Effect of hormone replacement therapy upon haemorheological variables.

It is already admitted that hormone replacement therapy (HRT) decreases the risk of developing cardiovascular disease, although its mechanism is not clear yet. In the present work, the effect of the HRT upon cellular and plasmatic haemorheological factors determining blood flow properties: blood viscosity, plasma viscosity, plasma fibrinogen, rigidity erythrocyte index and erythrocyte aggregation rate was studied. Menopausal women were followed through a whole year of HTR. Results demonstrate that after six months of treatment there is a diminution in relative blood viscosity and erythrocyte rigidity, with constant values along the second semester. Erythrocyte aggregation, plasmatic and blood viscosity diminution observed during the treatment can be explained by the simultaneous plasma fibrinogen decrease. Modified cellular and plasmatic rheology could produce beneficial effects on blood flow, particularly in microcirculation, presenting a possible mechanism by which HTR decreases the risk of cardiovascular disease development during menopause.

In postmenopausal osteoporosis the bone increasing effect of monofluorophosphate is not dependent on serum fluoride.

According to previous pharmacokinetic studies the bioavailability of fluorine (F) from sodium monofluorophosphate (MFP) doubles that of sodium fluoride (NaF). This paper reports a study designed to verify whether the vertebral bone mass increasing effect of NaF (30 mg F/day) was comparable to that of MFP (15 mg F/day), given for 18 months to osteoporotic postmenopausal women. The BMD of lumbar vertebrae of both groups showed significant increases (MFP: 60 +/- 15 mg/cm2, NaF: and 71 +/- 12 mg/cm2) over basal levels (P < 0.001). The difference between treatments was not significant (P = 0.532). The serum levels of ionic F (the mitogenic species on osteoblasts) were not related to the above mentioned effects. In NaF-treated patients, the fasting levels of total serum F increased significantly (6.7 +/- 0.9 microM vs. Basal: 2.0 +/- 0.8 microM; P < 0.001). This phenomenon was accounted for by ionic fluoride that increased over 20-fold (6.5 +/- 1.9 microM vs. Basal: 0.3 +/- 0.04 microM). In MFP-treated patients the fasting serum levels of total (7.0 +/- 0.7 microM vs. Basal: 2.2 +/- 0.9 M) and diffusible F (0.5 +/- 0.02 microM vs. Basal 0.2 +/- 0.02 microM) increased significantly (P < 0.001). The increase in the non diffusible F fraction is accounted for by protein-bound F, probably by the complexes formed between MFP and alpha 2-macroglobulin and C3. Serum diffusible F was formed by two fractions: ionic F and F bound to low molecular weight macromolecule/s (2,200 +/- 600 Da), in approximately equal amounts. The general information afforded by the present observations support the hypothesis that ionic F is released progressively during the metabolism of MFP bound to alpha 2-macroglobulin and C3. These phenomena explain why comparable effects to those obtained with 30 mg F/d of NaF could by obtained with one half the dose of MFP.

In postmenopausal osteoporosis the bone increasing effect of monofluorophosphate is not dependent on serum fluoride.

According to previous pharmacokinetic studies the bioavailability of fluorine (F) from sodium monofluorophosphate (MFP) doubles that of sodium fluoride (NaF). This paper reports a study designed to verify whether the vertebral bone mass increasing effect of NaF (30 mg F/day) was comparable to that of MFP (15 mg F/day), given for 18 months to osteoporotic postmenopausal women. The BMD of lumbar vertebrae of both groups showed significant increases (MFP: 60 +/- 15 mg/cm2, NaF: and 71 +/- 12 mg/cm2) over basal levels (P < 0.001). The difference between treatments was not significant (P = 0.532). The serum levels of ionic F (the mitogenic species on osteoblasts) were not related to the above mentioned effects. In NaF-treated patients, the fasting levels of total serum F increased significantly (6.7 +/- 0.9 microM vs. Basal: 2.0 +/- 0.8 microM; P < 0.001). This phenomenon was accounted for by ionic fluoride that increased over 20-fold (6.5 +/- 1.9 microM vs. Basal: 0.3 +/- 0.04 microM). In MFP-treated patients the fasting serum levels of total (7.0 +/- 0.7 microM vs. Basal: 2.2 +/- 0.9 M) and diffusible F (0.5 +/- 0.02 microM vs. Basal 0.2 +/- 0.02 microM) increased significantly (P < 0.001). The increase in the non diffusible F fraction is accounted for by protein-bound F, probably by the complexes formed between MFP and alpha 2-macroglobulin and C3. Serum diffusible F was formed by two fractions: ionic F and F bound to low molecular weight macromolecule/s (2,200 +/- 600 Da), in approximately equal amounts. The general information afforded by the present observations support the hypothesis that ionic F is released progressively during the metabolism of MFP bound to alpha 2-macroglobulin and C3. These phenomena explain why comparable effects to those obtained with 30 mg F/d of NaF could by obtained with one half the dose of MFP.

Outcome of hip fractures among elderly subjects.

This paper reports a retrospective study (1979-1995) on 200 patients (154 women and 46 men), 50-101 years old, who received medical attention because of unilateral hip fracture. Nine women and four men fractured twice. In 75% of women and 90% of men, surgery was carried out between one and five days after fracture. A non significant greater proportion of women (14/154) than men (6/46) died in the first year after injury (chi 2 = 3.459, P = 0.062). Survival was assessed using Cox proportional hazards model. Survival was a function of age (P = 0.000) and sex (P = 0.008). After adjustment to a common mean age (79 years), the median survivals for men and women were 3.9 and 8.4 years, respectively. Controlled concurrent life-threatening diseases, the kind of fracture [medial (subcapital and transcervical) or lateral (inter- and subtrochanteric)] and the type of prosthesis (total/partial articulation replacement) had no significant impact on survival. No differences in evolution were observed: 80% returned to their ambulatory status before injury, 8.5% required walking aids and 5.5% could not walk. The overall information afforded by this study suggests that with worldwide improvement of hip fracture outcome, the cost/effectiveness of surgical treatment of hip fracture may become, from the standpoint of public health investment, a favorable alternative with respect to cost/effectiveness of prevention-treatment measures.

The natural history of kyphosis in postmenopausal women.

A cross-sectional study of vertebral morphometry in 449 unscreened postmenopausal women, from the ages of 40 to 80, is reported. The wedge angles of thoracic vertebrae T4-12 were found to increase exponentially as a function of age, up to 70 years. In addition to age, the wedging phenomenon was found to be accentuated by increased bone turnover due to low calcium intake, reduced physical activity, each successive delivery, and breast feeding. Most of these variables were not correlated with isolated vertebral wedge angles, but rather with the sum of them (Sigma, sigma), assumed to assess the impact of those variables on thoracic kyphosis. In a subset of women, sigma was found to be inversely correlated with low spinal mineral density at L2-4. T-11 and T-12 were the vertebrae most frequently deformed (wedge angle exceeding mean +/- 3 SD in a group of 50 young healthy women, 25-45 years old). The distribution of deformed vertebrae was found to be significantly different from those qualified as "fractured" according to Kleerekoper et al.'s (1984) and Melton et al.'s (1989) criteria. The overall information afforded by past and present data indicates that in postmenopausal women, vertebral deformation may occur with the help of mechanical solicitations plus high bone remodeling rates, as well as by structural collapse (fracture). The information obtained does not allow one to quantify the relative contribution of each set of factors to the wedging phenomenon.

Hypercalciuria and urinary saturation measurements in climacteric women.

Fifteen percent (20/130) of a group of climacteric women on diets of their choice had urinary calcium (Ca) levels exceeding 4 mg/kg per day. Most of these hypercalciuric subjects had a daily Ca intake of 0.4-0.5 g. Their bone turnover rates were raised and high Ca absorption was observed in 4 cases. Serum Ca and total protein and glomerular filtration rates were normal in all the hypercalciuric patients. The calcium/creatinine (Ca/Cr) ratio (mg l-1/mg l-1, fasting, 09:00-10:00 h) was measured in 72 climacteric women, 35 of whom (49%) had ratios > 0.1. The latter defines a relative hypercalciuria as compared with premenopausal Ca excretion levels. Only 5 of the 35 subjects had calciuria levels above 4 mg/kg per day. The Ca/Cr ratio cannot replace daily urinary Ca measurements for the screening of subjects in whom calciuria may exceed net Ca absorption. Urinary saturation measurements were carried out in 70 women. Supersaturation was observed only in the case of Ca oxalate (CaOx) among several calcium salts usually found in urinary stones. CaOx supersaturation was observed in 95% of the hypercalciuric subjects and in 48% of the rest of the women investigated. The relatively high frequency of CaOx supersaturation can be attributed in part to the decreased excretion of citrate associated with ovarian failure. Oestrogen replacement therapy increased citrate excretion and lowered the level of CaOx supersaturation. Ca supplementation (1 g Ca/day) reduced the degree of supersaturation as a result of the concurrent reduction in oxalate excretion.

Estimation of bone turnover in climacteric women by the whole body retention of fluoride.

This paper reports the measurement of whole body retention using fluoride (WBRF) as an estimator of skeletal turnover in a group of climacteric women that received an oral dose of 700 mumol of sodium fluoride. WBRF is defined as 100(1-(urinary fluoride/fluoride load)). WBRF was significantly correlated with whole body retention of 99m-Tc-methylene-diphosphonate, the serum levels of the bone alkaline phosphatase and the urinary excretion of hydroxyproline. WBRF values ranged from 20% to 95% and were affected by calcium intake and the urinary calcium excretion. In normal subjects with high turnover, the measurement of serum alkaline phosphatase activity and/or urinary hydroxyproline excretion helps to distinguish these cases from patients with metabolic bone diseases due to metastases, Paget disease, etc. The fact that the fraction of fluoride not incorporated into bone is not further metabolized plus the accuracy, preciseness and rapidity of fluoride measurements in urine are the main advantages of this technique.

A clinical test for calcium absorption in climacteric women. A two tracer, single blood sample procedure with corrections for body size and skeletal turnover.

This paper reports a two tracers (45Ca for estimating calcium absorption and stable fluoride for assessing skeletal turnover), single blood sample procedure that estimates the absorption of calcium in climacteric women. The proposed technique determines the percentage (Ac) of the dose of 45Ca administered orally (in the fasting state, diluted with 150 ml of milk), present in the extracellular fluid (estimated as 15% of body wt) five hours after intake, corrected for skeletal turnover (assessed by the whole body retention of fluoride). In a series of 13 patients, Ac has been found to be operationally equivalent to the ratio: net Ca absorption/Ca intake, measured under balance conditions. The calcium balances of 60 climacteric women, estimated as: net Ca absorption (Ca intake factored by Ac) minus calciuria was found, as expected, to be correlated with skeletal turnover.

A clinical test for calcium absorption in climacteric women: a two tracer, single blood sample procedure with corrections for body size and skeletal turnover

Se ha desarrollado un método que estima la relación: absorción neta de calcio/calcio ingerido, mediante el empleo de dos trazadores (45Ca y fluoruro de sodio). Estos trazadores estiman, respectivamente, la absorción de calcio y el turnover óseo. Cada sujeto recibió una dosis oral de 700 micronmoles de fluoruro de sodio en ayunas, recogió la orina emitida en las 24 horas siguientes con el objeto de medir la fracción excretada de fluoruro y determinar la retención corporal de fluoruro (WBRF) que estima el turvnover óseo: WBRF = 100 (1 - (Fluoruro urinario/dosis de fluoruro)). Veinticuatro horas después de la dosis de fluoruro, cada paciente recibió 2 microcuries de 45Ca en 15 ml de leche. Se les extrajo sangre 5 horas más tarde para medir la radioactividad en el plasma y calcular la fraccioón del isótopo en el líquido extracelular, estimado en 15% del peso corporal: balances entre 0 y -100 mg Ca/d (n = 30) exhibieron una relación sigmoides en función de la WBRF

A clinical test for calcium absorption in climacteric women. A two tracer, single blood sample procedure with corrections for body size and skeletal turnover.

This paper reports a two tracers (45Ca for estimating calcium absorption and stable fluoride for assessing skeletal turnover), single blood sample procedure that estimates the absorption of calcium in climacteric women. The proposed technique determines the percentage (Ac) of the dose of 45Ca administered orally (in the fasting state, diluted with 150 ml of milk), present in the extracellular fluid (estimated as 15

of body wt) five hours after intake, corrected for skeletal turnover (assessed by the whole body retention of fluoride). In a series of 13 patients, Ac has been found to be operationally equivalent to the ratio: net Ca absorption/Ca intake, measured under balance conditions. The calcium balances of 60 climacteric women, estimated as: net Ca absorption (Ca intake factored by Ac) minus calciuria was found, as expected, to be correlated with skeletal turnover.

A clinical test for calcium absorption in climacteric women: a two tracer, single blood sample procedure with corrections for body size and skeletal turnover

Se ha desarrollado un método que estima la relación: absorción neta de calcio/calcio ingerido, mediante el empleo de dos trazadores (45Ca y fluoruro de sodio). Estos trazadores estiman, respectivamente, la absorción de calcio y el turnover óseo. Cada sujeto recibió una dosis oral de 700 micronmoles de fluoruro de sodio en ayunas, recogió la orina emitida en las 24 horas siguientes con el objeto de medir la fracción excretada de fluoruro y determinar la retención corporal de fluoruro (WBRF) que estima el turvnover óseo: WBRF = 100 (1 - (Fluoruro urinario/dosis de fluoruro)). Veinticuatro horas después de la dosis de fluoruro, cada paciente recibió 2 microcuries de 45Ca en 15 ml de leche. Se les extrajo sangre 5 horas más tarde para medir la radioactividad en el plasma y calcular la fraccioón del isótopo en el líquido extracelular, estimado en 15% del peso corporal: balances entre 0 y -100 mg Ca/d (n = 30) exhibieron una relación sigmoides en función de la WBRF (AU)

Endometrial cancer and its precursors: a comparison of histological and clinical features.

In this study, the histological definition of endometrial cancer precursor (ECP) lesions is discussed and a comparison is made of clinical and histological parameters of ECP patients and endometrial cancer (EC) patients. ECP lesions were divided in 3 types: adenomatous hyperplasia, atypical hyperplasia and in situ adenocarcinoma. The following parameters were analyzed: age, menopausal status, gynecological and extragynecological familiar cancer incidence, other cancers in the proband, diabetes, obesity, primary infertility, fertility and previous estrogen therapy. Results give support to the hypothesis of the existence of a common biological pathway between ECP and EC. The high frequency of coexistence of both types of lesions in hysterectomy specimens from EC patients studied by step sections adds a confirmatory supporting argument. Measures for primary and secondary prevention of these lesions are proposed.