[Peripheral polyneuropathy and bilateral optic neuropathy during treatment of chronic hepatitis C]. / Periphere Polyneuropathie und beidseitige Optikusneuropathie unter Behandlung einer chronischen Hepatitis C.

HISTORY AND CLINICAL FINDINGS: A 54-year-old female patient with recently confirmed chronic hepatitis C, genotype Ib and positive HCV-RNA was admitted for interferon induction therapy. EXAMINATIONS: Physical examination findings were normal. Ultrasound examination of the abdomen revealed slightly compacted liver structure with otherwise no pathological findings. Laboratory results showed marginally increased GPT value at 46 U/l with HCV-RNA of 769,000 U/ml. All other laboratory results were within the reference range. There was no indication for autoantibodies. THERAPY AND COURSE: After one-week induction therapy with interferon-alpha (IFN-alpha2a) plus ribavirin and amantadine, maintenance therapy with pegylated interferon-alpha (PEG-IFN-alpha2a) plus ribavirin and amantadine was initiated. Complete virus elimination was achieved after two and a half months. Five months after onset of therapy, painful peripheral neuropathy of the limbs occured and after one more month, severe vision impairment with opticus neuropathy and bilateral papilledema developed. Simultaneously, peripheral polyneuropathy progressed with additional motoric deficits. Interferon therapy was terminated and the patient received high-dose corticosteroids which resulted in an improvement of neuropathic complaints. Eight months later, only discrete bilateral vision impairment with optic nerve atrophy remained. CONCLUSION: Side effects occurring with interferon-alpha therapy and pegylated interferon-alpha therapy are generally low and well tolerated. However, in individual cases - as in our patient - side effects including severe peripheral neuropathy and optic neuropathy have been observed. In these cases, interferon therapy must be terminated immediately as severe damage of nerves may result.

Successful treatment of steroid refractory active ulcerative colitis with natural interferon-beta--an open long-term trial.

INTRODUCTION: In some steroid refractory patients with active ulcerative colitis (UC), treatment with immunosuppressive agents, such as cyclosporin, azathioprine or 6-mercaptopurin is effective. However, there are patients who fail to respond to these treatment options or who cannot tolerate them. Application of natural interferon-beta (nIFN-beta) may offer an alternative. Following our positive results with nIFN-beta in a previously published open-labeled study, the present study was designed as an extension with the hypothesis that administration of higher dosage of nIFN-beta (1.0 vs. 0.5 MIU) could result in fewer relapse events. PATIENTS AND METHODS: 46 steroid refractory patients with active UC and a mean clinical activity index (CAI) of 13.2 +/- 3.7 (range 9-23) were treated with nIFN-beta in addition to existing basic medication (5-ASA/SASP plus corticosteroids). During an induction period of eight weeks, 18 patients (group A) received 0.5 MIU nIFN-beta daily and 28 patients (group B), 1.0 MIU nIFN-beta daily intravenously as a bolus injection. Patients who achieved complete remission (decrease of CAI to < or = 4) during the induction period received maintenance therapy with nIFN-beta at the same dose level three times a week and corticosteroids were withdrawn. Remissions and maintenance of remissions were evaluated. RESULTS: In both groups, a comparable number of complete remissions occurred during the induction period: in 16 / 18 patients (89 %) in group A and in 24 / 28 patients (86 %) in group B. Duration of maintenance treatment was 60.0 +/- 90.0 weeks in group A and 52.7 +/- 9.6 weeks in group B. Under this treatment, relapses (increase of CAI to > or = 6) occurred in 5 / 16 patients (31 %) vs. 1 / 24 patients (4 %) (p < or = 0.05). Hence, regarding maintaining remissions, the 1.0 MIU group outscored the 0.5 MIU group. Apart from known flu-like side effects, the therapy was well tolerated by all patients in both groups. CONCLUSION: nIFN-beta may be a safe and effective alternative to induce and maintain remissions in patients with steroid refractory active UC. To validate the presented results, its effect has to be investigated in a randomized, placebo-controlled dose-finding trial.

Experimental study on the use of intravenous immunoglobulin (IVIg) in patients with steroid-resistant Crohn's disease.

INTRODUCTION: Treatment of Crohn's disease is based on anti-inflammatory and immunosuppressive therapy. Over time, however, approx. 20 % of patients develop steroid resistance. In these cases, alternative treatment methods are required. Short-term application of intravenous immunoglobulin (IVIg) may serve as an additional alternative. PATIENTS AND METHODS: In 19 steroid-resistant patients (case collection over 15 years) suffering from Crohn's disease (mean CDAI 284.1 +/- 149.8), IVIg therapy with Venimmun, Gamimmun, Octagam, respectively (7 days 10 g/day i. v.) or Sandoglobin (total dose: 72 g or 90 g i. v., respectively, over a period of 8 or 10 days) was applied in addition to basic medication (5-ASA/SASP plus corticosteroids). CDAI according to Best was assessed on a weekly basis starting 3 weeks prior to and ending 4 weeks after completion of therapy. 8 patients could be followed for a longer period. RESULTS: All patients benefited from this treatment and the effectiveness of IVIg therapy could not only be observed during therapy, but also during the four consecutive weeks after therapy. At 4 weeks after therapy, a total of 14 patients (73.7%) reached a clinical remission (CDAI < 150) and 14 patients (73.7%) showed a CDAI decrease of > 100 points. In the 8 patients who could be followed over a longer period of time, a mean remission duration of 20.6 months was observed. Apart from a slight rise in temperature in one patient, no significant side effects occurred. CONCLUSION: In patients suffering from Crohn's disease, IVIg therapy may be applied effectively and with few side effects, however, not as remission maintenance, but as a stopgap treatment during an acute attack with steroid resistance, e. g., until therapy with other immunosuppressive agents becomes effective. To validate our presented results, a prospective, randomised, placebo-controlled trial has to be proposed.

[Acute hepatitis due to kava-kava and St John's Wort: an immune-mediated mechanism?]. / Akute Hepatitis durch Kava-Kava und Johanniskraut: immun-vermittelter Mechanismus?

HISTORY AND CLINICAL FINDINGS: In an otherwise healthy 48-year-old female patient, acute hepatitis with transaminase increase (GOT up to 613 U/l, GPT up to 752 U/l), inconspicuous hepatitis serology findings, negative autoantibody status and negative virus serology was observed after a 10-week long intake of kava-kava (1-3 x 200 mg/day) and St John's Wort (1 x 425 mg/day). Biopsy of the liver showed lobular and portal necroinflammatory activity without indication of cirrhosis. DIAGNOSIS: Due to these findings with proven T-cell activity (lymphocyte typing, neopterin determination) as well as the aetiopathology, this form of hepatitis with histological characteristics of a nutritive/medicinal toxic origin was classified as induced immunologic idiosyncratic hepatitis, possibly in terms of an antibody-negative autoimmune hepatitis. TREATMENT AND CLINICAL COURSE: Discontinuation of the existing medication and simultaneous onset of immunosuppressive combination therapy of cortisone, azathioprine and ursodeoxycholic acid resulted in normalisation of the liver parameters within a period of two months. CONCLUSION: On the one hand, it appears that simultaneous intake of St John's Wort possibly potentiates the toxicity of kavapyrones. On the other hand, an immune-mediated mechanism, induced by kava-kava, cannot be completely excluded in the present case. It must be stressed that in patients with autoimmune hepatitis, precise history of medication intake should also be available.

[Severe exacerbation of chronic hepatitis B during therapy with corticosteroids and lamivudine therapy and successful short-term combination therapy with interferon-beta and interferon-gamma]. / Schwere Exazerbation einer chronischen Hepatitis B unter Therapie mit Kortikosteroiden und Lamivudin und erfolgreiche Kurzzeit-Kombinationstherapie mit Interferon-beta und -gamma.

Following an acute episode of undifferentiated collagenosis/autoimmune disease with joint pain, a 50-year-old female patient with known long-standing chronic hepatitis B was treated orally with corticosteroids (30 mg prednisolone in decreasing doses over a period of six months). During this treatment, exacerbation of hepatitis B and massive flare-up under simultaneous treatment with lamivudine occurred (GOT 530 U/L, GPT 791 U/L). Serology was positive for HBs-Ag and anti-HBc-lgM. HBV-DNA titer was > 400,000 copies/ml in polymerase chain reaction. Considering the increased risk of reactivation of autoimmune phenomena during a six months therapy with interferon-alpha, an intensive combination therapy with interferon-beta and -gamma (2 weeks: 1 x 3 MIU nIFN-beta Fiblaferon i.v.; 3 weeks: 1 x 3 MIU nIFN-beta i.v. plus 1 x 50 microg rIFN-gamma Imukine) was carried out over five weeks. After two months this resulted in a complete viral and biochemical response. During an observation period of twelve months no reactivation of the autoimmune disease occurred.

Intrapericardial instillation of mitoxantrone in palliative therapy of malignant pericardial effusion.

BACKGROUND: Pericardial effusions occurring with pericardial or myocardial metastases often cause serious complications, necessitating temporary or emergency relief by percutaneous pericardiocentesis. However, this often results in recurrences. For long-term therapy success, the intrapericardial instillation of anti-neoplastic agents is an alternative to surgical methods, which are stressful for the patient. Following our positive experiences with mitoxantrone in the treatment of malignant pleural effusions, we applied this substance for the therapy of malignant pericardial effusions. PATIENTS AND METHODS: 16 patients with cytologically verified malignant pericardial effusions (8 with bronchial carcinoma, 7 with carcinoma of the breast, 1 with adenocarcinoma of the stomach) received an intrapericardial instillation of mitoxantrone 1-3 x10-20 mg. Responses were evaluated by echocardiography 30 days after completion of therapy. RESULTS: 12 of 16 patients showed complete remission (no recurrence of a detectable effusion). 3 patients showed a partial remission (recurrence of non-drainage-dependent effusion) (CR + PR = 94%). Within the mean follow-up period of 189 days no recurrences occurred. The rate of side effects was low. CONCLUSION: Intrapericardial instillation of mitoxantrone is a feasible and effective palliative method for the control of malignant pericardial effusions with little strain on the patients, short duration of hospital stay, cytotoxic characteristics of the substance with a correspondingly high rate of response and low side effects.

Amifostine plus erythropoietin in a patient with low-risk myelodysplastic syndrome.

Increasingly, the therapeutic use of hematopoietic growth factors and immunomodulatory agents is under investigation in patients with low-risk myelodysplastic syndrome (MDS). Studies on amifostine therapy-alone or in combination with erythropoietin (EPO)-indicate that long-term treatment is possibly a decisive factor for therapy success. Therefore, we treated an 81-year-old female, transfusion-dependent patient with MDS and refractory anemia (RA) with amifostine and EPO over a period of 2 years. Following a 4-week induction phase of 5 x 500 mg amifostine plus 3 x 10000 IU EPO per week and maintenance therapy of 1 x 500 mg amifostine plus 3 x 10000 IU EPO per week, normal hemoglobin values were reached in week 14. A long-lasting erythroid response could be observed with a reduction of EPO to 2 x 10000 IU and 1 x 10000 IU and, at present, once a week application of amifostine alone (1 x 500 mg). Apart from the 1st week, the treatment was carried out at the outpatient department and was well tolerated by the patient. The patient experienced a good general clinical condition without further need for hospitalization or blood transfusions.

Palliation by intratumoral infiltration with natural interferon-beta.

BACKGROUND: Curative approaches to tumor therapy have achieved greater importance through new developments such as cytostatic agents and their combination with other therapy concepts, but for the majority of tumor patients only palliative therapy is possible. Size or location of tumor manifestations can result in severe discomfort for patients, in some cases even in a reduction of functionality. PATIENTS AND METHODS: For the purpose of this study, a total of 55 patients with a variety of advanced malignant diseases nonresponding or progressive under radio- and/or chemotherapy were treated by intratumoral injection of natural human fibroblast interferon (nIFN-beta). nIFN-beta was administered intralesionally 3 times per week for at least 4 weeks at doses of 2-8 MIU, depending on tumor size. Local tumor response was observed over a median follow-up period of 18 weeks. RESULTS: In 37 patients (67%) a complete or partial remission of the local tumor manifestation was achieved. Survival times of these patients were improved compared with those of patients without local tumor remission. 16 patients without significant change of tumor volume benefited from the palliative (extensive analgesic) effect of the nIFN-beta therapy. During treatment, none of the patients showed a progression of the locally treated tumor, even when the basic malignant disease progressed. The side effects of the nIFN-beta therapy were tolerable, and no patient discontinued therapy. CONCLUSION: From these observations, intralesional nIFN-beta therapy of malignant tumors appears to be a useful palliative addition to radio- and/or chemotherapy with the aim of local control of tumor growth.

Parenteral aluminum loading in critical care medicine. Part I: Aluminum content of infusion solutions and solutions for parenteral nutrition.

BACKGROUND: For patients with disturbed aluminum (Al) excretion, a high Al intake is not without risk. As main aluminum sources infusion solutions and solutions for parenteral nutrition have been identified. This study will give current survey of aluminum loading of the above-mentioned preparations. MATERIAL AND METHODS: The aluminum loading of 139 different infusion solutions and solutions for parenteral nutrition was determined. The solutions were from the clinical pharmacy of the Klinikum Steglitz of the Free University Berlin or were bought in a public pharmacy. The aluminum content was determined by means of two different, independent analytical methods: a) graphite furnace atomic absorption spectroscopy (GFAAS) and b) inductively coupled plasma atomic emission spectroscopy (ICP-AES). The agreement of the measured values was good except for five samples, where different values were found. Mistakes due to contamination were excluded on the basis of the results of measuring standard reference materials. RESULTS: Small-volume additives of TPN (total parenteral nutrition) formulations were highly contaminated with aluminum, e.g. Ca and phosphate solutions (29-12,000 micrograms/l), vitamin C solutions (700-1,200 micrograms/l) and trace element solutions (67-6,200 micrograms/l). Furthermore about 44% of the crystalline amino acid solutions and lipid emulsions had an aluminum content of 25 to 55 micrograms/l. Low aluminum levels were found in carbohydrate solutions, NaCl and KCl solutions and in distilled water (aqua ad injectabilia). CONCLUSIONS: Many of the solutions for parenteral nutritional support have an aluminum content which exceeds, in part considerably, the suggested threshold concentration of 25 micrograms/l (0.93 mumol/l), recommended by the American Society for Clinical Nutrition (ASCN) and the American Society for Parenteral and Enteral Nutrition (ASPEN). The pharmaceutical industry should be required to check the manufacturing process for avoidable sources of contamination, and threshold values for aluminum loading by intravenously applied pharmaceuticals should be laid down in the German and European pharmacopoeia. In cases where contaminations cannot be eliminated during the manufacturing process after careful checking, the aluminum content of the infusion solution should be declared for the user.