Predictors of functional capacity as measured by the Glittre activities of daily living test in women with rheumatoid arthritis.

Although pulmonary involvement is the most common extra-articular manifestation of rheumatoid arthritis (RA), traditional pulmonary function tests (PFTs) do not show a good correlation with the field tests usually performed in these patients. In recent decades, measurement of ventilation distribution heterogeneity through the nitrogen single-breath washout (N2SBW) test and evaluation of functional capacity during exercise using the Glittre activities of daily living test (GA-T) have been increasingly used. Therefore, the objective of this study was to evaluate predictors of GA-T outcomes in women with RA considering demographic, anthropometric, clinical, functional variables, and chest computed tomography (CT) findings. Forty-three women with RA underwent the GA-T, the N2SBW test, spirometry, measurement of the diffusing capacity for carbon monoxide (DLco), measurement of respiratory muscle strength, and evaluation of physical function of the lower and upper limbs through the Health Assessment Questionnaire Disability Index (HAQ-DI). Chest CT scans were analyzed retrospectively. The GA-T time showed significant correlations with the DLco (rs=-0.397, P=0.008), forced vital capacity/DLco (rs=0.307, P=0.044), phase III slope of the N2SBW test (SIIIN2, rs=0.644, P<0.0001), and the HAQ-DI (rs=0.482, P=0.001). Disease extent as assessed by chest CT was associated with the GA-T time. On multiple regression analysis, the SIIIN2 and HAQ-DI were the only predictors of the GA-T time, explaining 40% of its variability. Thus, ventilation distribution heterogeneity and worse physical function substantially explain the variability in GA-T time in women with RA and varying extents of disease on chest CT.

Predictors of functional capacity as measured by the Glittre activities of daily living test in women with rheumatoid arthritis

Although pulmonary involvement is the most common extra-articular manifestation of rheumatoid arthritis (RA), traditional pulmonary function tests (PFTs) do not show a good correlation with the field tests usually performed in these patients. In recent decades, measurement of ventilation distribution heterogeneity through the nitrogen single-breath washout (N2SBW) test and evaluation of functional capacity during exercise using the Glittre activities of daily living test (GA-T) have been increasingly used. Therefore, the objective of this study was to evaluate predictors of GA-T outcomes in women with RA considering demographic, anthropometric, clinical, functional variables, and chest computed tomography (CT) findings. Forty-three women with RA underwent the GA-T, the N2SBW test, spirometry, measurement of the diffusing capacity for carbon monoxide (DLco), measurement of respiratory muscle strength, and evaluation of physical function of the lower and upper limbs through the Health Assessment Questionnaire Disability Index (HAQ-DI). Chest CT scans were analyzed retrospectively. The GA-T time showed significant correlations with the DLco (rs=-0.397, P=0.008), forced vital capacity/DLco (rs=0.307, P=0.044), phase III slope of the N2SBW test (SIIIN2, rs=0.644, P<0.0001), and the HAQ-DI (rs=0.482, P=0.001). Disease extent as assessed by chest CT was associated with the GA-T time. On multiple regression analysis, the SIIIN2 and HAQ-DI were the only predictors of the GA-T time, explaining 40% of its variability. Thus, ventilation distribution heterogeneity and worse physical function substantially explain the variability in GA-T time in women with RA and varying extents of disease on chest CT.

Enhanced brain expression of genes related to cell proliferation and neural differentiation is associated with cortisol receptor expression in fishes.

Stress enhances or inhibits neurogenesis in mammals and some fish species. The link between the two processes is still unclear. Most studies have been performed in very specific stressful or altered environments. Despite the known inter-individual divergence in coping abilities within populations, the relationship between the stress axis and neurogenesis has never been addressed in unstressed individuals. Here we correlate brain expression of the pcna (proliferating cell nuclear antigen) and neurod1 (neurogenic differentiation factor 1) genes, two markers of neurogenesis, with transcripts of cortisol receptors in three fish species living in very distinct environments. Within the three species, individuals with the highest expression of neurogenesis genes were also those that expressed the high levels of cortisol receptors. Based on these correlations and the hypothesis that mRNA levels are proxies of protein levels, we hypothesize that within unstressed animals, individuals sensitive to cortisol perceive a similar environment to be more stimulating, leading to increased neurogenesis. Although it is difficult to determine whether it is sensitivity to cortisol that affects neurogenesis capacities or the opposite, the proposed pathway is a potentially fruitful avenue that warrants further mechanistic experiments.

ASSESSING THE EFFICACY OF NITAZOXANIDE IN TREATMENT OF CRYPTOSPORIDIOSIS USING PCR EXAMINATION.

Cryptosporidiosis is a gastrointestinal disease of humans and other animals, caused by the genus Cryptosporidium spp. It causes persistent diarrhea and malnutrition and is associated with increased mortality. This study aimed to assess the efficacy of nitazoxanide (NTZ) on clearing the oocysts of C. parvum among infected children using both parasitological and PCR techniques.120 children (1-12y) shedding Cryptosporidium oocysts in their stools were enrolled in the study. They were classified on the basis of the immune status into immunocompetent (ICT) and immunocompromised (ICZ) groups. Each group were subdivided into two groups one of them received'NTZ, and the other received placebo. The efficacy of nitazoxanide was assessed clinically, parasitologically and by nested-PCR technique. At the end of 1st week of treatment, 80% of ICT/ NTZ group and 40% of ICT/ placebo group were free by PCR and 83.3% & 20% respectively were microscopically free. While at the end of 4th week, 93.3% of ICT/NTZ group and 43.3% of ICT/ placebo group were free by PCR and 96.7% & 26.7% respectively were microscopically free. Among the ICZ group, diarrhea was resolved in most patients receiving NTZ within 21 to 28 days of treatment initiation While, it resolved in the ICT group receiving NTZ in most patients within 3 to 5 days of treatment initiation.

Biased sex ratio and niche restriction in Baruscapillaria obsignata (Madsen 1945) (Nematoda, Capillariidae) from Columba livia (Aves, Columbidae).

In the present study populations of the avian nematode species Baruscapillaria obsignata are described from Columba livia. Male and female individuals were obtained from 27 birds, fixed in alcohol/formalin/acetic acid (AFA) and preserved in 70% ethanol. Nematodes were identified and then counted under a stereoscopic microscope. Baruscapillaria obsignata were much more frequent in the anterior third of the small intestine, and females were more abundant than males in all infra populations. The prevalence was 55.6%, mean intensity was 11.8 (median 11.0; range 1-31) and abundance 6.56. In the present study, we observed an aggregated distribution of parasite infrapopulations, as demonstrated by the value of the exponent of the negative binomial distribution, K = 0.2773; by the discrepancy index, D = 0.656 and by the variance/mean ratio, 12.44. The female/male sex ratios found in all infrapopulations were always greater than 1, showing a bias in favour of female abundance. This tendency was especially marked in infrapopulations containing fewer individuals. The sizes of infrapopulations ranged from 5 to 31 individuals. The mean sex ratio observed was 2.69 ± 3.28 (median 1.83; range 0-11). In infrapopulations with 5-15 individuals, the sex ratios observed varied from 2.6 to 11, while in those with 17-31 individuals, the sex ratios were lower, ranging from 1.7 to 2.4. There was a negative correlation between the intensity of infection and the sex ratio of infrapopulations. Results are discussed in terms of possible factors influencing the processes that lead to niche restriction and biased sex ratios in parasite infrapopulations.

Avaliação da atividade moluscicida do látex de três espécies de Euphorbia (Euphorbiaceae) sobre Leptinaria unilamellata d'Orbigny, 1835 (Gastropoda - Subulinidae) / Assessment of moluscicidal activity of the latex of three Euphorbia (Euphorbiaceae) species on Leptinaria unilamellata d'Obigny 1835 (Gastropoda - Subulinidae)

Gastrópodes pulmonados terrestres podem atuar como hospedeiros intermediários de helmintos. Os primeiros registros do controle químico desses invertebrados datam do início do século XX e as substâncias utilizadas eram toxinas inespecíficas já empregadas no controle de outras pragas. Moluscicidas sintéticos apresentam limitações técnicas que estimularam a busca de substitutos naturais. Dentre as várias espécies vegetais com atividade moluscicida, Euphorbia cotinifolia L., Euphorbia milii des Moul. var. splendens (Bojer ex Hook) Ursch & Leandri e Euphorbia tirucalli L. despertam atenção pelos excelentes resultados obtidos sobre moluscos aquáticos. Contudo, estudos sobre a atividade de plantas moluscicidas em moluscos terrestres são pouco comuns, apesar de sua grande importância parasitológica e agrícola. As semelhanças anatomo-fisiológicas entre espécies de moluscos aquáticos e terrestres sugerem que estratégias de controle químico possam ter eficiência semelhante para os dois grupos de invertebrados. Com base nessa hipótese, o presente trabalho teve como objetivo avaliar a atividade moluscicida do látex de três espécies do gênero Euphorbia sobre Leptinaria unilamellata d'Orbigny, 1835, gastrópode terrestre descrito como hospedeiro intermediário de helmintos trematódeos digenéticos que parasitam animais domésticos. Destas E. milii var. splendens apresentou efeito moluscicida elevado sobre L. unilamellata, 100 por cento até uma diluição de 1:800, já nos primeiros minutos após a aplicação. Embora citadas na literatura como tóxicas para moluscos aquáticos, E. cotinifolia e E. tirucalli não exibiram atividade moluscicida sobre L. unilamellata. Os resultados do presente estudo indicam que o látex de E. milii var. splendens pode se constituir em uma estratégia viável de controle químico de moluscos terrestres.

Pulmonate terrestrial gastropods can be intermediate hosts for helminthes. The first records of chemically controlling these invertebrates date back to the beginning of the 20th century. The substances used were unspecific toxins which were already used for controlling other pests. Synthetic molluscicides have technical limitations that stimulated a search for natural substitutes. Among the many vegetal species that have molluscicidal activity, Euphorbia cotinifolia L., Euphorbia milii des Moul. var. splendens (Bojer ex Hook) Ursch & Leandri and Euphorbia tirucalli L. call attention because of the excellent results that have been obtained when they are used on aquatic mollusks. However, studies on the activity of molluscicidal plants on terrestrial mollusks are rare, in spite of its great importance in controlling parasites and to agriculture. Anatomical and physiological similarities among species of aquatic and terrestrial mollusks suggest that chemical control strategies can be effective on both groups of invertebrates. Based on this hypothesis, we assessed the molluscicidal activity of the latex of three species of the genus Euphorbia on the terrestrial gastropod Leptinaria unilamellata d'Orbigny, 1835, described as an intermediate host of digenetic trematode helminths that parasitize domestic animals. E. milii var. splendens had the highest molluscicidal effect on L. unilamellata, being 100 percent lethal in concentrations up to 1:1800 in the first minutes after application. Although E. cotinifolia and E. tirucalli have been cited in the literature as toxic to aquatic mollusks, they did not have molluscicidal activity on L. unilamellata. The results of our study indicate that the latex of E. milii var. splendens may be a viable strategy for the chemical control of terrestrial mollusks.

Occurrence Angiostrongylus vasorum (Baillet, 1866) (Nematoda, Angiostrongylidae) in Cerdocyon thous Linnaeus, 1766 (Carnivora, Canidae) in Minas Gerais State Brazil

Registrou-se a ocorrência de A. vasorum em C. thous no Estado de Minas Gerais, e estudaram-se aspectos de sua ecologia nessa população de hospedeiros. A partir da necropsia de seis espécimes, observou-se a presença de A. vasorum nos pulmões e átrio direito de C. thous. No total foram coletados 24 espécimes de A. vasorum, com prevalência de 50 por cento, abundância média de 4±4,47, intensidade média de 8±3,00 e razão sexual (machos/fêmeas) de 1:1,19. As infrapopulações de A. vasorum apresentaram padrão de distribuição espacial agregado (ID=5,70 e K=0,355). Este é o primeiro registro de A. vasorum em C. thous no estado, descrito no município de Juiz de Fora

A retrospective analysis of the outcome of patients with recurrent and/or metastatic squamous cell carcinoma of the head and neck refractory to a platinum-based chemotherapy.

AIMS: Recurrent and/or metastatic squamous cell carcinoma of the head and neck (SCCHN) develops in around 72,000 people in Europe every year. Treatment options are limited, mainly consisting of platinum-based palliative chemotherapy, with median overall survival times of only 6-8 months. No standard second-line treatment after progression on platinum-based chemotherapy is available. Few data have reported the efficacy of these treatments and the outcome of the patients. In an effort to generate such data, this retrospective study analysed clinical records from 151 patients with SCCHN refractory to platinum-based chemotherapy treated between 1990 and 2000 at seven different centres around Europe. MATERIALS AND METHODS: Most patients (45%) received only best supportive care (BSC), and had a median survival of 56 days. A total of 28.5% of the patients received second-line chemotherapies: 16.6% radiotherapy and 9.9% chemoradiotherapy. RESULTS: No objective response was observed with the various second-line chemotherapies. The overall median survival was 103 days (95% confidence interval [CI]: 77-126 days) for the whole cohort. The overall objective response rate (ORR) to second-line treatment in this population was calculated to be 2.6%. CONCLUSION: These results highlight the need for additional treatment options for this disease. Similar, if not superior, response rates have already been observed in initial clinical studies of novel, targeted anti-cancer agents.

Detection of anti-Fasciola isotypes among patients with fascioliasis before and after treatment with Mirazid.

Stool examination using modified Kato thick smear method was performed to detect Fasciola eggs and other parasites. Abdominal pain was the major presenting symptom (87.7%) followed by pallor (83.3%) and fever (16.7%). Anaemia and hepatomegaly were recorded in 77.7% of patients compared to 27.7% with splenomegaly. Abdominal ultrasonography revealed hepatomegaly and common bile duct dilatation in 77.7% of patients. Moreover, 5 cases showed diagnostic. Olympic game rings All patients had positive IgG4 levels, 55 cases were positive for specific total IgG and IgG1, whereas, only 24 cases had positive IgG2 levels (26.6%). All negative control group showed no cross reactions. On the other hand, ELISA detecting IgG4 showed the highest specificity (95%), followed by IgG2 (85%) and the least specific test was obtained with detection of IgG (70%) and IgG1 (65%). One month after treatment, 91.1% of patients (82/90) were completely cured and even after another two months follow-up. In completely cured patients none of anti-Fasciola isotypes was significantly changed. So, detection of anti-Fasciola isotypes especially IgG4 is very specific for the accurate diagnosis of human fascioliasis.

[Double-blinded controlled study comparing clodronate versus placebo in patients with breast cancer bone metastases]. / Essai comparatif randomisé en double aveugle clodronate oral 1 600 mg/j versus placebo chez des patientes avec métastases osseuses de cancer du sein.

One hundred forty-four patients with breast cancer and osteolytic bone metastases were randomized to receive either oral clodronate 1,600 mg/d (73 patients) or placebo (71 patients), in addition to either chemotherapy or hormonal therapy, for up to 12 months. Patients were withdrawn from the study when the 12 months of treatment had been achieve or a new bone event occurred, which was defined as: hypercalcemia (> 3 mmol/l), increase in, or onset of new bone pain due to metastases, requirement of radiotherapy for bone pain relief, pathological fractures (including vertebral collapse, spinal cord compression) or death due to bone metastases. Patients are well balanced according to age, performance status, bone condition, except for fractures, more frequent in the clodronate group (25% vs 12%). Of the 137 evaluable patients, 69 received oral clodronate and 68 placebo. Clodronate significantly delayed the median time to onset of new bone events compared to placebo, respectively 244 days and 180 days (p = 0.05). Hypercalcemia did not occur in the clodronate group but was observed in four placebo-treated patients. Clodronate-treated patients had a significant reduction in pain intensity compared to placebo (p = 0.01; measured using a visual pain scale) and significantly fewer patients receiving clodronate required analgesics (p = 0.02). The evaluation of global efficacy by physicians and patients indicated that clodronate was more efficacious than placebo (respectively p = 0.02 and p = 0.01). No significant difference in incidence of adverse effects was observed between the two groups. Clodronate therapy significantly delayed the occurrence of new bone events in these patients with bone metastases from breast cancer and adds to treatment of malignant osteolysis.

[Phase II study of docetaxel in inoperable advanced non small cell lung cancer]. / Etude de phase II: docétaxel dans les cancers bronchopulmonaires non à petites cellules inopérables.

The purpose is to determine the response to, and toxicity of docetaxel (Taxotère) in patients with inoperable non small cell lung cancer (NSCLC), previously untreated. Seventy patients with stage IIIB or IV NSCLC were treated by 100 mg/m2/ 3 weeks of docetaxel until tumor progression or severe toxicity. Premedication with diosmine and prednisolone was given in all patients: 66/70 were eligible and 55/70 were assessable for antitumoral activity. Median age: 63 years, WHO performans status 0-1: 83%, stage IV: 96%. For eligible patients, 17/66 (26%) achieved an objective response: 1 complete response and 16 partial response (IC 95% = 15-36). With a median follow-up of 23.4 months (range 14.9-28.7), for evaluable patients, the median response duration was 8 months, the median time to progression 4 months, and the median survival time 10 months. The median number of administered cycles is 5 (range 1-12). The estimate one year survival rate was 47%. Seventy-six patients presented neutropenia (grade 3-4); febrile neutropenia was observed in 7% of cycles. Non haematological toxicities are: fluid retention related to docetaxel (2.9%), diarrhea (6%), nausea-vomiting (4%), asthenia (3%), nail changes (6%). Docetaxel (Taxotère) administered at 100 mg/m2/3 weeks has relevant clinical activity in previously untreated NSCLC with a acceptable toxicity.

[Efficacy of docetaxel in non-small cell lung cancer patients previously treated with platinum-containing chemotherapy. French Group of Pneumo-Cancerology]. / Efficacité du docétaxel dans les cancers bronchopulmonaires non à petites cellules antérieurement traités par une chimiothérapie comportant des sels de platine. Groupe Français de Pneumo-Cancérologie.

PURPOSE: Determine the response to, and toxicity of docetaxel (Taxotere) in patients (pts) with inoperable non-small-cell lung cancer (NSCLC) previously treated with platinum-containing chemotherapy. PATIENTS AND METHODS: Twenty-seven patients with stage IIIB or IV NSCLC, having received one platinum-containing regimen were treated with 100 mg/m2/3 weeks of docetaxel until tumor progression or severe toxicity. Premedication with prednisolone and diosmin was given in all patients. Antitumoral activity was assessable in 21/27 pts. Median age: 52 years; WHO performance status 0-1: 77% pts, stage IV disease: 63% pts. RESULTS: 6/21 eligible pts (24%) achieved a partial response to treatment [C.I 95%: 5.6-42]. Median time to progression: 2.9 months, median survival: 8.5 months with a median follow-up of 23.7 months (range: 13.5-27). Hematologic toxicity: grade 3-4 neutropenia: 75% pts, febrile neutropenia: 11% cycles. Non hematologic toxicities: fluid retention, rash, alopecia, sensory neuropathy, asthenia, and nail changes. CONCLUSION: Docetaxel (Taxotere) administered at 100 mg/m2/3 weeks has relevant clinical activity against platinum treated NSCLC pts. Neutropenia is the main toxicity.

Radiation dose, chemotherapy and risk of osteosarcoma after solid tumours during childhood.

Osteosarcoma is the most frequent second primary cancer occurring during the first 20 years following treatment for a solid cancer in childhood. Using a cohort study of children treated for a solid cancer, we investigated the incidence and etiology of osteosarcoma as a second malignant neoplasm after childhood cancer in a cohort and a case-control study. We analysed the relationship between the local dose of radiation and the risk of osteosarcoma, taking into account chemotherapy received. A cohort study of 4,400 3-year survivors of a first solid cancer during childhood diagnosed in France or the United Kingdom, between 1942 and 1986, revealed 32 subsequent osteosarcomas. In a nested case-control study, we matched 32 cases and 160 controls for sex, type of first cancer, age at first cancer and the duration of follow-up. Parameters studied were the incidence of osteosarcoma, the cumulative local dose of irradiation and the cumulative dose of chemotherapy received by cases and controls. The risk of a osteosarcoma was found to be a linear function of the local dose of radiation (excess relative risk per gray=1.8), and was found to increase with the number of moles of electrophilic agents per square meter but not with other drugs. No interaction was noted between radiotherapy and chemotherapy. Bilateral retinoblastoma, Ewing's sarcoma and soft tissue sarcoma were found to render patients susceptible to a higher risk of developing an osteosarcoma as a second malignant neoplasm. We recommend long-term surveillance of patients who were treated during childhood for bilateral retinoblastoma, Ewing's sarcoma, soft tissue sarcoma, as well as other first cancer treated with radiotherapy plus high doses of chemotherapy, without focusing exclusively on the radiation field.

Effectiveness of cold cap in the prevention of docetaxel-induced alopecia.

Docetaxel is a new taxoid antineoplastic agent with clinical efficacy especially in breast cancer. One of the most distressing side-effects induced by docetaxel is alopecia. We studied the prevention of alopecia by using a cold cap in 98 patients receiving 100 mg/m2 docetaxel by 1 h i.v. infusion every 3 weeks. One patient was lost to follow-up. 83 patients (86%) were evaluated as a success to the cold cap, as they presented WHO grade alopecia < or = 2 and no need to wear a wig. 14 patients (14%) had to wear a wig; among them; 7 patients withdrew before the evaluation at three cycles. The cold cap is a very effective technique with minimal side-effects for docetaxel-treated patients.

Pharmacokinetics and distribution of 6-mercaptopurine administered intravenously in children with lymphoblastic leukaemia.

OBJECTIVE: The pharmacokinetics of 6-mercaptopurine, including cerebrospinal-fluid (CSF) distribution, and the erythrocyte 6-thioguanine nucleotide concentrations were determined in children randomised to receive intravenous mercaptopurine for acute lymphoblastic leukaemia (ALL), according to the EORTC protocol ALL n.58881. RESULTS: After 1 month of oral treatment at a dose of 50 mg.m-2.day-1, the pharmacokinetic parameters were determined after the first i.v. administration of 1 g.m-2 (bolus dose of 0.2 g.m-2 followed by an 8-h infusion of 0.8 g.m-2) in 11 patients: systemic clearance was 23.02 1.h-1, volume of distribution was 0.75 l.kg-1, and elimination half-life was 1.64 h. The erythrocyte thioguanine concentrations were measured in the same 11 patients and increased significantly between the beginning and the end of infusion (10 pmol x 10(8) packed RBC) or within 24 h of infusion (223 pmol x 10(8) packed RBC). The CSF concentration was 3.78 mumol.1(-1), 1-6 h after the beginning of infusion (n = 28) and the CSF to plasma ratio was 0.15 (n = 16). In patients receiving the oral dose of 50-165 mg.m-2.day-1 of 6-mercaptopurine, CSF concentrations were below 0.18 mumol.1(-1), 1-24 h after drug intake (n = 67), and the CSF to plasma ratio was not calculated. CONCLUSION: Following the i.v. administration of 6-mercaptopurine, we observed high CSF concentrations of 6-mercaptopurine and an acute increase of erythrocyte thioguanine nucleotide concentrations. The clinical trial (EORTC protocol ALL n[symbol: see text]5881), comparing the oral and i.v. administrations of mercaptopurine, will demonstrate if the i.v. administration reduces the incidence of CNS relapses.

Cerebrospinal fluid examination in a case of childhood orbital granulocytic sarcoma.

The diagnosis of a case of childhood orbital granulocytic sarcoma, initially classified as a poorly-differentiated malignant tumor, was finally considered at the time of relapse following primary treatment with chemotherapy and local irradiation. At this time, systematic cerebrospinal fluid examination showed numerous blast cells with Auer rods, consistent with the diagnosis of meningeal acute myeloid leukemia of M2 type, and concomitant biopsy of the tumor indicated the diagnosis of chloroma. Reevaluation of the primary biopsy confirmed this diagnosis.

Solid malignant neoplasms after childhood irradiation: decrease of the relative risk with time after irradiation.

The pattern of the temporal distribution of solid cancer incidence after irradiation in childhood is not well known, although, its importance in radioprotection is well known. We studied a cohort of 1,055 children from 8 European cancer centres, who received radiotherapy between 1942 and 1985 for a first cancer in childhood. After a mean follow-up of 19 years, 26 children developed a solid second malignant neoplasm (SMN), as compared to 5.6 expected from general population rates. Both the excess relative risk and the excess of absolute risk of solid SMN were higher among children who were younger at time of the irradiation. After reaching a maximum 15 to 20 years after irradiation, the excess relative risk of SMN decreased with time after irradiation, when controlling for age at irradiation and sex. The analysis of the risk of thyroid, brain and breast cancer together, as a function of the dose averaged on these 3 organs lead to similar results.

Thiopurine methyltransferase activity in a French population: h.p.l.c. assay conditions and effects of drugs and inhibitors.

1. Thiopurine methyltransferase (TPMT) is a cytosolic enzyme involved in the catabolism of thiopurine drugs, which are used to treat cancer patients and organ transplant recipients. Because TPMT activity is polymorphic and under genetic control, large interindividual variations in the immunosuppressive activity and toxicity of these drugs may, at least in part, be inherited. 2. We have developed a specific h.p.l.c. method for measuring 6-methyl mercaptopurine formed from 6-mercaptopurine (6-MP) in red blood cell lysates during the TPMT assay procedure. In blinded assays of 55 samples from adult blood donors, the results of the h.p.l.c. method correlated with those of the radiochemical reference method (r = 0.83, P < 0.001). 3. Using this h.p.l.c. assay, we tested the effect of known inhibitors of TPMT activity (syringic acid, p-anisic acid and tropolone) in vitro and showed that they were highly inhibitory. We also found that drugs often administered concomitantly with 6-MP (prednisone, prednisolone, 6-methylprednisolone, cyclophosphamide, methotrexate, and trimethoprim-sulphamethoxazole) had little or no effect on TPMT activity in vitro. 4. In a group of 300 French individuals, TMPT activity was highly variable, ranging from 4.7 to 35.3 nmol h-1 ml-1 of packed red blood cells (nmol h-1 ml-1 PRBC) with a mean value of 19.3 +/- 4.9. TMPT activity was not influenced by sex. 5. This sensitive and reproducible h.p.l.c. assay for TPMT activity in red blood cells may prove useful for prospective clinical studies designed to optimise dosage regimens of thiopurine drugs (detection limit for 6-methyl mercaptopurine is 5 ng ml-1, intra- and inter-assay variations are 6.8 and 8.2%, respectively).

[Tolerance and immunogenicity of the capsular polyoside vaccine against Haemophilus influenzae type b. A study of 325 children 15 to 71 months of age]. / Tolérance et immunogénicité du vaccin polyosidique capsulaire anti-Haemophilus influenzae type b. Etude chez 325 enfants de 15 à 71 mois.

The antigenic properties of the capsule polyoside (PRP) from Haemophilus influenzae type b (Hib) are adequate to form the basis for immunization designed to prevent the severe infections caused by this organism. The tolerance and immunogenicity of a vaccine containing either 12.5 or 25 micrograms PRP were studied in 325 healthy children aged 15 to 71 months after informed consent had been obtained from the parents. Each child was given one subcutaneous injection of 0.5 ml vaccine. Antibodies against Hib were assayed before and one month after the injection. Clinical tolerance was outstanding both locally (moderate and transient pain in 13% of cases) and systematically, with only eight (2.6%) febrile reactions in excess of 38.5 degrees C within 24 hours after the injection. A very significant rise in antibody titers was seen in all age groups, but a mean titer of 1 microgram/ml was achieved only in children aged 24 months or more. No significant difference was found between the two dosages. Individual analysis showed that following immunization antibody titers reached 0.15 micrograms/ml or more in 65% of infants aged 15 to 17 months, 71% of infants aged 18 to 23 months, 80% of infants aged 24 to 30 months and 95% of children older than 30 months. Despite the inadequate immune response evidenced in the younger age groups, our results confirm that Hib infections are preventable from the age of 2 years. Our results are consistent with those recorded with a similar vaccine in Finland.