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Oral trimethoprim/sulfamethoxazole in attempt to prevent infection after induction chemotherapy for acute leukemia.

The efficacy of orally administered trimethoprim/sulfamethoxazole for infection prevention following induction chemotherapy was evaluated in 43 patients with acute leukemia. Twenty patients were randomly assigned to treatment with trimethoprim/sulfamethoxazole during 20 episodes of profound granulocytopenia; 23 patients in the control group were followed through 25 granulocytopenic episodes. The incidences of superficial skin and overall infections were significantly lower in those patients with multiple relapses who received trimethoprim/sulfamethoxazole (p = 0.008); however, there was no difference between the groups in regard to days of fever, days of antibiotic administration, days of hospitalization, or gram-negative rod bacteremia. As a result of this study, this regimen cannot be unequivocally recommended for infection prevention in neutropenic patients with acute leukemia undergoing induction or reinduction chemotherapy.

Acute Disease↗

[Malassezia furfur septicemia after bone marrow graft].

BACKGROUND: Systemic Malassezia furfur (Mf) infections are only seen in neonates and immunocompromised patients. CASE REPORT: A 2-year-8-month-old boy was given chemotherapy for mediastinal T cell lymphoma. Meningeal relapse supervened 10 months later, requiring polychemotherapy plus CNS irradiation followed by bone marrow transplantation. Three days after transplantation, fever associated with neutropenia required administration of ceftazidime, amikacin, vancomycin plus acyclovir followed by amphotericin B, cefotaxime plus erythromycin. Blood cultures were negative, but blood swears showed yeasts into polynuclear cells after cytocentrifugation; these yeasts were also present in the central catheter removed after a few days course of amphotericin B, flucytosine plus fluconazole. The patient was then given GM-CSF subcutaneously (5 micrograms/kg/day), followed by progressive correction of aplasia and cure of the Mf infection. CONCLUSION: This is a new case of systemic Mf infection seen in an immunocompromised child receiving parenteral nutrition with lipids.

Bone Marrow Transplantation↗

Successful treatment of imported cerebral malaria with artesunate-mefloquine combination therapy.

Treatment of cerebral malaria with intravenous quinine is frequently associated with life-threatening cardiotoxicity. We report a case of imported cerebral malaria successfully treated with artesunate-mefloquine combination therapy. The 27-year-old woman presented with fever, sudden onset of binocular blindness and altered consciousness 10 days after a short stay in Indonesia. Hyperparasitemia with Plasmodium falciparum and P. vivax in more than 5% of red blood cells was demonstrated on peripheral blood smear. She was admitted to the intensive care unit due to shock, jaundice and acute renal failure. Because of a shortage of intravenous quinine, intravenous artesunate was given as an alternative. Her condition stabilized on the 3rd day of therapy, with resolution of fever and disappearance of parasitemia. Consolidation therapy with oral mefloquine and primaquine was then given to prevent recrudescence and relapse. The only adverse event associated with artesunate was transient reticulocytopenia, which resolved after discontinuation of therapy. Her vision completely recovered, along with renal and liver function.

Adult↗

[Mastitis puerperalis - causes and therapy].

Between 1995 and 2003 a total of 1 827 women suffering from puerperal mastitis was studied. Etiology of the disease was defined, white cell counts and microbiologic cultures were obtained. According to the results the illness was classified and treated. Since in all cases we found either simple congestion or non-infectious inflammation of the breast treatment consisted of intensified emptying of the breast by breast feeding every 2 hours and in some cases additional manual expression of milk. Antibiotics and bromocriptine were not used. In 1 826 cases fever and flue symptoms had resolved within 25-36 hours. Redness and soreness had resolved within 2-3 days. Relapse did not occur and none of the women developed an abscess. One woman had to be treated with antibiotics because the baby refused to nurse at the diseased breast and emptying had to be done by hand.

Breast Feeding↗

Use of protein A immunoadsorption as a treatment for thrombocytopenia in HIV-infected homosexual men: a retrospective evaluation of 37 cases.

Thirty-seven HIV-infected homosexual men with thrombocytopenia (less than 100 x 10(9)/l) received protein A immunoadsorption treatments to remove platelet-sensitizing immunoglobulin (Ig) G and circulating immune complexes (CIC) from plasma. Patients received an average of six treatments each, consisting of 250 ml plasma over a 3-week period. Clinical improvement in hemorrhagic symptoms associated with substantial increase in platelet counts was achieved in 18 patients. These responses were maintained over a median follow-up period of more than 7 months in 14 evaluable patients who were not lost to follow-up (three patients relapsed in 2 weeks and one received another therapy). Generally, moderate transient treatment-related side-effects included fever, musculoskeletal pain, chills and nausea. A transient serum sickness-like reaction was observed in seven patients, leading to termination of treatment in two. Clinical responses were associated with significant decreases in levels of platelet-sensitizing Ig, including CIC. Stimulation of broadly cross-reactive anti-antigen-binding fragment [F(ab)2], antibodies contributed to these responses. Protein A immunoadsorption is an effective alternative treatment for HIV-associated thrombocytopenia.

Adult↗

Stage I to IIB Hodgkin's disease: the combined experience at Stanford University and the Joint Center for Radiation Therapy.

The treatment records of 180 patients with pathological stage (PS) IB to IIB Hodgkin's disease treated at Stanford University Medical Center (SUMC) or the Joint Center for Radiation Therapy (JCRT) were reviewed. Pretreatment characteristics were analyzed to assess their influence on survival and freedom from relapse (FFR). The two most important disease characteristics predictive of relapse were the number and type of B symptoms present and the mediastinal mass ratio (MMR). Patients with both fevers and weight loss had a 7-year survival and FFR of only 57% and 48%, respectively. The poor prognosis in this group was apparent for treatment with either radiation (XRT) alone or combined modality therapy (CMT). Patients with night sweats only had no adverse effect of B symptoms on outcome. Patients with a MMR greater than 1/3 had a 7-year FFR of only 58% after XRT, but 79% after CMT (P = .12). The 7-year survivals for these patients were 85% and 88%, respectively. CMT improved the FFR of the entire group of 180 patients when compared with XRT (7-year FFR 86% and 74%, respectively, P = .02); however, survival in the two treatment groups was similar (88% and 89%). Among patients treated with radiation alone, there was a similar survival and FFR irrespective of whether pelvic irradiation was included in the initial treatment fields.

Adult↗

A patient with Graves' disease who developed hypothyroidism associated with thyroid stimulation blocking immunoglobulin during anti-thyroid drug therapy.

A girl, 12 years of age, developed Graves' disease compounded with rheumatic fever and idiopathic thrombocytopenic purpura. Thrombocytopenia improved under short-term treatment with steroids and her mitral valvular insufficiency, due to the rheumatic fever, disappeared 4 years later. Initially, she had been treated with propylthiouracil (PTU) for 28 months. She suffered a relapse 9 months after stopping PTU and so she was given further PTU therapy. However, hypothyroidism developed 11 months after the initiation of therapy and continued, though further PTU treatment was discontinued. She now receives 1-thyroxine and maintains a euthyroid state. At the onset of the patient's hyperthyroidism, the TSH-binding inhibitor immunoglobulin (TBII) and the thyroid stimulating antibodies (TSAb) were found to be positive. During the remission period, only the thyroid stimulation blocking immunoglobulin (TSBI) was weakly positive. At relapse, only TBII was mildly positive. When hypothyroidism developed, both TBII and TSBI were positive, and TSAb was negative in all testings of her diluted IgGs. The patient's TBII and thyroid dysfunction were unaffected by high-dose intravenous gammaglobulin therapy or by treatment with prednisolone 0.5 mg/kg/day for 2 weeks. In conclusion, the emergence of TSBI during or after anti-thyroid drug therapy might possibly lead to hypothyroidism in patients with Graves' disease.

Antithyroid Agents↗

Clinical experiences in the treatment of neuroblastoma with 131I-metaiodobenzylguanidine.

Treatment of neuroblastoma is an unsolved problem of pediatric oncology. In spite of highly intensified chemotherapy, the long-term survival rate of children with a metastatic neuroblastoma is below 10%. We therefore used 131I-metaiodobenzylguanidine (MIBG) for the first time to treat children with a neuroblastoma in relapse or primary unresponsiveness to chemotherapy. We had previously demonstrated that MIBG is useful for the scintigraphic imaging of neuroblastoma lesions and had investigated the cytotoxicity and uptake of MIBG in various neuroblastoma cell lines. We treated 6 children with neuroblastoma in a total of 19 courses. Three of the children suffered from a relapse of neuroblastoma; 3 had never gained a remission. Four of the 6 children lost their bone pain and fever during the first 3 days. In 5 of the 6 children the solid tumor as well as the bone marrow infiltration responded to MIBG treatment, with responses ranging from transitory decrease of the tumor mass to complete disappearance of abdominal tumors. We also witnessed a stabilization of osteolytic lesions, a decrease in elevated serum catecholamines, and a decrease in bone marrow infiltration. Five of the 6 children died of tumor progression 55-249 days after the first MIBG treatment.

3-Iodobenzylguanidine↗

[Invasive aspergillosis in hematological patients].

An increasing incidence of invasive aspergillosis over the last decades is well documented in patients with haematological malignancies and is the most significant fungal infection in patients undergoing bone marrow transplantation and in aplastic anaemia. The diagnosis is difficult as clinical signs and symptoms usually are non-specific, but can be supported by frequent radiological examinations of the chest and sinuses and successive demonstrations of Aspergillus antigen in serum. The prognosis depends on the course of the underlying disease. A regeneration of the neutrophil granulocyte number is a condition for successful treatment. Early antifungal therapy is often necessary in neutropenic patients with fever and a lung infiltrate that does not remit following broad spectrum antibacterial treatment. Because of the risk of relapse after successful treatment these patients should receive prophylactic antifungal treatment during subsequent neutropenic episodes.

Anemia, Aplastic↗

[The retinoic acid syndrome, a complication of acute promyelocytic leukemia therapy].

OBJECTIVE: To describe the retinoic acid syndrome, a complication of therapy with all-trans retinoic acid (ATRA) in acute promyelocitic leukemia (APL). PATIENTS AND METHODS: Retrospective study of five patients with a morphologic diagnosis of APL by the French-American-British (FAB) classification that were treated for remission induction with ATRA and developed the ATRA syndrome. RESULTS: Three patients in newly diagnosed APL and two in leukemia relapse were analyzed. All patients received with ATRA 45 mgrs/m2/day, and three of them also received chemotherapy. Patients developed fever, respiratory distress, pulmonary infiltrates, weight gain and edemas. The onset of this symptom complex occurred from 1 to 11 days after starting treatment and was preceded by an increased in peripheral blood leukocytes. Infections or congestive heart failure were ruled out. The clinical course progressed while patients being treated with wide spectrum antibiotics. Four patients were treated with high doses corticosteroid therapy (dexametasone 10 mgrs intravenously every 12 hours), in three of them full recovery was attained and one died. One patient that did not received steroids died. CONCLUSIONS: The use of all-trans retinoic acid to induce hematologic remission in APL patients is associated in same patients with the development of ATRA syndrome, a life threatening complication. Symptoms begin in the first days of treatment. If this syndrome is suspected, early treatment with high dose steroids should be initiated.

Adolescent↗

A randomized clinical trial of low dosage combination of pentamidine and allopurinol in the treatment of antimony unresponsive cases of visceral leishmaniasis.

OBJECTIVES: A randomized clinical trial of low dosage combination of pentamidine and allopurinol was carried out with objectives to assess the efficacy and toxicity as compared to full dosage of pentamidine in antimony unresponsive visceral leishmaniasis (VL) patients. METHODS: Using a randomized control clinical trial, a total of 158 antimony unresponsive patients of VL were randomly allocated into two treatment groups. Patients in one group (n=80) received half the dosage of pentamidine i.e. 2 mg/kg body weight by IM route on alternate day and allopurinol in dose of 15 mg/kg body weight in three divided dosages for 30 days; patients in the second group (n=78) received pentamidine in dose of 4 mg/kg body weight by IM route on alternate day for 15 injections in 30 days. The efficacy and safety of the two regimens were compared. RESULTS: Apparent cure i.e. clinical and pathological cure at the end of therapy, in 78 (97.5%) and 67 (86%), and ultimate cure i.e. clinical and parasitological cure at the end of follow-up of six months, in 73 (91.25%) and 58 (74.35%) patients was observed in the combination regimen and single regimen group respectively. The difference of the ultimate cure between two groups of the patients was statistically significant (p < 0.01). In single regimen group, 11 (14%) patients showed primary unresponsiveness (with no response during treatment) and nine (13%) relapse (after six months of follow-up) respectively, where as in combination regimen group, two (2.5%) patients showed primary unresponsiveness and five (6.4%) relapse respectively. By the end of the treatment, the incidence of injection-related toxicity, such as rigor and fever, was same in both groups. No hyperglycemia was observed in combination therapy probably due to reduced dose of pentamidine and three patients in single regimen developed hyperglycemia and one of them developed irreversible hyperglycemia. CONCLUSIONS: The study showed that the combination of pentamidine (half dose) and allopurinol is more effective in achieving ultimate cure with an added advantage of reduced toxicity in unresponsive cases as compared to full pentamidine dose.

Adolescent↗

[Sustained remission of MDS overt leukemia associated with abrupt discontinuation of immunosuppression following relapse after the second course of allogeneic hematopoietic stem cell transplantation].

The case of a 32-year-old female with relapsed myelodysplastic syndrome (MDS) after second course of allogeneic transplantation is described. The peripheral blood stem cell transplantation was performed as early as 3 months after the initial bone marrow transplantation because of rejection and relapse; however, the patient again relapsed 2 months later. Immediate discontinuation of cyclosporine resulted in the progression of pancytopenia and the development of high fever, liver dysfunction and skin eruption. The patient was then treated with dexamethasone, which successfully stabilized these symptoms. After these clinical events, a dramatic hematological response was obtained; the blast rate was reduced from 10.6 to 0% in bone marrow aspiration, and pancytopenia was restored to normal levels. Moreover, fluorescence in situ hybridization analyses with X and Y chromosome-specific probes revealed that hematopoietic precursor cells were predominantly of donor origin. The patient subsequently received donor lymphocyte infusion (DLI) from the original donor. Currently, 2 years after DLI, the patient continues to be in remission.

Adult↗

Comparison of the effectiveness of five different antibiotic regimens on infection with Rickettsia typhi: therapeutic data from 87 cases.

This study estimated the clinical effectiveness of five different antibiotic regimens (doxycycline, chloramphenicol, ciprofloxacin, doxycycline plus chloramphenicol, and doxycycline plus ciprofloxacin) administered for infection with Rickettsia typhi in terms of the duration of the fever. Eighty-seven patients with endemic typhus were hospitalized between 1993 and 1998 at the General Hospital of Chania in Chania, Crete, Greece. The mean time to defervescence was 2.9 days for doxycycline, 4.0 days for chloramphenicol, and 4.2 days for ciprofloxacin. In patients receiving combinations of doxycycline plus chloramphenicol and doxycycline plus ciprofloxacin, fever subsided in 3.4 and 4.0 days, respectively. The outcome was favorable in all patients, and no deaths or relapses were observed within two months.

Adolescent↗

[Cardiac effects of cytokines produced after rituximab infusion].

Rituximab (Mabthera) is used in the treatment of refractory low-grade non-Hodgkin's lymphoma or in case of relapse after chemotherapy. Among the different adverse reactions with this drug, the most common is a constellation of symptoms (fever, rigors and chills) that occur more frequently during administration of the first dose of drug. These symptoms could be related to a cytokine-release syndrome. We report the case of a 46 year-old patient, presenting a familial cardiomyopathy, deceased a few minutes after having developed this syndrome, at the time of the 2nd infusion of rituximab. Several hypothesis have been suggested to explain this sudden death: a cardiac failure following deterioration of the systolic function, potentially related to the negative inotropic effects of TNFalpha, and/or an impairment of the diastolic function following the volemic overload. The impact of the reflex "administration of monoclonal antibody/cytokine-release syndrome" was only little investigated under physiologic or pathologic conditions. In spite of a risk of adverse reactions apparently moderated compared to the other drugs used in this context, this case report underlines the need for a special attention when using rituximab among patients with cardiac risk factors (reassessment of the benefit-risk ratio, specific monitoring, pre medication). More generally, it underlines the need for a systematic and continuous identification and reporting of adverse drug reactions to the French network of regional pharmacovigilance centres.

Antibodies, Monoclonal↗

Peritonitis in children with nephrotic syndrome.

In a retrospective review of 214 children with nephrotic syndrome seen at Children's Medical Center and Parkland Memorial Hospital in Dallas throughout the 20-year period from 1967 to 1986, 62 cases of primary peritonitis were identified in 37 patients (17.3% rate). Streptococcus pneumoniae was the major pathogen, accounting for 38% of the cases. An additional 27% of patients had negative culture results but were clinically responsive to penicillin. Gram-negative organisms were cultured from only 3% of patients; 5% were caused by alpha-streptococci and 2% each by enterococcus and anaerobes. In 23% of cases the cause was unknown. Our findings differ from the recent trend in the literature in which Gram-negative organisms associated with these infections are increasingly implicated. The incidence and bacteriology of peritonitis do not appear to have changed significantly during the 20-year period. Clinically, peritonitis was characterized by abdominal pain (98%), fever (95%), rebound tenderness (85%), and nausea and vomiting (71%). A total of 79% of patients were either in relapse or receiving steroid therapy at the time peritonitis was diagnosed; 13% had infiltrates visible on their chest radiographs. Based on our data, it seems reasonable to initiate antimicrobial therapy in nephrotic children with suspected peritonitis using a combination of penicillin plus either an aminoglycoside or a cephalosporin. This regimen should continue until culture results are available, unless Gram-positive diplococci are identified in a Gram-stained specimen of peritoneal fluid, in which case penicillin alone should suffice.

Adolescent↗

FK506 (Tacrolimus) monotherapy for prevention of graft-versus-host disease after histocompatible sibling allogenic bone marrow transplantation.

FK506 (Tacrolimus) is an immunosuppressive drug that blocks the activation of antigen-specific T lymphocytes, a major component in the pathogenesis of graft-versus-host disease (GVHD). This study was designed to obtain first estimates of the safety and efficacy of FK506 monotherapy in the prevention of GVHD following HLA-identical sibling marrow transplantation. Additionally, a subset of patients was studied to define the pharmacokinetic profile of FK506. Twenty-seven adult patients with leukemia or myelodysplasia received FK506 starting the day before transplant at a dose of 0.04 mg/kg/d by continuous intravenous infusion. When clinically possible, FK506 was given orally in two divided doses starting at five times the daily intravenous dose. FK506 doses were adjusted to target a steady state or trough blood level between 10 to 30 ng/mL. These patients were followed for 6 months posttransplant. All patients had sustained marrow engraftment. Frequently noted adverse events included reversible renal dysfunction, diarrhea, fever, nausea, vomiting, and headache. Most patients required FK506 dose reductions associated with elevated serum creatinine. Two (7%) patients relapsed, one of whom died of the disease within the 6-month study period. A second patient died due to pulmonary mucor. Whole blood pharmacokinetic parameters indicated a half-life of 18.2 +/- 12.1 hours; volume of distribution of 1.67 +/- 1.02 L/kg; clearance of 71 +/- 34 mL/h/kg; and bioavailability of 32 +/- 24%. Eleven of 27 (41%) patients developed grade II to IV acute GVHD, including 10 grade II and one grade III. Six of 24 (25%) evaluable patients developed chronic GVHD. These data indicate that FK506 monotherapy has activity in preventing GVHD. Further studies of FK506 with lower doses to improve tolerability and in combination with other immunosuppressants to augment efficacy are warranted.

Adolescent↗

Acute lymphoblastic leukemia associated with brucellosis in two patients with fever and pancytopenia.

Brucellosis is a disease involving the lymphoproliferative system, which may lead to changes in the hematological parameters; however, pancytopenia is a rare finding. However, malignant diseases in association with brucellosis are rarely the cause of pancytopenia. Herein, two cases with fever and pancytopenia, diagnosed as simultaneous acute lymphoblastic leukemia and brucellosis are presented. Anti-leukemic therapy and brucellosis treatment were administered simultaneously, and normal blood parameters obtained. The first patient is in complete remission; the other recovered from the brucellosis, but later died due to a leukemic relapse.

Adult↗

Kikuchi disease presenting as a flu-like illness with rash and lymphadenopathy.

Kikuchi-Fujimoto disease (Kikuchi Disease) is a self-limited and benign systemic lymphadenitis of unknown cause, originally described by Kikuchi and Fujimoto and coworkers in 1972. Although relatively uncommon, it is increasingly discussed in the medical literature. Clinical presentation typically includes adenopathy, particularly cervical, with fever and flu-like symptoms. This constellation of symptoms, in the presence of a characteristic histiocytic necrotizing lymphadenitis, provides the clinicopathologic diagnosis. The immunopathogenesis of Kikuchi disease may lie in a hyperactive response to viral infection. We describe an African American man with Kikuchi disease, unusual in the extent of his rash and debilitation, and in the relapse of his clinical symptoms.

Adult↗