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PubMed1996

Production of interleukin-10 and transforming growth factor beta by peripheral blood mononuclear cells in Q fever endocarditis.

The pathophysiology of Q fever endocarditis is characterized by the suppression of antigen-specific cell-mediated immune responses. We investigated the production of interleukin-10 (IL-10) and transforming growth factor beta (TGF-beta), known to interfere with the development of protective cell immunity. IL-10 was markedly released by unstimulated peripheral blood mononuclear cells (PBMC) from patients with Q fever endocarditis. This release resulted from the upregulation of IL-10 gene transcription. Similarly, the release of TGF-beta1 and TGF-beta2 was significantly higher in patient PBMC than in control cells, but the expression of their respective mRNA was not enhanced in patient cells. In contrast, lipopolysaccharide-stimulated transcription and release of IL-10 and TGF-beta were similar in patients and controls. The release of IL-10 by PBMC but not that of TGF-beta was correlated with the clinical status of the patients. First, IL-10 production was correlated with specific antibody levels. Second, IL-10 release remained elevated in patients prone to relapse. Taken together, our results suggest that the release of IL-10 and TGF-beta is upregulated in Q fever endocarditis. IL-10 might be considered as a marker of disease relapses and might be instrumental in monitoring the efficiency of the treatment.

Adult↗
PubMed1980

Acute promyelocytic leukemia--clinical management of 15 patients.

Fifteen patients with acute promyelocytic leukemia (APL) were treated with anthracycline agents alone or combined with arabinosylcytosine (Ara C). Disseminated intravascular coagulation (DIC) was managed individually based on the presence of clinical as well as laboratory evidence of DIC. Ten patients received heparin. Eleven patients (73%) achieved complete remission (CR) but there were two early deaths from infection. The median duration of CR was 232 days (range, 41-780 days). Six patients were studied during ten relapses. In all cases, a morphologic picture more typical of acute myelocytic leukemia was seen during relapse but the DIC was similar in severity to that seen initially. Fever, without obvious infection and possibly due to the leukemic process, was a common presenting feature. Regenerating bone marrow aspirates in many patients who subsequently achieved CR without further treatment showed an inordinate number of promyelocytes, and this finding should not be immediately interpreted as disease resistant to therapy.

Adolescent↗
PubMed2005

[First-line liposomal amphotericin B for pediatric visceral leishmaniasis in southern France].

AIMS OF THE STUDY: First, to describe liposomal amphotericin B (AmBisome use as first line treatment of pediatric visceral leishmaniasis and secondly, to evaluate the incidence of the disease in southern France (Provence - Alpes - Côte d'Azur - Corse). MATERIAL AND METHODS: Retrospective chart review of children referred for visceral leishmaniasis from 1996 to 2003. RESULTS: Thirty-two children under 15 years of age and suffering from visceral leishmaniasis were treated with liposomal amphotericin B as first line treatment. Clinical and biological features were usual: age <5 years, no immunodeficiency, spleen enlargement and fever, cytopenia. In this population, treatment effectiveness was evaluated to 97% (one relapse). Under treatment, patients quickly improved. Drug regimens varied from 18 to 24 mg/kg (day 1 to 5, and day 10). Four other children were not treated with first-line liposomal amphotericin B during the period. Thus, the incidence of pediatric visceral leishmaniasis was evaluated to be 0.61/100,000 children <15 years/year in the region (2.74 in the Alpes-Maritimes department, French Riviera, and 0.6 in the Bouches-du-Rhône department, Marseilles area). CONCLUSION: Liposomal amphotericin B treatment is usual for children referred for visceral leishmaniasis in this region. This treatment may be approved regarding the high level of effectiveness and the low number of adverse events. A two days drug regimen with 20 mg/kg should be evaluated. Moreover, the incidence of the pediatric visceral leishmaniasis in southern France is decreasing, but local variations may be observed.

Adolescent↗
PubMed2001

Current use and future development of gemtuzumab ozogamicin.

The antigen CD33 is expressed on blast cells in 80% to 90% of acute myeloid leukemia (AML) cases but, importantly, is not expressed on pluripotent hematopoietic stem cells or on nonhematologic cells. Gemtuzumab ozogamicin (CMA-676) uses a recombinant humanized anti-CD33 monoclonal IgG4 antibody to deliver the potent cytotoxin, calicheamicin, into cells. Three multicenter trials have evaluated the efficacy and safety of gemtuzumab ozogamicin as a single agent in 142 patients with CD33+ AML in untreated first relapse. The median age was 61 years (range, 22 to 84 years), none had prior myelodysplasia, and all had had a first complete remission lasting > or = 3 months. Two doses of 9 mg/m2 were given 14 days apart by 2-hour intravenous infusion. The overall response rate was 30% (ie, < or = 5% blasts remaining in the bone marrow, neutrophils > or = 1,500/microL, and red blood cell and platelet transfusion independence). There was no significant difference in response rate between patients less than 60 years of age and those > or = 60 years old (34% v 26%, respectively) or between patients whose first remission had lasted less than 12 months or > or = 12 months (28% v 32%, respectively). Overall survival was 31% at 1 year; median survival was 5.9 months. Median relapse-free survival was 6.8 months. An infusion-related syndrome (chills, fever, rigors, nausea, hypotension, and pain) was common. Severe myelosuppression occurred in all patients, but severe mucositis (4%) and infections (23%) were relatively infrequent. Severe hyperbilirubinemia (23%) and elevated hepatic transaminases (18%) were usually transient. Among all 142 patients, the median total hospitalization was 24 days; 16% of patients required < or = 7 days in hospital. Additional studies are currently evaluating gemtuzumab ozogamicin in combination with, or as an alternative to, other standard AML chemotherapy.

Adolescent↗
PubMed2000

Health-related quality of life and patients' perceptions in interferon-treated multiple myeloma patients. Nordic Myeloma Study Group.

The effect of interferon on the health-related quality of life in multiple myeloma was assessed in two trials carried out by the Nordic Myeloma Study (Group (NMSG). In both trials, the EORTC QLQ-C30 questionnaire, supplemented with 11 items relating to interferon toxicity, was used. The first was a randomized controlled trial (NMSG 4/90) evaluating the addition of interferon alpha-2b to melphalan and prednisone during induction, maintenance and relapse. During the first 12 months, patients on interferon reported more chills, fever, fatigue, pain, nausea/vomiting, appetite loss and dry skin than the control patients, and a slight reduction of global health and quality of life. From 12 months onward there were no significant differences in any score between the two groups. In a later trial (NMSG 5/94) evaluating the effect of high-dose chemotherapy with stem cell support in patients under 60 years of age with newly diagnosed myeloma, interferon was used as maintenance. During the maintenance phase, symptom and toxicity scores were not significantly different from those in control patients under 60 years of age in the previous trial. Thus, interferon appeared to be well tolerated after high-dose chemotherapy with stem cell support.

Adult↗
PubMed1999

Profile of non-compressive myelopathy in eastern India: a 2-year study.

Eighty-two patients with non-compressive myelopathy have been studied from July 1994 to June 1996 in Bangur Institute of Neurology and S.S.K.M. Hospital, Calcutta, of which 48 patients were men and 34 patients were women. Presentation was acute in 40 patients (48.78%), subacute in 7 (8.53%), chronic in 27 (32.92%) and history of relapse and remission in 8 (9.75%) patients. Preceding as well as simultaneous fever was observed in 16 cases (19.5%); vaccination (anti-rabies) in 1 case (1.21%); drug abuse in 1 case (1.21%); arthralgia-myalgia and rash in 2 cases (2.42%) and history of electrocution in 2 cases (2.42%). Only pyramidal tract involvement was present in 24 cases (29.26%) and remaining 58 cases (70.73%) had pyramidal tract affection with other sites of involvement. CSF study carried out in 60 cases, revealed rise of protein in 31 (37.8%); oligoclonal band had been detected in 6 (7.31%), pleocytosis in 18 cases (21.95%) and increased IgG index greater than 6.66 in 2 cases (2.42%). CT myelogram done in 23 cases revealed no abnormality. MRI study carried out in 59 cases showed myelomalacia in 1 (1.21%); demyelination plaque in 14 cases (17.07%); atrophy of cord in 3 (3.65%); infarction of cord in 1 (1.21%) and in 40 cases (48.78%) no abnormality could be detected. Etiological diagnosis could be established in 59 (71.95%) cases such as transverse myelitis or myelopathy (post infectious) in 24 (29.26%); demyelination in 16 (19.51%); vascular and vasculitis in 3 (3.65%); toxic in 1 (1.21%); physical (electrocution) in 2 cases (2.42%). In the remaining 23 cases (28.04%) no aetiological factors could be found.

Adult↗
PubMed2003

Randomized trial of adjunctive interleukin-2 in adults with pulmonary tuberculosis.

Interleukin (IL)-2 has a central role in regulating T cell responses to Mycobacterium tuberculosis. Adjunctive immunotherapy with recombinant human IL-2 was studied in a randomized, placebo-controlled, double-blinded trial in 110 human immunodeficiency virus-seronegative adults in whom smear-positive, drug-susceptible pulmonary tuberculosis was newly diagnosed. Patients were randomly assigned to receive twice-daily injections of 225, 000 IU of IL-2 or placebo for the first 30 days of treatment in addition to standard chemotherapy. Subjects were followed for 1 year. The primary endpoint was the proportion of patients with sputum culture conversion after 1 and 2 months of treatment. After 1 month, the proportion of patients for whom sputum culture converted to negative was 17% for the IL-2 group compared with 30% in the control group (p = 0.14; chi2). After 2 months, 77% in the IL-2 group were culture negative compared with 85% of those receiving placebo (p = 0.29, chi2). Results were similar when patients with isoniazid monoresistance were included in the analysis. There were no differences in weight gain and no improvement in fever, cough, and chest pain between groups. One patient in each arm relapsed. IL-2 did not enhance bacillary clearance or improvement in symptoms in human immunodeficiency virus-seronegative adults with drug-susceptible tuberculosis.

Adult↗
PubMed2004

Successful treatment with rifampin for fulminant antibiotics-associated colitis in a patient with non-Hodgkin's lymphoma.

A 74-year-old man was admitted to the hospital because of chemotherapy for relapsed non-Hodgkin's lymphoma (NHL). The patient became febrile and experienced diarrhea after chemotherapy. Although ceftazidime and amikacin sulfate were administered as empiric therapy, diarrhea was continued. After several days, stool cytotoxin assay for clostridium difficile (C. difficile) was positive and he was diagnosed as having antibiotics-associated colitis (AAC). Although antibiotics were discontinued and both oral vancomycin and metronidazole were administrated, disease was not improved. To rule out the presence of an additional cause of diarrhea, colon fibroscopic examination was performed. It revealed multiple deep ulcerative lesions at right side colon, surface erosive and minute erosive lesions in all continuous colon. Pseudomembranes were not seen. These findings are compatible with AAC without pseudomembranes. There are no reports that the rifampin is effective on refractory AAC. However, we administered oral rifampin for the current patient. The reasons are 1) conventional antibiotics were not effective, 2) rifampin has excellent in vitro activity against C. difficile, and 3) the efficacy of rifampin on relapsing colitis due to C. difficile is established. After administration of rifampin, fever alleviated and diarrhea was improved. Because AAC may result in significant mortality, patients with refractory or fulminant AAC should be treated with oral rifampin from outset.

Administration, Oral↗
PubMed1999

Treatment of hairy cell leukemia with cladribine (2-chlorodeoxyadenosine).

Hairy cell leukemia is a rare lymphoproliferative disorder resistant to conventional chemotherapeutic agents. Recently, the purine analogue cladribine (2-chlorodeoxyadenosine, 2-CdA) was introduced for the treatment of this disease. We report on 14 patients with hairy cell leukemia who were treated with 2-CdA at our department between 1993 and 1997. The patients received a single cycle of 2-CdA at a dose of 0.07 or 0.09 mg/kg/day by continuous infusion, over a seven-day period. Five patients were previously untreated, while the others had received prior treatment with interferon-alpha (seven patients), interferon-alpha and splenectomy (one patient) or interferon-alpha, splenectomy and pentostatin (one patient). Six patients achieved complete remission, three a good partial response and three partial remission. Two patients did not respond to treatment and one of them died from septicemia in aplasia. Relapse of the disease occurred in two patients. Side effects such as fever (WHO grade 2) and/or neutropenia (WHO grade 4) were noted in eight patients. Thus, 2-CdA is an effective treatment of hairy cell leukemia that can induce long lasting remissions in both, previously treated and untreated patients.

Adult↗
PubMedDate not supplied

Generalized pustular psoriasis following withdrawal of efalizumab.

Efalizumab is one of the new biologic therapies targeting T-lymphocyte activity for the treatment of chronic plaque psoriasis. Common adverse effects include headaches, nonspecific infection, nausea, chills, and fever. Rebound of psoriasis following discontinuation of the drug has been reported. Relapse events can manifest as recurrent plaque psoriasis, guttate psoriasis, psoriatic erythroderma, and pustular psoriasis. We report a second case of withdrawal flare resulting in generalized pustular psoriasis.

Adult↗
PubMed2006

[Bortezomib-induced tumor lysis syndrome with a remarkable elevation of LDH in a case of relapsed and therapy-resistant multiple myeloma].

A 60-year-old female patient with a therapy-resistant Bence-Jones (BJ) lambda-type multiple myeloma was treated with bortezomib. She had been treated with tandem autologous stem cell transplantations and achieved complete remission before her disease relapsed. Sixteen hours after the first administration of bortezomib, an episode of fever, slight consciousness disturbance and vomiting occurred, which was accompanied by a remarkable elevation of LDH (3608 IU/l). Serum levels of creatinine, uric acid, and AST were also transiently elevated. Serum interleukin-6 level was also increased after the administration of bortezomib. The symptoms disappeared rapidly within 48 hours. Bortezomib at a 25%-reduced dose was administered again along with dexamethasone 26 days later, which caused a moderate increase in LDH levels, but no other symptoms. Further treatment caused no increase in LDH. The treatment was very effective and eradicated both urinary BJ protein and bone marrow myeloma cells after 8 sessions of bortezomib administration. These findings suggest that a bortezomib-induced rapid reduction in tumor burden led to tumor lysis syndrome, for which caution is needed when treating myeloma patients with this very effective agent.

Antineoplastic Agents↗
PubMed1991

Clinical experience on malaria.

The 11 cases of malaria admitted to Kaohsiung Medical College Hospital in the past 10 years were analyzed to assess the characteristics of patients who acquired malaria parasite infection. Nine of the patients contracted malaria in Southeast Asia. Two men had received antimalarial chemoprophylaxis before they went abroad and another two men relapsed after antimalarial treatment. The initial symptoms and signs were nonspecific, including fever, chills, abdominal pain and hepatosplenomegaly. Seven patients responded well to the antimalarial regimens. Two persons developed meningeal malaria. Resistance to chloroquine and primaquine and even to quinine was noted in another two cases. Hypoglycemia was diagnosed in one of latter two patients who developed heavy parasitemia (26%), acute renal failure and died 5 days after treatment. Peripheral blood smear examination is a simple and quick method to make a diagnosis in any suspicious case. Resistance to chloroquine and primaquine is not uncommon, especially in those who acquired the infection in Southeast Asia. Changing to more potent agents and aggressive management in complicated cases is necessary.

Adult↗
PubMedDate not supplied

Childhood non-Hodgkin's lymphoma--results of treatment with ALL high-risk protocol.

Between August 1984 and September 1990, 13 children with non-Hodgkin's lymphoma (NHL) were treated with ALL high-risk protocol (5 with TCLSG 842 regimen and 8 with TPOG 882B protocol) at Taichung Veterans General Hospital. Diagnosis of NHL was confirmed by histology. Nine had lymphoblastic lymphoma, three had histiocytic lymphoma and one had small non-cleaved cell lymphoma, according to the Rappaport classification. After thorough clinical evaluation eight children were NHL stage IV; four were stage III; and one was stage II. All these children had received chemotherapy as acute lymphocytic leukemia (ALL) high-risk protocol for a total of three years, including central nervous system (CNS) prophylaxis. Of the 13 patients, 9 (69.2%) gained complete remission. Over-all survival rate was 46.2%, with a median interval of 36 months. The complete remission rate and survival rate for the nine children with lymphoblastic lymphoma was better at 77.7% & 66.6% respectively. Within the nonresponsive group, two failed to remit because of early withdrawal from the protocol; the other two patients were refractory to treatment. Relapse was noted in one patient. As to the side effects, neutropenic fever was the most common problem encountered (9 occurrences in 13 patients). Other major complications included severe mucositis, massive GI bleeding, intracranial thrombosis induced by l-asparaginase and tumor lysis syndrome. Childhood NHL is often of diffuse types in pathology, and most affected children have advanced diseases at diagnosis. Choosing an optimal treatment protocol is important for good treatment results.

Adolescent↗
PubMed2004

Gemcitabine and oxaliplatin (GEMOX) in patients with cisplatin-refractory germ cell tumors: a phase II study.

BACKGROUND: To investigate the efficacy and toxicity of the combination of gemcitabine and oxaliplatin (GEMOX) in patients with relapsed or cisplatin-refractory non-seminomatous germ cell tumors (NSGCT). PATIENTS AND METHODS: Twenty-nine patients with relapsed or cisplatin-refractory NSGCT were treated with gemcitabine 1000 mg/m2 on days 1 and 8 followed by oxaliplatin 130 mg/m2 on day 1 every 3 weeks for a maximum of six cycles. Twenty-four patients (83%) were considered refractory and five (17%) absolutely refractory to cisplatin. RESULTS: Twenty-eight patients were assessable for response. Overall, nine patients (32%) achieved a favourable response (complete response, four; partial response, five). One of the complete responders relapsed after 7 months and went into disease-free status lasting for 11+ months after resection of lung metastases. The rest of the complete responders are continuously disease-free at 14+, 19+ and 28+ months with the study regimen plus or minus surgery. One of the complete responders had absolutely cisplatin-refractory disease and another one presented with a late relapse. Toxicity was primarily hematological and generally manageable: 62% of patients experienced grade 3/4 neutropenia, 10% neutropenic fever and 41% grade 3/4 thrombocytopenia. Non-hematological toxicity consisted mainly of nausea/vomiting. Three patients (10%) developed grade 3 neurotoxicity and discontinued treatment. CONCLUSIONS: The combination of GEMOX is an active, moderately toxic and easily administered regimen in patients with relapsed or cisplatin-refractory NSGCT. The 14% long-term disease-free status accomplished in this heavily pretreated patient population is quite encouraging.

Adolescent↗
PubMed1991

Enzymes and factors controlling vitamin D metabolism and action in normal and milk fever cows.

In milk fever (parturient paresis), calcium homeostatic mechanisms, regulated by parathyroid hormone and 1,25-dihydroxyvitamin D, fail to maintain normal blood calcium concentrations, resulting in severe hypocalcemia. The precise nature of the endocrine defect is unknown. Secretion of parathyroid hormone and production of 1,25-dihydroxyvitamin D is similar in most cows with milk fever or without. However, there are some cows that fail to produce adequate 1,25-dihydroxyvitamin D at the onset of lactation. These tend to be cows that will suffer prolonged hypocalcemia and relapse after treatment. Assuming that most cows produce adequate amounts of both hormones, the next logical cause of milk fever might be a failure of tissues to respond to calcium-regulating hormones. Older cows are more likely to develop milk fever than younger ones. We have found that tissue 1,25-dihydroxyvitamin D receptor concentrations decline with age, leaving the tissues less able to respond to 1,25-dihydroxyvitamin D. We also have found that tissue 1,25-dihydroxyvitamin D receptor concentrations increase during pregnancy and lactation in the cow. Intestinal 1,25-dihydroxyvitamin D receptor concentration does not appear to be different in cows with or without milk fever in cows of similar ages. However, intestinal 1,25-dihydroxyvitamin D receptor numbers decrease precipitously at parturition, which may in part be responsible for the development of hypocalcemia in dairy cattle.

Absorption↗
PubMedDate not supplied

Amphotericin B in resistant kala-azar in Bihar.

BACKGROUND: During the recent epidemic of kala-azar in Bihar, we identified a group of patients who were unresponsive to the two commonly used drugs--sodium stibogluconate and pentamidine. We evaluated the use of amphotericin B in these patients because it has been shown to be active in experimental animals against amastigotes and promastigotes, it has been found to be useful in South American patients and is now recommended by the World Health Organization as a second line drug. METHODS: We selected 300 patients who were unresponsive to sodium stibogluconate and pentamidine (out of 500 patients with kala-azar confirmed by demonstration of Leishmania donovani bodies in their splenic aspirates). Amphotericin B was given in a dose of 1 mg/kg body weight on alternate days starting with 0.05 mg/kg body weight with daily increments till a 1 mg dose was reached. A total dose of 20 mg/kg was given initially and repeated if the parasites persisted. The investigations done before and after treatment were splenic or bone marrow aspiration, measurement of the spleen and liver size, body weight, total and differential white cell counts, haemoglobin level, total serum protein, blood urea, serum creatinine, serum potassium, blood sugar, serum alanine and aspartate transaminase, electrocardiography and a chest X-ray. The efficacy of treatment was assessed at the end of treatment and after 6 months of follow up. RESULTS: After treatment with amphotericin B, 298 (99%) of the patients had been cured of their disease as evidenced by the disappearance of fever, reduction of hepatosplenomegaly, clearance of the parasites from the spleen and bone marrow and an absence of relapse on 6 months of follow up. Two hundred and sixty-eight (89%) patients required 1 g of the drug, 24 (8%) required 1.5 g and 6 (2%) required 2 g. All patients had shivering and fever during the infusion. Two had a cardiac arrest from which they could not be revived. Other complications included anorexia, stomatitis, jaundice, hypokalaemia and a rise in blood urea. However, these were only mild and improved after treatment was stopped. CONCLUSION: Amphotericin B is an effective drug for patients with kala-azar unresponsive to treatment with sodium stibogluconate and pentamidine, but it should be administered under close medical supervision.

Adolescent↗