Short-term effects of surgery in post-menopausal patients with primary hyperparathyroidism and normal bone turnover.

The most common clinical presentation of primary hyperparathyroidism (PHPT) is nowadays characterized by a slight skeletal involvement. We studied 5 consecutive female patients with PHPT presenting with bone turnover marker levels within the reference range of our Center and whose bone mineral density values were above the usual fracture risk threshold. In each patient we measured, both in basal conditions and daily, for the first 5 days after surgery, the following indexes: serum total (T-ALP) and bone-specific (B-ALP) alkaline phosphatase activity, osteocalcin (BGP, by two different assays), together with the 24-hour urinary excretions of total pyridinoline (Pyr/Cr) and deoxypyridinoline (DPyr/Cr), free deoxypyridinoline (FD-Pyr/Cr), cross-linked N-telopeptide of type I collagen (NTx/Cr), and type I C-telopeptide (CTx/Cr). The markers of both bone formation and resorption significantly decreased after surgery (p<0.001 by multiple ANOVA). Individual post-surgical markers changes were all significant but T-ALP and FD-Pyr, the most pronounced percent reductions being shown by NTx and CTx. The time-course of such variations substantially differed among the various indexes. These results show that bone formation and resorption markers are up-regulated also in PHPT patients with mild skeletal involvement; acute removal of parathyroid hormone excess differently affected the markers of bone turnover in terms of both entity and time-course.

Could local anesthesia while breast-feeding be harmful to infants?

BACKGROUND: Few studies have been carried out on the levels and possible toxicity of local anesthetics in breast milk after parenteral administration. The purpose of this study is to determine the amount of lidocaine and its metabolite monoethyl-glycinexylidide (MEGX) in breast milk after local anesthesia during dental procedures. METHODS: The study population consisted of seven nursing mothers (age, 23-39 years) who received 3.6 to 7.2 mL 2% lidocaine without adrenaline. Blood and milk concentrations of lidocaine and its metabolite MEGX were assayed using high-performance liquid chromatography. The milk-to-plasma ratio and the possible daily doses in infants for both lidocaine and MEGX were calculated. RESULTS: The lidocaine concentration in maternal plasma 2 hours after injection was 347.6 +/- 221.8 microg/L, the lidocaine concentration in maternal milk ranged from 120.5 +/- 54.1 microg/L (3 hours after injection) to 58.3 +/- 22.8 microg/L (6 hours after injection), the MEGX concentration in maternal plasma 2 hours after injection was 58.9 +/- 30.3 microg/L, and the MEGX concentration in maternal milk ranged from 97.5 +/- 39.6 microg/L (3 hours after injection) to 52.7 +/- 23.8 microg/L (6 hours after injection). According to these data and considering an intake of 90 mL breast milk every 3 hours, the daily infant dosages of lidocaine and MEGX were 73.41 +/- 38.94 microg/L/day and 66.1 +/- 28.5 microg/L/day respectively. CONCLUSIONS: This study suggests that even if a nursing mother undergoes dental treatment with local anesthesia using lidocaine without adrenaline, she can safely continue breastfeeding.

Longitudinal evaluation of vitamin D status in healthy subjects from southern Italy: seasonal and gender differences.

Vitamin D status is currently considered among the relevant determinants of skeletal integrity. Since vitamin D levels present seasonal variations, we longitudinally studied young healthy men and women in order to investigate the related physiologic modifications of both calcium homeostasis and bone remodeling. Thirty-two men (mean age 39.4 +/- 7.8 years) and 58 premenopausal women (aged 36.9 +/- 6.4 years) from southern Italy were studied. In all subjects the following parameters were measured both in winter and in summer: serum calcium, phosphorus, creatinine, total alkaline phosphatase activity, 25-hydroxyvitamin D (25OHD), parathyroid hormone (PTH), osteocalcin (BGP), together with urinary calcium (Ca/Cr), total pyridinoline (Pyr/Cr) and deoxypyridinoline (d-Pyr/Cr), corrected for creatinine excretion. In both sexes 25OHD levels were significantly higher in summer, while PTH values were lower, than in winter. The prevalence of hypovitaminosis D, defined by concentrations of 25OHD lower than 30 nmol/l, was 17.8% in winter and 2.2% in summer in the whole sample, while it was 27.8% and 3.4%, respectively, among female subjects. Indeed male subjects did not display hypovitaminosis D, having throughout the year significantly higher calcium and 25OHD levels together with lower PTH values, than the women. Moreover, alkaline phosphatase total activity was more elevated in men both in winter and in summer. In women, during winter, bone remodeling markers levels were higher while urinary calcium levels were lower than in summer. In the whole sample serum 25OHD correlated positively with serum calcium and inversely with PTH. The seasonal percentage variations in PTH were inversely correlated with those of Ca/Cr. Our results show a relatively high prevalence of subclinical vitamin D deficiency among young healthy women from southern Italy. Significant gender-specific differences have been demonstrated in both calcium homeostasis and skeletal remodeling indexes; the seasonal fluctuations in the vitamin D-PTH axis are accompanied by cyclical variations of bone turnover rate, which were more pronounced in women.

Altered bone mass and turnover in female patients with adrenal incidentaloma: the effect of subclinical hypercortisolism.

The strategy of treatment for patients with adrenal incidentalomas (AI) may depend upon the presence of hormonal hypersecretion. Although alterations of bone turnover have been recently reported, data on bone mineral density (BMD) are not available in AI patients. We evaluated bone turnover and BMD in 32 female AI patients and 64 matched controls. Spinal and femoral BMD were similar in patients and controls. Serum bone GLA protein (6.8+/-3.5 vs. 8.8+/-3.2 ng/mL; P<0.005) and PTH (48.8+/-15.1 vs. 37.2+/-10.9 pg/mL; P<0.0001) were different in patients and controls. Patients were then subdivided into 2 groups: with (n = 8; group A) or without (n = 24; group B) subclinical hypercortisolism. PTH was higher (P<0.05) in group A than in group B and in both groups than in controls (57.1+/-13.6, 46.0+/-14.8, and 37.2+/-10.9 pg/mL, respectively), and bone GLA protein was lower in group A than in group B and controls (3.8+/-2.3, 7.5+/-3.1, and 8.8+/-3.2 ng/mL, respectively; P<0.05). Serum type I cross-linked C telopeptide and fasting urinary deoxypyridinoline/ creatinine were not different in the three groups. BMD at each site was lower (P<0.05) in group A than in group B and controls. Bone mass and metabolism are altered in AI patients with subclinical hypercortisolism and should be taken into account, therefore, when addressing the treatment of choice for these patients.

Alterations of bone turnover and bone mass at different skeletal sites due to pure glucocorticoid excess: study in eumenorrheic patients with Cushing's syndrome.

The aim of the present investigation was to study the effect of glucocorticoid excess on bone mass and turnover not influenced by other diseases known to affect skeleton and/or by different gonadal status and sex. We studied several markers of bone turnover and bone mineral density (BMD) by both quantitative computed tomography (at spine and forearm) and dual x-ray absorptiometry (at spine and three femoral sites) in 18 eugonadal female patients affected by Cushing's syndrome (CS) compared to 24 eugonadal healthy female subjects matched for age and body mass index. In CS patients, serum bone Gla protein, a marker of osteoblastic function, was reduced (3.28 +/- 2.3 vs. 6.47 +/- 2.5; P < 0.01), and bone resorption was increased, as indicated by increased urinary hydroxyproline (36.6 +/- 12 vs. 29.0 +/- 9.1, P < 0.05) and urinary deoxypyridinoline (22.1 +/- 8.0 vs. 16.4 +/- 6.3; P < 0.05). BMD was significantly (P < 0.05 or P < 0.01) reduced at all sites, except cortical forearm, in CS patients compared to controls. By comparing z-scores of reduced BMD in CS patients, spinal trabecular BMD was found to be the most severely affected. Furthermore, disease activity, as measured by urinary free cortisol, was significantly correlated with bone Gla protein (r = -0.57; P < 0.02), urinary hydroxyproline (r = 0.57; P < 0.02), urinary deoxypyridinoline (r = 0.48, P < 0.05), and BMD measured at spine and femur. Our results show that compared to matched control subjects, female eumenorrheic CS patients have reduced osteoblastic function, increased bone resorption, and reduced BMD, and that the severity of these abnormalities is statistically related to the severity of disease activity, as indicated by urinary free cortisol. Moreover, our data suggest a site and tissue specificity of the effect of glucocorticoid excess on bone mass.

Skeletal involvement in female acromegalic subjects: the effects of growth hormone excess in amenorrheal and menstruating patients.

Bone involvement is a common clinical feature in acromegalic patients, though previous studies gave divergent results possibly because of the different gonadal status of the patients studied. To study the influence of estrogen milieu in these patients, we evaluated 23 acromegalic patients with active disease, subdivided into two groups: menstruating and amenorrheal patients, comparable for duration and activity of disease. Forty-two matched women served as controls. Skeletal involvement was studied by measuring: (a) the main biomarkers of bone turnover: serum alkaline phosphatase total activity (AP), bone GLA protein (BGP), serum carboxy-terminal propeptide of type I collagen (PICP), serum type I cross-linked N-telopeptide (ICTP), and urinary pyridinoline and deoxypyridinoline corrected for creatinine (Pyr/Cr, D-Pyr/Cr) and urinary calcium/creatinine ratio (Ca/Cr); (b) bone mineral density (BMD), as measured by quantitative computed tomography both at lumbar spine and distal radius, and by dual X-ray absorptiometry both at lumbar spine and at three femoral sites (Ward's triangle, femoral neck, and great trochanter). AP, BGP, ICTP, Pyr/Cr, D-Pyr/Cr were significantly higher in patients than in controls, independent of the menstrual pattern. Higher PICP levels were found in the whole group and in menstruating acromegalics when compared with control women; no difference was found in amenorrheal patients, who in turn showed higher urinary Ca/Cr values. When patients were considered all together, BMD at spine, femoral neck, and trochanter was higher than in controls. In contrast, when the gonadal status was taking into account and, menstruating and amenorrheal subjects were considered separately, BMD at spine, but not in other sites, was significantly higher in menstruating patients than in controls. In contrast, no difference of BMD values at any site was observed between amenorrheal patients and controls. The mean BMD Z scores allowed us to detect an unequal involvement of different skeletal sites. Our results show that bone turnover is increased in acromegalic women and suggest that GH anabolic effect on bone is more evident in the presence of estrogens and that different skeletal sites may be affected differently by hormone excess.

Age-related changes in the global skeletal uptake of technetium-99m methylene diphosphonate in healthy women.

A short-term evaluation of global skeletal uptake (GSU) of technetium-99m methylene diphosphonate (MDP) was performed in 40 healthy female subjects with a wide age range in order to investigate the clinical performance of the technique and to detect the age-related changes in bone turnover. The results obtained were compared with measurements of the main biochemical markers of skeletal metabolism. We found that GSU increases progressively with age, independently of concomitant changes in renal function; significant correlations with biochemical markers of bone formation were also found. Therefore, the method appears to provide useful information concerning the bone turnover rate, and is also applicable to elderly people owing to its simplicity.

Primary carcinoma of the fallopian tube.

BACKGROUND: Because of the rarity of fallopian tube cancer, clinical approaches have changed during the last 18 years. METHODS: Twenty-nine patients with fallopian tube cancer were treated at the Gynecologic Oncology Department of Milan University from 1970 to 1988. The mean patient age was 59 years. Parity, symptomatology and histology were considered. Distribution by stage was as follows: I, 11 (37%); II, 10 (34%); III, 8 (27%) according to the Dodson classification. Twenty patients (69%) underwent surgery followed by pelvic irradiation. Adjuvant chemotherapy was performed in the treatment of 5 women with stage I disease, 6 with stage II, and all 8 with stage III. RESULTS: Five-year overall survival was 41.38%: 47.6% at stages I and II, 25% at stage III. Radiotherapy has not been replaced by cisplatin-based multiagent chemotherapy. Optimal surgical debulking combined with accurate lymph node sampling are not followed by systematic use of repeat laparotomy. CONCLUSIONS: The procedures described in this work improve the clinical assessment and patient survival, and make different series comparable.

Studies on the selective chemical inhibition by urea of alkaline phosphatase isoenzymes in the reaction course.

Urea inhibits the activity of alkaline phosphatase during the reaction course. The inactivation is progressively stronger for the placental, intestinal and renal subforms. Influence of reaction temperature, pH, type and molarity of buffer, magnesium chloride, albumin and enzyme concentration on the inactivation mechanism is evaluated. In all experimental conditions the process follows pseudofirst-order kinetics and the inactivation profiles are distinct and typical for each enzymatic subform. With a simple graphical analysis, a single inactivation curve in controlled experimental conditions, allows the identification of each isoenzyme from the slope and the calculation of the respective fractional amount from the intercept of the time-activity plot.