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Biomedical subjects

L Christou

Publications and source records attributed to L Christou.

At least 19 recordsLinked to original sources

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.

Animals↗

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.

Anti-Infective Agents↗

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.

Acute Disease↗

Isolated ACTH deficiency associated with Crohn's disease.

We report a case of a 37-yr-old man with a 11-yr history of Crohn's disease (CD), who presented with mucous diarrheas of 1-week duration and a 3-month history of anorexia, increasing fatigue and weight loss of 7 kg. The patient was treated with sulfasalazine 3 g/day until 2 weeks prior to the present admission, when he reduced the dose to half as he considered the drug responsible for his symptoms. Despite aggressive iv rehydration and resolution of diarrheas with an increase in sulfasalazine dose, the patient remained hemodynamically unstable, while laboratory results showed anemia, hypoglycemia, hypertransaminasemia and hyponatremia with marked natriuresis. Thyroid function tests were consistent with primary hypothyroidism, without evidence of autoimmunity. Further laboratory investigation revealed a low basal cortisol and undetectable ACTH with preserved secretory responses of the other trophic pituitary hormones, establishing the diagnosis of isolated ACTH deficiency. Hydrocortisone replacement treatment induced a clinical and laboratory improvement. The autoimmune basis of isolated ACTH deficiency is discussed in association with the presumed contribution of immunologic reactions in the pathogenesis of CD. However more evidence is needed before isolated ACTH deficiency is added to the list of extraintestinal manifestations of CD.

Adrenocorticotropic Hormone↗

Treatment of resistant/relapsing chronic lymphocytic leukemia with a combination regimen containing deoxycoformycin and rituximab.

BACKGROUND: Patients with chronic lymphocytic leukemia (CLL) are sometimes resistant to treatment or relapse soon after the administration of the currently available frontline therapy including chlorambucil-prednisolone CHOP and fludarabine. We report the beneficial effect of an alternative chemotherapeutic regimen containing 2'-deoxycoformycin (pentostatin) and the monoclonal antibody anti-CD20 (rituximab) in 5 patients with resistant/relapsing CLL. PATIENTS: Five patients (4 men and 1 woman) with CLL at stage C, according to Binet's classification, were included in the therapeutic protocol. The median age of the patients was 76 years (range 57-84 years). Previous treatment consisted of chlorambucil-prednisolone, fludarabine, and CHOP. The current regimen comprised six 2-week cycles of pentostatin, 4 mg/m(2) i.v., combined with four cycles of rituximab, in a dose of 375 mg/m(2), every other week. RESULTS: Three patients responded to therapy, 2 achieved complete remission and 1 a partial response. Two patients did not respond to treatment. Toxicity was mild and well tolerated. The median survival duration of the responders was 19 months. These promising results suggest that salvage therapy with a combination regimen including pentostatin and rituximab may have a beneficial effect in patients with resistant/relapsing CLL.

Aged↗

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.

Aged↗

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.

Adult↗

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.

Adult↗

Treatment of plasma cell leukemia with vincristine, liposomal doxorubicin and dexamethasone.

Primary plasma cell (PCL) leukemia is a rare lymphoproliferative disorder characterized by a malignant proliferation of plasma cells in the bone marrow and peripheral blood. Survival with standard therapy using melphalan is very poor. Doxorubicin encapsulated with liposomes has less cardiotoxicity, is at least as efficient and has fewer side effects than conventional doxorubicin. Two female patients (69 and 54 yr old) with primary PCL are described in this study. They both received a modified form of VAD (vincristine, doxorubicin and dexamethasone), a regimen which includes liposomal doxorubicin (40 mg/m2 for 1 d), vincristine (2 mg for 1 d) and dexamethasone 40 mg per os on days 1-4, 9-12 and 17-20. A disease evaluation of the first patient after six courses of the modified \VAD regimen showed no plasma cells in the peripheral blood, a decrease in the serum M protein level and a plasma cell infiltration in the bone marrow of less than 5%. The patient died from a cardiac episode 24 months post-diagnosis, while she was in complete hematological remission. The second patient also exhibited good tolerance to liposomal doxorubicin with no side effects, achieved complete haematological remission and remains in good condition 7 months after the last VAD administration. These results suggest that this modified form of VAD regimen also seems to work in PCL and is well tolerated with no side effects.

Aged↗

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.

Aged↗

A patient with essential thrombocytosis and multiple sclerosis.

We report on a patient with a 5-year history of essential thrombocytosis (ET) who developed multiple sclerosis (MS) during the last 5 months. The patient was treated for MS with interferon-beta (IFN-beta), which also had a beneficial effect on the ET. We describe the patient's history and the beneficial effect of IFN-beta administration in reducing the number of platelets. We also discuss the possible link between the pathogenesis of ET and MS.

Journal Article↗

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.

Adult↗

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.

Antineoplastic Combined Chemotherapy Protocols↗

A patient with multiple myeloma, amyloidosis and light-chain deposition disease in kidneys with a long survival.

We report a case of a 39-year-old man with lambda-light-chain multiple myeloma, nephrotic syndrome due to lambda-light-chain deposition disease in kidneys and amyloidosis in other tissues. The patient was treated with melphalan and prednisone for 1 year. After that, he was administered interferon-alpha2b (IFN-alpha2b; 3 MU, 3 times a week) as maintenance therapy for 2 years. At present, 5 years and 6 months after the initial diagnosis, the patient receives IFN-alpha2b (3 MU, twice a week) and remains in complete haematological remission.

Adult↗

Rituximab (anti-CD20 monoclonal antibody) administration in a young patient with resistant B-prolymphocytic leukemia.

Following the administration of the human anti-CD20 monoclonal antibody IDEC-C2B8 (rituximab), a 31-year-old woman with B-prolymphocytic leukemia, who had been resistant to CHOP, fludarabine, pentostatin and 2-CdA, achieved complete remission. Rituximab was administered intravenously once a week for 4 weeks. The patient only had mild but tolerable side effects during the first cycle of therapy. She remains in complete remission 8 months following the discontinuation of treatment.

Adult↗

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.

Aged↗