Simple lifestyle recommendations and the outcomes of gestational diabetes. A 2 × 2 factorial randomized trial.

The benefits of exercise and behavioural recommendations in gestational diabetes mellitus (GDM) are controversial. In a randomized trial with a 2 × 2 factorial design, we examined the effect of exercise and behavioural recommendations on metabolic variables, and maternal/neonatal outcomes in 200 GDM patients. All women were given the same diet: group D received dietary recommendations only; group E was advised to briskly walk 20-min/day; group B received behavioural dietary recommendations; group BE was prescribed the same as B + E. Dietary habits improved in all groups. In a multivariable regression model, fasting glucose did not change. Exercise, but not behavioural recommendations, was associated with the reduction of postprandial glucose (p < 0001), glycated haemoglobin (HbA1c; p < 0.001), triglycerides (p = 0.02) and C-reactive protein (CRP; p < 0.001) and reduced any maternal/neonatal complications (OR = 0.50; 95%CI=0.28-0.89;p = 0.02). In GDM patients a simple exercise programme reduced maternal postprandial glucose, HbA1c, CRP, triglycerides and any maternal/neonatal complications, but not fasting glucose values.

[Serious pulmonary embolism and thromboaspiration]. / Embolie pulmonaire grave et thrombo-aspiration.

Pulmonary embolism is a common disease with a mortality rate of approximately 3%. Polytraumatised patients are particularly susceptible to thromboembolism because of prolonged immobilisation and inflammatory syndrome, thrombembolic risk also increases significantly during the peripartum period. Rapid diagnosis and intervention are essential for survival. Conventional treatment consists of systemic intravascular thrombolysis, but this procedure is often contraindicated in intensive care patients because of the high risk of haemorrhage. We report two cases of successful treatment using radiological endovascular thrombectomy.

Syntheses, in vitro antibacterial and antifungal activities of a series of N-alkyl, 1,4-dithiines.

A series of dithiines were synthesized by cyclization of 4-(alkylamino)-4-oxobutanoic acids under the action of SOCl2. Their in vitro antibacterial and antifungal activities have been evaluated against reference strains and versus reference compounds. The so-called 'isoimides' 2a, 2b were totally inactive whereas some imides had low MICs for few bacteria and for few fungal microorganisms.

Anorexia nervosa: slow regain of bone mass.

In a retrospective study of women aged 18-30 years, aimed at assessing factors associated with peak bone mass (PBM), 13 of 239 study cases reported having had anorexia nervosa. The mean total femoral and lumbar bone mineral density (BMD) values were not significantly lower in women who had had anorexia than in the pooled group (mean Z-scores of -0.60 and -0.48). Cases with less than 6 years since the anorexia had on average a present weight 5.7 kg less than their premorbid weights, while cases with more than 6 years since the eating disorder had an average weight 22.5 kg above their pre-morbid weights. The cases who had not regained their weight had BMD values significantly lower than the pooled material (mean Z-scores -1.15 and -0.9 in the lumbar spine and total femur respectively). Those who had regained their weight had BMD values as predicted from their present anthropometric data, while those who had not regained their weight had BMD values that were substantially below that predicted from their present weight. Anorexia nervosa seems to be associated with a low BMD which is even lower than that which can be predicted from the weight loss alone. This suggests that weight loss and other factors, such as menstrual dysfunction and estrogen deficiency, are independent and thus additive causes of bone loss in anorexia nervosa. Recovery of BMD seems slow, but the BMD may become as predicted from the anthropometric data after restoration of body weight and menses. The potential for recovery of BMD seems intact for several years after menarche.

N-conjugates of 2,5-disubstituted pyrrole and glutathione. Evaluation of their potency as antioxidants against photosensitization of NCTC 2544 keratinocytes by excess endogenous protoporphyrin IX.

A novel glutathione compound in which the amino group has been derivatized by a 2,5-dimethyl pyrrole is shown to be very effective against cell photosensitization in vitro. Protoporphyrin IX either added to the medium or produced endogenously by incubation of NCTC 2544 keratinocytes with 5-aminolevulinic acid has been chosen as the photosensitizer. The antioxidant effectiveness of glutathione-pyrrole derivatives against protoporphyrin photosensitization depends critically on the type of 2,5 substitution on the pyrrole ring. This structure-function relationship may be attributed to the difference in compartmentation and/or uptake of the various glutathione-pyrrole derivatives under study. The 2,5-dimethyl pyrrole derivative is much more effective than glutathione as a protective agent against phototoxic reactions induced by protoporphyrin IX.

[Mass screening for colorectal cancer in France. Experience in 165,000 people in the department of Calvados]. / Le dépistage de masse du cancer colorectal en France. Expérience auprès de 165,000 personnes dans le Calvados.

OBJECTIVES: Screening for colorectal cancer is a major public health problem in France as in most developed countries. Several controlled trials are on-going in Europe. The aim of the study was to determine requirements for success of mass-screening for colorectal cancer in France. METHODS: A mass-screening program has been conducted between April 1991 and June 1994 in the department of Calvados for 164,364 people aged 45-74 years. The screening test was first proposed by general practitioners and occupational doctors during appointments. Secondly, a postal invitation to obtain the test, free of charge, by doctor or chemist, was sent. RESULTS: Global participation rate was 43.4%; 40.2% of tests were distributed during the first phase, 47.1% during the second phase and 12.7% were distributed by a private health institute. Participation was higher for females (47.1%) than males (39.2%) and for urban districts (46.5%) than rural districts (24.4%). In case of positive test, colonoscopy has been more frequently achieved in urban districts and when test has been distributed by a physician. Positivity rate was 2.8%. Positive predictive value was 8.0% for a cancer and 13.5% for an adenoma larger than 1 cm. Because both positivity rate and positive predictive value were higher for males than females and increased with age, rate of cancer or large adenoma screened was almost three times higher for males than females and markedly increased with age. CONCLUSIONS: In France, different recruitment methods have to be used to reach a satisfactory participation to a mass-screening campaign. Such a program requires involvement of general practitioners and close coordination between practitioners and health care insurance agencies.

Haemoccult test properties according to type and number of positive slides in mass screening for colorectal cancer.

Despite encouraging results from recent studies, there is still no consensus to undertake mass screening using the Haemoccult test in the general population. The success of mass screening for colorectal cancer depends among other things on Haemoccult test properties. In on-going screening programmes, the Haemoccult test consists of six slides and a test is considered positive if at least one slide is coloured. The aim of this work was to study the influence of the type and number of positive slides on the Haemoccult test's positive predictive value and characteristics of screened lesions. This work focuses on 63,958 first tests in a mass screening programme in Calvados (France) among people aged 45-74 years. There was a linear relation between the positive predictive value for cancer or an adenoma larger than 1 cm and the number of positive slides (P < 10(-4)). The positive predictive value for cancer or large adenoma was significantly higher when 4-6 slides were positive (44.3%) than when only 1-3 were positive (19.1%) (P < 10(-4)). In this latter group, the subjects in whom tumours were detected were younger and had significantly less extensive cancers. Borderline tests (no slides positive and at least one slide with a blue coloration confined to the edges) had a positive predictive value for cancer or an adenoma larger than 1 cm no different to that of tests with 1-3 positive slides. Subjects with borderline results were markedly younger than the others and had less extensive cancers and rectal localisation more often than the others. Our results suggest that (1) increasing the number of positive slides required to declare a test positive leads to an increase in the positive predictive value but is not to be recommended because of the sensitivity of the test and (2) considering borderline Haemoccult tests as positive in on-going and future mass screening campaigns would allow an increase in the sensitivity of the test, especially for rectal cancer and low extensive tumours without any decrease in its positive predictive value.

Participants' characteristics in a French colorectal cancer mass screening campaign.

BACKGROUND: Participation by the target population is clearly a key element in the success of mass screening programs for colorectal cancer. In France, involvement of general practitioners in test distribution is essential to reach a satisfactory participation rate, but other forms of recruitment also have to be organized. The aim of this study was to determine the influence of demographic characteristics such as sex, age, and place of residence on the participation rate in a French mass screening according to different recruitment methods. METHODS: The Hemoccult IIR test was proposed in three consecutive ways: spontaneously by general practitioners and occupational doctors during appointments (phase 1), by postal invitation (phase 2), and finally by direct mailing of the test (phase 3). The target population consisted of 11,947 people between 45 and 74 years of age, living in a district of the French county of Calvados, between March 1991 and April 1993. RESULTS: The overall participation rate was 51.3%. Forty-nine percent of all the tests were done during phase 1, 31% during phase 2, and 20% during phase 3. The overall participation rate varied essentially according to the place of residence, from 65.5% in urban areas and 48.9% in intermediate areas to 27.7% in rural areas. The overall participation rate was also higher for females (57%) than for males (45%) and for those 60 years and older (53.9%) than for those below this age (49.2%). The proportion of tests done during phase 1 was lowest among the youngest and the oldest age groups (37.5% in the 45- to 49-year class and 45.2% in the 70- to 74-year class) and among people living in the rural environment (respectively 55.3%, 45.5%, and 35.9% in urban, intermediate, and rural areas). CONCLUSIONS: This study shows that place of residence strongly influences the global participation rate in mass screening for colorectal cancer in France, whereas sex and age have little influence. Recruitment methods complementary to distribution by general practitioners must be organized, especially for the youngest and oldest age groups (45-49 years and 70-74 years) and above all for people living in rural areas. The social, cultural, and psychological reasons for these differences remain to be investigated, with the aim of adapting mass screening strategies to the different population groups.

Long-term results of a multicentre randomised, comparative phase III trial of CHOP versus CNOP regimens in patients with intermediate- and high-grade non-Hodgkin's lymphomas. Novantrone International Study Group.

59 previously untreated patients with intermediate- or high-grade, stage II-IV non-Hodgkin's lymphoma (NHL) were entered into an open-label, randomised, multicentre study to compare the efficacy and safety of CHOP (cyclophosphamide, doxorubicin, vincristine and prednisolone) with that of CNOP (cyclophosphamide, mitoxantrone, vincristine and prednisolone). 10 patients refused treatment following randomisation. The remaining 349 patients received either the CHOP or CNOP regimen every 3 weeks for a maximum of six to eight cycles. The randomisation procedure was violated for 34 patients treated at two study centres. Data from these 34 patients were analysed separately for efficacy and survival. Data from the remaining 325 patients, 164 assigned to CHOP and 161 to CNOP, were used in the major efficacy and survival analyses. Of these 325 patients, 263 (81%) met the eligibility criteria of the protocol. Supplementary analyses of data from these 263 patients, 132 assigned to CHOP and 131 to CNOP, were conducted for efficacy and survival. Data from all 349 treated patients were analysed for safety. In the 325 randomised patients, the overall objective response rate was not significantly different between the two groups (chi 2 test, P = 0.35). The CHOP regimen had a 51% (83/164) complete remission (CR) rate compared with 40% (64/161) for the CNOP regimen (P = 0.05). Among those with CR, the median time to response was 104 days with the CHOP regimen and 77 days with the CNOP regimen, and the median duration of CR was 667 and 1833 days, respectively. The median time to progression was 449 days for CHOP patients and 564 days for CNOP patients. The median survival time was 932 days for CHOP patients and 1801 days for CNOP patients, with a risk of death on CNOP relative to CHOP of 0.93% (95% confidence interval 0.68-1.27). After 5 years, 50% of patients in the CNOP arm and 40% of patients in the CHOP arm were still alive; these differences between treatment groups were not statistically significant. The median time to treatment failure (TTF) was 285 days for patients on the CHOP arm and 282 days for patients on the CNOP arm. Separate analyses of 263 eligible randomised patients, and 34 patients in whom the randomisation procedure was not followed, yielded similar results for remission rate, TTF, duration of CR and estimated overall survival. The incidence of non-haematological events, such as severe nausea and vomiting (P < 0.01), mucositis (P < 0.05) and alopecia (P < 0.001), were significantly lower in were significantly lower in patients treated with CNOP as compared with those who received the CHOP regimen. The incidence of cardiovascular toxicity of any severity was similar in the two groups. While severe and potentially life-threatening neutropenia occurred more frequently in patients treated with CNOP compared with CHOP (0.05 > P > 0.10), the incidence of infection of any severity was similar in both arms. We conclude that CHOP and CNOP regimens were both efficacious in patients with previously untreated aggressive NHL.

[Objectives and means of screening of colorectal cancer]. / Objectifs et moyens du dépistage du cancer colorectal.

Despite numerous publications on the subject, the debate over the merits of the various methods available for screening for colorectal cancer is continuing. Choice of the method depends on the patient being treated. In the present state of our knowledge, mass screening by Hemoccult, which is of low cost but of poor sensitivity and only fairly well accepted, cannot be used routinely but must be further evaluated and developed. In persons willing to undergo regular examinations, an annual or biannual Hemoccult examination associated with rectosigmoidoscopy every 5 years appears appropriate. In subjects having a familial history in first-degree relatives, colonoscopic examination every 5 years is adequate. Lastly, in patients with a personal history of cancer or adenoma, screening consists of colonoscopic follow-up adapted to the individual case.

Glutathione peroxidase and glutathione reductase activities towards glutathione-derived antioxidants.

A new class of glutathione derivatives with antioxidant properties has been prepared by transformation of the NH2 group into a pyrrole ring with various substitutions at the 2 and 5 positions. Due to steric hindrance and/or hydrophobicity of the 2-5-disubstituted pyrrole ring, the reduced glutathione derivatives are poor substrates of the glutathione peroxidase and do not effectively compete with GSH. The oxidized glutathione derivatives are, in turn, relatively good substrates (Km = 1.5 mM) of the glutathione reductase as compared to natural oxidized glutathione (Km = 0.51 mM) but are not effective competitors of the enzyme. It can be considered that the new glutathione derivatives do not strongly interfere with the natural enzymatic defence against fatty acid hydroperoxides formed during an oxidative stress.

A pulse radiolysis study of one-electron oxidation and .OH radical reaction of a new class of antioxidants: 2,5 dimethylpyrrole--amino acid N-conjugates.

A new class of 2,5 dimethylpyrrole functionalized amino acid and peptide antioxidants has been synthesized. Pulse radiolysis studies have been carried out on these compounds to determine their reactivity in one-electron oxidation reactions with Br2- and (SCN)2-, as well as their reactivity toward the water radicals .OH and eaq-. When compared to similar reactions with parent amino acids and peptides, both rate constants and transient spectra indicate considerable interaction between the electronic states of the pyrrole moiety and amino acid or peptide. Where comparison data is available, radical reactions are significantly more rapid with these derivatives than with the parent compounds. Exceptions occur in some cases of .OH attack where steric hindrance may be evoked to explain a lower rate constant in the derivative compounds. Electron attachment rates are also found to be enhanced by the presence of the pyrrole ring.

Biodistribution and excretion of a mixed fluorocarbon-hydrocarbon "dowel" emulsion as determined by 19F NMR.

To investigate the biodistribution, possible metabolism and excretion of mixed fluorocarbon-hydrocarbon "dowel" molecules used as stabilizers of fluorocarbon emulsions, we have prepared a 25% w/v emulsion of such a molecule, and quantitatively evaluated, by means of 19F NMR, its behavior in the blood and reticuloendothelial system (RES) of rats. C6F13CH = CHC10H21 (F6H10E) was emulsified using egg yolk phospholipids (EYP). The emulsion (F6H10E/EYP: 25/6% w/v) was injected intravenously into 33 Sprague Dawley female rats at a 3.6 g/kg body weight dose of F6H10E. The animals were sacrificed at regular intervals of time. 24 hours after the injection, 70% of the injected dose was located in the liver, 17% in the spleen, 4% in the lungs, 2% in the kidneys and 2% in the blood. The half-time retention of the dowel molecule in the liver was estimated to be 25 +/- 5 days. None of the 33 treated animals died prior to the planned sacrifice date. The dowel molecule F6H10E proved to be well tolerated, and excreted reasonably fast, without metabolism. This appears to warrant the use of such molecules as stabilizers in injectable fluorocarbon emulsions destined to serve as oxygen carriers, contrast agents or drug delivery systems.

RP-HPLC peptide mapping methods for the analysis of recombinant human pro-urokinase.

Among the techniques available for the detection of protein structure variants such as single point mutations, RP-HPLC peptide mapping plays a key role owing to the high reproducibility of peptide retention times, determined as identity indexes. Because of the possible co-elution of some proteolytic fragments, an improvement of the array of information given by the technique can be achieved by setting up a series of experiments under hydrolytic conditions with different enzymes, followed by appropriate RP-HPLC gradient elutions. Such an experimental approach appears to be particularly useful in the examination of proteins with a high molecular weight, where the resulting RP-HPLC maps are complex. Therefore different RP-HPLC peptide mapping methods have been studied for recombinant human pro-urokinase (r-h-proUK), a thrombolytic agent of apparent molecular weight of 46 kD. The RP-HPLC maps indicate that the methods developed are not only suitable for the qualitative control of the amino acid sequence and arrangement of disulphide bonds but also represent the first demonstration of the identity of the primary structure of the recombinant and of the native species, within the limits of the technique.

[Leukocyte depletion of blood products and anti-HLA immunization]. / Déleucocytation des produits sanguins et immunisation anti-HLA.

HLA alloimmunization and subsequent refractoriness to platelet transfusions are frequent complications of transfusion therapy in patients with hematologic malignancies. Contaminating leukocytes in red cell and platelet concentrates are responsible for primary HLA alloimmunization. In many clinical trials, it has been demonstrated that the use of leukocyte-poor blood products prepared by filtration could reduce HLA-alloimmunization from 40% to 15%. The immunogenic level cannot be determined accurately, but the previous studies show that a residual contamination below 1.10(6) leukocytes was efficient to prevent primary alloimmunization. Leukocyte depletion does not avoid secondary responses in patients having an history of pregnancies or transfusions. The UV-B irradiation of platelet concentrates, in combination with filtration, should further reduce alloimmunization in these presensitized patients.

Involvement of general practitioners in mass screening. Experience of a colorectal cancer mass screening programme in the Calvados region (France).

Good compliance with screening programmes is essential and experience from ongoing studies points to the importance of involving general practitioners (GPs). The aim of this study was to evaluate factors influencing the participation of GPs in a screening programme, as well as acceptance of the test by the population. Fifty GPs were randomly chosen among the 117 practices of three districts in Calvados (France) where haemoccult test-based mass screening for colorectal cancer was underway. Each GP was asked to fill in a personal questionnaire as well as a detailed record for each patient between 45 and 74 years seen in the practice during a 1-week period. The GPs offered the test to 95% of the patients. The overall refusal rate was 7.8%, and was higher in women than in men (9.9% vs 5.9%; P < 0.05). Manual workers had a lower refusal rate than other occupational groups (2.5% vs 8.5%; P < 0.05). The GP's motivation was an important factor in patient compliance: the refusal rate was 5.4% in the case of highly motivated GPs, against 20.0% when the GP was poorly motivated (P < 0.01). GP motivation was higher in urban than in rural areas (P < 0.05) but did not depend on sex, age or the duration or type of practice. According to the GPs, motivating factors were the perceived need for screening, involvement in planning the campaign, and regular feedback. Conversely, a lack of time and the possibility of false-negative results were the most important impediments. This study demonstrates that patient compliance is closely linked to practitioner motivation.(ABSTRACT TRUNCATED AT 250 WORDS)

[Descriptive modeling of the chemical structure-biological activity relations of a group of malonic polyethylenic acids as shown by different pharmacotoxicologic tests]. / Essai de modélisation descriptive des relations structure chimique-activité biologique d'une population d'acides maloniques polyéthyléniques vis-à-vis de différents tests pharmacotoxicologiques.

48 new polyethylenic-malonic acids have been submitted to an antimicrobial and antifungal screening. After a suitable recording, the experimental results were analyzed according to two mathematical multivariate analysis using a computer process i.e. Correspondence Factorial Analysis and Cluster Analysis. These methods allowed an accurate study of the structure of the system and a thorough investigation of the structure-activity-specificity relationships. On the other side, magnitude and/or specificity of the observed biological effects were related to structural features. These results should be useful in order to elaborate synthetic strategies.

Assessment of portal contribution to liver perfusion by quantitative sequential scintigraphy and Doppler ultrasound in alcoholic cirrhosis. Diagnostic value in the detection of portal hypertension.

To assess the portal contribution to liver perfusion, we carried out quantitative sequential scintigraphy in 110 patients with alcoholic cirrhosis (22 Child-Pugh class A, 39 class B, 49 class C) and 15 normal subjects. Duplex Doppler ultrasound found a type of intrahepatic circulation that made the standard scintigraphic procedure inaccurate in four cases of cirrhosis, which were reevaluated. Portal contribution to liver perfusion was lower in cirrhotics than in normal subjects (48.7 +/- 29% versus 78.4 +/- 6%; p < 0.001). The sensitivity of scintigraphy in detecting portal hypertension, based on portal contribution < or = 66%, was 61.8% (with a 100% specificity) compared with 66.7% for endoscopy (diagnosis based on existence of varices). The overall sensitivity of the two tests together was 86.1%. Portal contribution to liver perfusion was inversely correlated to Child-Pugh score (r = 0.53; p < 0.001), to prothrombin time (r = 0.52; p < 0.001), and to hepatic venous pressure gradient (r = 0.43; p < 0.001) and positively correlated to albuminemia (r = 0.42; p < 0.001). Concurrent alcoholic hepatitis and the existence of large portosystemic collaterals were related to a decrease in portal contribution to liver perfusion. We conclude that quantitative sequential scintigraphy, which shows a direct relationship between portal contribution to liver perfusion, on the one hand, and the amount of portosystemic shunting, the progression of liver disease, and/or acute liver injury, on the other, could serve as a diagnostic test for portal hypertension. The addition of scintigraphy improves the overall sensitivity of endoscopy.