Kaybolan bir sanat dalı:Meddahlık

Taha Toros Arşivi, Dosya No: 179-Meddahlarİstanbul Kalkınma Ajansı (TR10/14/YEN/0033) İstanbul Development Agency (TR10/14/YEN/0033

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

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

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

Calcium Homeostasis in Myogenic Differentiation Factor 1 (MyoD)-Transformed, Virally-Transduced, Skin-Derived Equine Myotubes

Dysfunctional skeletal muscle calcium homeostasis plays a central role in the pathophysiology of several human and animal skeletal muscle disorders, in particular, genetic disorders associated with ryanodine receptor 1 (RYR1) mutations, such as malignant hyperthermia, central core disease, multiminicore disease and certain centronuclear myopathies. In addition, aberrant skeletal muscle calcium handling is believed to play a pivotal role in the highly prevalent disorder of Thoroughbred racehorses, known as Recurrent Exertional Rhabdomyolysis. Traditionally, such defects were studied in human and equine subjects by examining the contractile responses of biopsied muscle strips exposed to caffeine, a potent RYR1 agonist. However, this test is not widely available and, due to its invasive nature, is potentially less suitable for valuable animals in training or in the human paediatric setting. Furthermore, increasingly, RYR1 gene polymorphisms (of unknown pathogenicity and significance) are being identified through next generation sequencing projects. Consequently, we have investigated a less invasive test that can be used to study calcium homeostasis in cultured, skin-derived fibroblasts that are converted to the muscle lineage by viral transduction with a MyoD (myogenic differentiation 1) transgene. Similar models have been utilised to examine calcium homeostasis in human patient cells, however, to date, there has been no detailed assessment of the cells’ calcium homeostasis, and in particular, the responses to agonists and antagonists of RYR1. Here we describe experiments conducted to assess calcium handling of the cells and examine responses to treatment with dantrolene, a drug commonly used for prophylaxis of recurrent exertional rhabdomyolysis in horses and malignant hyperthermia in humans

Successful desensitization with human insulin in a patient with an insulin allergy and hypersensitivity to protamine: a case report

<p>Abstract</p> <p>Introduction</p> <p>Insulin allergy may occur in patients treated with subcutaneous applications of insulin preparations. Besides additives in the insulin preparation such as protamine, cresol, and phenol, the insulin molecule itself may be the cause of the allergy. In the latter case, therapeutic options are rare.</p> <p>Case presentation</p> <p>A 68-year-old man with poorly controlled type 2 diabetes mellitus received different insulin preparations subcutaneously while on oral medication. Six to eight hours after each subcutaneous application, he developed pruritic plaques with a diameter of >15 cm at the injection sites that persisted for several days. Allergologic testing revealed positive reactions against every insulin preparation and against protamine. Investigation of serum samples demonstrated IgG antibodies against human and porcine insulin. We treated the patient with human insulin using an ultra-rush protocol beginning with 0.004 IU and a rapid augmentation in dose up to 5 IU. Therapy was accompanied by antihistamine therapy. Subsequent conversion to therapy with glargine insulin (6 IE twice daily) was well-tolerated.</p> <p>Conclusion</p> <p>As reported in this case, desensitization with subcutaneously administered human insulin using an ultra-rush protocol in patients with an insulin allergy may present an easy form of therapy that is successful within a few days.</p

A Double Mutation of the Ryanodine Receptor Type 1 Gene in a Malignant Hyperthermia Family with Multiminicore Myopathy

Background and PurposeᄏAt least 100 Ryanodine receptor type 1 (RYR1) mutations associated with malignant hyperthermia (MH) and central core disease (CCD) have been identified, but 2 RYR1 mutations accompanying multiminicore myopathy in an MH and/or CCD family have been reported only rarely. MethodsᄏFifty-three members of a large MH family were investigated with clinical, histopathologic, RYR1 mutation, and haplotyping studies. Blood creatine kinase (CK) and myoglobin levels were also measured where possible. ResultsᄏSequencing of the entire RYR1 coding region identified a double RYR1 mutation (R2435H and A4295V) in MH/CCD regions 2 and 3. Haplotyping analysis revealed that the two missense heterozygous mutations (c.7304G>A and c.12891C>T) were always present on a common haplotype allele, and were closely cosegregated with histological multiminicores and elevated serum CK. All the subjects with the double mutation showed elevated serum CK and myoglobin, and the obtained muscle biopsy samples showed multiminicore lesions, but only two family members presented a late-onset, slowly progressive myopathy. ConclusionsᄏWe found multiminicore myopathy with clinical and histological variability in a large MH family with an unusual double RYR1 mutation, including a typical CCD-causing known mutant. These results suggest that multiminicore lesions are associated with the presence of more than two mutations in the RYR1 gene.ope

Serum vascular cell adhesion molecule-1 (VCAM1) level is elevated in colorectal cancer regardless of the tumor stage

Purpose: Vascular cell adhesion molecule-1 (VCAM1) is a transmembrane glycoprotein, which is expressed on endothelium and plays role in inflammation. It is over-expressed on colorectal cancer (CRC) cells and plays role in metastasis development and angiogenesis. We aimed to compare serum VCAM1 levels of CRC patients with heathy controls and evaluate its relationship with clinicopathological parameters, treatment response and overall survival (OS).Methods: The study enrolled 111 patients with histopathologically confirmed CRC followed-up in our clinic and 30 sex- and age-matched healthy controls. Pre-treatment serum VCAM1 levels were determined by the solid-phase sandwich ELISA method.Results: Metastatic disease was present in 57 patients. Forty percent of 40 metastatic patients receiving systemic therapy had partial or complete response. The median serum VCAM1 level was significantly higher in CRC patients than controls (p&lt;0.001). In addition, serum VCAM1 level was significantly higher in diabetic CRC patients than those without diabetes (p = 0.03). There was no significant relationship between VCAM1 and other clinicopathological parameters including stage and response to systemic therapy. The median follow-up period was 12 (±8.2) months. Twenty patients were dead at the time of analysis. The presence of metastasis (p &lt; 0.001) and elevated CEA level (p &lt; 0.001) were factors affecting OS significantly. However, serum VCAM1 did not have a significant impact on OS (p = 0.55).Conclusion: Serum VCAM1 level is significantly elevated in CRC patients regardless of the tumor stage. However, it has no prognostic or predictive role for response to systemic therapy

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

Genome-wide joint SNP and CNV analysis of aortic root diameter in African Americans: the HyperGEN study

<p>Abstract</p> <p>Background</p> <p>Aortic root diameter is a clinically relevant trait due to its known relationship with the pathogenesis of aortic regurgitation and risk for aortic dissection. African Americans are an understudied population despite a particularly high burden of cardiovascular diseases. We report a genome-wide association study on aortic root diameter among African Americans enrolled in the HyperGEN study. We invoked a two-stage, mixed model procedure to jointly identify SNP allele and copy number variation effects.</p> <p>Results</p> <p>Results suggest novel genetic contributors along a large region between the <it>CRCP </it>and <it>KCTD7 </it>genes on chromosome 7 (p = 4.26 × 10^<b>-7</b>); and the <it>SIRPA </it>and <it>PDYN </it>genes on chromosome 20 (p = 3.28 × 10^<b>-8</b>).</p> <p>Conclusions</p> <p>The regions we discovered are candidates for future studies on cardiovascular outcomes, particularly in African Americans. The methods we employed can also provide an outline for genetic researchers interested in jointly testing SNP and CNV effects and/or applying mixed model procedures on a genome-wide scale.</p