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PubMedDate not supplied

[Immuno-allergic accidents with rifamipcin].

We report 2 new cases of immuno-allergic side-effects of rifampicin (RMP), occurred in leprosy patients treated by multidrug therapy. These cases illustrate the various features of this type of complication. In one case, the patient exhibited few days after restarting of RMP (600 mg daily), a typical flu syndrome associated to a thrombopenia. Previously, the patient had received discontinued RMP (300 mg, 3/5 days) that had to be stopped after 11 months for "general malaise" that in fact corresponded to a flu syndrome. The second patient developed a flu syndrome associated with a diffuse eczematous eruption one year after the onset of daily RMP (600 mg). Anti-RMP antibodies were detected only in the first case. The pathogenic mechanisms and the clinico-biologic features are discussed.

Anti-Bacterial Agents↗
PubMed2002

[A collective malarial infestation during a humanitarian mission in west Africa].

Four truck drivers involved in a humanitarian mission across the Sahara towards Mali fell ill 15 days after their return. Plasmodium falciparum malaria (thankfully, non pernicious) was diagnosed with 3 to 4 days delay. The four drivers had been treated with chloroquine and proguanil but the dosage may have been insufficient with regard to their body weight (average weight = 110 kg). These 4 travelers had all slept outside (in Tintane, near Kiffa in Mauritania), without any anti-vectorial protection, whereas their other 8 companions (none of whom caught malaria) had slept in their vehicles. The evolution of the 4 cases was favourable despite the difficulties involved in urgently obtaining sufficient amounts of quinine for treatment. How can these cases be explained in relation to prophylactic treatment of associated chloroquine and proguanil? One explanation might be resistance of the P. falciparum strain. We were unable to study this possibility. The high incidence and similitude of cases points towards a hypothesis of resistance both to proguanil and chloroquine. Resistance to chloroquine, as has been formally ascertained in Mauritania, reinforces such a conviction. And yet prophylaxis does not prevent pernicious malaria. This clinical form of the disease, with P. falciparum primo-invasion occurring under rigorous chemoprophylaxis is characteristic of a partially resistant strain. The most reasonable explanation besides "chance" is that we are dealing here with a partially resistant strain of Plasmodium falciparum which is thus also partially sensitive to--in this case highly effective--therapeutic treatment. Indeed, chloroquino-resistant strains are more sensitive to mefloquine and halofantrine. Another explanation might be under-dosage of Savarine with relation to the body weight of these 4 patients. We should be aware of adapting more rigorously the posology of prescribed prophylaxis. But above all, this outbreak should remind us that we should recommend to travelers and drivers planning a trip to Sub-Saharan Africa to take with them anti-vectorial protective gear. Finally, the observation of these cases indicates once more the difficulty in France of establishing a proper diagnosis in face of malaria. Health personnel must systematically call to mind malaria in face of thrombopenia or fever following a sojourn in an endemic area even when chemoprophylaxis has been correctly followed.

Adult↗
PubMed2002

[Gaucher's disease ].

Gaucher disease is an uncommon autosomic recessive disorder. The disease is caused by a deficiency in the activity of the lysosomal enzyme glucocerebrosidase which is responsible for the degradation of glucosylceramide, résulting from the breakdown of red and white cell-membranes. In the absence of enzyme glucosylceramide accumulates in the lysosomes of macrophages. This accumulation leads to hepatomegaly, splenomegaly with subsequent haematologic abnormalities (leucopenia, anemia, thrombopenia) and bone manifestations. Three types of Gaucher disease are described: type 1 is the most common, type 2 and 3 are associated with neurologic symptoms. Macrophages are the likely cellular source of biochemical abnormalities: elevated blood level of ferritin, angiotensin converting enzyme, immunoglobulins and haemostasis abnormalities. Lysosomal perturbations lead to increased blood level of tartrate resistant acid phosphatase and chitotriosidase. Enzyme replacement therapy is available in France since 1991. In 2002, 136 patients are treated. The efficacy is overt on the asthenia, organomegaly and haematological manifestations. Bone pains disappear or decrease in intensity, however bone complications may be irreversible justifying treatment initiations before the appearance of lesions that may lead to serious functional impairment.

Biomarkers↗
PubMed2002

[Epidemiologic, clinical and cytohematologic characteristics of adult acute lymphoblastic leukemia in Tunisia].

Through a national retrospective study, the authors report the clinical and hematological characteristics of 124 acute lymphoblastic leukemia of the adult diagnosed during 5 years (1993-1997). The national prevalence is of 0.28/100.000 inhabitants/year. The sex-ratio is of 1.3. Sixty six per cent of patients were 16-35 years of age, and only 10% of them were more than 60 years of age. A tumoral syndrome was present at 71% of the cases with peripheral adenopathies in 55%, splenomegaly in 40%, hepatomegaly in 19% and a mediastinal tumor in 18% of the cases. The bone pain were rarely signaled (10%) and neuro-meningeal affection was found in only 3% of cases. There was no testicular lesions. The white blood cells count was less than 30.000/mm3 in 60% whereas an important hyperleucocytosis superior than 100.103/mm3 was observed in 20% of the cases. Anemia and thrombopenia were noted in 94% and 90% of the cases respectively. Acute lymphoblastic leukemia typing by cytological study of Bone marrow according to the Fransh-American-Britain criteria (FAB) had found 43%, 48% and 4% for type 1,2 and 3 respectively. In 5% of the cases the type of the acute lymphoblastic leukemia was not precised (diagnosis based on the Bone biopsy).

Adolescent↗
PubMed2002

[Contact dermatitis with Hirudo medicinalis].

BACKGROUND: Hirudine is the first natural anti-coagulant ever described. It is used for its anti-coagulant properties in plastic surgery or for the treatment of post-phlebitic diseases. Natural hirudine is extracted from the saliva of the Hirudo medicinalis leech, but it can also be found in crushed leech and included in a cream (Hirucrème). Side effects to hirudine are considered to be rare. CASE REPORT: We report a contact eczema caused by an extract from the medicinal Hirudo medicinalis leech. This was confirmed by the patch tests. However, we noticed a negativity of these tests with two analogs of the recombinant hirudine. DISCUSSION: Several cases of contact dermatitis with Hirucreme have been described. The analogs of recombinant hirudine, which share similar biological activity, have a very close molecular structure. They are indicated via the systemic route for thrombopenia related to heparin for the prevention of severe thromboses. The negative patch tests does not allow definite conclusion, but they prove that these molecules do not always lead to cross-allergies.

Administration, Topical↗
PubMedDate not supplied

A phase I study of continuous administration of 5-fluorouracil/cisplatin in advanced uterine cervical cancer.

BACKGROUND: The aim of this study was to assess the toxicity of a neoadjuvant chemotherapy (NAC) regimen consisting of cisplatin (CDDP) and 5-fluorouracil (5-FU) through 24-hour intravenous continuous infusion on days 1-4 in a Phase I study. PATIENTS AND METHODS: Thirteen patients were recruited for this study. All patients were treated with a regimen consisting of CDDP and 5-FU through a 24-hour intravenous continuous infusion on days 1-4, followed by radical hysterectomy and/or radiation. Each initial dose of CDDP and 5-FU was 20 mg/m2/day and 750 mg/m2/day, respectively, for 4 days. RESULTS AND CONCLUSION: In the third step, seven patients were treated at 25 mg/m2 day CDDP and 1000 mg/m2/day 5-FU, respectively, for 4 days. One of seven patients showed Grade 4 thrombopenia. However, in this dose step, all the patients showed an objective response. Although maximum tolerated doses (MTDs) were not reached, we decided to stop the escalation and to recommend this level for the Phase II study.

Adult↗
PubMed2002

[Stormorken's syndrome].

In 1985, a new syndrome with the following characteristics was described: thrombopathia, thrombopenia, asplenia, miosis, headache, ichthyosis, dyslexia, muscle defect, and subsequently also hypocalcaemia. Skin and deep bleedings, leg spasms, disturbed dark vision and dyslexia are main worries. This paper describes these patients with a review of the investigations performed. Causes of the bleeding tendency are complex disturbances of the platelet membrane causing insufficient stability of the haemostatic plug, the nature of which is unresolved, but involves membrane scrambling. The muscle defect consists in tubular aggregates and high blood values of creatine kinase. A connection with the hypocalcaemia is possible, because increasing the ionic Ca with calcitriol significantly improves muscle function. Miosis is resistant to mydriatics and causes decreased dark vision, possibly also influencing dyslexia. The asplenia has little influence on immunocompetence, and the patients have survived 300 patient years without critical infections. The gene defect has not yet been unravelled.

Adult↗
PubMed2002

[Fatal complications in pre-eclampsia and eclampsia].

OBJECTIVE: Analysis of preeclampsia and eclampsia--one of the major contributor to life-threatening maternal morbidity frequently leading to maternal mortality in the Czech Republic till late 70's. Our goal was to mention major causal links in clinical courses of individual maternal death and to highlight main mistakes and faults, and to provide frequencies and basic characteristics of risk groups. DESIGN: Retrospective epidemiological study. SETTING: Department of Obstetrics and Gynecology of the 1st Medical School of Charles University and General University Hospital, Prague. Institute for the Care of Mother and Child, Prague-Podoli; 1st Intern Department of the 1st Medical School of Charles University and General University Hospital, Prague. METHODS: Analysis of 31 cases of maternal deaths associated with severe preeclampsia and eclampsia in the Czech Republic during 1978-2000, using a database of 470 maternal deaths during the observed period. We analyzed clinical course with special attention to obstetrical surgery and clinical management. We considered timelines of life-threatening events, age of mother, parity, and place of death. RESULTS: There were 36 maternal deaths associated with severe preeclampsia and eclampsia in the Czech Republic in 1978-2000, contributing 7.7% to total maternal mortality. Group A1 was 5th most frequent cause of maternal death. We analyzed 31 cases closely related to severe preeclampsia and eclampsia. During 1978-1990 there was 1 death per 74,263 live-born babies in this category, while during 1991-2000 we observed only 1 death per 171,137 live-born babies. Clinical management was not adequate in 15 cases of death (48%) and content of care did not reflect possibilities of prevention, diagnosis and therapy. Severe preeclampsia and eclampsia was more frequent among older women and multiparae. First group (61%) is composed of women with manifest convulsions, 25% of them experienced convulsion after delivery, and only few cases had mild preeclampsia ante partum. Eclampsia with convulsions leading to coma were in 10 cases complicated with DIC, two cases in this group had premature separation of placenta. Besides classic symptoms of preeclampsia there were within this group 5 cases of multiple pregnancy, history of unstable hypertension, hepatopathy in previous pregnancy and chronic nephrosis. The second group (39%) were cases without convulsions. These cases were complicated with severe liver disorders and renal failure, and 5 cases of intra-cranial hemorrhage. Several cases had combination of symptoms. DIC was present in 6 cases. In both groups there were 5 cases with hemorrhagic skin symptoms, thrombopenia, symptoms of DIC and liver and renal failure, which would fall into HELLP syndrome according to current classification. The most of women died during the postpartum period (87%) mostly after emergency operative deliveries. The fact that no women died during pregnancy indicates the effort to perform life-saving operative delivery. Forty two percent of women were in term. Especially at the beginning of observed period we noticed tendency to prolong gestation in order to save the baby. The mortality of fetuses or newborns was 71%. Operative deliveries accounted for 71%, the majority of them were caesarean sections. More than 50% of cases were operated in coma. We indicate major mistakes and failures in organization of care, primary prevention, diagnosis, and consequent care. CONCLUSION: Positive results in area of maternal deaths in association with severe preeclampsia and eclampsia during last 10 years are due to improved diagnostic and therapeutic measures in our field, especially in neonatology, because obstetricians currently terminate pregnancies early than before while symptoms of preeclampsia get worse. We focus on early recognition of symptoms of coagulopathy in combination with symptoms of preeclampsia, especially on early detection and treatment of HELLP syndrome.

Adult↗
PubMed2000

[Portal hypertension caused by intra-hepatic block during chronic lymphoid leukemia].

Portal hypertension in chronic lymphocytic leukemia is rare. A 66 year-old man was admitted for splenomegaly, thrombopenia and cholestasis. Endoscopy showed esophageal varices. The hepatic venous pressure gradient was 15 mmHg. The liver biopsy showed dense leukemia cells in sinusoidal and portal sites. After splenectomy, the hepatic venous pressure gradient normalized, but esophageal varices and cholestasis persisted. The authors discuss the mechanisms of portal hypertension in chronic lymphocytic leukemia. Previously reported cases are summarized.

Aged↗
PubMed2003

[Epidemiologic, clinical, biological and therapeutic aspects of Gaucher disease].

GENERAL CHARACTERISTICS: Gaucher's disease is a genetic disease of autosomal recessive transmission due to a deficit in a lysosomal enzyme: beta-glucocerebrosidase. The disease is characterised by deposits of glucosylceramide in the cells of the liver, spleen and bone marrow. Acute or chronic neurological forms (type 2 and 3) account for only 5% of patients suffering from Gaucher's disease and are less frequent than the non-neurological forms (type 1). CLINICAL AND BIOCHEMICAL MANIFESTATIONS: Gaucher's disease is associated with spleno- or hepato-megalia, asthenia, bone complications (Erlenmeyer flask deformity, osteopenia and osteonecrosis), as well as with haematological (thrombopenia, anaemia) or biochemical abnormalities (increase in angiotensin-converting enzyme, ferritin, tartrate-resistant acid phosphatase and chitotriosidase). Central nervous system involvement is only found in the type 2 and 3. Diagnosis relies on measurement of beta-glucocerebrosidase activity in the circulating leukocytes. REGARDING TREATMENT: Treatment with enzyme replacement (imiglucerase: recombinant enzyme preparation) improves the haematological abnormalities, hepatosplenomegalia and quality of life in a matter of a few months. Regression of the bone disorders is usually observed only after 3-4 years of treatment. Recently, gene therapy trials have successfully been started.

Chromosome Aberrations↗
PubMed2003

[Frequency, risk factors and prognostic value of anemia associated with HIV/AIDS in the adult in Mali].

Anaemia is a common complication of the HIV infection. To understand the mechanism of HIV associated anaemia and to suggest a consequent therapeutic approach in adults in Mali, we undertook a prospective case/control study in two services of reference with essentially adults recruitment in Bamako. We studied the frequency, the risk factors and the prognosis value of this complication in 133 patients with HIV infection matched to 133 others non HIV infected. The average age of our patients was 36.08 +/- 8.80 years (age range: 19 to 66 years). The frequency of anaemia was significantly higher in patients with HIV infection compared to the controls (78.9% vs. 51.9%; OR = 2.46; 95% CI [1.56-3.92]). Anaemia was more frequent in women than in men (p = 0.00003). A significant association between anaemia and thrombopenia or lymphopenia was observed only in patients with HIV infection. The severity of anemia was positively associated with the HIV2 infection and the progression of the HIV disease. Mortality was more frequently associated to the anaemia (p < 10(-5)) in patients infected by HIV. These findings suggest that bone marrow depression leading to a decreased red blood cells production is the main mechanism of HIV associated anaemia in adult in Mali. Therefore, without evidence of a best cost-effectiveness ratio of a human recombinant erythropoietin treatment in the context of countries with a low income, the therapy of this haematological complication must be an emergency focusing on red blood cells transfusions.

Acquired Immunodeficiency Syndrome↗
PubMed2003

[Pharmacokinetics of paclitaxel and carboplatin in a hemodialysis patient with metastatic urothelial carcinoma--a case report].

A 69-year-old-man undergoing hemodialysis for 8 years developed metastatic urothelial carcinoma and received combination chemotherapy with paclitaxel and carboplatin. Paclitaxel 175 mg/m2 was given as a 3-hour intravenous infusion, and carboplatin was dosed to the area under the plasma concentration-time curve (AUC) of 5 mg.min/ml calculated according to the Calvert formula as a 30-minute intravenous infusion immediately after paclitaxel. Hemodialysis was started 1 hour after carboplatin, then their pharmacokinetics was determined in the patient. The AUC of paclitaxel and carboplatin were 15.2 and 64.56 micrograms.h/ml, respectively. The metastatic tumor size was reduced by more than 20% after 3 courses of this chemotherapy. Grade 3 neutropenia and grade 1 thrombopenia were observed. This is the first report that the combination of paclitaxel and carboplatin is feasible in a patient with metastatic urothelial carcinoma undergoing hemodialysis, with low toxicity and safety.

Aged↗
PubMedDate not supplied

Phase I study of pegylated liposomal doxorubicin (Caelyx) in combination with carboplatin in patients with advanced solid tumors.

PURPOSE: To determine the maximum tolerated dose of the combination of Carboplatin and Caelyx, a pegylated liposomal doxorubicin, with promising activities in various solid tumors. PATIENTS AND METHODS: Twenty-two patients with various advanced solid tumors were included. Three dose levels of Caelyx were explored: 30, 35 and 40 mg/m2 in association with a fixed dose of Carboplatin (AUC 5) every 3 weeks. Dose escalation followed a modified continuous reassessment method. RESULTS: Dose-limiting toxicities were almost exclusively hematological: 3 febrile neutropenia, 1 grade 4 neutropenia lasting more than 7 days and 2 grade 4 thrombopenia were observed. Grade 4 neutropenia and febrile neutropenia were observed in 20 and 10% of courses, respectively. The median interval between courses was 25 days after cycle 1 and 27-28 days after subsequent cycles. Palmar-plantar erythrodysesthesia, mucositis and other non hematological toxicities were mild and uncommon. One patient experienced a severe anaphylactic reaction immediately after Caelyx infusion. No clinical heart dysfunction was observed. Three patients responded to therapy including 2 clinical complete responses in relapsing ovarian cancer. CONCLUSION: The recommended dose for future studies is Caelyx 35 mg/m2 + Carboplatin AUC 5 every 3 or 4 weeks. Antitumor activity, especially in ovarian cancer, warrants further investigation in phase II studies.

Adult↗
PubMed2003

Weekly paclitaxel for advanced non-small cell lung cancer patients not suitable for platinum-based therapy.

Platinum-based combinations are efficacious in the treatment of advanced non-small cell lung cancer (NSCLC) but their toxicity makes them unsuitable for elderly and for patients with co-morbidities. We assessed the efficacy and toxicity of low-dose of paclitaxel in patients who were elderly or who had contraindications against cisplatin therapy. Seventy-one patients (median age 68; range 42-82 years) with unresectable NSCLC were treated with weekly paclitaxel (80 mg/m2) infusion (1 h) for several cycles without intervening rest periods. Thirty-seven patients had PS 1 and 34 had PS 2 status. A total of 614 courses were administered (median 9, range 2-20). There were no episodes of grade 4 toxicities and only 1 patient had grade 3 thrombopenia. Grade 3 anemia or neutropenia were not observed and severe non-hematological toxicity was uncommon: grade 1-2 fatigue in 52%; grade 1-2 motor neuropathy in 42% and grade 3 in 5.5%; grade 1-2 sensory neuropathy in 46.3% of patients. Twenty-seven of the 67 evaluable patients (40.3%) had an objective response, whereas 26 patients (38.8%) had stable disease. The median overall survival for the entire group was 8.4 months (95% CI = 5.6 to 11.2) and the 1-year and 2-year survival was 37.4% and 12.1%, respectively. The median time-to-progression was 5.4 months (95% CI = 3.3 to 7.4). Our data show that low-dose weekly paclitaxel is active and well tolerated in this group of patients with NSCLC and poor prognosis and, as such, is useful for patients in whom platinum-based combinations are not suitable.

Adenocarcinoma↗
PubMed2003

[Floxuridine-containing regime in the treatment of gestational trophoblastic tumor].

OBJECTIVE: To analyse the efficacy of the floxuridine (FUDR)-containing regime (single agent or in combination) in the treatment of gestational trophoblastic tumor. METHODS: Seventy-four patients with gestational trophoblastic tumors (GTT), 47 invasive mole and 27 choriocarcinoma, were treated with FUDR-containing regime. The clinical staging of the disease were: 33 cases of stage I, 3 cases of stage II, 31 cases of stage IIIa, 6 cases of stage IIIb, and 1 case of stage IV. RESULTS: The cure rate of FUDR-containing regime in the treatment of GTT was 91.9% (68 out of 74 cases). Twenty-one out of these 74 patients showed drug resistant to 5-FU-containing or MTX-containing regime and were cured after they changed to the FUDR-containing regime. All 7 patients of advanced stage (> or = III b) got cured. The major adverse event of FUDR-containing regime was myelodepression and gastrointestinal toxicity: III-IV degree granulopenia 26%, III-IV thrombopenia 6.2%, III degree vomiting 57.1%, and III degree diarrhea 4.3%. CONCLUSION: FUDR-containing regime is efficient for the treatment of GTT, even for those with advanced stage or drug-resistant disease.

Adolescent↗
PubMed1992

Hypothyroidism associated with myeloid neoplasia. About 2 cases.

We report 2 cases of hypothyroidism in whom the associated haematological disturbances (macrocytic anaemia in both cases, mild leukopenia and thrombopenia in one patient) failed to be corrected by thyroid hormone replacement therapy. Further investigations led to the diagnosis of acute myeloid leukaemia (AML) in the first patient and myelodysplastic syndrome (MDS) in the other. The reasons of the delayed diagnosis and the possible mechanisms explaining this rare combination are discussed. The hypothesis of a purely coincidental association seems most likely.

Aged↗
PubMed1992

[Comparison of 2 cisplatin and etoposide dosages in relapsing small cell lung cancer].

The synergistic combination of cisplatinum and etoposide appears as the best second line treatment in patients relapsing from small cell lung carcinoma (SCLC). In order to test the dose-effect relationship of cisplatinum and etoposide in this situation, we have performed a randomised phase II trial comparing 2 five-day regimens: cisplatinum 20 mg/m2/day+etoposide 60 mg/m2/day (arm A) versus cisplatinum 40 mg/m2/day+etoposide 100 mg/m2/day (arm B) every 4 weeks. Thirty-seven patients were included (arm A: 18, arm B: 19), and 32 were considered to be eligible (arm A: 15, arm B: 17). Eight patients were non evaluable, five of them because of toxic death occurring prior to the second course (arm A: one from neutropenia; arm B: three from neutropenia and one from thrombopenia). The two groups were well balanced with regard to the main prognostic factors (age, sex, performance status, LDH level, response to induction chemotherapy). An objective response was observed in 10/24 evaluable patients (arm A: 4, arm B: 6) and was considered as complete in one patient in arm A and in 2 pts in arm B; these two patients presented with cerebral metastases and their response lasted 9 and 15 weeks respectively. The mean duration of response was 11 weeks in arm A and 10.5 weeks in arm B. The median actuarial survival of the overall population of eligible patients was 15 weeks: 13 weeks in arm A and 16.5 weeks in arm B. The study was discontinued because of the 23.5% toxic deaths rate in the high doses arm in this heavily pre-treated population of patients. However, the high response rate (54% overall, 35% considering toxic death as a failure) is impressive and presents evidence for the dose/effect relationship in SCLC.

Aged↗
PubMed2003

[Manifestations of rifampicin-induced hypersensitivity].

INTRODUCTION: The side effects of rifampicine due to an immunoallergic mechanism are rare and usually observed during discontinued treatment or administration of high doses. OBSERVATIONS: An immediate hypersensitivity reaction with anaphylactic manifestations and increase in IgE occurred in a 39 year-old man suffering from resistant tuberculosis. The reaction occurred within the first hour following a low dose of rifampicin administered in a desensitisation attempt, the outcome of which was favourable after administration of corticosteroids and antihistamines. A type II hypersensitivity reaction occurred in a 76 year-old male patient in the form of thrombopenia on D76 of a twice weekly treatment, diagnosed because of hemoptysis with normalisation of platelet level on withdrawal of rifampicin. An immune complex hypersensitivity reaction was responsible for hepato-renal failure on D68 of twice weekly treatment and required permanent withdrawal of rifampicin and dialysis, which led to subsequent improvement. COMMENTS: These clinical cases illustrate the variability of the hypersensitivity mechanisms observed with rifampicin, the difficulty in imputability tests and methods for immunological confirmation, the interest of continuous treatment which avoids a certain number of these accidents, and that of desensitisation during immediate hypersensitive reactions which permits the continuation this major anti-tuberculosis drug.

Acute Kidney Injury↗