Quinolones for brucellosis: treating old diseases with new drugs.

Although quinolones are theoretically interesting candidates for the treatment of brucellosis, the existing data concerning their efficacy are limited and conflicting. A number of small clinical studies with combination regimens that include quinolones have shown adequacy, but not superiority, although cost-effectiveness, excluding certain disease complications, is an important issue. The emergence of quinolone resistance and its implications is another drawback. Experimental data have yielded contradictory results, although most studies do not indicate a bactericidal effect for quinolones. However, in-vitro studies contrast repeatedly with the clinical response, both in terms of clinical failure, despite in-vitro success, and vice versa.

D-penicillamine induced myasthenia gravis: clinical, serological and genetic findings.

Eight cases of D-penicillamine (DP) induced myasthenia gravis (MG) are presented. Seven patients were being treated for rheumatoid arthritis (RA) and one for scleroderma. The mean duration of DP treatment until the myasthenic symptoms developed ranged from 2-8 months. The DP dose reached 500 mg daily. It was found that the clinical and immunological findings were almost similar to those of idiopathic MG, but were less severe. All patients had increased titers of acetylcholine receptor antibodies in their sera. Discontinuation of D-penicillamine resulted in the complete resolution of myasthenic symptoms after 2-6 months. One patient required ventilation, immunosuppressive therapy and plasma exchange. No association was found between DP related MG and the various autoantibodies tested. Immunogenetic analysis showed that three patients had HLA-DR1, two HLA-DR3, one HLA-DR4 and one HLA-DR5. In conclusion, the clinical presentation of DP-induced MG seems similar to idiopathic MG. DP-related MG is relatively benign, although it sometimes can cause life-threatening muscle weakness requiring aggressive therapy. The relatively small number of patients included in this study, however, does not permit any firm conclusions regarding the HLA associations of DP-related MG.

Unusual causes of reactive arthritis: Leptospira and Coxiella burnetii.

Reactive arthritis is a well-defined clinical syndrome occurring after various infections, although most cases are usually associated with Chlamydiae and gastrointestinal pathogens. Its immunologic background has been extensively studied, as has its relationship with HLA-B27. We describe two cases of reactive arthritis arising after infections with two pathogens not so far related to the occurrence of reactive arthritis: one patient exhibited migratory oligoarthritis shortly after the course of acute Q fever, and another patient developed monoarthritis during recovery from leptospirosis. Arthritis was transient and did not exhibit a chronic course in either patient. We further discuss the context of pathophysiology of the arthritis in these patients, with an emphasis on the immunomodulatory properties of these two pathogens.

Two siblings with chronic myelogenous leukemia.

In the present study we report the occurrence of Chronic Myelogenous Leukemia in two siblings (brother and sister) 47 and 62 years old respectively. These two cases raised the question of a possible genetic prodiathesis or a possible trasmission (environmental factor) cause.

Interleukins, TNF-alpha and beta-2M in patients with B cell chronic lymphocytic leukemia.

In order to investigate the possible existence of a prognostic factor for B cell chronic lymphocytic leukemia (B-CLL), we determined the serum levels of TNF-alpha, IL-1a, IL-1b, IL-2, sIL-2R, IL-6, IL-10 and beta-2M in 20 patients. We observed significant changes in sIL-2R and beta-2M levels, whereas in all stages of disease, TNF-alpha and other interleukins exhibited only mild changes. An excellent correlation between sIL-2R and beta-2M levels and disease activity wes reported. Patients with aggressive disease (Rai stages III and IV and Richter's syndrome) had increased levels. Patients who responded to therapy and with improved clinical status had decreased sIL-2R and beta-2M levels. However, patients with progressive disease and no response to therapy were associated with increased levels of sIL-2R and beta-2M. In conclusions, as serum levels of sIL-2R and beta-2M are increased in the aggressive stages of B-CLL, they may be used as reliable markers for monitoring B-CLL activity, showing response to treatment and early relapse and/or disease progression.

Preliminary results of amifostine administration in combination with recombinant human erythropoietin in patients with myelodysplastic syndromes.

Amifostine is a cytoprotective agent mainly used in cancer therapies, in order to ameliorate the toxic effects of anticancer chemotherapy and radiotherapy. In the past years an intriguing number of applications of amifostine have been identified; one of these is bone marrow cells protection and stimulation. Amifostine was administered in seven patients with myelodysplastic syndromes, four males and 3 females aged between 67 and 78 years old, in order to estimate its efficacy in reducing the need for red blood cells transfusions. Two patients had RAEB, four RA and one RARS. The drug was administered in an outpatient basis in a dose of 300 mgr/m2, three times weekly for at least four weeks. We administered at the same time erythropoietin 10.000 U subcutaneously. All patients received daily supplementation of oral ferrum sulfate and folic acid. Three patients, a woman with RA and two men, one with RA and another with RAEB improved the levels of Hb beyond 12,0 gr/dl and did not receive blood transfusions after the second week of treatment. The drug was well tollerated without any side effects in all of the patients.

Patients with multiple myeloma and solid tumors: six case reports.

Six patients with multiple myeloma (MM) and a second non-hematological neoplasm (solid tumor) are documented in this study. Two patients had a previous history of adenocarcinoma of the colon prior to MM diagnosis; in three patients a second neoplasm (lung cancer, adenocarcinoma of the urinary bladder and adenocarcinoma of the colon) appeared at the time of MM diagnosis; one patient, a woman with a six-year history of MM, developed hepatoma. The two patients who had had a neoplasm of the colon ten years before and the patient with bladder carcinoma, responded to MM therapy. The patient with lung cancer and the patient with adenocarcinoma of the colon died; the last patient, with MM and liver cancer, is alive but with aggressive disease. In conclusion we have found that in MM patients a second neoplasm may develop or co-exist, in greater frequency than that of the general population.

Chronic myelogenous leukemia terminating in acute megakaryoblastic leukemia. Case report.

A case of chronic myelogenous leukemia (CML) terminating in acute megakaryoblastic leukemia (AMKL) is here presented. Megakaryoblasts were identified by the presence of platelet peroxidase in the bone marrow as well as in pleural effusion and ascites. The clinical course, morphology and immunologic studies of the blast cells are described in this report.

Successful treatment of refractory anemia with a combination regimen containing recombinant human erythropoietin, low-dose methylprednisolone and nandrolone.

Myelodysplastic syndromes (MDS) are a heterogenous group of hematological clonal malignancies. Patients belonging to the refractory anemia (RA) subtype are usually treated with recombinant human erythropoietin (EPO). Not all patients respond to EPO administration and they are strictly dependent on supportive therapy with red cell blood (RBC) transfusions. The aim of this study was to investigate the efficacy of an alternative combination regimen containing EPO, low-dose methylprednisolone and nandrolone decanoate, in patients with RA unresponsive to EPO administration alone. Ten patients, 4 women and 6 men, median age: 70 years (range: 55-78 years) with refractory anemia unresponsive to EPO administration and RBC transfusion-dependent were included in the study. Median hematological data at baseline were Hb: 8.7 g/dl, (range 6.2-9.8), WBC: 3.35x10(9)/l (range 2.1-4), PLT: 82.5x10(9)/l (range 59-110). EPO 150 U/Kg three times/week subcutaneously, low-dose methylprednisolone 8 mg/day orally and nandrolone decanoate (Decadurabolin) 50 mg two-times/week intramuscularly were administered. As complete response (CR) to treatment was considered the normalization of the peripheral blood and bone marrow smears and biopsy. As partial response (PR) was considered increase in Hb level > or = 2 g/dl, or up to 10 g/dl and discontinuation of RBC transfusions. The response to therapy was evaluated on the 4th week after the initiation of the combination treatment. Bone marrow smear evaluation was carried out at baseline and every six months afterwards. After a 4-week treatment all patients achieved PR and discontinued RBC transfusions. Median and range hematological values on the 4th week after treatment initiation were Hb: 11.2 g/dl, (range: 9.8-12.8), WBC: 4.4x10(9)/l (3.5-6.6), PLT: 130x10(9)/l (95-160). The increase observed in hematological values was significant (p = 0.0001, 0.0004 and < 0.0001, respectively, for Hb, WBC and PLT counts). Treatment was well tolerated. Furthermore, two women, on treatment with the combination regimen, achieved CR one after six months and the second after 12 months. They are alive after 5 years from initiation of the combination treatment. After a median period of 18 months (range 12 to 20 months) in PR three men developed acute leukemia; they received intensive antileukemic chemotherapy without any response and died during the phase of pancytopenia. Three other men achieved CR, one after 6 and two after 12 months of therapy and they are on regular follow-up. Two women after 10 and 14 months in PR developed acute leukemia and died. In conclusion, combination therapy with EPO, nandrolone decanoate and low-dose methylprednisolone may be effective as an alternative treatment for RBC transfusion-dependent patients with RA unresponsive to EPO administration alone.

Hepatitis E virus in the Western world--a pork-related zoonosis.

Hepatitis E virus (HEV) is a common cause of waterborne epidemics of acute hepatitis worldwide, but its natural history, ecology, clinical significance and presentation are entirely different in the developed world, where, apart from the typical travel-associated imported cases, the majority of the observed cases involve older adults with comorbidities or forms of immune compromise who acquire HEV genotype 3, mostly through direct or indirect (consumption of meat products) contact with pigs. Thus, HEV is zoonotic in the developed world, a fact that has been recently recognized, and is of major importance in medical, veterinary and public health terms. The present article evaluates the current knowledge about the zoonotic nature of HEV in the industrialized world, outlines the numerous questions that still exist regarding the role of pigs in viral ecology, summarizes knowledge about clinical disease in its zoonotic form, and discusses where future scientific efforts should focus.

The global burden of bacterial and viral zoonotic infections.

Bacterial and viral zoonotic infections comprise a practically endless, ever-expanding list of pathogens that have the potential to induce human disease of varying severity, with varying means of transmission to humans (including vector-borne and foodborne agents) and of varying epidemiology. Not all theoretically zoonotic pathogens are truly zoonotic in practice, the prime example being influenza viruses; aviann H5N1 influenza remains strictly zoonotic, whereas novel H1N1 influenza displays an anthropocentric cycle that led to a pandemic, despite being of zoonotic origin. The burden of disease induced by zoonotic and viral pathogens is enormous: there are more than ten bacterial zoonoses, each of which affects hundreds of thousands patients annually, often leading to chronic infections and causing significant economic losses of a medical and livestock-related nature. Viral zoonotic agents are constantly emerging or re-emerging, and are associated with outbreaks of limited or expanded geographical spread: the typical trends of viral zoonotic infections, however, is to extend their ecological horizon, sometimes in an unexpected but successful manner, as in the case of West Nile virus, and in other instances less effectively, as was the case, fortunately, in the case of avian influenza. The majority of bacterial and viral zoonotic infections attract disproportionately low scientific and public health interest. Understanding their burden may allow for improved surveillance and prevention measures.

Multiple myeloma presenting with an acute bacterial infection.

Increased susceptibility to bacterial infections is a common manifestation of multiple myeloma (MM), arising mainly from a defect in humoral immunity and is associated with major morbidity and mortality. The propensity to infection is increased in the first months after the initial diagnosis and in patients with renal dysfunction. Gram-positive infections, mainly pneumonia from Streptococcus pneumoniae, occur more frequently in patients with untreated disease while Gram-negative infections, mainly of the urinary tract, are more common after chemotherapy. However, an acute bacterial infection is rarely reported as the first manifestation of underlying MM. In this review, we analysed data from 17 such cases reported between 1978 and 2008. Median age was 65.5 years and most patients were females; monoclonal paraprotein was IgG in 92%. In contrast to diagnosed treated or untreated MM, musculoskeletal infections predominated in these early cases (47%) followed by pneumonia (29%). In particular, septic arthritis, mainly of the knee, was the most common infectious complication (35%). Streptococcus pneumoniae was isolated in two-thirds of infections and bacteremia was common (80%). In this early phase, immunodeficiency arised from a decreased synthesis of polyclonal immunoglobulins. White blood cell counts were frequently normal, particularly in musculoskeletal infections. Renal impairment occurred in 67% and correlated with increasing monoclonal paraprotein levels. The outcome was favorable in most cases (79%). MM should be considered in previously asymptomatic middle-aged patients who present with a major acute bacterial infection, without an apparent predisposing factor. In particular, suspicion should be high in cases of septic arthritis and pneumococcaemia.

Brucella as a biological weapon.

Brucella has traditionally been considered a biological weapon. It was the subject of extensive offensive research in the past, and still belongs to category B pathogens on most lists. Its propensity for airborne transmission and induction of chronic debilitating disease requiring combined antibiotic regimens for treatment, its abundance around the world and its vague clinical characteristics defying rapid clinical diagnosis are some of the characteristics that apply to the pathogen's weapons potential. Yet minimal mortality, availability of treatment options, protracted inoculation period and the emergence of new, more virulent potential weapons means that its inclusion among agents of bioterrorism is nowadays mainly of historical significance. Nevertheless, in the interest of literacy and of avoiding panic, physicians and the public both should be aware of the most common zoonosis worldwide.

Cutaneous manifestations in brucellosis: case report and review of the literature.

Brucellosis is a classical common zoonotic disease of worldwide distribution. Skin complications are infrequent and affect less than 5% of patients with brucellosis, although they may occasionally occur during the clinical course of the disease. Here, we report a case of a shepherd presenting with fever and a diffuse maculopapular rash due to Brucella melitensis infection, and we provide a review of the relevant literature.

Treatment of 34 patients with myelodysplastic syndromes with 13-CIS retinoic acid.

Thirty-four patients with myelodysplastic syndromes, 23 men and 11 women, aged between 47 and 80 years, with all types of myelodysplastic syndromes were treated with 13-cis-retinoic acid. The dose of retinoic acid ranged between 10 and 60 mg/m2/daily and was administered in combination with vitamin E to diminish side effects. The duration of treatment was 3 months to 5 years. Partial remission was achieved in 4 patients, 1 with RA type, 2 with RAEB and 1 with CMML. Survival ranged from 1 to 5 years. Patients who received retinoic acid developed mild side effects. In conclusion, the administration of 13-cis-retinoic acid improves the hematological picture in a small number of MDS patients (11.7%).

Immune thrombocytopenia attributed to brucellosis and other mechanisms of Brucella-induced thrombocytopenia.

Thrombocytopenia often complicates the course of acute brucellosis, mainly due to bone marrow suppression or hypersplenism. Immune thrombocytopenia is also reported in brucellosis, resulting usually in massive thrombocytopenia, purpura, and spontaneous hemorrhage. We describe a case of acute brucellosis in an 85-year old woman, who presented with fever, purpuric skin lesions, anemia, and rhinorrhagia. The absolute platelet count was 1000/microL. Direct and indirect Coombs tests were positive, and a cold-agglutinin was detected. The patient was diagnosed as suffering from brucellosis on the basis of a strongly positive serologic reaction and was treated with doxycycline, streptomycin, and a short course of corticosteroids, with a rapid rise in platelet number.

Serum levels of IL-6 and its soluble receptor (sIL-6R) in Waldenström's macroglobulinemia.

BACKGROUND: Interleukin-6 (IL-6) is a multifunctional cytokine that plays roles in the immune response, inflammation and hematopoiesis. Serum IL-6 levels have reported to reflect disease severity and high tumor burden in multiple myeloma (MM) patients and to correlate with several other laboratory parameters. Serum-soluble IL-6 receptor (sIL-6R) plays an agonist role in IL-6 signaling, enhancing its biological activity tenfold. PURPOSE-METHODS: We measured IL-6 and sIL-6R levels in 11 patients (7 male, 4 female, mean age 66.9 yr) with Waldenström's macrobulinemia (WM) using a commercially available enzyme-linked immunoassay in order to investigate their biological role and to find any possible relationship with disease severity, tumor burden or response to treatment. RESULTS: Serum IL-6 and sIL-6R concentrations at diagnosis were significantly higher than in healthy controls (Mann Whitney U-test, p < 0.001 and p < 0.01, respectively). Patients who were effectively treated had a significant reduction in IL-6 levels (p = 0.017). With regard to sIL-6R levels, no specific tendency was observed. In some of the responsive patients the levels increased whereas in others they decreased. No correlation was found between IL-6 and sIL-6R levels at diagnosis (p = 0.9, r = 0.036) or after treatment (p = 0.083, r = 0.3). CONCLUSIONS: Our results suggest that IL-6 may be a marker reflecting tumor burden, disease severity and response to treatment in WM. With regard to sIL-6R, we believe that it does not seem to be of much value, and its role remains to be clarified. However, future studies are needed to confirm and further extend the present results.

Pleural effusion in chronic myelomonocytic leukemia.

Pleural effusion in 4 patients with chronic myelomonocytic leukemia (CMML) is described in this report. According to the literature, pleural effusion in CMML is a poorly understood and rare occurrence. Two of our patients presented with pleural effusion as an initial symptom while the other 2 developed it during the course of the disease. In only 1 patient was the pleural effusion due to leukemic infiltration while in the other 3 it was a reactive phenomenon. Peripheral lymphadenopathy was observed only in the former patient who died of acute leukemia. After prednisolone therapy the pleural effusions resolved in the other 3 patients.

Administration of a modified chemotherapeutic regimen containing vincristine, liposomal doxorubicin and dexamethasone to multiple myeloma patients: preliminary data.

For elderly patients with multiple myeloma (MM), conventional melphalan and prednisone (MP) therapy has been the treatment of choice; the vincristine, doxorubicin and dexamethasone (VAD) regimen is preferred for younger patients who also receive high-dose melphalan in combination with autologous or allogeneic bone marrow transplantation (BMT). Although survival time is similar in both the MP and VAD regimens, the continuous infusion of doxorubicin which the latter treatment entails constitutes a disadvantage along with the 4-day hospitalization required. Doxorubicin also induces cardiotoxicity, particularly in the elderly. A modified form of VAD therapy includes liposomal doxorubicin (Caelyx) (40 mg/m2 for 1 d) [corrected], oncovin (2 mg for 1 d) and dexamethasone 40 mg for 4 d per os. Doxorubicin encapsulated with liposomes has less cardiotoxicity, is more efficient and has fewer side effects than conventional doxorubicin, and it can be administered on an outpatient basis: dexamethasone can be given orally and vincristine in bolus infusion. In order to estimate its efficacy and tolerability, we administered this regimen to 12 patients (first-line treatment in 6 patients, salvage therapy in 6 patients). All patients exhibited good tolerance to liposomal doxorubicin with no severe side effects. Eight patients achieved complete hematological remission and three partial response. One patient died before completing the treatment. In conclusion, compared to other therapies, this modified VAD regimen containing liposomal doxorubicin can be more easily administered to MM patients, without severe side effects and with increased full remission rates, almost similar to those with the conventional VAD treatment.