Burkitt lymphoma following splenic marginal zone lymphoma. evidence for two independent B-cell clones

We report the progression of splenic marginal zone lymphoma (SMZL) with circulating villous lymphocytes to Burkitt lymphoma with the presence of a t(8;14)(q24;q32) followed by a highly aggressive course. While the initial indolent lymphoma had an IgM lambda immunophenotype the Burkitt lymphoma was IgM kappa-positive. Immunoglobulin heavy chain gene (IGH) sequence analysis showed no identity between the two clones. We conclude that Burkitt lymphoma can occur in patients with SMZL, although not necessarily of identical clonal origin.     

Noninvasive diagnosis in dermatology

In addition to dermoscopy, there are other imaging and biophysical methods for the noninvasive diagnosis of skin lesions. Confocal laser microscopy allows for high‐resolution imaging of the epidermis and upper dermis. It is particularly suitable in the differential diagnosis of melanocytic lesions. Optical coherence tomography (OCT) has a lower resolution compared to confocal laser microscopy but a greater depth of penetration. It is primarily used for imaging epithelial skin cancer, especially in the context of monitoring the effectiveness of nonsurgical therapies. Electrical impedance spectroscopy does not yield cutaneous images but rather provides a score based on the cellular irregularity of the skin. Multispectral analysis involves illumination of the skin with different wavelengths and likewise results in the computation of a score. Both methods are used in the differentiation of dysplastic nevi from melanoma. Other diagnostic imaging and biophysical methods are currently still in the developmental stages. By increasing the sensitivity and specificity of clinical and dermoscopic findings, the aforementioned methods bring about an improvement in noninvasive diagnosis. They allow for skin lesions to be monitored over time and therapeutic effects to be quantified. Finally, they facilitate early diagnosis of skin cancer, and help avoid unnecessary surgery of benign lesions.     

Bromocriptine lessens the incidence of mortality in L-Dopa-treated parkinsonian patients: Prado-study discontinued

Summary L-Dopa supplemented by a peripheral decarboxylase inhibitor is considered the most potent therapeutic regimen prolonging active life in Parkinsonian patients. The long-term benefit of therapy is limited by adverse effects, such as dyskinesia and on-off phenomena, which can be mitigated by the concomitant administration of dopamine agonists, such as bromocriptine. In order to quantify the beneficial impact of early combination therapy, a controlled clinical trial (PRADO:PRA vi-del¹ +DOpa) in patients with early Parkinson's disease was carried out, whereby L-Dopa monotherapy (in a fixed combination with benserazide (DoBe) was being compared with the same combination plus bromocriptine (DoBeBro). Patients were recruited and treated by 101 practising neurologists in the Federal Republic of Germany and in Hungary. 'Twenty seven clinical university centers cross-checked the patients at regular intervals. The trial started with 3 months of DoBe monotherapy (median dose of 375 mg L-Dopa for both randomized groups) followed by gradual substitution of DoBe by bromocriptine over 3 months in one of the groups (250 mg L-Dopa/10 mg bromocriptine). The target medication was maintained from study months 6 to 54.Parkinsonian symptoms were classified according to the Webster rating scale, the Hoehn and Yahr scale and the Zung Self-Rating Depression Scale. Adverse events and life status were checked at regular intervals. Special emphasis was given to motor performance tests. 587 patients (302 in the DoBe group and 285 in the DoBeBro group) were available for intention-to-treat analysis. Both groups were homogeneous at baseline in all observed parameters. DoBe and DoBeBro proved equi-effective in terms of antiparkinsonian activity after the substitution phase (P II) had been completed. In September 1991, after a median observation period on target medication of 38.4 months in the DoBe group and 40.1 months in the DoBeBro group, 18 versus 8 deaths had been registered. The Logrank test as well as analysis using the Cox model, both adjusted for age and sex, showedP-values of 0.018 and 0.021, respectively. The mortality risk associated with L-Dopa therapy was reduced by more than 50 % by its combination with bromocriptine. The study was terminated due to this difference in mortality. The causes of death were classified by the treating physicians and consultants. At the time of study termination 152 patients in the DoBe group and 121 in the DoBeBro group had already discontinued study medication. Of those further 26 patients had died by the date of the final evaluation, 15 on DoBe and 11 on DoBeBro.The results imply that combination therapy with bromocriptine should be preferred over L-Dopa monotherapy from the very beginning.Dedicated to E. D. Schneider on the occasion of this 60th birthday.Pravidel = brand of Bromocriptine     

Reduction of reactivity to allergic rhinitis with intravenous administration of calcium. Clinical-experimental study on the effect of changes of local airway resistance after nasal allergen provocation

The antiallergic activity of calcium was investigated in 25 patients with allergic rhinitis by nasal provocation with increasing doses of phleum pratense during a symptom free interval. Prior to that provocation, the patients received 9 mmol calcium (Calcium-Sandoz) i.v. or placebo respectively (double blind cross-over design). The concentration of serum calcium increased after calcium injection by 0.45 +/- 0.055 mmol/l. Calcium exerted a significant protective effect as compared to placebo: higher allergen doses, (p = 0.021) i.e. 20433 biological units/ml vs. 7494 biological units/ml, were required in order to induce a defined allergic reaction (50% decrease of nasal air flow). The data thus furnish evidence that intravenous calcium reduces the allergic response in type I allergy.     

Pyoderma gangrenosum and orbital pseudotumor

Pyoderma gangrenosum belongs to the chronic, neutrophilic and necrotic dermatoses. These very painful, inflammable and purulent skin-ulcers often arise after injury or surgical intervention. About half of the patients suffer from systemic disease, for example hematological, gastrointestinal or rheumatic diseases. Our report includes a 77-year-old female with a multilocular emergence of pyoderma gangrenosum following surgery for an orbital pseudotumor. An additional lesion was detected on her anterior neck. Because the possibility of wound-infection was suspected, the lesion was treated locally and with a systemic antibiotic therapy. After this treatment the condition of the wound deteriorated. Upon dermatological examination, pyoderma gangrenosum was identified and a immunosuppressive therapy with corticosteroids and cyclosporin was initiated. As a result of this treatment the lesion healed slowly--with the formation of typical, atrophic and reticular scars. A connection between the pyoderma gangrenosum and the orbital pseudotumor can, on the basis of similar clinical and structural characteristics, not be excluded. A related disease was not diagnosed in this patient. Recurrence can be predicted in patients who have had skin injuries, therefore strict observation is required.     

Differentiation of white,mixed, and red thrombi: value of CT in estimation of the prognosis of thrombolysis phantom study

PURPOSE: To test with serial computed tomographic (CT) scans whether white, mixed, and red thrombi could be differentiated according to their CT attenuation. MATERIALS AND METHODS: Platelet-enriched plasma and whole blood were mixed to produce samples with hematocrit levels of 0, 0.005, 0.03, 0.15, and 0.35. A thrombin solution was added, and after 2 hours the retracted clots were transferred into polyethylene tubes with a length of 4 cm and an inner diameter of 3 mm. Ten probes of each sample were placed into a plastic box filled with a solution of gelatin, gadopentetate dimeglumine, and distilled water. Ten tubes filled with gelatin served as control. With this phantom, the CT numbers of white, mixed, and red thrombi were measured over 144 hours. CT was performed with a multisection scanner and a collimation of 0.5 mm. Statistical analyses were performed for differences between groups and over time. RESULTS: The CT numbers of white, mixed, and red thrombi differed significantly (P <.05) for most time measurements, except for white and mixed thrombi, which had a low hematocrit level at 24 and 144 hours (P >.05). CONCLUSION: With CT it appears feasible to differentiate thrombi according to their hematocrit level and thus estimate the effectiveness of thrombolysis.     

Comparative evaluation of radiochemotherapy with temozolomide versus standard-of-care postoperative radiation alone in patients with WHO grade III astrocytic tumors

Outcome after radiochemotherapy (RCHT) with temozolomide (TMZ) versus radiotherapy (RT) for WHO grade III astrocytic tumors was evaluated. No significant difference in overall survival or progression-free survival between both groups was calculated. RCHT seems not to result in an improved outcome. Further randomized studies are needed to support these results.     

Interferon-gamma inhibits growth of human neuroendocrine carcinoma cells via induction of apoptosis

Although biotherapy of gastroenteropancreatic neuroendocrine tumors (NET) provides excellent control for the hypersecretion syndrome, tumor regression is rarely observed, implying the need for novel antiproliferative strategies. Here, we demonstrate that human pancreatic QGP-1 NET cells express functionally intact interferon-gamma (IFN-gamma) receptors and downstream effectors, including the putative tumor suppressor interferon regulatory factor-1 (IRF-1). IFN-gamma treatment profoundly inhibited anchorage-dependent and anchorage-independent growth of QGP-1 cells. Concomitant with the onset of growth inhibition, apoptotic cells were detected in cell cycle analyses of IFN-gamma treated cultures. Apoptosis was confirmed by evaluation of DNA fragmentation and PARP cleavage. Immunoblots of IFN-gamma treated QGP-1 cells revealed a substantial upregulation of caspase-1, followed by the appearance of active proteolytic fragments of caspase-3, suggesting that autocatalytic activation of caspase-1 might initiate the caspase cascade. Apoptosis induction by IFN-gamma was also observed in two of four primary cultures established from tumors of patients with for- and midgut NETs, respectively. Taken together our results characterize IFN-gamma as a potent proapoptotic stimulus in a subset of gastrointestinal NETs and suggest an IRF-1 mediated induction of caspase-1 as a relevant underlying mechanism. Based on these results, the potential of IFN-gamma in experimental biotherapeutic treatment of NETs can be further explored.