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[IDA-FLAG (idarubicin, fludarabine, high dosage cytarabine and G-CSF)--an effective therapy regimen in treatment of recurrent acute myelocytic leukemia in children and adolescents. Initial results of a pilot study].

Intensive chemotherapy has improved the prognosis of patients with AML. The success rate of relapse treatment correlates with the length of first remission. Thus early relapses and primarily refractory diseases have a grave prognosis. New chemotherapeutic regimens could be useful for those patients. Patients treated for newly diagnosed or relapsed AML with polychemotherapy regimen of the AML-BFM-studies containing induction, consolidation and high-dose cytarabine combined with mitoxantrone (HAM) and relapsed within 2 up to 31 months after the first CR entered a pilot trial, the so called IDA-FLAG regimen. This regimen includes G-CSF (day 0 up to ANC > 1000/microliter, 400 micrograms/m2.d), fludarabine (day 1-4, 30 mg/m2.d), high-dose cytarabine (day 1-4, 2000 mg/m2.d) and idarubicin (day 2-4, 12 mg/m2.d). 10 patients aged 1,8 to 28,1 years (mean = 9,6 years) having the first (n = 8) or second relapse (n = 1) of AML or an acute blastcrisis of myelodysplastic syndrome (n = 1) (FAB classification: M1/M2 = 3, M4/M5 = 5, M7 = 1, CMML = 1) received 14 courses. Overall, 7 patients achieved CR with a mean duration of 8,9 months (1-22 months), one patient showed a partial remission and two were nonresponders. 4 patients are in continuous CR for 7,5 to 22 months (mean = 13,2 months). 3 patients got a bone marrow transplantation (allogenic = 2, autologous = 1) in CR following this treatment. Toxicity was considerable, mainly bone marrow aplasia with leucopenia < 1000/microliter for 15 to 40 days (mean = 26,1 days), neutropenia < 500/microliter for 14 to 39 days (mean = 26,0 days) and thrombocytopenia < 30,000/microliter for 14 to 90 days (mean = 36,5 days). Further important side effects were fever, mucositis and pneumonia. One patient died from an fulminant aspergillus sepsis during long-term neutropenia. The sequential administration of G-CSF, fludarabine, cytarabine and idarubicin is effective in treatment of relapsed AML in childhood and an advisable option prior to allogenic or autologous bone marrow transplantation. With regard to the unfavorable prognosis of relapsed or refractory AML the toxicity of this regimen seems acceptable.

Adolescent↗

[Typhoid fever in Vietnam. I. Bacteriological study (607 Salmonella strains isolated from 1961 to 1975 at the Grall Hospital of Saigon)].

From 1961 to 1975, researches on salmonellosis have been carried out in Hospital Grall, in Saigon, mainly during two periods (1961-1964, then 1971-1975). 607 strains of Salmonella have been isolated for these 15 years (558 S. typhi and 49 Salmonella, among several other serotypes). As typhoid fever is most important, the authors have studied this disease very carefully. The most efficacious technique of isolating is hemoculture. With coproculture, the results are disappointing. Scarcely, some strains have been found in samples of various origins. Indirect diagnosis methods are less interesting. They may induce only a presumptive diagnosis. S. typhi is always predominant : 86,5 p. 100 from 1961 to 1964 and 96,1 p. 100 from 1972 to 1975. Diffusion of this germ during the second period is linked to the occurring of resistance to chloramphenicol. Some other serotypes are observed scarcely. The lysotypes have been determined for almost all the strains (202, then 323, during the two phases of this study). From 172 to 1975, 24 different lysotypes have been found. Lysotype I + IV is predominant (59 p. 100), but the incidence of D 6 and of 46 (6,8 p. 100) is somewhat high, if it is compared to the others. Lysotype 46 has been observed only since 1971. It has been spreading up to now in South East Asia. Stretching of this lysotype, out of its original focus, is an important epidemiological character. In 1972, resistance of S. typhi to chloramphenicol appeared and it has been increasing mostly during the following years. From 1972 to 1975, 211 strains on 288 were found resistant (highest point in 1975 : 85,4 p. 100). It was a multiresistance to 4 antibiotics (antibiotype : CTSSu). This pehnomenon of plasmidic resistance was investigated in Institut Pasteur (Paris). Many lysotypes have been involved in resistance (14 among 24). Clinical study has been realized for 189 patients. During the typical period of the disease, fever is the major symptom. More scarcely, other clinical features are observed. Various complications have been related. The evolution of the disease has been generally satisfactory, as far as mortality (less than 2 p. 100), sequelae (1 p. 100) and relapses (2 p. 100) are concerned. Clinical course has not been modified by resistance of the germs.

Anti-Bacterial Agents↗

Is Crohn's disease rare in India?

BACKGROUND: Crohn's disease (CD) is believed to be rare in India. OBJECTIVE: To analyze the data pertaining to patients with CD seen in a tertiary referral center. METHODS: Data on patients with chronic inflammatory bowel disease attending our Unit over a 5-year period were analyzed. The diagnosis of CD was established by the presence of characteristic segmental bowel involvement, consistent histological picture, exclusion of infectious causes, relapsing nature of the disease, response to appropriate drug therapy, and lack of evidence for another etiological factor. RESULTS: Of the 25 patients (age range 12-52, mean 31.7, years) 13 were men. Abdominal pain was present in 21 (84%) patients, diarrhea in 20 (80%), blood per rectum in 11 (44%) and fever in 4 (16%). The ileocecal region was involved in 6 (24%) patients and anal canal in 4 (16%); 19 (76%) had patchy involvement of different segments of the large bowel. Colonoscopic biopsies revealed granulomas in 12 (48%). During a mean follow up of 36.4 (range 6-54) months, 15 (60%) patients had 21 relapses. Despite initial response to 5-aminosalicylic acid in five patients, 23 needed glucocorticoid therapy at least once. CONCLUSIONS: CD may not be rare in India. Because of the high prevalence of intestinal tuberculosis there is a possibility that CD may be under-recognized in India.

Adolescent↗

Randomized prospective study comparing two dosage regimens of ciprofloxacin for the treatment of typhoid fever.

Sixty-two patients with blood culture-proven typhoid fever were randomly assigned to receive either 500 or 750 mg of ciprofloxacin orally, twice daily for 7 days or for two days following defervescence, whichever was greater. Thirty-four and 28 patients received 500 mg and 750 mg respectively. Strains of Salmonella typhi resistant to ampicillin, chloramphenicol and co-trimoxazole were isolated from the blood of 27 patients (43.5%). No resistance to ciprofloxacin was encountered. Both regimens were equally effective; fever subsided in mean times of 4.9 +/- 1.7 days in the 500 mg group and 5.2 +/- 2.2 days in the 750 mg group (P = 0.54). All patients were cured, although one patient in the 750 mg group experienced a presumed relapse two months following completion of therapy. Ciprofloxacin administered for 7-10 days was adequate treatment for 57 of the 62 patients (92%); only five patients required therapy for more than 10 days. Patients with pretreatment symptoms of > or = 10 days duration defervesced in a mean of 5.7 +/- 2.3 days compared with 4.5 +/- 1.3 days (P = 0.01) for those with symptoms of shorter duration. We conclude that 500 mg of ciprofloxacin taken orally twice daily is adequate treatment for typhoid fever.

Administration, Oral↗

Acne fulminans: report of clinical findings and treatment of twenty-four patients.

BACKGROUND: Acne fulminans is an ulcerative form of acne with an acute onset and systemic symptoms. It most commonly affects adolescent boys. OBJECTIVE: Clinical and laboratory findings and treatment results of patients with acne fulminans were reviewed to obtain a better understanding of the clinical course and outcome of the disease. METHODS: Data of patients with severe acne were collected from the Dermatology Departments of Finnish hospitals during the years 1970 to 1991. RESULTS: Twenty-four patients with acne fulminans are described. All patients had ulcerative acne with acute onset. In 22 patients acne was associated with high fever for at least 1 week. All patients had musculoskeletal pain. Increased uptake in bone scan or radiographic findings compatible with an infectious origin were detected in 17 patients. Eight patients were treated with antibiotics alone, but the response was poor; three patients had a relapse of musculoskeletal symptoms. Ten patients were given systemic steroids in addition to antibiotics. In this group the response was rapid, but acne and musculoskeletal symptoms tended to relapse when the steroid dosage was reduced. Four patients were treated with a combination of antibiotics, systemic steroids, and isotretinoin; all responded well, but one of these patients also had a relapse. CONCLUSION: Musculoskeletal symptoms are common in patients with acne fulminans. Systemic steroid treatment rapidly controls the skin lesions and systemic symptoms. The duration of steroid treatment should be 2 to 4 months to avoid relapses. Therapy with isotretinoin, antibiotics, or both was often combined with steroids, but the role of these agents is still uncertain.

Acne Vulgaris↗

Both paracetamol and ibuprofen are equally effective in managing flu-like symptoms in relapsing-remitting multiple sclerosis patients during interferon beta-1a (AVONEX) therapy.

Interferon beta-1a is an established therapy for patients with relapsing-remitting multiple sclerosis (MS). Adverse effects in the first weeks of treatment are common. This open-label, multicenter, randomized, prospective study compared treatment of flu-like symptoms (FLS) with paracetamol versus ibuprofen administered 48 h within interferon injection. The percentage of patients with FLS was comparable between both treatment groups and improved during the course of the study (baseline: paracetamol 92%, ibuprofen 90%; week 12: paracetamol 60%, ibuprofen 57%). More than 75% of patients receiving either paracetamol or ibuprofen reported no or only mild impairment of daily activities. There was no significant difference in general satisfaction or incidence of additional symptoms (weakness, nausea, headache; paracetamol 84.6% patients, ibuprofen 86.0% patients) between the two groups. A significant overall improvement from baseline to week 12 was observed for all parameters studied (paracetamol and ibuprofen groups were pooled). These results indicate that neither the paracetamol nor the ibuprofen treatment regimen is better.

Acetaminophen↗

Therapy of multidrug-resistant typhoid fever with oral cefixime vs. intravenous ceftriaxone.

We randomly allocated 80 children with suspected multidrug-resistant tyhpoid fever to therapy with either cefixime or ceftriaxone. Of these, an alternative diagnosis was subsequently made in 10 children and another 10 were excluded because cultures were negative. In 9 cases the typhoidal organisms isolated were susceptible to first-line drugs. In all, 50 children were randomly allocated to receive therapy with either intravenous ceftriaxone (65 mg/kg/day once daily, Group A, n = 25) or oral cefixime (10 mg/kg/day divided every 12 hours, Group B, n = 25) for 14 days. The two groups were comparable in their clinical characteristics, duration and severity of illness at the time of admission. The time to defervescence was comparable in both groups (8.3 +/- 3.7 vs. 8.0 +/- 4.1 days, P = not significant). An equal number (3 in each group) failed to respond and underwent a change in therapy. Three children in Group A and one in Group B relapsed. No adverse effects were seen in either group during the course of therapy. Our data suggest that oral cefixime can be used as effectively as parenterally administered ceftriaxone for management of typhoid fever in children.

Administration, Oral↗

Scrotal ulcer occurring in patients with acute promyelocytic leukemia during treatment with all-trans retinoic acid.

Although all-trans retinoic acid (ATRA) has been shown to improve the outcome of patients with acute promyelocytic leukemia (APL) compared with chemotherapy alone, various adverse effects have been reported. We report here the development of scrotal ulcer in four patients with APL during ATRA treatment. ATRA 45 mg/m2 was administered orally to four patients with newly diagnosed APL, two of whom also received chemotherapy. Scrotal ulcers appeared in all four patients after a median of 22 days (range: 17-29 days) of ATRA treatment. ATRA was discontinued in only one patient, who was then treated with methylprednisolone pulse therapy. The fever resolved, and scrotal ulcer improved after this treatment. The other three patients were treated with steroid or antibiotic ointment for scrotal ulcers. ATRA was re-administered 2 years later in one patient who had relapse of APL. Ulcers appeared again on the scrotal and lower abdominal skin on day 27 of ATRA treatment. These findings strongly suggest that scrotal ulcer is a potential adverse effect of ATRA.

Abdomen↗

Human recombinant GM-CSF in allogeneic bone marrow transplantation for leukaemia: double-blind placebo controlled trial.

A double-blind randomised trial compared 20 patients with leukaemia receiving human recombinant granulocyte macrophage colony stimulating factor (GM CSF), with 20 patients receiving placebo for 14 days after allogeneic matched sibling bone marrow transplantation. The median neutrophil count at 14 days was significantly higher in the GM CSF group (1.90 vs. 0.46 x 10(9)/l). The duration of hospital stay, the number of antibiotic days, and the number of fever days was the same for both patient groups. The lymphocyte count was significantly higher in the GM-CSF group than in the placebo group between days 10 and 15 after transplantation. The GM-CSF group had lower haemoglobin concentrations and platelets counts, and higher plasma urea creatinine and bilirubin, than the placebo group. There was no evidence that GM CSF was associated with a greater incidence of leukaemic relapse.

Bone Marrow Transplantation↗

In vitro susceptibility of Francisella tularensis to fluoroquinolones and treatment of tularemia with norfloxacin and ciprofloxacin.

The in vitro susceptibility of ten strains of Francisella tularensis to four fluoroquinolones (ciprofloxacin, norfloxacin, ofloxacin and pefloxacin) was investigated by determining the MBCs of these quinolones. The results were as follows (mean +/- SE): ciprofloxacin 0.13 +/- 0.03 mg/l, norfloxacin 0.24 +/- 0.07 mg/l, ofloxacin 2.16 +/- 0.78 mg/l and pefloxacin 0.51 +/- 0.50 mg/l. These concentrations can be achieved in clinical practice. In addition, four tularemia patients were treated with an oral regimen of 750 mg ciprofloxacin b.i.d. and one patient with norfloxacin 400 mg b.i.d. The fever experienced by these volunteers vanished within a couple of days and they were able to resume normal work one week after receiving the antibiotics without any relapses later. These in vitro and in vivo results show that orally administered fluoroquinolones are promising antimicrobial agents for the treatment of human tularemia.

Anti-Infective Agents↗

Allogeneic peripheral blood hematopoietic stem cell transplantation for patients with hematologic malignancies.

To investigate the therapeutic effects and associated complications of allogeneic peripheral blood stem cell transplantation (allo-PBSCT). 40 patients with various malignant hematopoietic diseases received allo-PBSCT. The preparative regimens were based on BUCY2 or modified BUCY2. The acute graft-versus host disease (aGVHD) was prevented by cyclosporin A and short-term MTX regimen in all patients. Two patients from donors with one fully mismatched HLA on DRB1 locus and 4 from unrelated donor also administered Zenapox (CD25 MAb) at dosage of 1 mg/kg every day on the day before transplantation and day 4 after transplantation. These 6 patients were also treated with mycophenolate mofetil (MMF). Transfusion of the donor cells: The median of the transfused nucleated cells was 5.38 x 10(8)/kg and that of the CD34+ cells was 7.8 x 10(6)/kg respectively. All the patients gained hematopoietic reconstruction except one who died of infection before engraftment. Seven patients got II degrees-IV degrees aGVHI) and the incidence was 17.5%. Fourteen patients got cGVHD and the incidence was 53.8% in the patients who survived over 6 months. Twenty-eight patients had fever or other characteristics of infection. The median follow-up time was 13.8 months. The incidence of transplantation related mortality (TRM) was 17.5% and 2 patients relapsed (5.0%). It was concluded that allo-PBSCT can reconstruct hematopoiesis quickly and is a favorable therapeutic method for leukemia.

Adolescent↗

Aortic graft infection by Lactobacillus casei: a case report.

A 65-year-old man with an abdominal aortic endoprosthesis presented with fever without other symptoms. Investigations revealed Lactobacillus casei bacteraemia. The Lactobacillus graft infection was at first successfully treated by antibiotic therapy. However, during follow-up a relapse occurred, and after surgical replacement of the graft the patient was cured. At surgery an aortoenteric fistula was found as source of the infection.

Aged↗

Allogeneic stem cell transplantation in the myelodysplastic syndromes: interim results of outcome following reduced-intensity conditioning compared with standard preparative regimens.

Conventional allogeneic stem cell transplantation (SCT) for myelodysplastic syndrome (MDS) is associated with excessive procedure-related mortality. The outcome following volunteer-unrelated donor (VUD) or sibling allogeneic SCT was therefore evaluated in 23 MDS patients conditioned with reduced-intensity regimens (fludarabine/busulphan/Campath-1H) because of advanced age (48 vs 37 years, P = 0.002) and/or co-morbidity (19 vs 3, P < 0.0001) which precluded conventional transplantation, and compared with 29 treated with standard protocols [busulphan/cyclophosphamide (Bu/Cy); Bu/Cy/total-body irradiation/Campath-1G]. Graft-versus-host disease (GVHD) prophylaxis comprised of cyclosporine/methotrexate. One hundred per cent donor engraftment (variable number tandem repeat analysis/cytogenetics/fluorescence in situ hybridization) was achieved in 18/19 (95%) evaluable patients receiving reduced-intensity regimens, although six (32%) have subsequently shown mixed chimaerism. Reduced-intensity conditioning was associated with significantly reduced duration of aplasia, less mucositis, fever, antibiotic, analgesia, parenteral nutrition use, less acute and chronic GVHD, and lower early procedure-related mortality [two (9%) vs nine (31%), P < 0.05]. Six patients relapsed (two standard, four reduced-intensity) and two (reduced-intensity) experienced late graft failure. The 2 year actuarial overall/disease-free survival (OS/DFS) was 48/39% in the reduced-intensity arm and 44/44% in the standard group. The 2 year non-relapse mortality was 31% and 50% respectively. In VUD recipients, OS was superior in the reduced-intensity arm (49%vs 34%). Predictors of DFS included good/intermediate-risk karyotype, low/intermediate-1 International Prognostic Scoring system score, human leucocyte antigen compatibility and attainment of complete remission. Our data demonstrates that VUD or sibling allogeneic SCT following reduced-intensity conditioning is feasible in high-risk MDS patients considered unsuitable for standard transplantation and is associated with comparable 3.5 year DFS to those receiving conventional regimens.

Adult↗

Evaluation of the safety and efficacy of micronized halofantrine in the treatment of semi-immune patients with acute, Plasmodium falciparum malaria.

The efficacy of the standard formulation of halofantrine hydrochloride has been compromised by the formulation's irregular bio-availability. A micronized preparation of the drug has now been evaluated in the treatment of malaria in northern Tanzania. Overall, 100 patients with mild to moderate Plasmodium falciparum malaria were recruited and treated with the preparation over 18 h. Those weighing > 40 kg were each given three, 500-mg doses and those weighing less were given roughly equivalent doses/kg. The 95 evaluable patients were all successfully treated, with a mean fever-clearance time of 22.5 h (range 4-76 h) and a mean parasite-clearance time of 35.6 h (range 15-66 h). There were no relapses. Abdominal pain was the commonest adverse event reported (22 cases). A single patient died suddenly in the recovery phase; the cause of this event was not determined. Further studies are required to evaluate the pharmacokinetics of the halofantrine formulation under field conditions.

Adolescent↗

Cryptococcal meningitis in patients with AIDS.

In the U.S., cryptococcal meningitis is the most common form of fungal meningitis and a major cause of morbidity and mortality among immuno-suppressed patients. In the AIDS patient, cryptococcal meningitis often presents with fever and headache and is best treated with intravenous amphotericin B and oral flucytosine, or fluconazole. However, toxic effects may result from the therapy. This disease frequently relapses necessitating life-long treatment to prevent reactivation. Essential management principles focusing upon health education are presented to promote comprehensive nursing care for patients testing positive for the human immunodeficiency virus who also have cryptococcal meningitis.

AIDS-Related Opportunistic Infections↗

Infantile eczema: A long-term follow-up study.

A 15-17 year follow-up study was conducted on ninety-nine patients who had suffered from infantile eczema. The persistance of the eczema and the occurrence of related conditions were noted. The persistence of eczema was shown to be greater in those patients with a positive family history of eczema and in those who had developed asthma or hay-fever. An attempt was made to see if the persistence of eczema was affected by the position of the child in the family, and some factors provoking relapses were noted. The patients were also questioned with regard to their achievements in academic examinations, and to their social, artistic and sporting activities. The results showed a success rate in examinations not significantly higher than average. It was not possible to show if there is a particular type of atopic personality. There was no constant characteristic in social or artistic patterns. The group as a whole were normal at the milestones of early development, i.e. walking, talking and reading, and also normal with regard to weight and height.

Adolescent↗

Atopy and immunoglobulin E concentrations in Hodgkin's disease and other lymphomas.

Serum immunoglobulin E (IgE) concentrations are increased in Hodgkin's disease (HD) but not in other types of lymphoma. The prevalence of atopic disease is similar to normal in both groups. Patients with high IgE concentrations and HD were separated into atopic and non-atopic groups, which were found to differ clinically. Atopic patients had a significantly lower incidence of night sweats, fever, and weight loss, and treatment had no significant lasting effect on their IgE concentrations. In the non-atopic group there was a striking correlation between high IgE concentrations and a histological appearance of nodular sclerosis, particularly in the presence of night sweats, fever, and weight loss. Successful treatment in the non-atopic group led to a noticeable fall in IgE concentrations, in most cases to normal, though on relapse of the disease they rose again.

Hodgkin Disease↗

Treatment of acquired immunodeficiency syndrome--related Kaposi's sarcoma with lymphoblastoid interferon.

Twelve homosexual patients with Kaposi's sarcoma associated with the acquired immune deficiency syndrome (AIDS) were treated with a preparation of purified human lymphoblastoid interferon (Wellferon [Burroughs Wellcome, Research Triangle Park, NC]). They were given a dose of 20 X 10(6) U/m2 intramuscularly daily for approximately two months. Responders continued their treatment on a maintenance schedule of 20 X 10(6) U/m2 three times a week. Four patients experienced complete remissions, and four experienced partial remissions that resulted in a total response rate of 67%. The median duration of treatment was 14 weeks (7 to 28+ weeks), and the median response duration was 28+ weeks (19 to 29+ weeks). Of the four patients in complete remission, one relapsed at 25 weeks and one at 26 weeks; the other two remained in complete remission at 28 and 29+ weeks. The clinical toxicity consisted of chills, fever, fatigue, and asthenia. Hematologic toxicity was similar to that previously described for other preparations of alpha-interferon and consisted of moderate leukopenia and thrombocytopenia. Asthenia, a condition present in all 12 patients, was severe in 50%. A minimal tumor burden, the absence of circulating interferon before treatment, and a performance status of greater than or equal to 90% on the Karnofsky scale were related to an improved response rate. Measurement of immunologic parameters showed significant declines in the already impaired T cell levels, lymphocyte blastogenic response to concanavalin A, monocyte-mediated antibody-dependent cellular cytotoxicity, and monocyte-adherence. Activation of natural killer cells was not noted, and no life-threatening infections occurred during treatment. These data suggest that human lymphoblastoid interferon is an active agent in the treatment of Kaposi's sarcoma, and its use warrants further study in a larger number of patients.

Acquired Immunodeficiency Syndrome↗