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[Imported malaria in Bordeaux in 1989. Epidemiologic, clinical and therapeutic study of 71 cases].

In 1989 there were 71 cases of imported malaria admitted to the hospital in Bordeaux. This is 16.5% and 29% lower than in 1988 and 1987 respectively, thanks to the widespread use in Africa of mefloquine chemoprophylaxis. Sub-Saharan Africa is involved in 95% of cases, mainly West Africa (70% of cases), unlike the situation in 1987, and the first cases of paludism despite mefloquine chemoprophylaxis appeared during the second semester from the seasonal mid-summer recrudescence onwards, in travellers returning from this region. The most frequent species is still Plasmodium falciparum (80% of declared cases). This imported disease especially affects young adults despite regular prophylaxis in 59% of cases. It is therefore important to recommend rigorous protection against anopheles. Male predominance (sex ratio: 5.5) was greater in 1989 than in the previous two years, and French nationals represented 85% of the population. Falciparum malaria presents symptoms in 95% of cases before the end of the month following the patient's return to France, while for P. ovale the time for symptoms to appear is between 39 days and two years after return. Management of patients on their return poses a problem of information, since in 40% of cases diagnosis is made more than a week after the first symptoms. Attacks are mild in most cases (93%); among the serious cases death occurred in a 3-year-old child. Thrombopenia is the most frequent biological sign (22.5% of cases), followed to a lesser degree by anaemia and leukopenia. Mild attacks respond well to classical treatment (halofantrine, mefloquine, quinine, chloroquine), while two cases of more complicated symptoms required exchange transfusion.

Animals↗

[Nosocomial bacteremia caused by Serratia marcescens: analysis of 44 cases].

We have evaluated 44 cases of Serratia marcescens bacteremia (SB). Most took place in surgical services (57%) and the ICU (34%). In one occasion, the cases developed as an epidemic outbreak. SB basically developed in patients with underlying diseases (neoplasia in 32%, heart disease in 16%, chronic bronchitis in 14% and miscellaneous in 20%) in whom some invasive procedure had been carried out (98%). The most common complication was septic shock. In 17 cases the infection was polymicrobial. The most common serogroup was 0:5 (41%). 98% of strains were resistant to cephalothin, 78% to ampicillin and 29% to tobramycin. The mortality rate was 39% and the most common cause of death was septic shock. The factors which adversely influenced prognosis were as follows, in order of decreasing importance: leukocytosis, thrombopenia, associated gram-positive infection, age older than 65 years, "non-typable" serogroup, unknown portal of entry, epidemic case and septic shock.

Adult↗

[Neurological complications of Argentinian hemorrhagic fever].

The Argentine hemorrhagic fever (AHF) is an infectious disease, endemo-epidemical, of viral etiology, produced by the Junin virus and limited to the Buenos Aires Province, South of Córdoba, East of La Pampa, and South of Santa Fe. It generally assails rural workers at harvest-time, especially during corn-harvest. The incubation period of the disease does not exceed 12 days. A feverish syndrome with asthenia, adynamia, myalgias, migraine, photophobia, epigastralgia etc., appear. The patient has a facial erythema, petechias on the skin, enantema on the palate, conjunctive micropolyadenopaty injection. The laboratory shows a low erytro, leukopenia with aneosinophilia, thrombopenia and a urine with albuminuria and virous cells. After the fourth day, hemorrhage and a neurological case appears. The laboratory tends to normalize and cast appears in the urine. The most striking neurological signs are the following: muscular hypotonia, proprioceptive hyporreflexia or arreflexia, marinesco reflex, shakings, difficulty to stand and walk, oscillations in consciousness level, and ocular disturbances. The cytochemical test of the C.L. Rachis in the usual ways of the AHF is within its normal characteristics; on the other hand there are modifications in the nervous cases: the total proteins are nearly always increased and the cells augmented with a great predominance of mononuclear cells. The electroencephalogrammes were always abnormal, varying from a brief disorganization up to a diffusive and permanent slowness. The half of which additionally presented paroxisms generalized by slow waves. The pathological anatomy over the central nervous system makes us think that the lesion would not primitively neuronal but that the action of the virus would be indirectly done through the capillar wall. This capillar lesion is produced by multiple focuses. The neuronal destruction with necrosis by microinfarcts is minimum. The symptoms and neurological signs are present in 10% of the clinical cases; the death-rate in the nervous clinical cases having reached 50% of them. The premature treatment allows the death-rate to diminish and the cases that survive have not many after effects.

Adult↗

[Long-term tolerability of tiopronin (Acadione) in the treatment of rheumatoid arthritis. Apropos of 140 personal cases].

One hundred and forty patients with classic or definite rheumatoid polyarthritis were treated with N2 mercapto-propionly-glycine: thiopronine (Acadione) at an average dose of 1 g per day over a mean duration of 11.7 months + 10.7 months. The retrospective study of these cases, followed between 1980 and 1988 by the same medical team, permits to evaluate the long-term tolerance of the product. Adverse reaction, always subsiding were observed in 55 p. cent of the patients, requiring discontinuation of the treatment in 40 p. cent of the cases. These side effects occur in 3/4 of the cases, during the first 6 months of the treatment. The intolerance mainly affect skin and mucosae: 46 cases (32.8 p. cent) resulting in 32 instances (22.8 p. cent) discontinuation of the treatment because of stomatitis, pruritus, various types of erythema, pemphigus (1 case). Fourteen patients presented a renal failure (10 p. cent) requiring in 8 instances (5.7 p. cent) discontinuation of the thiopronine because of nephrotic syndrome (3 case) and proteinuria (5 cases). Haematological disorders were observed in 13 instances (9.2 p. cent), justifying, in 10 instances (7.1 p. cent) discontinuation of the treatment because of thrombopenia or leucothrombopenia. The other side effects observed are the following: digestive disorders 15 cases (10.7 p. cent) requiring discontinuation of the treatment in 3 instances (2.1 p. cent), agueusia in 6 instances (4.2 p. cent) requiring discontinuation of the treatment in one case; miscellaneous disorders 13.5 p. cent for which the responsibility of thiopronine is not precisely established (especially hepatic cholostasis, muscle disorders), requiring discontinuation the the treatment in 1.4 p. cent of the cases.(ABSTRACT TRUNCATED AT 250 WORDS)

Arthritis, Rheumatoid↗

[Doxifluridine toxicity, a fluorouracil analog with low myelosuppressive effect].

Doxifluridine, a new fluorouracil analog with a low myelosuppressive effect, has recently been subject to various disease-oriented, Phase II trials. For the present evaluation of drug tolerance, the Phase II data of 114 patients having received 376 doxifluridine cycles has been used. The treatment cycles consisted of 5 daily intravenous injections of 4,000 mg/m2 non-pretreated patients, and 3,000 mg/m2 in pretreated patients. Previous observations showing that doxifluridine is less myelotoxic than fluorouracil have been confirmed. 54% of the patients had no leucopenia (maintaining WBC counts over 3,000/mm3 and 90% had no thrombopenia (platelets not lower than 100,000/mm3) throughout treatment. However, a WHO grade 4 hematologic toxicity was observed in 9 patients, and 2 toxic deaths were related to severe granulocytopenia and sepsis. Digestive tract toxicity was similar and equally frequent as the one observed with fluorouracil: mucositis with oral ulcerations (19%), nausea and vomiting requiring specific treatment (8%) and severe but never hemorrhagic diarrhoea (5%). Neurologic toxicity was frequent, with 20% of patients complaining of somnolence and/or peripheral neuropathy, 7% of impaired consciousness and 1% of WHO grade 4 cerebellar ataxia. Among the 10% of patients with cardiac symptoms, 6% were benign and transient arrhythmias, and 4% were severe, including 1 myocardial infarction, 1 spontaneously reversible cardiac arrest and 2 ventricular fibrillations successfully treated with cardioversion. In spite of its encouraging antitumor activity and its good hematologic tolerance, intravenous doxifluridine, as used in this study, cannot be recommended because of the observed neurologic and cardiac toxicity. Oral doxifluridine is presently under investigation with preliminary results suggesting a lack of neuro- or cardiotoxicity.

Administration, Oral↗

[Neoadjuvant chemotherapy with MVC (methotrexate, vinblastine, cisplatin)in the treatment of infiltrating transitional carcinoma of the bladder].

Of 19 patients with advanced transitional bladder cancer (T2-T4, N0-N+, M0) who received two or three cycles of pre-emptive MVC (Methotrexate, Vinblastine, Cisplatin), pathological partial (PR) and complete (CR) remissions were observed in 67% (50% and 17% respectively). The toxicity of chemotherapy was generally acceptable but 5 patients required hospitalization for neutropenia and thrombopenia . In one of them chemotherapy was stopped for severe sepsis. No death was observed. In 11 patients follow-up is greater than 12 months. In this group, 10 patients are actually alive and disease-free, while the other one was dead owing to brain metastasis, after eight months from surgery.

Aged↗

[Evans' syndrome during acute myelomonocytic leukemia. 2 cases].

The immune abnormalities observed during acute myeloblastic leukemia often remain undiagnosed for they generally have no practical consequences. The association of peripheral thrombopenia and a positive direct Coomb's test, during two cases of acute myelo-monocytic leukemia should be recognised owing to the difficulty of interpretation and the therapeutic consequences.

Anemia, Hemolytic, Autoimmune↗

[Myelodysplasias: clinical experience with 35 patients].

Myelodysplasia, characterized by varied reductions of peripheral blood elements with normal or hypercellular bone marrow, is relatively frequent among older patients and may evolve to acute leukemia. We reviewed findings in 35 patients whom, according to the FAB classification were distributed as follows: simple refractory anemia (RA) 34%, sideroblastic refractory anemia (SRA) 14%, refractory anemia with excess blast forms (RAEB) 31%, chromic myelomonocytic leukemia (CMML) 12% and refractory anemia with excess blast forms in transformation (RAEBT) 9%. Cytogenetic studies performed in 16 patients were abnormal in 5 (31%), all among patients with poor prognosis forms of the disorder. All patients had anemia; thrombopenia and neutropenia were more frequent in subtypes RAEB, CMML and RAEBT). Mean survival rate was 30 months, significantly greater in RA and SRA compared to the other groups. Infections and development of acute leukemia were the causes of death.

Actuarial Analysis↗

[Report of a case of Gaucher's disease in adult].

The authors report a case of Gaucher's disease in an adult. This is a rare disease due to the accumulation of a glucoceramide in the reticulo-endothelial cells and may remain for long clinically symptomless, as in this case. The diagnosis suggested by the biological disturbance, viz. moderate thrombopenia, hypergammaglobulinemia, increase in SGPT, was conformed by the presence of Gaucher's cells in the liver and in the bone marrow, and by the existence of an intraleukocytic glucosidase deficiency. The authors recall the clinical forms of this disease, and recent clinical trials.

Adult↗

[Radiation tolerance of partially irradiated liver in a multidisciplinary treatment for hepatoma].

Radiation tolerance of the partially irradiated liver was studied in eight patients with primary hepatoma treated by a multimodal approach. Seven patients were treated by transarterial embolization therapy (TAE) with Lipiodol-MMC, and two patients were treated by operation, combined with radiotherapy. Six patients had liver cirrhosis and the other one had renal dysfunction. Respiration-gated irradiation was employed to reduce a treatment volume for seven patients. Radiation portals were carefully tailored using the embolized Lipiodol or a metal clip inserted into the tumor as references. Two or three portals were used for each patient. The treatment volume ranged from 64 to 1400 cm3. The target dose ranged from 50.4 Gy to 81.0 Gy, from 73.5 to 108.6 in TDF. Liver function tests (GOT, GPT, LDH, ALP, ChE and total Bilirubin) were examined for 30 weeks after initiation of irradiation. Three patients showed abnormal value in more than 5 tests. Of these three patients, the hepatic hilum was included in the treatment volume in two, and the tumor progressed during the observation period in two. Leukopenia and thrombopenia were observed, but these values were not below 2000 and 40000/mm3, respectively, although the thrombocyte count before irradiation was below 100000/mm3 in 7 patients. AFP titers decreased after the treatment in six out of seven patients with abnormally elevated pretreatment titer. The survival period after staring irradiation was 6.5 to 25 months. "The volume dose" did not correlate well with the degree of the liver function aggravation.(ABSTRACT TRUNCATED AT 250 WORDS)

Carcinoma, Hepatocellular↗

[Factors influencing leukemic transformation in myelodysplastic syndrome].

Prognostic factors affecting the leukemic transformation were studied in 43 patients with myelodysplastic syndrome (MDS). Acute leukemia developed in 17 cases and it was nonlymphocytic leukemia in every case. No remission was achieved following antileukemic therapy and most of the cases proved to be true drug-resistant leukemia. Initial granulopenia, thrombopenia or anemia alone did not influence the occurrence of leukemic transformation but pancytopenia indicates bad prognosis. According to FAB classification especially refractory anemia with excess of blasts (RAEB) and RAEB in transformation (RAEB-T) were often followed by leukemic transformation. The granulocyte-macrophage progenitor cell (GM-CFC) content of bone marrow were also studied. The GM-CFC content was decreased in each patient. There was no correlation between GM-CFC number and leukemic transformation, the growth-pattern in agar-gel culture, however, turned out to have prognostic importance. Leukemic type of growth, namely always preceded leukemic transformation.

Antineoplastic Combined Chemotherapy Protocols↗

[A case of fatal graft-versus-host disease following blood transfusion in esophageal cancer documented by homozygous changes of HLA typing].

A 72 year-old Japanese male with esophageal cancer underwent esophagectomy. After seemingly uneventful recovery, he developed high fever on 11 post-operative day (POD), rashes over the whole body on 13 POD and leukopenia on 15 POD. On 22 POD, thrombopenia and parenchymal bleeding of lungs were noted. He died on 26 POD after progressive hypoxia and hypotension. HLA type of peripheral lymphocytes on him changed homozygously to that of the transfused fresh blood. Skin biopsy showed mild leukocyte infiltration in the epidermis and the dyskeratotic keratinocytes were associated with a contiguous lymphocyte, the so-called satellite cell necrosis. In the findings of autopsy, aplastic bone marrow and atrophied spleen, whose weight was 14g, were noted. Based on the clinical picture, skin biopsy and HLA study findings, we diagnosed this case as post-transfusion GVHD. We think that high age, operative injury and preoperative irradiation might be inducement to reveal post-transfusion GVHD in this case.

Aged↗

[D-penicillamine in rheumatoid arthritis : hematological incidents and accidents (author's transl)].

From literature data and their own experience, the authors comment hematological complications, related to the use of D-penicillamine, mainly in theumatoïd arthritis. Hypereosinophilia is more common than thrombopenia, but, both complications are usually benign. Anemia alone is very rare. Leukopenia appears in 6% of treated patients, but pancytopenia is rare. Leukopenia and pancytopenia are the most severe complications, even fatal in some cases. The safest dose of D-penicillamine seems to be between 600 and 900 mg per day, provided that, however, regular hematological controls may be achieved.

Anemia↗

[Anesthesia and intensive therapy of pregnant women with the HELLP syndrome].

The HELLP syndrome (hemolysis, elevated liver enzymes, low platelet count) is a severe complication of pre-eclampsia with high risk for mother and fetus. During the last 40 months 27 parturients met the diagnostic criteria for HELLP syndrome in the University Hospital of Kiel (Tables 1-3). In 24 cases cesarean section was performed. Fetal mortality was 17.2%. In 13 women an uneventful clinical course resulted, all other patients developed complications: renal insufficiency (11 cases), disseminated intravascular coagulation (DIC) (4), intracerebral hemorrhage (1), cerebrovascular ischemia (1), eclamptic convulsions (3), reoperation due to intra- or extra-abdominal hemorrhage (4), severe blood loss ex vagina following spontaneous delivery (1), and liver rupture (1). Despite these severe complications no maternal death was observed. DIC, intrauterine death, and a rapid increase in liver enzymes are considered to be serious prognostic factors that could help to identify high-risk patients. The following recommendations for therapy of parturients suffering from HELLP syndrome are given: epidural anesthesia is not an appropriate method in HELLP syndrome because of the risk of epidural hemorrhage due to thrombopenia. At the present time general anesthesia seems to be the method of choice. Inhalation anesthetics such as halothane, enflurane, or isoflurane should probably be omitted in view of the preexisting hepatopathy. The high risk and the unpredictable postpartum course strongly indicate intensive care for parturients with HELLP syndrome. Antihypertensive, antieclamptic therapy and prophylactic measures to avoid renal insufficiency or hemorrhage (e.g. early substitution of erythrocytes, thrombocytes, and coagulation factors) deserve special attention. Co-operation between obstetrician and anesthesiologist is essential to obtain optimal therapy for these high-risk patients.

Adult↗

[Combination radiotherapy and chemotherapy in the treatment of locally advanced adenocarcinoma of the pancreas. Experiences of the Gustave Roussy Institute].

Non-resectable pancreatic adenocarcinomas (PA) are of poor prognosis with median survival of 4-6 months. Radiotherapy (RT) and chemotherapy (CT) association are potential palliative treatments recently investigated. We have tested such an association in a pilot study. Twelve patients (pts) with non-resectable PA and localized tumors were treated by 2 cycles of CT (5-FU + adriamycin + cisplatinum) and then 2 or 3 split courses of RT (20 Gy/12 days and 8 fractions with a 16 day interval). CT was reintroduced, if initially active, for 3 cycles. Results were: 3 CR (11+, 13+, 16 months) for a response rate of 25%, 1 MR (4 months) and 5 stabilizations longer than 6 months. The 1 year survival was 56 +/- 15% with no patient surviving longer than 2 years. Tolerance was acceptable for RT and toxicity with CT was digestive (grade II) for all pts, leucopenia grade III for 3 pts and thrombopenia grade II for 2 pts. Two pts experienced digestive hemorrhage for anastomatic ulceration, responsible for death in one case. This pilot study confirms the transient efficacy of RT + CT association for non-resectable PA. However, the toxicity and treatment duration lead us to recommend other studies of less toxic association before initiation of randomized trials.

Actuarial Analysis↗

[Relay chemotherapy using continuous perfusion of cisplatin and fluoro-uracil in advanced cancer of the breast. Analysis of a series of 50 cases].

Fifty patients with advanced breast cancer (21 undergoing first and second stage palliative treatment: group 1, and 29 undergoing stage three or more: group 2), were included in a phase II trial with administration of a combination relay chemotherapy consisting of cisplatin (100 mg/m2/day) and fluorouracil (1,000 mg/m2/day), in continuous perfusion during 4 days, in cycles of five days repeated every three weeks (mean duration: 12 weeks). Toxicity was frequent and severe (a total of 17 treatments discontinued, and five deaths, 3 in group 1, 2 in group 2). The main manifestations of intolerance were threefold: haematological and leucopenia, in almost half of the patients, including 2 severe with 1 case of infectious complication and 4 thrombopenias requiring discontinuation of the treatment, including 2 with a severe haemorrhagic syndrome; cardiovascular, with three deaths due to heart failure; renal, most of the time laboratory tests disorders with 1 clinical syndrome. An objective response of more than fifty p. cent was obtained in five patients in group 1 (29.4%) and 3 patients in group 2 (11.1%); it lasted an average of 6.5 months and varied according to the locations: nodes (43%), liver (40%), pleuro-pulmonary (22%). Responses were obtained (13%) for lesions which resisted to previous chemotherapy. Five patients (14%) presented a functional improvement. The survival (mean = 4.8 months) was correlated, in group 1, to initial life conditions (p = 0.01) and was longer in group 1 for menopausal patients who had well tolerated the treatment (p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Antineoplastic Combined Chemotherapy Protocols↗

[Unusual causes of hemoperitoneum of genital origin].

Extra-uterine pregnancy is the most common emergency in gynaecology and obstetrics in the Hospital Centre of Libreville, and the diagnosis of blood in the peritoneal cavity is synonymous with extra-uterine pregnancy. All the same, when the authors reviewed 429 cases of haemoperitoneum 17 were shown not to be due to ectopic pregnancy. Ruptures of ovarian cysts and uterine perforation from illegal abortions are often found but more rarely, have been rupture in the blind horn of a bicornuate uterus, choriocarcinoma in the tube, tubal bilharzia and thrombopenia due to AIDS. It is essential to carry out histological examination for the differential diagnosis between an ovarian pregnancy and a ruptured cyst as well as choriocarcinoma or bilharzia. If it is not possible to find the site of the bleeding even after looking underneath the mesocolon, a search must be made for coagulation disorders due to a virus such as HIV.

Choriocarcinoma↗

[Blast crisis of chronic myeloid leukemia with positive Philadelphia chromosome: course and clinico-hematologic profile in 80 patients].

The major initial clinical, hematological and cytogenetical features of a series of 80 patients with blastic crisis (BC) in chronic myelocytic leukemia with positive Philadelphia chromosome (Ph) were evaluated, and also were their outcome and response to therapy. Mean age of patients was 45 years (SD: 14.3). Ten patients fulfilled the criteria for initial BC, and 14 had extramedullary blastic infiltration. In one third there was an acceleration phase before the development of BC. The mean leukocyte count was 69 (SD 75) X 10(9)/l. In 40% there was anemia with hemoglobin less than 90 g/l, and 37.5% had thrombopenia with less than 100 X 10(9) cells/l. In most patients, serum lactic dehydrogenase activity was increased, and in one fourth the index of granulocyte alkaline phosphatase was high. In 9 patients, blast cells had a lymphoid phenotype and in 47 (59%) cytogenetic abnormalities in addition to Ph chromosome were found, usually consisting of 8 trisomy, duplication of Ph chromosome, and the presence of a 17q isochromosome. The median survival of the series was 4.8 months. When analyzed as a time-dependent variable, the achievement of a favorable therapeutic response (found in 26% of patients) was associated with a longer survival.

Blast Crisis↗