Descriptive epidemiology of gynecologic and breast cancers]

The epidemiology of gynecological and breast cancers are better known in France as a result of the mortality data provided by INSERM and the mortality data obtained from the French Tumor Register. Breast cancers are the most common form of cancer in women, accounting for about 30 p. cent of tumors (excluding skin cancers) followed by cancers of the uterine cervix, uterine body and the ovary. The change in incidence shows a definite reduction in the number of uterine cancers over the past 10 years, whereas the incidence of breast cancers is rising by 1 to 2 p. cent per year. Mortality due to breast cancer has risen steadily in France since 1950, particularly in higher age groups. At birth, the risk of developing a breast cancers is 7 p. cent, i.e. one woman in 14 will develop a breast cancer. The figures for cancers of the uterus and ovary are much lower. Survival curves for various types of cancer confirm the steady decline in survival for breast cancers, whereas for cancers of the cervix, uterine body and ovary, mortality rates stabilize after 5 years. The risk of a secondary cancer remains very high for breast tumors, and half the cases of a secondary tumor involve a contralateral breast tumor. In general, there is an increased risk of a secondary cancer after a primary gynecological tumor.     

Developmental regulation of angiotensinogen gene expression in sheep

It has been suggested that the liver is not the main source of angiotensinogen during fetal life in rats, but that the kidney is an important site of fetal angiotensinogen synthesis. In an effort to determine if this phenomenon is specific to the rat or applicable to other species, we compared the ontogenic changes in hepatic and renal angiotensinogen mRNA expression in fetal (60, 90, 118, and 138 d of gestation, term being 145 d), newborn (7 d postnatal), and adult sheep. Total RNA was extracted, subjected to Northern blotting and hybridized using a full-length rat radiolabeled antisense RNA. Angiotensinogen mRNA sequences were detected in all fetal liver samples and appeared to increase 3-fold from 60 to 138 d gestation and then to decrease after birth. In contrast, angiotensinogen mRNA could not be detected in renal cortical tissue of 118 or 138 d fetuses, or newborn or adult sheep. We conclude that, unlike in the rat, liver angiotensinogen gene expression is detectable during the 2nd trimester of gestation in sheep and is developmentally regulated. Furthermore, in contrast to the fetal rat, angiotensinogen mRNA sequences were undetectable in fetal sheep kidney.     

Atrial natriuretic factor, digoxin-like immunoreactive substance, norepinephrine, epinephrine, and plasma renin activity in human fetuses and their alteration by fetal disease

We measured five hormones presumably involved in fetal homeostasis in specimens obtained by cordocentesis for clinical indications from 106 fetuses. Norms for atrial natriuretic factor, digoxin-like immunoreactive substance, plasma renin activity, norepinephrine, and epinephrine were derived from fetuses ultimately shown to be free of detectable abnormality. Atrial natriuretic factor, digoxin-like immunoreactive substance, and plasma renin activity were unrelated to umbilical vessel source or gestational age. Digoxin-like immunoreactive substance was directly related to PCO2 (r = 0.63, p = 0.02). Digoxin-like immunoreactive substance level was elevated in all fetal disease states studied except isoimmunization. The level of atrial natriuretic factor was elevated in fetuses with immune hydrops (NS). Norepinephrine and epinephrine levels were higher in the umbilical artery than in the vein (p = 0.05 and 0.006, respectively). There was a significant correlation between norepinephrine and gestational age in normal fetuses (r = 0.7637, p less than 0.025) and between both catecholamines and many of the respiratory blood gas measurements, with pH and PCO2 being the major determinants. Most disease states were associated with an elevated norepinephrine concentration. There was a negative correlation between plasma renin activity and base deficit (p less than 0.0001). Plasma renin activity was elevated in fetuses with idiopathic growth retardation and nonimmune hydrops (p less than 0.05 for each). In summary, fetal homeostasis as reflected by these five hormones was altered by a variety of disorders. With these baseline values the effects of direct or indirect fetal therapy can begin to be studied.     

A clinical correlation between hypozincemia and tinnitus

Summary We examined a group of 115 patients suffering from tinnitus and have attempted to find a statistically significant correlation between the tinnitus experienced and low blood zinc levels (hypozincemia). No particular correlation could be made between the nature of the tinnitus experienced and hypozincemia except for the continuation of head noises, these being more frequently associated with hypozincemia when they are intermittent. Two hypotheses of pathogenesis are proposed to explain this phenomenon and are based on the importance of zinc to the syntheses of enzymes and proteins.     

Revalidation of radical mastoidectomy cavities: reconstruction with bone dust and bio-materials

The joint use of biocompatible ceramic granules coated with a thin layer of bone dust and temporalis fascia would appear to us to offer a solution in the rehabilitation of the radical mastoidectomy cavity. The practical simplicity and the plasticity of the system, as well as the excellent biocompatibility and bioactivity of the materials used, combine to make this a highly satisfactory procedure.     

Factors controlling aldosterone secretion during hypoxemia in fetal lambs

Factors modulating the fetal aldosterone response to hypoxemia were studied in three groups of chronically catheterized fetal lambs between 131 and 143 days of gestation (term, 145 days). One group (control group) received an infusion of 5% dextrose in water; the second group (captopril-treated group) was given captopril, an inhibitor of angiotensin-converting enzyme; the third group (captopril plus dexamethasone-treated group) received dexamethasone in addition to captopril. In all groups of fetuses, hypoxemia was associated with a significant increase in plasma K+ concentration (+0.7 +/- 0.1 meq/liter). In control fetuses, changes in plasma aldosterone concentration during hypoxemia correlated closely with changes in plasma K+ concentration r = 0.79; P less than 0.001) and with changes in plasma angiotensin II concentration (r = 0.77; P less than 0.001). In the captopril-treated fetuses, the rise in plasma aldosterone concentration during hypoxemia correlated closely with plasma K+ (r = 0.79; P less than 0.001) but not with plasma angiotensin II values (r = 0.17). No significant correlation was found between percent changes in maternal aldosterone and percent changes in fetal aldosterone during hypoxemia and following recovery (r = 0.36; P greater than 0.1) in captopril-treated fetuses. Administration of dexamethasone to fetuses receiving captopril completely inhibited the rise in plasma aldosterone associated with hypoxemia. Taken together, the present results suggest that the rise in plasma aldosterone during hypoxemia is not related to the level of activity of the renin-angiotensin system but depends probably on the increased secretion of adrenocorticotrophin by the fetus.(ABSTRACT TRUNCATED AT 250 WORDS)     

Farnesyl transferase inhibitor R115777 induces apoptosis of human myeloma cells.

R115777, a nonpeptidomimetic farnesyl transferase inhibitor has recently demonstrated a significant antileukemic activity in vivo in acute myeloid leukemia. Multiple myeloma (MM) is a fatal hematological malignancy characterized by an accumulation of long-lived plasma cells within the bone marrow. In the present study, we have investigated the effect of the R115777 on growth and survival of myeloma cells. We have found that R115777 induced (1) a significant and dose-dependent growth inhibition of the three myeloma cell lines tested; and (2) a significant and time-dependent apoptosis. R115777 also induced apoptosis in the bone marrow mononuclear cell population of four MM patients, being almost restricted to the malignant plasma cells. Finally, we have investigated the effect of the R115777 in the Ras/MAPK and JAK/STAT pathways which are implicated in survival and/or proliferation in MM. The phosphorylation of both STAT3 and ERK1/2 induced by IL-6 was totally blocked at 15 microM of R115777 and partially blocked when R115777 was used at 10 and 5 microM. The induction of apoptosis by R115777 in myeloma cells and its implication in the regulation of JAK/STAT signalling suggest that R115777 might be an interesting therapeutical approach in MM.