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The efficacy and safety of pefloxacin in the treatment of typhoid fever in Algeria.

The efficacy and safety of pefloxacin 400 mg twice daily for seven days in the treatment of typhoid fever was investigated in an open, non-comparative study involving 37 patients infected with Salmonella typhi. Between day 5 and the end of treatment, all patients showed clinical improvement. The clinical cure rate at the end of the treatment period was 89.2%. One month after the end of treatment, the final assessment showed a clinical cure rate of 94.6% with relapses occurring in only two patients. Both these patients belonged to the group with negative blood cultures but positive serodiagnostic tests. Bacteriological tests confirmed eradication of the pathogen in 94.6% of patients and the relapses in the two serologically positive patients. Temperature became normal in a mean of 5.14 days. Clinical adverse reactions were reported in 5.9% (3/51) of patients (vomiting in two, transient pruritic rash in one). The results of this study indicate that a seven-day course of pefloxacin 400 mg twice daily provides a suitable alternative in the treatment of typhoid fever.

Administration, Oral↗

Cisplatin treatment triggers familial Mediterranean fever attacks.

A 42-year-old familial Mediterranean fever (FMF) patient who was treated with cisplatin-based chemotherapy for adenocarcinoma of the lung developed severe and frequent attacks of FMF during treatment. Abdominal pain, arthralgia and fever occurred for a few days following each cisplatin cycle. His FMF worsened, the abdominal pain and fever lasted longer and treatment with colchicine was ineffective. It has been hypothesized that the link between cisplatin treatment and FMF attacks lies in an increased production of serotonin, IL-6, IL-1, IL-8 and TNF-alpha. These inflammatory cytokines have been reported to be overproduced during cisplatin treatment and are known to play an important role in FMF relapse. The oncologist should be made aware of the possibility of disease aggravation in FMF patients during cisplatin-based chemotherapy.

Acute Disease↗

A comparison of outcome from febrile neutropenic episodes in children compared with adults: results from four EORTC studies. International Antimicrobial Therapy Cooperative Group (IATCG) of the European Organization for Research and Treatment of Cancer (EORTC).

The object of this study was to determine whether there were any differences between the 'typical' child with fever and neutropenia and their adult counterpart with regard to infection type and outcome, by analysis of 3080 patients, including 759 children < 18 years of age and 2321 adults. These represented patients randomized in previous trials, between 1986 and 1994, which compared empirical antibiotic regimens for fever in neutropenic patients. There were fewer childhood acute myeloid leukaemia patients than adults but more acute lymphoblastic leukaemia cases and more with solid tumours undergoing intensive myelosuppressive therapy. The children were less likely to be undergoing first induction therapy but the relative incidence of patients receiving relapse schedules or maintenance therapies were not significantly different in the two age groups. Children less frequently had a defined site of infection than adults and where they had a defined site there were more upper respiratory tract but fewer lung infections. There was a similar low incidence of shock at presentation in the two groups but the children's median neutrophil count was lower, and their median duration of granulocytopenia before the trial was shorter. The incidence of bacteraemia was similar, but clinically documented infection was less frequent and fever of unknown origin consequently more common in children. Children developed more streptococcal bacteraemias and fewer staphylococcal bacteraemias than adults (P=0.003) but the relative incidence of various gram-negative species was similar (P=0.57). In general, the children had a better overall success rate and lower mortality than adults. Death from infection was only 1% in children versus 4% in adults (P=0.001), and time to defervescence was shorter in children. In the younger age group, univariate logistic regression models showed high temperature, prolonged neutropenia before the trial and shock as prognostic indicators for the presence of bacteraemia. Solid tumour patients were significantly less likely to have a bacteraemia. Multivariate analysis confirmed the independent prognostic value of these indicators. Using the logistic equation of the selected model, the overall discriminant ability was poor. However, it was possible to identify a small subgroup without shock or high fever and with a short prior duration of neutropenia which carries a particularly low risk of bacteraemia, who could be considered for early discharge, monotherapy and shortened courses of antibodies, in prospective trials.

Acute Disease↗

Acute disseminated encephalomyelitis: a follow-up study in Taiwan.

BACKGROUND: Acute-disseminated encephalomyelitis (ADEM) is a demyelinating disorder of the central nervous system, whose epidemiology, clinical presentations and functional outcome are incompletely understood in Asian populations. OBJECTIVE: To assess the clinical presentations, predisposing factors and functional outcome of ADEM in Taiwan. METHODS: 50 patients initially diagnosed with ADEM (male, 19; female, 31) were enrolled from 1991 to 2005. Diagnosis of ADEM or multiple sclerosis was established during a follow-up period of 2-120 months. 8 adult patients were noted to have taken the immunomodulatory drug, levamisole, within 3 months before onset of symptoms. The remaining 42 patients (male, 17; female, 25) were categorised by age as children (<16 years, n = 12), young adults (16-49 years, n = 21) and elderly adults (> or =50 years, n = 9). The clinical manifestations, predisposing factors and radiological findings were compared between different age groups and adult patients with or without levamisole use. Functional outcome was compared by a log-rank test. RESULTS: Preceding upper respiratory tract infection was evident in 21 (50%) patients and only one young-adult patient had received Rubella vaccine immunisation. The frequency of fever was higher in children (p = 0.04) and psychiatric symptoms were more prevalent in elderly patients (p = 0.03). Functional recovery was faster in children than in adults (p = 0.002). Initial Expanded Disability Status Scale score (odds ratio (OR) 1.9, p = 0.03) and no fever (OR 0.04, p = 0.06) were associated with poor outcome (modified Rankin scale > or =2). After a mean (SD) follow-up of 31.8 (9.9) months, 4 (9.5%) patients developed multiple sclerosis (3 (25%) children, 1 (4.7%) young adult, p = 0.03). The neurological disability, radiological and cerebrospinal fluid findings did not differ between patients with and without levamisole use. One elderly adult patient previously receiving levamisole developed multiple sclerosis of relapse-remitting type after a mean follow-up period of 36.9 months. CONCLUSION: The clinical presentations, functional outcome and risk of developing multiple sclerosis differed between different age groups. Functional recovery was faster in children than in adults. Poor functional outcome was related to initial high Expanded Disability Status Scale score and absence of fever.

Adolescent↗

Prognostic factors in Hodgkin's disease.

The clinical records and treatment results of 163 patients with Hodgkin's disease, who were seen at Ellis Fischel State Cancer Hospital (EFSCH) between 1940 and 1971, were reviewed and analyzed. More than 200 clinical and histological variables were recorded for each case of Hodgkin's disease, including details of radiotherapy and chemotherapy. Statistical studies were carried out in order to evaluate the independent prognosis significance of each of these factors. All of the lesions were reclassified according to the Lukes proposal which was modified and recommended at the 1965 Rye classification (except for hepatomegaly which was included in Stage IV). This is a retrospective study, and the modern techniques of staging were rarely used in pretreatment studies (since 1965, only ten patients have had an abdominal exploration). The basic work-up consisted of a complete blood count, urinalysis, blood type, chest X ray, and EKG. Lymphangiogram and radioisotope liver scans were used on less than 10% of the patients. About 30% of the patients had gastrointestinal X rays and 70% had IVP. Bone marrow biopsies -- the majority of which were done by needle aspiration -- were obtained for approximatley 50% of the patients. Clinical stage, histological type, and presence of absence of systemic symptoms appeared to be themost significant prognostic factors. The classification of systemic symptoms according to the criteria of either the Rye or Ann Arbor conferences showed no particular difference in determining the survival rate. Among the systemic symptoms, fever appeared to be the most important for survival rate. Survival rates were higher in nonanemic and nonlymphocytopenic patients. Eosinophilia, blood group, and Rh factor had no prognostic significance. The relapse-free interval was an important indicator of long-term prognosis. The unfavorable influence of relapse in ultimate prognosis was clearly seen; however, the extent of the relapse site was shown to have no significant influence on survival.

Adolescent↗

Juvenile gangrenous vasculitis of the scrotum: Is it a variant of pyoderma gangrenosum?

Juvenile gangrenous vasculitis of the scrotum was described by Piñol et al in 1974 as a unique variant of scrotal gangrene of unknown origin, occurring exclusively in young individuals. It was characterized by an acute onset of skin ulcers undergoing complete resolution after appropriate therapy, with no relapses. We present a typical case of this extremely rare disease affecting a 16-year-old boy in whom the scrotal ulcerations were preceded by an episode of pharyngitis with fever. The condition promptly regressed after administration of intramuscular betamethasone in combination with oral ciprofloxacin. According to Piñol et al, juvenile gangrenous vasculitis of the scrotum, although poorly known to dermatologists, should be regarded as a distinctive entity within the wide group of scrotal gangrenes. On the other hand, the hypothesis that this condition may well represent a variant of pyoderma gangrenosum is discussed.

Adolescent↗

Treatment of advanced seminoma with cyclophosphamide, vincristine and carboplatin on an outpatient basis.

This study describes the efficacy and toxicity of a combination regimen consisting of cyclophosphamide, vincristine (oncovin) and carboplatin (COC) for advanced seminoma on an outpatient basis. Twenty-seven patients (mean age 43 years, range 28-63 years) were classified as stage IIC (n = 5), stage IID (n = 12), stage III (n = 9) or stage IV (n = 1). Six had been treated with prior radiotherapy; elevated beta-HCG and elevated LDH serum levels were observed in 15 and 25 patients respectively. Patients were treated with four cycles of 750 mg m-2 cyclophosphamide intravenously (i.v.), 1.4 mg m-2 vincristine i.v. (maximum 2 mg) and carboplatin adjusted to creatinine clearance. Cycles were given at 3 week intervals. The median dose of carboplatin administered was 400 mg m-2 (range 300-450 mg m-2). Six patients [22%; 95% confidence interval (CI), 6-38%] achieved a complete response (CR), 19 (70%; 95% CI, 51-88%) a partial response and two (8%; 95% CI, 0 18%) showed only a response in tumour markers but not a reduction of retroperitoneal mass (NR). Post-chemotherapeutic masses were not removed surgically or irradiated. After a median follow-up of 26 months (range 5-69 months), two patients have died, one from cardiac arrest 2 years after achieving CR, the other with relapsed seminoma 5 months after therapy. None of the other patients relapsed. Main toxicity was haematological, with 22 patients (81%) experiencing thrombocytopenia WHO grade III/IV and 27 (100%) leucocytopenia WHO grade III/IV, requiring dose reduction in five patients. Seven patients experienced granulocytopenic fever. Non-haematological toxicity was rare. Peripheral neuropathy grade I was observed in four patients and grade III in one. Haemorrhagic cystitis occurred once. In conclusion, despite considerable haematological toxicity, COC is feasible on an outpatient basis, even after prior radiotherapy, and is an effective regimen for advanced seminoma with only 1/27 treatment failures after a median follow-up of 26 months.

Adult↗

Hematologic and cytogenetic remission by STI571 (Glivec) in a patient relapsing with accelerated phase CML after second allogeneic stem cell transplantation.

We describe the clinical activity of the ABL kinase inhibitor STI571 in a patient with accelerated phase of chronic myeloid leukemia (CML) relapsing after a second allogeneic BMT and with minimal levels of donor chimerism. STI571 resulted in rapid elimination of leukemic cells with ensuing prolonged severe leukopenia and neutropenia complicated by neutropenic fever and colitis. Subsequent hematopoietic recovery was driven by donor derived cells and was associated with grade 3 graft-versus-host disease (GVHD). STI571 induced sustained hematological and cytogenetic remission combined with controllable GvHD, therapeutic goals not achieved by two preceding allogeneic transplants and repeated donor lymphocyte transfusions (DLT).

Antineoplastic Agents↗

Pulmonary blastomas of childhood: histologic, immunohistochemical, ultrastructural aspects and therapeutic considerations.

Pulmonary blastomas are rare neoplasms typically occurring in patients of pediatric age, clinically characterized by fever, respiratory distress, and radiologic findings of a pulmonary cystic and/or solid mass with partial or complete obliteration of emithorax. Their behavior is aggressive and outcome is poor due to frequent relapses and metastases. The histological, immunohistochemical, and ultrastructural aspects of a personal series of 6 cases of pulmonary blastoma are described and the differences between childhood and adult types are stressed. Due to the aggressiveness of these rare tumors, therapeutic management is quite difficult. The expression of the transmembrane tyrosin kinase receptor c-kit in all the solid cases of this series leads the authors to hypothesize new possible therapeutic implications for these tumors.

Biomarkers, Tumor↗

Disseminated testicular cancer with bulky disease: results of a phase-II study with cisplatin ultra high dose/VP-16/bleomycin.

This is a preliminary analysis of the AIO-Testicular Tumour Study Group trial in patients with disseminated bulky testicular cancer. Treatment plan: cisplatin 35 mg/m2 days 1-5, VP-16 120 mg/m2 days 1-5 (two daily divided doses), bleomycin 15 mg/m2 days 1, 8, 15. Of 98 patients at present evaluable 63% had complete remission or have no evidence of disease (CR/NED), 30% had partial remission (PR) and 7% had no change or progressive disease (NC/P). Relapse-free survival is 93% for the CR/NED group after a median follow up of 2.2 years: the overall survival for the entire patient population is 70%. Toxicity included predominantly granulocytopenic fever and infection with septicaemia, thrombocytopenia, nausea, vomiting, neurotoxicity and lung toxicity, with 7% fatal toxicity. A prospective randomized trial is warranted to evaluate the apparent superior activity of ultra high dose cisplatin in combination with VP-16 and bleomycin.

Adolescent↗

Unusual cranial and abdominal computed tomographic (CT) scan appearances in a case of systemic lupus erythematosus (SLE).

A 35 year old woman presented with headache and fever. Computed brain tomography showed diffuse low attenuation in the cerebral white matter. Several months later, serological tests for systemic lupus erythematosus (SLE) became positive. In spite of immunosuppressive therapy she relapsed after six months of treatment, presenting with abdominal symptoms and signs. On this occasion an abdominal CT scan showed distended and oedematous loops of bowel attributed to an underlying vasculitis. This case illustrates novel CT scan appearances in two systems involved in SLE.

Adult↗

Autologous Epstein-Barr virus (EBV)-specific cytotoxic T cells for the treatment of persistent active EBV infection.

Chronic active Epstein-Barr virus (CAEBV) infection syndrome is a heterogeneous EBV-related disorder characterized by chronic fatigue, fever, lymphadenopathy, and/or hepatosplenomegaly, associated with abnormal patterns of antibody to EBV. CAEBV can range from disabling mild/moderate forms to rapidly lethal disorders. Even patients with mild/moderate disease frequently suffer adverse effects from long-term anti-inflammatory agents and have a quality of life that progressively deteriorates. It is still unknown why these individuals are unable to produce an effective immune response to control EBV, and no effective treatment is currently available. Since ex vivo-expanded EBV-specific cytotoxic T lymphocytes (EBV-CTLs) can safely restore EBV-specific cellular immune responses in immunodeficient patients, we assessed the possibility that adoptive immunotherapy might also effectively treat CAEBV infection. Following stimulation with irradiated EBV-transformed lymphoblastoid cell lines (LCLs), EBV-CTLs were successfully generated from 8 of 8 patients with the mild/moderate form of CAEBV infection. These CTLs were predominantly CD3(+) CD8(+) cells and produced specific killing of the autologous LCLs. There were 5 patients with 1- to 12-year histories of disease who were treated with 1 to 4 injections of EBV-CTLs. Following infusion, there was resolution of fatigue and malaise, disappearance of fever, and regression of lymphadenopathy and splenomegaly. The pattern and titers of anti-EBV antibodies also normalized. No toxicity was observed. There were 4 patients who did not show any relapse of disease within 6 to 36 months follow-up; one patient had recurrence of fatigue and myalgia one year after CTL infusion. We suggest that adoptive immunotherapy with autologous EBV-CTLs may represent a safe and feasible alternative treatment for patients affected with mild/moderate CAEBV infection and that this approach should be evaluated in the more severe forms of the disease.

Adolescent↗

Four cycles of paclitaxel and carboplatin as adjuvant treatment in early-stage ovarian cancer: a six-year experience of the Hellenic Cooperative Oncology Group.

BACKGROUND: Surgery can cure a significant percentage of ovarian carcinoma confined to the pelvis. Nevertheless, there is still a 10-50% recurrence rate. We administered paclitaxel/carboplatin as adjuvant treatment in early-stage ovarian carcinoma. METHODS: Patients with stages Ia or Ib, Grade 2 or 3 and Ic to IIb (any grade) were included. Patients were treated with 4 cycles of Paclitaxel 175 mg/m2 and Carboplatin [area under the curve (AUC) 6 (Calvert Formula)] every 3 weeks. RESULTS: Sixty-nine patients with no residual disease following cytoreductive surgery and minimal or modified surgical staging were included in this analysis. Grade 3 or 4 neutropenia occurred in 29.9% of patients, while neutropenic fever was reported in 4.5%. Neurotoxicity (all Grade 1 or 2) was reported in 50% of cases. Median follow-up was 62 months. 5-year overall survival (OS) and relapse-free survival (RFS) were: 87% (95% confidence intervals [CI]: 78-96) and 79% (95% CI: 69-89), respectively. Significantly fewer patients with stages Ic-IIb and tumor grade 2 or 3 achieved a 5-year RFS than patients with only one of these two factors (73% vs 92%, p = 0.03). CONCLUSION: Paclitaxel/Carboplatin chemotherapy is a safe and effective adjuvant treatment in early-stage ovarian carcinoma. Patients with stages Ic-IIb and tumor grade 2 or 3 may benefit from more extensive treatment.

Adult↗

Acute tubulointerstitial nephritis following intravenous immunoglobulin therapy in a male infant with minimal-change nephrotic syndrome.

A boy aged 4 years with nephrotic syndrome (NS) was referred to our hospital because of the third relapse of NS. Hypogammaglobulinemia associated with massive proteinuria was observed at the presentation. Residual urinary tract infection required intravenous piperacillin and immunoglobulin therapy (IVIG). Soon after IVIG, he complained of high fever with chills, bilateral knee joint pain, dry cough and chest discomfort. Although he did not develop renal insufficiency, a transient increase in the urinary beta2-microglobulin and decrease in the serum complement hemolytic activity were observed. These clinical manifestations spontaneously ceased. A percutaneous renal biopsy for his NS performed 19 days after the episode of allergic reaction revealed tubulointerstitial nephritis (TIN) with marked eosinophil infiltrates. Glomeruli showed minor glomerular abnormalities. Renal complications associated with IVIG treatment have been reported to date, however, acute TIN has rarely been seen.

Acute Disease↗

Sweet's syndrome and a Mirena intrauterine system.

A woman fitted with a Mirena intrauterine system (IUS) for menorrhagia presented with a short history of fever and progressive skin lesions. Histological examination of a skin biopsy was compatible with the clinical diagnosis of Sweet's syndrome. Treatment was with topical and oral steroids, however the condition relapsed on reduction of the steroid dose. Symptoms finally resolved on removal of the IUS and the patient remained symptom free at 9-month follow-up. There have been previous reports of Sweet's syndrome in association with hormonal contraceptives, however this is believed to be the first reported case in association with a Mirena IUS.

Anti-Inflammatory Agents↗

Autoimmune phenomena in patients with myelodysplastic syndromes.

Autoimmune syndromes are common in patients with myelodysplastic syndromes (MDS). Clinical manifestations include an acute systemic vasculitic syndrome (characterized by skin vasculitis, fever, arthritis and sometimes associated with pulmonary infiltrates and peripheral edema), chronic autoimmune disorders, including chronic cutaneous vasculitis, polyneuropathy, inflammatory bowel disease and glomerulonephritis, and classical connective tissue disorders, most notably relapsing polychondritis. Asymptomatic immunologic abnormalities are also common and include hypergammaglobulinemia and a positive FANA. Autoimmune syndromes may be the primary cause of death in some patients with MDS. However, these syndromes frequently respond to immunosuppressive agents and occasional dramatic hematologic responses to steroid therapy are seen. We review the incidence, nature, course and response to therapy of these manifestations and discuss potential pathogenic mechanisms.

Autoimmune Diseases↗

Serum sickness-like syndrome due to mosquito bite.

Local inflammatory reactions at the site of a mosquito bite are frequent. Immediate systemic reactions have occasionally been reported. The first case of a patient with relapsing episodes of a serum sickness-like syndrome following mosquito bites is reported herein. A 62-year-old patient came to the emergency room complaining of sudden malaise, chills, fever, headache, cervical lymph node enlargement, arthromyalgia, generalized purpura and leukopenia 6 h after a mosquito bite. He had experienced multiple similar episodes in the last 20 years, also following mosquito bites. Infectious and autoimmune diseases were ruled out. Serum IgE was 9,102 kU/l. Prick test of whole-body Culex pipiens extract was positive. Specific IgE to Aedes communis was 2.25 kU/l. SDS-PAGE immunoblotting of the patient's serum with whole-body C. pipiens extract revealed 43 and 17 kDa IgG-binding proteins and 22 and 17 kDa IgE-binding proteins, neither of which were found with control sera. Skin biopsy was consistent with leukocytoclastic vasculitis. The presence of both mosquito-specific IgE and IgG in the patient's serum suggest a possible cooperative immune response leading to clinical manifestations of serum sickness.

Animals↗

Clinical features of GCA/PMR.

Giant cell arteritis (GCA) is a common vasculitis of unknown cause that affects persons in middle age and older. Its incidence rises with increasing age. The inflammatory lesions involve larger arteries that contain an abundance of elastic tissue. Although cranial symptoms such as headache, tender scalp, jaw claudication and visual symptoms are common, the disease presents in many different fashions, often with symptoms not directly related to the arteries. These latter presentations include fever, severe malaise, polymyalgia rheumatica, high erythrocyte sedimentation rate and anemia, thrombocytosis, sore throat, and hepatic dysfunction. GCA appears to have a self-limited course, but is also characterized by relapses and recurrences. Visual loss due to occlusion of the optic arteries is the most important early manifestation and aortic aneurysm is the most important late complication. Patients respond promptly to varying doses of glucocorticoids but drug side effects are common.

Giant Cell Arteritis↗