Smoking in pregnancy: A survey from Northern Italy

Summary The prevalence of smoking in pregnancy was analyzed in a survey of women delivering between January and March 1989 in a large maternity clinic in Milan, Northern Italy. Out of the 528 women interviewed, 183 (35%) were current smokers before pregnancy and 99 stopped smoking during pregnancy. The probability of stopping smoking decreased with increasing age and was lower in less educated women, but these findings were not statistically significant. Considering persistent smokers only, the mean number of cigarettes per day fell from 13 before to 8 during pregnancy; this reduction was generally consistent in various subgroups of age and education. The reductions, however, are probably overestimated, since they are based on the women's reports only. Thus, there still appears to be ample scope for intervention on smoking in pregnancy, particularly in older and less educated women.

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Zusammenfassung Die Rauchprävalenz während der Schwangerschaft wurde in einer Querschnittstudie bei Frauen untersucht, welche zwischen Januar und März 1989 in einer grossen Frauenklinik in Mailand ein Kind zur Welt brachten. Von 528 befragten Frauen hatten 183 (35%) vor der Schwangerschaft geraucht, und 99 Frauen war es gelungen, während der Schwangerschaft mit Rauchen aufzuhören. Die Wahrscheinlichkeit für letzteres nahm mit zunehmendem Alter ab und war kleiner für Frauen mit geringer Ausbildung (statistisch nicht signifikant). Bei den Raucherinnen wurde eine Reduktion der mittleren Anzahl Zigaretten von 13 Stück vor der Schwangerschaft auf 8 während der Schwangerschaft festgestellt. Diese Reduktion fand sich in allen Alters- und Ausbildungsgruppen. Wahrscheinlich wurde die Reduktion aber überbewertet, weil sich ihre Berechnung nur auf die Aussagen der Frauen abstützte. Für Gesundheitsaktionen, die ein Rauchstopp während der Schwangerschaft zum Ziele haben, besteht immer noch ein grosser Bedarf, besonders bei älteren und weniger ausgebildeten Frauen.

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Résumé La prévalence du tabagisme durant la grossese a été étudiée lors d'une enquête des parturientes entre janvier et mars 1989 dans une grande maternité de Milan. Parmi les 528 femmes interrogées, 183 (35%) étaient tabagiques avant la grossesse et 99 avaient arrêté de fumer durant la grossesse. La probalité de cesser l'habitude diminue lorsque l'âge augmente, et est basse chez les femmes dont le niveau d'éducation est bas, sans significantion statistique. En considérant uniquement les parturientes tabagiques, le nombre quotidien de cigarettes fumées passe de 13 avant la grossesse à 8 durant la grossesse; cette diminution se retrouve dans tous les groupes d'âge et tous les niveaux d'éducation. Ces diminutions sont probablement surestimées, puisqu'elles sont basées sur les seules déclarations des parturientes. Cette enquête montre qu'il existe encore une large place por la prévention.

     

Ipriflavone inhibits osteoclast differentiation in parathyroid transplanted parietal bone of rats

Summary Ipriflavone, a synthetic isoflavone-derived flavonoid, was shown to have inhibitory effect on bone resorption. In order to study its mechanism of action directly on bone, 46 female Wistar rats were divided into six groups and medicated orally for 25 days as follows: groups 1 and 2 were given 1% carboxymethylcellulose solution (vehicle), groups 3, 4, 5, and 6 were administered ipriflavone at doses of 0.178, 0.356, 0.712, and 1.424 mmol/kg/day (suspended in vehicle), respectively. On the 22nd day, parathyroid glands, taken from donor rats, were transplanted in contact with the outer surface of the periosteum of both the right and the left parietal bones of rats from groups 2, 3, 4, 5, and 6. The group 1 rats underwent sham operation. Bone histomorphometry, performed on the ectocranial periosteum of parietal bones, showed that absolute erosion boundary, absolute eroded area, absolute erosion depth, number of tartrate-resistant acid phosphatase (TRAP)-positive polinucleated osteoclasts, and number of TRAP-positive mononucleated cells decreased in ipriflavone-treated rats compared with group 2 rats. The reduction was roughly proportional to the increase of drug dosage and reached statistical significance in rats of groups 5 and 6. The same parameters were extremely low in group 1 rats. Mineral apposition rate did not differ in any of the groups. Significant increase of serum calcium and significant decrease of serum phosphate were found in group 2 rats compared with group 1 rats, whereas no differences from controls were detected in ipriflavone-treated animals.The results demonstrate that ipriflavone has a direct inhibitory effect upon bone resorption, probably by reducing recruitment or differentiation of osteoclasts, rather than by inhibiting the resorption activity of differentiated osteoclasts. Ipriflavone also seems to exert a protective action against parathyroid hormone (PTH) diffusion from the site of parathyroid gland transplantation.     

Acquired hyperoxaluria and haematuria in children

Two children with extensive ileal resection are reported. They developed gross haematuria of non-glomerular origin, without stones or nephrocalcinosis. Previous reports indicate that acquired hyperoxaluria is common in children with a variety of intestinal disorders. Our patients had hyperoxaluria. We think that hyperoxaluria may be the cause of haematuria through a pathogenetic mechanism similar to the one ascribed to haematuria secondary to hypercalciuria and hyperuricosuria.     

Early kinetics of the human thyroid trap estimated with 99mTc and 131I

Kinetic parameters of ^99mTc and ¹³¹I thyroid trapping were compared in 13 patients (30 dynamic studies). The data were analyzed with a six-compartment model including three compartments for extrathyroid spaces. There was a good correlation between the estimates of the total iodide and pertechnetate pools (V₄+V₅). As expected, the ₁₄ loss rate constant for technetium was always higher than that for iodide.In five euthyroid patients, the unidirectional clearances (R₄₁) with TcO₄ ^– and I^– were generally of the same magnitude. The effect of TSH stimulation appears to be identical for both isotopes: an increase of R₄₁ and the total iodide and pertechnetate pool (V₄+V₅), a decrease of the isotope loss rate constant (₁₄).In two untreated thyrotoxic patients, the unidirectional clearance of ^99mTc was 2.5 times higher than that estimated with ¹³¹I. Under administration of antithyroid drug, unidirectional TcO₄ ^– clearance was lower than that of iodide in the six patients studied.A similar and greater discrepancy between early ¹³¹I and ^99mTc kinetics was observed in a patient with congenital goiter. The technetium thyroid trap was only slightly elevated, whereas unidirectional iodide clearance and (V₄+V₅) were clearly increased.This series of patients suggests that whereas there is a good correlation between early ¹³¹I and ^99mTc kinetics in euthyroid subjects, a discrepancy exists in patients with spontaneous or acquired dyshormonogenesis. This is confirmed by the segmentary study of a patient with a nodule appearing hot on the ^99mTc scintigram and cold on the ¹³¹I scan.Research supported by INSERM (CRL 7750943 B)     

Putative host resistance and long-term survival in breast cancer

Lymphocytic infiltration in and around the tumor together with sinus histiocytosis and follicular hyperplasia in regional nodes has been studied in a group of 310 patients with breast cancer treated by standard radical mastectomy. The semiquantitative grading of these particular changes made possible the division of patients into 3 classes of putative host resistance, namely, no or poor reaction, good reaction, and strong reaction. The grading was shown to have a close correlation with prognosis both 5 and 10 years after surgery. More interestingly, the incidence of metastases in the 3 classes was significantly different, i.e. much higher in the non-responder group, thus supporting the hypothesis that prognosis in breast cancer is closely related to a histological picture of cell-mediated immunity against the tumor, and that this resistance probably acts as a local barrier to the diffusion of the tumor.

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Résume Chez 310 malades atteintes de cancer du sein et traitées par mastectomie radicale, nous avons étudié l'infiltration lymphocytaire intra- et péritumorale et, dans les ganglions régionaux, l'histiocytose sinusale et l'hyperplasie folliculaire. Par une gradation semiquantitative, les malades ont été divisées en trois groupes de résistance potentielle: pas ou peu de réaction, réaction d'intensité moyenne, forte réaction. Cette gradation est en bonne corrélation avec le pronostic à 5 et 10 ans. De plus, la fréquence des métastases diffère dans les trois groupes; elle est beaucoup plus élevée dans le groupe à réaction nulle ou faible. Ces données confirment l'hypothèse qui admet que le pronostic du cancer du sein est en relation avec les aspects histologiques d'immunité cellulaire antitumorale et que celle-ci agit vraisemblablement comme un barrage local s'opposant à la diffusion de la tumeur.

     

Guidelines for routine assessment of cardiologic surgical risk: electrocardiogram

Cardiac complications are the main cause of perioperative mortality. A preoperative electrocardiogram and cardiologist's consultation are usually performed to get information about cardiac state of patients undergoing surgery and to prevent complications. In their study the Authors applied to 1715 patients undergoing surgery an evaluation schedule for the cardiac surgical risk, including an ECG as first-level test, performed systematically on the whole sample. The aim was to assess predictive value of this preoperative examination to verify its efficacy as routine test. Basing on results achieved, electrocardiogram is not routinely indicated before noncardiac elective surgery, but it should be requested for the patients having high risk of cardiac complications at an accurate clinical-anamnestic examination. Therefore, clinical judgement, that is the first level of any preoperative evaluation, should be the basis for ordering an ECG to be considered a second-level test.     

Schedule-dependent cytotoxic interaction between epidoxorubicin and gemcitabine in human bladder cancer cells in vitro.

PURPOSE: The aim of the study was to evaluate the activity of epidoxorubicin (EPI) and gemcitabine (GEM) and to define the most effective schedule in human bladder cancer cells. EXPERIMENTAL DESIGN: The study was performed on HT1376 and MCR cell lines. Cells were exposed for 1 and 24 h to drugs used in different schemes. Cytotoxic activity was evaluated by the sulforhodamine B assay, potential clinical activity was estimated by relative antitumor activity, and the type of drug interaction was assessed using the method of Chou and Talalay. Cell cycle perturbations and apoptosis were assessed by flow cytometry; BAX, BCL-2, and P53 expression was evaluated by Western blot; and DNA damage was assessed using the alkaline Comet assay. RESULTS: EPI and GEM produced a cytotoxic effect in both cell lines, with 50% inhibitory concentration and relative antitumor activity values suggestive of a high clinical activity. Simultaneous treatment with EPI and GEM and the sequence GEM-->EPI caused an antagonistic interaction (combination index > 1) after both 1- and 24-h treatments. Conversely, the inverse sequence, EPI-->GEM, produced a synergistic interaction that was more pronounced in MCR cells than in HT1376 cells. The increase in DNA-damaged cells from 10% to 20% after single-drug exposure to 40-60% at the end of EPI-->GEM treatment may explain the synergistic interaction produced by the anthracycline-antimetabolite sequence. CONCLUSIONS: Our findings show that the efficacy of the EPI and GEM combination is highly schedule dependent and indicate that the most active scheme is EPI followed by GEM, which is currently being validated in an ongoing intravesical Phase I-II clinical protocol.     

Phase I pharmacological and bioavailability study of oral diflomotecan (BN80915), a novel E-ring-modified camptothecin analogue in adults with solid tumors.

PURPOSE: Diflomotecan (BN80915) is an E-ring modified camptothecin analogue that possesses greater lactone stability in plasma compared with other topoisomerase I inhibitors, a potential advantage for antitumor activity. As with other camptothecins, oral administration has pharmacological and clinical advantages. This Phase I study was performed to assess the feasibility of the administration of oral diflomotecan, to determine the maximum-tolerated, dose its bioavailability, and to explore the pharmacokinetics. EXPERIMENTAL DESIGN: An initial i.v. bolus was administered to assess the bioavailability of diflomotecan. Fourteen days later, diflomotecan was administered p.o. once daily for 5 days to adult patients with solid malignant tumors and repeated every 3 weeks. BN80915 and its open lactone form BN80942 were measured. RESULTS: Twenty-two patients entered the study and received a total of 57 cycles of oral diflomotecan at flat dose levels of 0.10, 0.20, 0.27, and 0.35 mg. The main toxicity was hematological, but some patients experienced alopecia, mild gastrointestinal toxicity, and fatigue. At the 0.35-mg dose level, 2 of 4 patients experienced dose-limiting toxicity comprising grade 3 thrombocytopenia with epistaxis and febrile neutropenia in 1 patient and uncomplicated grade 4 neutropenia lasting for >7 days in another. Toxicity was acceptable at the 0.27-mg dose level at which dose-limiting toxicities were observed in 3 of 12 patients (grade 4 neutropenia > 7 days, complicated by fever in 1 patient but without other signs of infection). After two cycles of diflomotecan, 6 patients had disease stabilization, which was maintained in 2 patients for 9 months and >1 year, respectively. Diflomotecan pharmacokinetics were linear over the dose range studied. Systemic exposure correlated with the fall in WBC counts. The mean oral bioavailability (+/-SD) was 72.24 +/- 59.2% across all dose levels. Urinary excretion of BN80915 was very low. CONCLUSIONS: The recommended oral diflomotecan dose for Phase II studies is 0.27 mg/day x 5 every 3 weeks. This regimen is convenient and generally well tolerated with a favorable pharmacokinetic profile and high but variable bioavailability.