromes in adults (e.g. primary biliary cirrhosis, primary sclerosing cholangitis) and in the newborn or children (e.g. alphal antitrypsin deficiency, cystic fibrosis) makes good sense. Decisive for the diagnosis are, depending on the disease presenting, a typical constellation of laboratory results, detection of autoantibodies, imaging procedures (e.g. ERC, MRI), liver biopsy where indicated, or suspected drug-induced cholestasis. Byway of treatment, ursodeoxycholic acid, an antibiotic in cholestasis, and liver transplantation in some cases, are possible options. Supportive treatment should be aimed at extrahepatic manifestations of cholestasis (e.g. osteoporosis, vitamin deficiency, pruritus).

[Medication-related diarrhea]. / Nebenwirkung chronische Diarrhö. Sind die Medikamente schuld?

Numerous medications can trigger diarrhea. In some cases it is a common side effect, and the relationship is evident (e.g. acarbose, somatostatin analogs and antibiotics). When diarrhea does occur, the therapeutic benefit of the drug should be weighed against the negative results of the side effect. If pseudomembranous colitis is suspected, prompt action is required, since a fatal outcome cannot be excluded. A particular challenge is a suspected drug association in a multimorbid patient taking several drugs, each associated with an only low diarrhea risk. In such a case, it may be necessary to discontinue drugs consecutively, or to replace a drug by another, until the diarrhea ceases, without lessening the effectiveness of the treatment.

Paroxetine for the treatment of interferon-alpha-induced depression in chronic hepatitis C.

BACKGROUND: Psychiatric side-effects may require dose reduction or premature discontinuation of interferon therapy in chronic hepatitis C. New strategies are needed in order to prevent the premature termination of interferon therapy. AIM: To evaluate prospectively the efficacy and tolerability of antidepressant therapy (paroxetine, a selective serotonin reuptake inhibitor) in patients with chronic hepatitis C treated with interferon-alpha who have developed interferon-induced major depression. METHODS: A sub-group of 14 individuals from 121 consecutively treated hepatitis C patients developed substance-induced major depression without suicidal ideation during interferon-alpha treatment. The individuals in this sub-group received paroxetine after the occurrence of depression (20 mg daily until termination of interferon therapy). Diagnostic scores for depression (and anger-hostility) were obtained in a repeated measures design (Hospital Anxiety and Depression Scale and Symptom Checklist 90 Items Revised). RESULTS: Eleven of the 14 patients (78.6%) with interferon-induced major depression were able to complete interferon-alpha therapy as scheduled under concomitant paroxetine treatment (three dropouts: insufficient improvement of depression, occurrence of epileptic seizures, paroxetine-induced nausea/dizziness). Within 4 weeks after the start of paroxetine medication, depression scores declined significantly in all patients. CONCLUSIONS: Our data suggest that concomitant therapy with paroxetine is an effective way to treat interferon-induced depression in patients with chronic hepatitis C.

[Primary glomangioma of the liver. A new differential benign liver tumor diagnosis]. / Primäres Glomangiom der Leber. Eine neue Differenzialdiagnose benigner Lebertumoren.

Glomus organs are arteriovenous anastomoses which control the thermoregulation of the extremities. Benign tumors of these glomus organs, termed "glomangiomas", are therefore most frequently located in the fingers and toes. Case reports of primary glomangiomas in the respiratory- and gastrointestinal tracts as well as in the genital organs have been published. On the other hand, glomus tumors of the liver have not yet been described. We report the case of a 61-year-old patient with a smooth subcapsular lesion within the liver detected by a routine ultrasound scan. Further diagnostic imaging did not match with one of the common liver tumors. The diagnosis of a glomangioma was finally made by liver biopsy and subsequent histology. A review of the literature revealed a potential transformation of glomangiomas. Since the patient reported on inappetence weight loss and the tumor showed growth tendency, the indication for surgical excision was made. Final histologic investigation revealed no signs of malignancy. The primary glomangioma of the liver is a new differential diagnosis of benign liver tumors. As there is a possibility of malignant degeneration, we propose the decision for surgical removal once there are clinical symptoms and a growth tendency of the lesion.