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Plasmodium vivax malaria late-forms rarely exceed two years--the authors reported a late-form more than twenty years after a stay in endemic area. This late-form occurred in an immunocompromised patient with two terminal-stage neoplasia receiving radio, chimio corticotherapy associated with anemia and thrombopenia. Repeated-tests allowed the diagnostic.
Loss of physical performance is a universal problem of cancer patients undergoing chemotherapy. We postulated that this impairment can be partially prevented by aerobic exercise. In a randomized study, 33 cancer patients receiving high-dose chemotherapy followed by autologous peripheral blood stem cell transplantation (training group, T) performed an exercise program consisting of biking on an ergometer in the supine position after an interval-training pattern for 30 minutes daily during hospitalization. Patients in the control group (C, n = 37) did not train. Maximal physical performance was assessed with a treadmill test by admission and discharge. Physical performance of the two groups was not different on admission. The decrement in performance during hospitalization was 27% greater in the control group than in the training group (P = .05); this resulted in a significantly higher maximal physical performance at discharge in the trained patients (P = .04). Duration of neutropenia (P = .01) and thrombopenia (P = .06), severity of diarrhea (P = .04), severity of pain (P = .01), and duration of hospitalization (P = . 03) were reduced in the training group. We conclude that aerobic exercise can be safely carried out immediately after high-dose chemotherapy and can partially prevent loss of physical performance. Based on the potential significance of the observed outcomes, further studies are warranted to confirm our results.
We applied thermoradiotherapy combined with daily administration of low dose cisplatin (CDDP) to five patients with locally advanced laryngeal carcinoma. The total response rate (CR + PR) was 100% after irradiation of 30 or 40 Gy. One case showed CR, and the larynx could be preserved by adding a full dose of irradiation. CDDP administration was discontinued in two cases due to renal dysfunction or thrombopenia, but other cases tolerated the therapy without severe side effects. Total laryngectomy and bilateral neck dissection was carried out in four cases after irradiation of 30 or 40 Gy. Removed larynxes were prepared for light microscopic observations of the serial sections. One of the four specimens revealed a CR histologically. The combination of thermoradiotherapy with low dose CDDP showed a remarkable effect on reduction of tumor size and cytotoxicity of tumor cells. This might contribute to saving the larynx of patients with locally advanced laryngeal carcinoma.
Twenty-one cases of adverse reactions to mebeverine use were reported to the Inspectorate for Health Care in the Netherlands since 1978. In 12 patients (five men and seven women) this was an immunological hypersensitivity reaction. All patients recovered after drug withdrawal. The time between start and onset of symptoms varied from several minutes to 14 days. Most reactions consisted of urticaria or maculopapular rash, sometimes accompanied by fever, polyarthritis, thrombopenia or angioedema. In contradiction to the manufacturer's claims adverse reactions to the use of mebeverine do occur.
BACKGROUND: A pilot study of a new chemotherapy, the CIVIC regimen, was performed in 58 patients with metastatic breast carcinoma previously treated with chemotherapy with or without hormonal therapy (n = 41). Cisplatin, 20 mg/m2/day, was given (Days 1-5) every 21 days during a 1-hour intravenous (i.v.) infusion, and vinorelbine (VNB) was delivered at a dose of 6 mg i.v. bolus followed by VNB, 6 mg/m2/day, in continuous i.v. infusion (Days 1-5) every 21 days. METHODS: Fifty-eight patients were included in this trial between June 1992 and March 1994 (median age, 46.5 years; range, 28-69 years). The number of previous chemotherapy in the adjuvant or metastatic phase were: 1 in 9 patients, 2 in 33 patients, and > or = 3 in 16 patients. Forty-four and 12 patients, respectively, were previously treated in metastatic phase with regimens containing anthracyclines and paclitaxel. Overall, 210 cycles were given (median, 3 cycles; range, 1-6 cycles). RESULTS: Among the 58 patients assessable for tumor response to the CIVIC regimen, 24 patients (41%) (95% confidence interval, 28-54) achieved an objective response (complete response or partial response) with 2 complete response (3%) and 22 partial response (38%). The median time to response was 11 weeks (range, 4-16 weeks). The median survival time from the initiation of the CIVIC regimen was 9.2 months (range, 0-45 months). The response rate was 43% (19 of 44 patients) in patients refractory to anthracyclines and 58% (7 of 12 patients) in patients with disease progression after treatment with anthracyclines and paclitaxel. Myelosuppression was the most frequent side effect. World Health Organization Grade 3 neutropenia occurred in 8 of 58 patients (14%) and in 41 of 210 cycles (20%), Grade 4 neutropenia occurred in 37 of 58 patients (64%) and in 63 of 210 cycles (30%), and Grade 3 and 4 thrombopenia occurred in 7 of 58 patients (12%) and in 9 of 210 cycles (4%). Grade 2 peripheral neuropathy was observed in 6 of 58 patients (10%) and in 12 of 210 cycles (6%), and Grade 3 peripheral neuropathy was observed in 3 of 58 patients (5%) and in 4 of 210 cycles (2%). The risk of Grade 2-3 neuropathy was significantly higher after the fourth chemotherapy cycle (14 of 23 patients vs. 3 of 35 patients: P = 0.00002). CONCLUSIONS: The CIVIC regimen is effective and has acceptable tolerance in patients with metastatic breast carcinoma refractory to previous anthracycline- and/or paclitaxel-containing chemotherapy. Four cycles were found to provide the best toxicity-efficacy ratio.
It is not known whether frequent platelet donations provoke the platelet precount of the donor to rise or to decline. Therefore, with regard to the maximally possible safety of our donors we looked back onto the platelet counts of platelet donors who had given their platelets at constant 2-week intervals. Even frequent plateletphereses at 2-week intervals do not provoke thrombocytosis or thrombopenia for donors with normal platelet counts (> 200/nl, < 400/nl). Moreover, our donors appeared to regulate their platelet counts in an 'intelligent' manner.
The aim of the study was to determine the fetal and neonatal outcomes of pregnancies conceived during the inactive phase of systemic lupus erythematosus (SLE). Fetal and neonatal outcomes in 75 pregnancies of 33 patients with SLE were analyzed. In 19 patients (57.6%) the SLE also had hematological autoimmune presentations prior to gestation, such as anemia, thrombopenia, garnulocytopenia, and antiphospholipid antibody and/or lupus anticoagulant (APA). Out of 75 pregnancies, 19 elective terminations were carried out because the disease was active or for non-medical reasons. The adverse fetal outcomes of those 56 pregnancies which occurred during the inactive phase were compared with those of the control patients. In SLE, the rates of spontaneous abortions (46.4%) and newborns with low (< 2500 gr) birthweight (36.7%) were found to increase roughly three times that of the controls and the perinatal fetal loss (16.7%) also increased significantly as compared with the control group (28.5 per thousand). APA noted at any time before pregnancy increased the low birthweight rate (75%) six fold and the perinatal loss (33.3%) more than ten fold but did not affect the rate of spontaneous abortions. Any kind of hemocytopenias without APA, noted before pregnancy did not worsen the fetal outcome in SLE. Neonatal lupus was diagnosed in 2 out of the 30 newborns. Our results suggest that among the hematologic manifestations of SLE presenting before pregnancy, APA can predict the high risks of low birthweight and perinatal fetal loss as opposed to hemocytopenias.
UNLABELLED: We report a series of 27 patients included on the basis of either thrombotic microangiopathy (TMA) at renal histology (13 cases) or, in the absence of histology, non-immunological hemolytic anemia with schizocytes and thrombopenia (14 cas). The etiopathogenic treatment consisted in the administration of antiagregating agents (in all patients except 3 of group I because of the severity of thrombopenic), corticosteroids (1 case), intravenous immunoglobulins (2 cases) fresh frozen plasma (FFP) without plasma exchange (PE) in 7 cases and PE with FFP in 13 patients. According to the 6 months outcome, 4 groups were considered I: death due to neurological damage; II: chronic hemodialysis; III: partial renal recovery; IV: complete renal recovery. COMMENTS AND CONCLUSIONS: a/Patients with neurological complications have poor prognosis in spite of minor renal involvement and use of PE whose indication is validated in these cases. b/When renal involvement predominates, accelerated hypertension is linked to arteriolar or mixte type of TMA, exposes to an increased risk of hemorrhagic complications of the renal biopsy (4 out fo 5) which questions the usefulness of such biopsy (group II). c/TMA may precede cancer. It has per se a favorable outcome even when metastases are already present, warranting aggressive treatment.
A rare SLE patient with central nervous system involvement (CNS-SLE) who relapsed presenting new symptoms associated with the development of serum anti-Sm antibody and was then successfully treated with cyclophosphamide (CY) pulse therapy is presented here. A 47-years old housewife was admitted to Kushiro City General Hospital because of fever, limb erythema and drowsy consciousness in September 1995. On the basis of convulsion, proteinuria, leukopenia, thrombopenia, serum positive tests for both anti-nuclear antibody and anti-SSA antibody and low complement levels, as well as elevations of IgG index and IL-6 in the cerebrospinal fluid (CSF), she was diagnosed as having CNS-SLE. Serum tests for anti CL-beta 2 GPI antibody and lupus anticoaglant was negative. Serum test for HBs antigen was positive. She was treated successfully with methylprednisolone (mPSL) pulse therapy and plasma exchange (PE). Prednisolone was gradually tapered to the dosage of 17.5 mg per day and she was discharged in April 1996. She was re-admitted because of fever, an exacerbation of skin eruption and arthralgia in October 1996. Serum anti-Sm antibody was found to be positive. mPSL pulse therapy was not effective. On the basis of hallucination and elevations of IgG index and IL-6 in the CSF, a diagnosis of relapsed CNS-SLE was made. However the level of IFN-alpha in the CSF was normal. Although PE was not effective, CY pulse therapy was markedly effective.
INTRODUCTION: Toxoplasma gondii is a ubiquitous parasite of all species of mammals and birds (1). Most often the infection in the immunocompetent persons is asymptomatic. Symptoms (if present) are usually mild and self-limited. Infection in the fetus and immunodeficient patients may lead up to clinically severe and often fatal toxoplasmosis (2). ETIOLOGY: Toxoplasma exists in three forms: oocysts, tissue cysts and tachyzoites. The definitive hosts of Toxoplasma are members of the cat family. They shed unsporulated oocysts in the feces. After sporulation oocysts become infectious. Tachyzoites are crescent-shaped forms responsible for manifestations of acute Toxoplasma infection in the intermediate hosts (6,7). Cysts are formed, particularly in brain, heart muscle and skeletal muscles. The cyst forms of the parasite are seen in the latent stage of the infection. Postnatally acquired toxoplasmosis is a consequence of infection from cysts (by ingestion of undercooked meat of infected animals), oocysts (by ingestion of soil, fruits, vegetables contaminated by cat feces) and tachyzoites (by blood transfusion). Congenital Toxoplasma infection causes congenital toxoplasmosis. PATHOGENESIS: Some authors represented the concept that latent (chronic) infection with Toxoplasma during pregnancy can result in congenital infection in the offspring (8-11). Now it is generally agreed that congenital transmission of Toxoplasma occurs only when the infection is acquired during gestation (6,7, 12-16). More than half of the fetuses escape infection, one-third are definitely infected, and the infection is more often subclinical than clinically obvious (15). The fetus is infected hematogenously from inflammatory foci in the placenta formed during parasitemia in the mother. CLINICAL MANIFESTATIONS: Approximately 75% of congenitally infected newborns are asymptomatic. Wilson's study indicates that nearly all such children will develop adverse sequelae (neurologic, intellectual, audiologic and ophthalmologic) 21). Severe forms of congenital toxoplasmosis occur only in 10% of infected offsprings. Clinical manifestations of congenital toxoplasmosis are different. Clinical findings in patients with congenital toxoplasmosis may include: chorioretinitis and other ocular findings, central nervous system abnormalities (such as microcephaly, hydrocephalus, encephalomyelitis, seizures and mental retardation), icterus, hepatosplenomegaly, rash, anemia, erythroblastosis, thrombopenia. INCIDENCE: Incidence of human congenital toxoplasmosis is different in different countries. The incidence in Britain is 0.6 subclinical infection and 0.09 severe illnesses per 1000 births (22). The incidence in USA is between 1/1000 and 1/8000 live births (23). In France the incidence is 1/2000. In Slovenia the incidence is 2.3 cases per 1000 births (25). DIAGNOSIS: Diagnostic methods are: 1. Isolation of the parasite from the placenta, blood, body fluids (by inoculation of specimens into mice or tissue cultures). 2. Histologically by demonstration of tachyzoites in tissue sections or smears of body fluids. 3. Serologic diagnosis. The most important diagnostic methods are serologic tests. For diagnosis of congenital toxoplasmosis determination of IgM antibody (in the serum of newborn infant) has the greatest importance. The fetus is able to produce IgM specific antibody. The presence of IgM antibodies in serum obtained from the neonate is an evidence of fetus infection in utero. Maternal IgM antibodies do not pass the placenta. IgM antibodies may be demonstrable by indirect fluorescent antibody test (IgM-IFA), enzyme linked immunosorbent assay (IgM-ELISA), double sendwich IgM enzyme-linked immunosorbent assay (DS-IgM-ELISA), IgM immunosorbent agglutination assay (IgM-ISAGA) and reversed enzyme immunoassay (REI). For diagnosis of congenital toxoplasmosis the next tests are also applied: Sabin-Feldman Dye test, indirect fluorescent antibody test for IgG antibodies (IgG-IFA) and enzyme
The efficacy and safety of TAT-59 (miproxifene phospate) were compared with tamoxifen citrate (TAM) in ER-positive or ER-unknown patients with advanced or recurrent breast cancer, using the double-blind method. TAT-59 and TAM were both given 20 mg/body orally for over 12 weeks in daily doses. Eligible cases were 93 in the TAT-59 group and 102 patients in the TAM group. The response rate was shown to be 30.1% (28/93) in the TAT-59 group and 26.5% (27/102) in the TAM group. Statistical equivalence between both treatments was proven at 90% confidence interval (-8.5% < or =, < or = 12.8%). Adverse reactions observed in the patients receiving TAT-59 were hot flush, nausea and vomiting, sweating, anorexia, abnormal values in liver function tests, and anemia, showing no differences from the TAM group. Leukopenia (4.9%) and thrombopenia (2.9%) reactions were found only in the TAM group. Two patients in the TAT-59 group and three in the TAM group discontinued treatment due to adverse reactions. However, these adverse reactions were reversible in both groups. In conclusion, TAT-59 was showed comparable efficacy and safety with TAM in ER-positive or ER-unknown patients with advanced or recurrent breast cancer.
BACKGROUND: Various skin and mucosal reactions can be observed after administration of quinidine derivatives. CASE REPORT: A patient who was taking Natisédine (quinidine phenylethyl barbiturate) intermittently and at reintroduction developed a papulopurpuric eruption (without thrombopenia) producing extensive centrifugal annular infiltration and central healing which regressed approximately one week after drug withdrawal. This eruption was associated with moderate 24 h proteinuria. The clinical aspect was that of vasculitis purpura as confirmed histology. Direct immunofluorescence only demonstrated C3 deposits in the vessel walls of the superficial dermis. The quinidine moiety of this drug (currently removed from the formulation) appears to be the responsible agent (imputability score: 13 B3). DISCUSSION: Thrombopenic purpura by synthesis of anti-platelet antibodies induced by quinidine derivatives is well known. Inversely, cases of non-thrombopenic purpura imputable to these same derivatives is uncommon (7 reported cases). The pathophysiological mechanisms involved might be similar (antigenic similarity between the platelet surface and endothelium).
A significant link between 5-fluorouracil (5FU) plasma concentration and its therapeutic activity has been demonstrated in colon and head and neck cancer patients for 5FU used as a continuous infusion. Dose adjustment based on pharmacokinetic follow-up has been proposed to decrease hematological and digestive toxicities, but the clinical impact of this approach has not yet been demonstrated. A randomized multicentric study was conducted to evaluate the clinical interest of 5FU dose adaptation guided by pharmacokinetics. One hundred twenty-two head and neck cancer patients were randomly assigned to receive induction chemotherapy with cisplatin (100 mg/m2, day 1) and 5FU (96-h continuous infusion), either at standard dose (St-arm; 4 g/m2) or at a dose adjusted according to the 5FU area under the curve (AUC0-48h; PK-arm). In total, 106 patients were evaluable for toxicity and response. In the PK-arm (n = 49), 5FU doses and area under the curve were significantly reduced during cycle 2 and cycle 3 (P < 0.001) as compared with the St-arm (n = 57). Grade 3-4 neutropenia and thrombopenia were significantly more frequent in the St-arm as compared with the PK-arm (17.5% versus 7.6%, respectively; P = 0.013). No grade 3-4 mucositis occurred in the PK-arm, whereas 5.1% was observed in the St-arm (P < 0.01). The objective response rate was comparable in the two treatment arms: 77.2% in the St-arm versus 81.7% in the PK-arm. The present study is the first to demonstrate, in a randomized design, the clinical interest of an individual 5FU dose adaptation based on pharmacokinetic survey, in terms of therapeutic index improvement.
Fourty-six patients (41 evaluable) were treated in second line chemotherapy of metastatic breast cancer (MBC) by an association of mitomycin (M), vinorelbine (V) (M 8 mg/m2 D1, V 25 mg/m2 D1 and DI 8 every 4 weeks). Median age was 58 years (36-78), median performance status 1 (0-3). Thirty-seven per cent of the tumors were estrogen receptors positive and 17% progesterone receptors positive.eventeen patients received an adjuvant chemotherapy and 39 a first line chemotherapy with anthracyclin (A). The median number of metastatic sites was 2 (1-4) and 27 patients (67%) had visceral metastases. Twelve patients were refractory to anthracyclins and 5 resistant. No toxic death nor hemolytic uremic syndrom were observed.even (3,7%) febrile neutropenias happened responsible for 4 hospitalizations. A grade 3 or 4 neutropenia was noted in 34% of the cycles but no other clinic toxicity nor grade 3 or 4 thrombopenia. The rate of objective response (OR) was 37,5% with 2 complete responses (CR) and 13 partial responses (PR).even patients had stable disease and 18 progressed. The rate of hepatic OR was 31%. Five (40%) A-refractory patients responded but no resistant patient. Median OR time was 10 weeks (8-12) and median OR duration was 5 months (3-6). Median survival was 11,5 months. MV association is well tolerated and effective in second line chemotherapy for MBC even with hepatic metastasis and in patients refractory to anthracyclins.
Fourty-six patients (41 evaluable) were treated in second line chemotherapy of metastatic breast cancer (MBC) by an association of mitomycin (M), vinorelbine (V) (M 8 mg/m2 D1, V 25 mg/m2 D1 and DI 8 every 4 weeks). Median age was 58 years (36-78), median performance status 1 (0-3). Thirty-seven per cent of the tumors were estrogen receptors positive and 17% progesterone receptors positive. Seventeen patients received an adjuvant chemotherapy and 39 a first line chemotherapy with anthracycline (A). The median number of metastatic sites was 2 (1-4) and 27 patients (67%) had visceral metastases. Twelve patients were refractory to anthracyclines and 5 resistant. No toxic death nor hemolytic uremic syndrome were observed. Seven (3.7%) febrile neutropenias happened responsible for 4 hospitalizations. A grade 3 or 4 neutropenia was noted in 34% of the cycles but no other clinic toxicity nor grade 3 or 4 thrombopenia. The rate of objective response (OR) was 37.5% with 2 complete responses (CR) and 13 partial responses (PR). Seven patients had stable disease and 18 progressed. The rate of hepatic OR was 31%. Five (40%) A-refractory patients responded but no resistant patient. Median OR time was 10 weeks (8-12) and median OR duration was 5 months (3-6). Median survival was 11.5 months. MV association is well tolerated and effective in second line chemotherapy for MBC even with hepatic metastasis and in patients refractory to anthracyclines.
In the palliative treatment of advanced SCLC and NSCLC there is a big need for effective and well tolerable drugs. Bendamustin is an alcylatic agent which had shown activity in the treatment of Non Hodgkin- and Hodgkin-Lymphoma as well as in the treatment of solid tumors like Mamma-Carcinoma and Colorectal-Carcinoma. We treated 21 patients with NSCLC (5 pat. Stad. III b, 16 pat. Stad. IV) and 22 pat. with Extensive Disease SCLC with Bendamustin 70 mg/m2 i.v., day 1-4 (q.28 days). We observed a response rate of 40.9% in the patients with SCLC (9 PR/40.9%), (0 CR) and no response in the patients with NSCLC. Hematologic toxicity in both groups was mild (Leucopenia WHO 1 + 2: 13 pat./30.2%, WHO 3: 2 pat./4.6%; Anemia WHO 1 + 2: 13 pat./30.2%, WHO 3: 1 pat./2.4%; Thrombopenia WHO 1 + 2: 4 pat./9.6%, WHO 3: 1/2.4%). Non Hematologic toxicity consisting of Nausea/Vomiting (WHO 2 + 3:13 pat./30.2%), Diarrhea (WHO 2 + 3:3 pat./7%), Obstipation (WHO 1 + 2: 2 pat./4.6%), Fever (WHO 1 + 2: 9 pat./20.9%) and Alopecia (WHO 1 + 2: 13 pat./31.7%, WHO 3: 1 pat./2.4%) was well tolerable. Cardiac Arrhythmias occurred in 7 pat./16.3% and PNP in 2 pat./4.6%. Treatment had to be stopped in one patient because of an allergic skin reaction. Bendamustin is a well tolerable cytostatic drug with a remarkable activity in advanced SCLC which is comparable to other well known agents in the treatment of this disease. Because of the good toxicity profile a combination with other compounds might be feasible. In advanced NSCLC Bendamustin showed no activity.
OBJECTIVE: Study of hemostatic disorders during eclampsia, their risk factors, maternal complications and associated mortality. METHODS: Retrospective study concerning 106 cases of severe eclampsia treated in intensive care between September 1992 and December 96. Patients with or without hemostatic disorders were compared for laboratory findings, maternal complications and mortality. RESULTS: Forty patients had hemostasis disorders as follows: isolated thrombopenia in 19 cases, disseminated intravascular coagulation (DIC) in 5 cases, Hellp syndrome associated to DIC in 7 cases and Hellp syndrome in 9 cases. Hemostasis disorders were associated to maternal advanced age, but not with gestational age or blood pressure in admission or time of convulsions. Complications and mortality associated with hemostasis disorders were more frequent compared to patients without hemostasis disorders. Among the 17 deaths of our series, 10 had hemostasis disorders. CONCLUSION: Hemostasis disorders were prognosis factors in eclampsia requiring systematic laboratory tests at admission and immediate delivery.
OBJECTIVE: To study the variations of type II soluble receptors for tumor necrosis factor (sR-TNF) in patients with systemic lupus erythematosus and investigate their use in the clinical setting. PATIENTS AND METHODS: Twenty-six patients with systemic lupus were followed for a mean 3 years. sR-TNF and other immunological parameters (C reactive protein, anti-DNA antibodies, C3 and C4 complement fractions, soluble receptors for interleukin 2) were measured in sera at different points of the disease course. The systemic lupus activity measure (SLAM) was determined at each point, and confronted with the biology results. The study was cross sectional for the group and longitudinal for the patients. RESULTS: sR-TNF was the immunological parameter which correlated best with SLAM. It also correlated with sedimentation rate, C reactive protein, thrombopenia, anemia, creatinine level, anti-DNA antibodies and sR-IL2. The longitudinal study pointed out however that this finding is not consistent for each patient. CONCLUSION: A rise in sR-TNF related to systemic lupus activity but is of limited practical interest for individual patient follow-up.