Behaviour of vaginal epithelial maturation and sex hormone binding globulin in post-menopausal breast cancer patients during the first year of tamoxifen therapy.

To evaluate the effect of tamoxifen on vaginal epithelial maturation and on oestrogen-related hepatic synthesis, we prospectively studied the karyopyknotic index (KPI), the maturation index (MI), expressed as a percentage of parabasal (MI-1), intermediate (MI-2) and superficial (MI-3) cells, as well as the serum levels of the oestrogen-dependent sex hormone binding globulin (SHBG). Tests were performed at baseline, after 1, 3, 6 and 12 months of therapy in 64 post-menopausal breast cancer patients. Basal KPI ranged from 0 to 9 (mean 1.5 +/- 0.3) and rose 13.5-fold to 21 +/- 2.5 (P = 0.000) after the first 30 days of tamoxifen. Absence of KPI rise was observed in 23% of patients. Pretreatment MI figures 1, 2 and 3 were 56.9 +/- 5.6, 41.7 +/- 5.4 and 1.4 +/- 0.3, respectively, and sharply shifted to the right (P = 0.000) after 1 month of therapy, indicating an increase of vaginal epithelial maturation. At baselines the SHBG mean value was 62.1 +/- 3.3 nmol/l and underwent an increase of 44% (P = 0.000) after 30 days of tamoxifen. All of these observed 1-month modifications remained stable up to the studied 12 months of therapy. Present findings indicate an early and persistent oestrogenic effect of tamoxifen on the vaginal epithelium and the hepatic synthesis of SHBG.

Different dietary calcium intake and relative supersaturation of calcium oxalate in the urine of patients forming renal stones.

1. Dietary calcium restriction, an efficient practice in reducing urinary calcium excretion, has been reported to induce either an increase or no change in oxalate excretion, questioning its use in hypercalciuric stone-forming patients. In addition, calcium restriction has been previously demonstrated to induce other urinary changes which might influence the relative supersaturation of calcium oxalate. So the overall effect of calcium deprivation on the relative supersaturation of calcium oxalate is unpredictable. 2. The aim of the study was to evaluate the effect of dietary calcium restriction on the relative supersaturation of calcium oxalate in the urine of stone-forming patients utilizing a computer methodology which takes into account the main soluble complex species of oxalate. 3. We studied 34 stone-forming patients on both a free-choice diet, whose Ca and oxalate content (24 and 1.2 mmol respectively) was assessed by dietary inquiry, and after 30 days on a prescribed low-calcium and normal oxalate diet (11 and 1.1 mmol respectively). Under both conditions, the excretion of the main urinary parameters related to dietary composition, electrolytes, oxalate and daily citrate urinary excretion, were measured. The relative supersaturation of calcium oxalate was calculated by means of an iterative computer method which takes into account the main soluble complex species on which the solubility of calcium oxalate is dependent. In addition, intact parathyroid hormone and 1,25-dihydroxyvitamin D blood levels were also evaluated. In 13 of the patients intestinal calcium absorption was evaluated during both a free- and a low-calcium diet, utilizing kinetics methodology. 4. The low-calcium diet induced, together with an expected reduction of calcium excretion, a marked increase in oxalate urinary output. This finding was independent of the presence or otherwise of hypercalciuria and of the serum levels of parathyroid hormone and vitamin D. Intestinal calcium absorption was also stimulated by calcium deprivation and its levels were well correlated with oxalate excretion. Minor changes in magnesium and citrate excretion were also observed. The overall effect on the relative supersaturation of calcium oxalate consisted in a substantial increase in this parameter during the low-calcium diet. 5. In conclusion, our data reinforce the concept that dietary calcium restriction has potentially deleterious effects on lithogenesis, by increasing the relative supersaturation of calcium oxalate.

Impact of the method of calculation on assessment of the PTH-calcium set point.

BACKGROUND: Although the methodology for calculating the PTH secretory parameters is well established, a consensus on a common methodology for calculation of the set point value has not yet been achieved. This is probably one of the major reasons for the conflicting results obtained for this secretory parameter. The aim of the present study was to analyse the influence of the different methods of calculation on the values of set point obtained in clinical nephrology practice. METHODS: We analysed 68 PTH-calcium sigmoidal curves, obtained by infusion of 37 mg/kg Na2-EDTA i.v. in 2 h and 8 mg/kg Ca gluconate based on the calcium element i.v. in 2 h on two separate days. The set point was calculated according to three different methods: method A, the originally described method, based on the classical four-parameter model, which considers the set point as the calcium concentration corresponding to the PTH value intermediate between the maximal and minimal values (the midrange value method); method B (set point = calcium concentration corresponding to 50% of maximal PTH), and method C (set point = calcium concentration corresponding to 50% inhibition of basal PTH value). The three different sets of set point values were entered into the formula of the sigmoidal curve to test the best fitting of the PTH experimentally observed values. RESULTS: The set point values calculated with the classical midrange value method were lower than the corresponding values calculated by the other two methods; method C gave the highest values. Furthermore the best fitting of the experimentally observed PTH levels was obtained by method A the worst by method C, while method B gave intermediate results. The difference between method A and method B was analysed in order to see if this difference is constant over the whole range of PTH secretory conditions and calcium concentrations. The higher the basal serum calcium concentrations and the lower the suppressibility of PTH, the greater was the overestimation of set point values by method B compared to the midrange value method. CONCLUSIONS: Method A, the midrange value method, gives the set point values closest to the original concept of the four parameter model. Although method B (50% of maximal PTH) is well correlated with the original method, it overestimates the set point values and most importantly, this overestimation is not constant, but largely affected by calcium concentration and by the secretory conditions of parathyroid glands.

The calcitonin-calcium relation curve and calcitonin secretory parameters in renal patients with variable degrees of renal function.

Increased calcitonin (CT) levels have been reported in chronic renal failure, even before the uraemic phase and in the absence of hypercalcaemia. Furthermore, a sigmoidal CT-calcium relationship was recently observed in rats and haemodialysed patients. We carried out the present investigation in order to assess: (a) whether the sigmoidal CT-calcium relationship is also evident in renal patients with a variable degree of renal failure and in normal subjects; (b) whether the four secretory parameters already described for the PTH-calcium relation curve might be described for CT too; (c) whether any change in some, if any, of these secretory parameters could be found at a variable degree of renal insufficiency. We studied 33 renal patients (RP), with a variable degree of renal failure (creatinine clearance ranging from 16 to 164 ml/min), and 10 normal subjects (C). All RP and C were submitted to a basal evaluation including the assessment of (1) basal concentrations of 1,25(OH)2 vitamin D, 25(OH) vitamin D, monomeric CT, intact PTH; (2) GFR by Cr51EDTA clearance. On the 2 subsequent days, a hypocalcaemic test (Na2-EDTA about 37 mg/kg of body-weight/2 h) and a hypercalcaemic test (Ca gluconate giving 8 mg/kg body-weight/2 h of Ca element) were carried out for the assessment of both CT and PTH secretory parameters. According to GFR values, the RP were divided into three groups: group RP1 (GFR > 70 ml/min per 1.73 m2; n = 10), group RP2 (GFR between 30 and 70 ml/min per 1.73 m2; n = 15), group RP3 (GFR < 30 ml/min per 1.73 m2; n = 8). In most, but not all, RP and C a sigmoidal CT-calcium relationship was evident, opposite in direction to the PTH-calcium relation curve. In these RP and C the four secretory parameters, characteristic for the PTH-calcium secretion curve, were calculated for CT too. When pooled RP and C were considered, both minimal (9.0 +/- 6.4 pg/ml) and maximal CT levels (71.8 +/- 56.2 pg/ml) significantly differed from basal levels (24.3 +/- 18 pg/ml; P < 0.001). The CT set point (CT SP) and sensitivity (CT SENS) values were significantly higher and lower than the corresponding PTH secretory parameters (CT SP 1.39 +/- 0.08 mmol/l, PTH SP 1.23 +/- 0.05 mmol/l, P < 0.001) (CT SENS 243 +/- 67%/mmol, PTH SENS 598 +/- 329%, P < 0.001). However, the CT SP values were strictly correlated with PTH SP values (r = 0.78, P < 0.001). When CT secretory parameters were considered separately in the RP groups, increased levels of basal (36.1 +/- 28.6 pg/ml), minimal (17.9 +/- 10.4), and maximal (139.9 +/- 39.7) CT levels were found in the RP3 group, when compared with both the other RP groups and C. No significant difference was found as regards the CT SP and CT SENS values between RP and CT. These results suggest that (1) CT secretion is homeostatically controlled by calcium changes in the same range of the PTH-calcium system; (2) a sigmoidal CT-calcium relationship is demonstrable in most (but not all) RP and C; in these subjects it is possible to calculate the CT secretory parameters as for PTH; (3) the increase in CT levels in the course of chronic renal failure is quite similar to the already known increase of PTH, and is characterized by the increase of basal, minimal and maximal CT values, suggesting that an increased secretion of CT by the thyroid C-cells (rather than CT retention due to a decrease in renal function), is responsible for these findings.

Direct in vivo assessment of parathyroid hormone-calcium relationship curve in renal patients.

Secondary hyperparathyroidism (SHP) is a well documented finding even in the early stages of chronic renal failure (CRF). A sigmoidal relationship, fitting a four parameter model, links PTH secretion rate and calcium concentration changes. To our knowledge, PTH secretory parameters have only been studied in uremic patients who are in dialysis treatment. As a result of these studies, a possible role for derangement in setpoint values (that is, the serum calcium concentration corresponding to the mid-range value on the sigmoidal curve) has been suggested in the pathogenesis of SHP in CRF. Our study was undertaken to gain insight into the calcium-PTH relationship curve in the first course of CRF and to assess whether a change in any of the secretory parameters is related to the beginning of SHP. We studied 27 male renal patients with a variable degree of renal function (creatinine clearance 12 to 164 ml/min) and 9 control subjects. In all patients and controls the following parameters were evaluated: (1) basal 1,25(OH)2 vitamin D, 25(OH)vitamin D, calcitonin (CT), intact PTH; (2) GFR by Cr51EDTA clearance; (3) the sigmoidal PTH-ionized calcium relation curve, by means of a hypocalcemic stimulating test (Na2-EDTA 37 mg/kg body weight/2 hr) and a hypercalcemic test (Ca gluconate giving 8 mg/kg of body weight/2 hr of Ca element), performed on two consecutive days.(ABSTRACT TRUNCATED AT 250 WORDS)

Urinary citrate, bone resorption and intestinal alkali absorption in stone formers with fasting hypercalciuria.

Reduced citrate in urine and increased fasting excretion of calcium are abnormalities frequently reported in stone forming (SF) patients. Increased dietary acid (or reduced alkali) introduction or absorption may be a potential cause of both these pathological findings. To test this hypothesis, we studied 64 SF patients (32 with fasting hypercalciuria (FH) and 32 without FH (NFH)). After a basal evaluation for nephrolithiasis, while on a 500 mg calcium diet, they were evaluated for: (1) daily intestinal alkali absorption (IAA), by urinary electrolyte excretion; (2) basal concentrations of PTH, calcitonin (CT) and 1,25(OH)2-VitD; (3) oral calcium load for evaluation of changes in calcium and hydroxyproline urinary excretions; (4) intestinal calcium absorption (18 patients), with double curve analysis (stable Sr as tracer); and (5) changes in citrate excretion after an alkali load (50 mEq of a mixture of calcium gluconate, lactate and carbonate) in 10 patients. The results demonstrated: (1) FH stone formers had reduced citrate excretion and lower mean IAA levels than NFH stone formers; (2) FH stone formers also had higher bone resorption levels with lower PTH and higher CT levels; (3) IAA levels were related to both citrate excretion and bone turnover indices; and (4) the increases in citrate excretion after oral alkali load were strictly related to basal IAA values (index of alkali absorption and/or generation after oral load), demonstrating that a different absorptive capacity of alkali rather than a different dietary content may underlie these metabolic abnormalities.

L-thyroxine malabsorption due to the injection of herbal remedies.

Two patients are described in whom the absorption of l-thyroxine was impaired by non-prescription herbal and nutritional remedies. The absorption of thyroid hormones is discussed and an approach to the problem of patients who appear to be unresponsive to the usual doses of thyroid hormones is suggested.

[Carcinoembryonic antigen (CEA) and non-oncological liver diseases (case report)]. / Antigene carcinoembrionario (CEA) e patologia epatica non oncologica (contributo casistico).

Carcinoembryonic antigen (CEA), an oncofetal glycoprotein, has been originally suggested as a tumor marker for colorectal cancer and afterwards has been regarded as a specific marker for different cancers. The determination of CEA in 73 patients with "benign" hepatic diseases points out the limitation of test's diagnostic value on account of the not infrequent observation of false positives in the examined cases. In particular the greatest incidence and intensity of elevated levels of CEA has been found in hepatic cirrhosis. However must be mentioned that the highest values of CEA has been documented nearly constantly in the comparison's group of some forms of malignancies, between which nevertheless there have been sporadically false negatives.