No evidence of skin infection with Chlamydia pneumoniae in patients with cutaneous T cell lymphoma

Recently, Chlamydia pneumoniae-specific DNA and antigens were reported in the skin of patients with Mycosis fungoides (MF), the most common form of cutaneous T-cell lymphomas. In order to revalidate these data we analyzed skin sections of patients with MF for the expression of three different chlamydial antigens and C. pneumoniae DNA by immunohistochemistry and PCR according to previously described protocolls. Neither C. pneumoniae-specific DNA sequences nor antigens were detected in any of the skin biopses from 24 MF patients tested, suggesting that further studies are needed to establish any pathogenetic relevance of C. pneumoniae in MF

Dacarbazine and interferon α with or without interleukin 2 in metastatic melanoma: a randomized phase III multicentre trial of the Dermatologic Cooperative Oncology Group (DeCOG)

In several phase II-trials encouraging tumour responses rates in advanced metastatic melanoma (stage IV; AJCC-classification) have been reported for the application of biochemotherapy containing interleukin 2. This study was designed to compare the efficacy of therapy with dacarbazine (DTIC) and interferon α (IFN-α) only to that of therapy with DTIC and IFN-α with the addition of interleukin 2 (IL-2) in terms of the overall survival time and rate of objective remissions and to provide an elaborated toxicity profile for both types of therapy. 290 patients were randomized to receive either DTIC (850 mg/m2every 28 days) plus IFN-α2a/b (3 MIU/m2, twice on day 1, once daily from days 2 to 5; 5 MIU/m23 times a week from week 2 to 4) with or without IL-2 (4.5 MIU/m2for 3 hours i.v. on day 3; 9.0 MIU/m2i.v. day 3/4; 4.5 MIU/m2s.c. days 4 to 7). The treatment plan required at least 2 treatment cycles (8 weeks of therapy) for every patient. Of 290 randomized patients 281 were eligible for an intention-to-treat analysis. There was no difference in terms of survival time from treatment onset between the two arms (median 11.0 months each). In 273 patients treated according to protocol tumour response was assessable. The response rates did not differ between both arms (P = 0.87) with 18.0% objective responses (9.7% PR; 8.3% CR) for DTIC plus IFN-α as compared to 16.1% (8.8% PR; 7.3% CR) for DTIC, IFN-α and IL-2. Treatment cessation due to adverse reactions was significantly more common in patients receiving IL-2 (13.9%) than in patients receiving DTIC/IFN-α only (5.6%). In conclusion, there was neither a difference in survival time nor in tumour response rates when IL-2, applied according to the combined intravenous and subcutaneous schedule used for this study, was added to DTIC and IFN-α. However, toxicity was increased in melanoma patients treated with IL-2. Further phase III trials with continuous infusion and higher dosages must be performed before any final conclusions can be drawn on the potential usefulness of IL-2 in biochemotherapy of advanced melanoma. © 2001 Cancer Research Campaign http://www.bjcancer.co

Temozolomide plus pegylated interferon alfa-2b as first-line treatment for stage IV melanoma: a multicenter phase II trial of the Dermatologic Cooperative Oncology Group (DeCOG)

Background: Combination of temozolomide (TMZ) with nonpegylated interferon alfa is associated with increased efficacy in terms of response rates compared with monotherapy. A multicenter phase II study was carried out to assess the activity and toxicity of TMZ plus pegylated interferon alfa-2b (peg-IFNα-2b), hypothesizing improved efficacy due to modified pharmacokinetic properties of the novel interferon (IFN) formulation. Patients and methods: In all, 124 patients with stage IV melanoma without prior chemotherapy and no cerebral metastases were treated with 100 μg peg-IFNα-2b s.c. per week and oral TMZ 200 mg/m2 (days 1-5, every 28 days). Primary study end point was objective response, and secondary end points were overall and progression-free survival (PFS) and safety. Results: In all, 116 patients were assessable for response: 2 (1.7%) had a complete response and 19 (16.4%) a partial response (overall response rate 18.1%). Of total, 25.0% achieved disease stabilization and 56.9% progressed. Overall survival was 9.4 months; PFS was 2.8 months. Grade 3/4 thrombocytopenia occurred in 20.7% and grade 3/4 leukopenia in 23.3%. Conclusions: The efficacy of TMZ plus peg-IFNα-2b in this large phase II study is moderate and comparable to published results of the combination of TMZ with non-peg-IFN. Likewise, the safety profile of peg-IFNα-2b seems to be similar to non-peg-IFN when combined with TM

Diagnostik arbeitsbedingter Erkrankungen und arbeitsmedizinisch-diagnostische Tabellen

Eine ganze Reihe von beruflichen Belastungen und ungünstigen Arbeitsbedingungen kann zu zahlreichen berufsbedingten Erkrankungen und Beschwerden führen, von denen nur ein kleiner Teil als Berufskrankheit oder Arbeitsunfall anerkannt wird. Der größere, versicherungsrechtlich nicht anerkannte Teil gilt als "arbeitsbedingte Erkrankung" im engeren Sinne. Es sind Erkrankungen und Beschwerden, die beruflich verursacht, teilweise beruflich verursacht oder in ihrer Dynamik beeinflusst werden. Neue Technologien und andere Arbeitsanforderungen führen zu einem geänderten Spektrum und zur Zunahme der arbeitsbedingten Erkrankungen und Beschwerden. Während einzelne Berufskrankheiten aufgrund der Präventionsmaßnahmen seltener geworden sind, verbergen sich viele arbeitsbedingte Erkrankungen im allgemeinen Krankheitsspektrum der Bevölkerung und sind bei der hausärztlichen und klinischen Betreuung zunehmend zu berücksichtigen. Unsere "Diagnostik arbeitsbedingter Erkrankungen und arbeitsmedizinisch-diagnostische Tabellen" gehen einerseits von allgemeinen und speziellen Krankheitsbildern aus und geben eine Übersicht über die möglichen Ursachen. Andererseits werden bestimmte Gefährdungen und die möglichen Beschwerden und Erkrankungen aufgeführt. Bei ausgewählten Erkrankungen werden Hinweise zur spezifischen Diagnostik und Differentialdiagnostik gegeben. Die Darstellungen orientieren sich daher auch am allgemeinen Krankheitsspektrum und sind nicht nur auf die anerkannten Berufskrankheiten eingeengt. Unsere Ausführungen und Tabellen, die in Kooperation mit den jeweiligen Fachvertretern der Medizinischen Fakultät in Homburg erarbeitet wurden, umfassen arbeitsbedingte Atemwegs- und Lungenkrankheiten, Herz- und Kreislaufkrankheiten, Karzinome, Leberkrankheiten, neurologische Krankheiten, Nieren- und Harnwegserkrankungen, ophthalmologische Krankheiten, orthopädisch-chirurgische Erkrankungen der Bewegungsorgane, sensibilisierende Arbeitsstoffe, Virus- und Infektionskrankheiten und verschiedene aktuelle Kurzinformationen. Aufgrund unserer besonderen poliklinischen Tätigkeit haben wir über Jahrzehnte Informationen über arbeitsbedingte Erkrankungen gesammelt und im Jahr 2000 in einer ersten Form zusammen gestellt und im Internet veröffentlicht. Die jetzige Fassung 2007 gehört längst zur Pflichtlektüre für unsere Studierenden und für die Facharztweiterbildung. Die Aktualisierung und Ergänzung ist laufend vorgesehen

Malignant hyperthermia

Malignant hyperthermia (MH) is a pharmacogenetic disorder of skeletal muscle that presents as a hypermetabolic response to potent volatile anesthetic gases such as halothane, sevoflurane, desflurane and the depolarizing muscle relaxant succinylcholine, and rarely, in humans, to stresses such as vigorous exercise and heat. The incidence of MH reactions ranges from 1:5,000 to 1:50,000–100,000 anesthesias. However, the prevalence of the genetic abnormalities may be as great as one in 3,000 individuals. MH affects humans, certain pig breeds, dogs, horses, and probably other animals. The classic signs of MH include hyperthermia to marked degree, tachycardia, tachypnea, increased carbon dioxide production, increased oxygen consumption, acidosis, muscle rigidity, and rhabdomyolysis, all related to a hypermetabolic response. The syndrome is likely to be fatal if untreated. Early recognition of the signs of MH, specifically elevation of end-expired carbon dioxide, provides the clinical diagnostic clues. In humans the syndrome is inherited in autosomal dominant pattern, while in pigs in autosomal recessive. The pathophysiologic changes of MH are due to uncontrolled rise of myoplasmic calcium, which activates biochemical processes related to muscle activation. Due to ATP depletion, the muscle membrane integrity is compromised leading to hyperkalemia and rhabdomyolysis. In most cases, the syndrome is caused by a defect in the ryanodine receptor. Over 90 mutations have been identified in the RYR-1 gene located on chromosome 19q13.1, and at least 25 are causal for MH. Diagnostic testing relies on assessing the in vitro contracture response of biopsied muscle to halothane, caffeine, and other drugs. Elucidation of the genetic changes has led to the introduction, on a limited basis so far, of genetic testing for susceptibility to MH. As the sensitivity of genetic testing increases, molecular genetics will be used for identifying those at risk with greater frequency. Dantrolene sodium is a specific antagonist of the pathophysiologic changes of MH and should be available wherever general anesthesia is administered. Thanks to the dramatic progress in understanding the clinical manifestation and pathophysiology of the syndrome, the mortality from MH has dropped from over 80% thirty years ago to less than 5%

Interleukin 2: immunologic background and clinical use in tumor therapy

The cytokine interleukin 2 (IL 2) has proved to be an effective agent in immunotherapy of human cancers. Natural killer cells and cytotoxic T-lymphocytes are activated via membrane receptors by IL 2. IL 2-activated natural killer cells and cytotoxic T-lymphocytes develop high cytolytic activity against a variety of tumor cells in vitro. After extensive animal experiments, IL 2 was used in humans either alone or in combination with lymphokine-activated killer cells or tumor-infiltrating lymphocytes. Its application in humans is still experimental, although initial results are very promising. Further studies are necessary to establish treatment protocols with high therapeutic efficacy and tolerable side effects