Increased Serum Ca Research Articles

A 26-week repeated subcutaneous dose toxicity study of calcipotriol (MC903) followed by a 5-week recovery test in rats

A 26-week repeated subcutaneous dose toxicity of calcipotriol (MC903), an anti-psoriasic agent, followed by a recovery for 5 weeks was studied in Slc:SD rats at doses of 0.4, 2 and 10 micrograms/kg/day as low, mid and high dose levels. 1. No mortality during the experimental period was observed in both sexes of all groups including control. An increased incidence of opacity of the eyeball surface in males was noted at high dose. There were no difference in body weight and food consumption between control. An increased water consumption in both sexes was observed at high dose. 2. An increased incidence of the corneal opacity was noted significantly at high dose in both sexes compared with that observed in control. Urinalysis revealed the increased excretions of Ca at more than mid dose, and Na, Cl and IP in males at high dose, and an decreased urinary volume in females and lower pH in both sexes at high dose. An increased serum Ca level in males at mid dose and in both sexes at high dose, and an elevated ALP activity in males at high dose were observed. The increased weights of the kidney in males at more than mid dose and adrenal gland in both sexes at high dose were observed. The increased incidence of mineralization of the cornea and kidney was noted significantly in males at more than mid dose as compared with control. Dilatation of endoplasmic reticulum of distal tubular cells of the kidney in both sexes was observed at high dose on electron microscopic examination. 3. After a 5-week recovery period, the changes related with the treatment of MC903 almost disappeared except for mineralizations of the cornea and kidney. 4. On the basis of results obtained in the present study, it is considered that 0.4 microgram/kg/day is the no-toxic dose of MC903 administered subcutaneously in both sexes of rats.

A study of calcium metabolism in calcium-containing stone formers

To clarify the pathogenesis of calcium-containing urinary stone, calcium metabolism of the 113 patients with calcium-containing stone was studied by fasting and oral calcium loading test. The stone patients were classified into four groups. Those were normocalciuria (NC, n = 60), absorptive hypercalciuria-1 (AH-1, n = 26), absorptive hypercalciuria-2 (AH-2, n = 16) and renal hypercalciuria (RH, n = 11). In the AH-1 group, hypercalciuria resulted from enhancement of intestinal calcium (Ca) absorption. The increase in serum Ca from absorbed Ca increased renal filtered load of Ca. Urinary excretion of Ca was correlated to that of sodium (Na) in fasting and Ca load, and both increments were also correlated in Ca load. As of this fact, the increase in Na excretion was responsible for a cause of hypercalciuria in the AH-1 group. In the RH group, the serum ionized Ca level and % tubular reabsorption of Ca were significantly lower than those of other groups. Urinary excretion of Ca and Na ratio was significantly higher than that of the NC and AH-1 groups. This condition was due to an impaired renal tubular reabsorption of Ca and the resulting secondary hyperparathyroidism. These findings suggested was response disorder of distal tubular to parathyroid hormone. Urinary excretion of phosphorus (P) was correlated to that of Na in fasting and Ca load, and both increments were also correlated in Ca load in the AH-1 group. The increase in urinary excretion of P resulted from the secondary hyperparathyroidism in the RH group.(ABSTRACT TRUNCATED AT 250 WORDS)

Elevated serum ICTP concentrations reflect poor prognosis in patients with ovarian carcinoma.

The effect of ovarian carcinoma on the circulating concentration of the cross-linked carboxyterminal telopeptide of type I collagen (ICTP) was studied in 17 patients before and during treatment. ICTP is a complex peptide released from type I collagen, which is the main organic component of bone matrix but also induced in ovarian carcinoma tissue and the peritoneal cavity by the tumour. CA 125 and the aminoterminal propeptide of type III procollagen (PIIINP) were also measured. The preoperative CA 125, PIIINP and ICTP concentrations were pathological in 16 (94%), nine (53%) and seven (41%) patients, respectively. There was a positive correlation between the PIIINP and ICTP levels in serum. After surgery and one course of cytotoxic chemotherapy, the median CA 125 concentration decreased whereas those of PIIINP and ICTP increased. During monitoring of the treatment response, patients with regressive disease showed lower CA 125 concentrations than those with stable or progressive disease. For PIIINP and ICTP there was no clear difference between these response categories, but altogether, simultaneously increasing serum CA 125, PIIINP and ICTP concentrations were consistently associated with poor prognosis.

Intracellular ionized calcium and increasing doses of lithium chloride therapy in healthy Sprague-Dawley rats

The use of lithium salts in the prophylaxis and treatment of several psychiatric and neurologic disorders continues to be well accepted despite the apparent lack of understanding regarding its mode of action at the molecular level. This lack of delineation in the mechanism of action is supported by numerous conflicting publications. Despite the lack of understanding, a role for calcium in the manifestation of lithium's action is a constant singular consensus. Intracellular ionized calcium ([Ca ++] i) is involved in the proper functioning of cells because of its role in the second messenger pathway. It is therefore essential to evaluate the effect of lithium on intracellular calcium metabolism in a well-defined system. In this study, platelets loaded with Fura-2-Acetoxymethyl were used to evaluate the effect of intraperitoneally administered lithium chloride at 0, 2.5, 5.0, 7.5, and 10 mmol/kg body wt. on [Ca ++] i. The results showed a slight relative increase in serum Ca ++ that correlated well with the dose of LiCl administered to the rats. The baseline [Ca ++] i were comparable in the study groups, but the response to thrombin stimulation was more pronounced at LiCl doses of 2.5, 5.0, and 7.5/kg body wt. compared with control and rats treated with 10 mmol LiCl/kg body wt. This finding suggests a dose-dependent response of [Ca ++] i to LiCl treatment. The observation may therefore explain the variations that have been reported in [Ca ++] i studies with respect to LiCl therapy using different doses.

Serum increase and liver overexpression of carbohydrate 19.9 antigen in patients with genetic haemochromatosis.

CA 19.9 antigen is mainly secreted by biliary and pancreatic duct cells. Its metabolism could be modified in genetic haemochromatosis by iron accumulation within these cells. Therefore, CA 19.9 was assayed in the serum samples of 84 patients with genetic haemochromatosis before and after iron depletion and immunolocalised in the liver of 24 untreated genetic haemochromatosis cases. The study showed that serum CA 19.9 (N < 37 IU/l) was increased (SD) before treatment (41.2 (34)) when compared with after the venesection period (16 (12)), and correlated, before treatment, with the amount of iron excess, transaminases, fibrosis, and biliary iron deposits. Hepatic CA 19.9 was located within the cytoplasm of bile duct and cholangiolar cells. In conclusion, this study shows that a mild, reversible, and non-specific increase in serum CA 19.9 is common in genetic haemochromatosis patients and shows that this increase is related to iron excess, directly or through associated liver damage. The unexplained finding of a mild increase in serum CA 19.9 should lead, in a patient with no diagnosis, to the search for liver iron overload, and, in a patient with untreated genetic haemochromatosis, not to further diagnostic procedures unless this finding persists after completion of the venesection treatment.

Treatment of malignancy-associated hypercalcemia with YM175, a new bisphosphonate: elevated threshold for parathyroid hormone secretion in hypercalcemic patients.

The effect of a new third generation bisphosphonate, YM175 (cycloheptylamino-methylene bisphosphonate), on serum calcium (Ca) and intact PTH levels was examined in 79 malignancy-associated hypercalcemia patients with serum Ca levels higher than 2.75 mmol/L. A single infusion of 2.5, 5, and 10 mg YM175 reduced serum Ca levels in a dose-dependent manner. YM175 was about 6 times more potent than 3-amino-hydroxypropylidene-1,1-bisphosphonate. Among 23 patients treated with 10 mg YM175, serum Ca decreased by more than 0.5 mmol/L in 20 patients and was normalized in 11 patients. Serum intact PTH was subnormal in all of these patients before treatment and remained subnormal in 12 patients (suppressed PTH group), but was elevated to normal or high levels after treatment in the remaining 11 patients (responsive PTH group). Serum Ca was significantly higher throughout the study period in the suppressed PTH group, and mean serum Ca at the nadir did not decrease below 2.90 mmol/L in this group. However, the rate or magnitude of reduction in serum Ca was not different in the two groups. Polynomial regression analysis revealed that the threshold of serum Ca for PTH secretion was elevated to 2.75 mmol/L in the responsive PTH group, whereas it was about the upper limit of normal when both groups were combined (2.59 mmol/L). Furthermore, in the responsive PTH group, the threshold for PTH secretion during the decreasing serum Ca phase (days 4 and 6) was higher than that during the increasing serum Ca phase (days 10 and 14). The changes in the threshold for PTH secretion were also observed in patients treated with lower doses of YM175. These results demonstrate that YM175 is one of the most potent currently available bisphosphonates, and that the threshold for PTH secretion is elevated in at least some malignancy-associated hypercalcemia patients. In addition, there appears to be a difference in the threshold for PTH secretion between the decreasing and increasing serum Ca phases similar to the previously reported hysteresis phenomenon.

Predicting cholangiocarcinoma in patients with primary sclerosing cholangitis: an analysis of the serological marker CA 19-9.

Primary sclerosing cholangitis (PSC) predisposes to the development of cholangiocarcinoma, a usually fatal complication that is difficult to diagnose. Serum concentrations of CA 19-9, a tumor-associated antigen, are frequently increased in patients with only cholangiocarcinoma. The aim of this study was to assess the value of an increased serum CA 19-9 level for the diagnosis of cholangiocarcinoma in patients with preexisting PSC. We analyzed serum samples from 9 patients with PSC and superimposed cholangiocarcinoma and from 28 patients with only PSC. Serum concentrations of CA 19-9 were measured in a blinded manner with use of an immunoradiometric assay. The serum CA 19-9 concentrations were increased in 8 of 9 patients (89) with PSC and cholangiocarcinoma (mean±SE, 391 ± 86 U/ml; range, 4 to 677), whereas they were increased in only 4 of 28 patients (14) with only PSC (mean ± SE, 61 ± 16 U/ml; range, 2 to 370). The sensitivity of a CA 19-9 value greater than 100 U/ml for cholangiocarcinoma in PSC was 89, and the specificity was 86. The measurement of serum concentrations of CA 19-9 is a promising test for detecting cholangiocarcinoma in patients with PSC.

Diagnostic Role of Serum CA 19-9 for Cholangiocarcinoma in Patients With Primary Sclerosing Cholangitis

Primary sclerosing cholangitis (PSC) predisposes to the development of cholangiocarcinoma, a usually fatal complication that is difficult to diagnose. Serum concentrations of CA 19-9, a tumor-associated antigen, are frequently increased in patients with only cholangiocarcinoma. The aim of this study was to assess the value of an increased serum CA 19-9 level for the diagnosis of cholangiocarcinoma in patients with preexisting PSC. We analyzed serum samples from 9 patients with PSC and superimposed cholangiocarcinoma and from 28 patients with only PSC. Serum concentrations of CA 19-9 were measured in a blinded manner with use of an immunoradiometric assay. The serum CA 19-9 concentrations were increased in 8 of 9 patients (89%) with PSC and cholangiocarcinoma (mean +/- SE, 391 +/- 86 U/ml; range, 4 to 677), whereas they were increased in only 4 of 28 patients (14%) with only PSC (mean +/- SE, 61 +/- 16 U/ml; range, 2 to 370). The sensitivity of a CA 19-9 value greater than 100 U/ml for cholangiocarcinoma in PSC was 89%, and the specificity was 86%. The measurement of serum concentrations of CA 19-9 is a promising test for detecting cholangiocarcinoma in patients with PSC.

Effects of 1,25-dihydroxyvitamin D 3 and growth hormone therapy on serum osteocalcin levels in children with growth hormone deficiency

In order to investigate the influence on bone metabolism of growth hormone (GH), we evaluated the response to an acute load of 1,25(OH)2D3 (Rocaltrol) (1.5 micrograms/day for 4 days) in 16 growth hormone-deficient prepubertal children (11 boys and 5 girls, aged from 6.2 to 9.6 years) both before and after 1 month of human GH (hGH) therapy (0.1 IU/kg/day, 6 times per week). Before and after the 1,25(OH)2D3 load, serum IGF-I, osteocalcin, Ca, P, alkaline phosphatase (ALP) and urinary excretion of Ca and P were measured. The serum levels of osteocalcin rose significantly after the first 1,25(OH)2D3 load, without an increase in IGF-I values and with a slight non-significant increase in serum Ca and P. Almost superimposable increases of osteocalcin, Ca and P were observed after 1 month of hGH therapy, with a significant increase of IGF-I, but they did not rise further after the second 1,25(OH)2D3 load. On the basis of our results, 1,25(OH)2D3 seems to have a stimulatory action on osteoblastic activity even in the absence of normal levels of GH. However, there is no apparent additional stimulatory activity after administration of hGH. Osteocalcin level behaviour during our study might suggest that GH and 1,25(OH)2D3 have a common and easily saturable stimulatory pathway on osteoblastic function.

Interactive effects of calcium and short chain fatty acids on absorption in the distal colon of man

Dietary fibers may entrap or bind with minerals and inhibit their absorption in the small intestine. Nevertheless, their fermentation by bacteria present in the colon may produce short chain fatty acids (SCFA) and release the minerals for potential absorption. To determine whether SCFA can enhance calcium absorption from the colon, six healthy male subjects were given rectal infusions of isotonic solutions of saline with and without the addition of Ca and SCFA. The results showed a significant increase in serum Ca after the addition of graded doses of SCFA to rectal infusions containing 30 mmoles Ca (mean increments of serum Ca in mmoles/L: 0 mmoles SCFA=0.02±.04, 22.5 mmoles SCFA=0.05±.05, 45 mmoles SCFA=0.27±.02; P<0.0001). However, increasing amounts of Ca added to 45 mmoles SCFA resulted in a significant decrease in the serum acetate (Ac) response (mean increments of serum Ac in umoles/L: 0 mmoles Ca=40±16, 10 mmoles Ca=26±24, 30 mmoles Ca=6±9; P<0.0001). We conclude that SCFA increase Ca absorption in the distal colon and that Ca may lower serum Ac levels but the mechanism needs further investigation.

Effects of calcium restriction on metabolic characteristics of premenopausal women.

We studied 28 healthy premenopausal women before and after manipulating Ca intake, and then in response to a hypercalcemic challenge. Women with low Ca intakes at entry (< 17.5 mmol/day) were restricted to about 5 mmol/day (low-Ca), and those with higher self-selected intakes were supplemented to about 70 mmol/d (high-Ca). After 8 weeks on these regimens, more bone resorption was occurring among the low-Ca women, as evidenced by their higher values for immunoreactive PTH and urine hydroxyproline. There was a 7-fold range in 24-h urine Ca among the low-Ca women, with upper values equivalent to about 80% of intake. In response to induced hypercalcemia (0.5 mmol Ca/kg lean body mass, infused over 4 h), the low-Ca group had greater increases in serum Ca (1.31 vs. 1.05 mmol/L, P < 0.05) and reached a marginally higher peak (3.64 vs. 3.50 mmol/L, P < 0.1). Despite these greater calcemic responses, the low-Ca women excreted a smaller fraction of the infused Ca (44.3 vs. 62.2%, P < 0.02). Furthermore, preinfusion urine Ca was directly correlated with excretion of infused Ca in the low-Ca women, but not in the high-Ca women. Preinfusion differences between groups in immunoreactive PTH and urine hydroxyproline tended to reappear within 2 days. Our findings show that there are detectable differences in the Ca regulatory system between subjects at practical extremes of Ca intake, and that these differences persist through exposure to a temporary Ca surfeit. Ca-restricted women have higher levels of PTH and of bone remodeling activity. There is considerable variation in the apparent capacity to conserve Ca among women with low intakes. None of our subjects had high-P diets. Thus, our findings show that Ca restriction can evoke a persistent PTH response in the absence of a high P intake.

Calcitonin effects on osteoclastic resorption: the ‘escape phenomenon’ revisited

Prolonged administration of calcitonin in vivo results in an apparent loss of respousiveness to this hormone. No controversy exists with regard to this loss of responsiveness when low to intermediate doses of calcitonin (CT) are used [l-3]. However, when high doses are administered to rats for periods up to 42 days, a persistent significant decrease in ionized calcium levels is observed [4]. Removal of the CT-releasing mini pumps at day 7 in the experiments of Lausson et al. resulted in an immediate (O-2 h after removal) increase of serum Ca, thus suggesting that the apparent loss of responsiveness was not caused by a loss of response to CT, but by compensatory mechanisms. Measurement of serum PTH levels in the experiments of Glajchen et al, indeed showed that infusion of salmon Ct (sCT) resulted in secondary hyperparathyroidism, which partially compensated the sCT-induced hypocalcaemia. This confirmed the initial suggestion by Bastian et al. [S] that the develop ment of tolerance to sCT might be due, at least in part, to an increase in endogenous parathyroid hormone secretion. In humans, loss of responsiveness to sCT during prolonged administration in patients with Paget’s disease or various osteoporotic syndromes is also observed. This has been attributed in some of the patients to formation of neutralizing antibodies [6] but occurs in others without detectable antibody formation. In bone cultures in vitro Raisz and co-workers were the first to observe that the inhibition of bone resorption by CT was transient. Their original studies [7-W] suggested that the inhibitory effect of CT on PTH-induced bone resorption in cultured rat long bone shafts lasted from 48-96 h, depended on the CT concentration used, was not due to inactivation of the hormone, was dependent on the calcium concentration of the media and occurred with salmon, human and rat CT. This phenomenon, as observed in vitro, was described as the ‘escape phenomenon’, and has since been used (and misused) frequently as the explanation for the observed loss of response to CT upon continuous administration in vivo and in vitro, Tashijan et al. [ll], in an extensive and detailed re-examination of the escape phenomenon using mouse calvariae, essentially confirmed the original observations of Raisz et al.

Effects of 1α(OH)-Vitamin D&lt;sub&gt;3 &lt;/sub&gt;and 24,25(OH)&lt;sub&gt;2&lt;/sub&gt;-Vitamin D&lt;sub&gt;3 &lt;/sub&gt;on Long Bones of Glucocorticoid-Treated Rats

Glucocorticoids may induce osteopenia in experimental animals and in man. In order to study the possible effects of vitamin D metabolites in the prevention of glucocorticoid-induced osteopenia in rats, we administered 1 alpha(OH)-vitamin D3, 24,25(OH)2-vitamin D3 or a combination of both metabolites, by intragastric intubation, to rats treated daily by intramuscular injections of 10 mg/kg cortisone acetate. Treatment with the vitamin D metabolites started after 1 month of glucocorticoid therapy, at the time osteopenia was already present. Cortisone acetate decreased the gain weight, increased alkaline phosphatase (AP) and decreased Ca serum levels. It also decreased tibial wet and ash weight and tibial Ca content. Computerized histomorphometry of sections from the upper tibia showed decreased epiphyseal bone volume and increased bone marrow volume; decreased height of hypertrophic cartilage in the growth plate and decreased amount of persisting cartilage in the metaphyseal bone trabeculae were also observed. Administration of 24,25(OH)2D3 alone did not reduce these glucocorticoid-induced bone changes and sometimes even worsened them. 1 alpha(OH)D3 reversed many of the deleterious effects of cortisone acetate. It reduced serum AP levels, increased serum Ca levels, increased bone ash weight, epiphyseal and metaphyseal bone volume, with a concomitant reduction in epiphyseal and metaphyseal bone marrow volume. The best results were obtained by a combination of 1 alpha(OH)D3 and 24,25(OH)2D3. It is presumed that both metabolites are needed to reduce the impact of glucocorticoids on bone. 1 alpha(OH)2D3 acts on the gut, increasing Ca absorption (which was decreased by glucocorticoids), and 24,25(OH)2D3 directly acts on bone to enhance bone formation and mineralization.

Antihypertensive effect of dietary calcium loading in angiotensin II-salt rats

To clarify the hypotensive effect of high dietary Ca intake on salt-sensitive hypertension, 7-wk-old Sprague-Dawley rats, 3.15% Na and/or 4.07% Ca diet loaded, were administered 125 ng/ml of angiotensin II (ANG II) intraperitoneally for 12 days. Compared with control rats (mean blood pressure 108 +/- 2 mmHg), ANG II administration caused hypertension (131 +/- 4 mmHg, P less than 0.05). Na loading enhanced the hypertensive effect of ANG II (161 +/- 4 mmHg, P less than 0.01). Dietary Ca loading did not significantly inhibit the pressor effect of ANG II alone (119 +/- 4 mmHg). However, Ca loading suppressed hypertension in ANG II-salt rats (126 +/- 4 mmHg, P less than 0.01). Plasma total catecholamine (norepinephrine + epinephrine) was increased in ANG II-salt rats (176 +/- 14 vs. 290 +/- 23 pg/ml, P less than 0.05), but Ca loading decreased plasma catecholamine (182 +/- 13 pg/ml, P less than 0.05). In contrast, plasma catecholamine was not significantly different between ANG II-treated rats with and without Ca loading. Ca loading increased serum Ca in ANG II rats (10.9 +/- 0.1 vs. 11.7 +/- 0.1 mg/dl, P less than 0.05) but did not do so significantly in ANG II-salt rats (10.8 +/- 0.2 vs. 10.9 +/- 0.1 mg/dl). Thus Ca loading exclusively ameliorated salt-sensitive hypertension, which was induced with ANG II administration and Na loading in rats, probably through suppression of the increased sympathetic activity. In addition, these effects of Ca loading were not mediated through an increased blood level of Ca.

Effects of carbetimer, a new antineoplastic drug, on bone metabolism

Carbetimer is a new antineoplastic agent whose main side effects consist of neurotoxicity and long-term dose-dependent hypercalcemia. We previously showed that Carbetimer is a potent calcium chelator responsible for an acute decrease in ionized Ca levels observed in vivo. However, the mechanism of the progressive increase in serum Ca remains unknown. We have evaluated the bone-resorbing effects of Carbetimer on 45Ca-prelabelled neonatal mouse calvariae. Carbetimer induced a dose-dependent increase in 45Ca release which started at a concentration of 1 mg/ml and reached a mean of 3.3 times the control values at 10 mg/ml. This marked increase in 45Ca release was similar on previously killed bones and could not be inhibited by calcitonin. Such concentrations are probably therapeutically relevant given the known affinity of Carbetimer for bone and the large daily doses administered to cancer patients (10–15 g). Since Carbetimer could exert its antineoplastic action through immunomodulation, we also studied its effects on the production of TNF-α and IFN-γ which are also known to affect bone metabolism. Carbetimer did not stimulate TNF-α release from isolated normal human monocytes or lymphocytes, but it markedly inhibited T-lymphocyte production of IFN-γ, which became undetectable at a concentration of 1 mg of Carbetimer/ml. In summary, Carbetimer-induced hypercalcemia appears to be due to a direct stimulation of osteolysis, but possibly also to an inhibition of IFN-γ production.

Effect of swimming to exhaustion, at low temperatures, on serum Zn, Cu, Mg and Ca in rats

In order to study the response of plasma trace minerals during exercise in cold water at varying temperatures, three groups of ten male Wistar rats each were forced to swim until exhaustion in water at different constant temperatures (10, 20 and 32°C), while another 3 groups were kept at rest in water at the same temperatures and another group at rest out of the water, at room temperature (21°C). Rectal temperature (RT) was measured before and after the exercise. Samples of arterial blood were obtained under anaesthesia (pentobarbital) from the abdominal aorta after the exercise, and serum concentrations of Cu, Zn, Mg and Ca were determined by flame atomic absorption spectrophotometry (FAAS). The swimming time (ST) decreased in cold water, the values obtained at 10 and 20°C being 3.3% and 8.5%, respectively, of those observed at 32°C. The RT of the animals swimming at 32°C was 32.5 ± 1.8°C (mean ± SD) and fell to 25.0 ± 2.0 and to 19.1 ± 1.5°C in those swimming, respectively, at 20 and 10°C. The concentrations of Mg, Cu and Ca were significantly higher ( +50%, +36% and +7%, respectively) in animals subjected to exercise with respect to the control groups in water, although there were no differences among the three groups. On the contrary, Zn rose progressively with the increase of WT ( +32% at 10°C, +60% at 20°C and +76% at 32°C). The present data show that exercise in cold water causes in rats: 1) a significant decrease in the swimming time; 2) an increase in serum Ca, Cu and Mg not related to WT or RT and 3) an increase in serum Zn which appears to be related to WT and/or to RT.

Serum CA 12‐5 concentrations and CA 12‐5/CEA ratios in patients with epithelial ovarian cancer

In attempts to increase the specificity of the CA 12-5 test the ratio of CA 12-5 and CEA concentrations has been determined in 155 cancer patients, all of whom had an increased serum CA 12-5. The patients included 47 with epithelial ovarian cancer, 38 with colorectal cancer, 24 with cervical cancer, 20 with lung cancer, 17 with gastric cancer, and 9 with pancreatic cancer. The CA 12-5/CEA ratio in serum of patients with ovarian cancer ranged from 30 to 920 (mean 251), whereas in other types of cancer the highest ratio was 240 and the mean was 13. All 47 patients with ovarian cancer, but only 7 of the 108 patients with other types of cancer, showed a CA 12-5/CEA ratio greater than 25. About 10% of the patients with gastric or colorectal cancer but none of those with other types of cancer showed an increased ratio. As the predictive value of a CA 12-5/CEA ratio of less than 25 excluding ovarian cancer is 100%, we recommend measuring the CEA concentration in all those with increased CA 12-5 and calculation of the CA 12-5/CEA ratio.

Alterations in rat bone composition related to polyol supplementation of the diet

The effect of dietary supplements of xylitol, sorbitol and glucose on bone composition was studied in rats. The supplementation, expressed as a % of the dry diet, was gradually increased up to 20% over 3 weeks and continued for 5 weeks. The control group was fed a stock diet only. Each group consisted of nine rats aged 12 weeks at the beginning of the experiment. Ca, Mg, P, CO 3 and citrate were analysed from the femur and Ca and citrate also from the serum and urine. The results showed that xylitol supplementation significantly increased the concentrations of Ca and citrate in bone ( P < 0.001) and sorbitol that of Ca only, whereas glucose slightly reduced both CO 3 and citrate. The citrate concentration was found to correlate significantly with Ca and P ( P < 0.001), and also with Mg ( P < 0.002). Both xylitol and sorbitol increased serum Ca and the urinary excretion of Ca and citrate. In conclusion, high xylitol or sorbitol supplementation affects Ca and citrate metabolism. The results suggest a connection between citrate and Ca in bone.

Serum CA 15-3 assay in the diagnosis and follow-up of breast cancer.

Serum CA 15-3 values were determined in 177 patients with primary breast cancer and in 41 with non-malignant breast disease. Increased preoperative serum CA 15-3 values (greater than 38 U ml-1) were observed in 7%, 17%, 64% and 67% of patients with stage I, II, III and IV disease, respectively and in none of the patients with benign breast disease. Patients with elevated serum CA 15-3 values had poor 3-year cumulative survival (27%). In the postoperative follow-up 9% of patients with no clinical evidence of disease, 33% with a single metastasis and 67% with two or more metastases had elevated values. Increasing or decreasing serum CA 15-3 values correlated with the clinical outcome in 26 out of 27 cases (96%), whereas serum values remaining in the reference range had no predictive value. At the time of recurrence elevated serum CA 15-3 values were also observed in patients with normal preoperative values. Increased serum CA 15-3 values preceded the clinical detection of tumour recurrence by up to 13 months. In conclusion, serum CA 15-3 levels had prognostic value in breast cancer, reflected the extent of clinically detectable disease and the presence of occult metastatic disease. Further research is warranted on the benefits of CA 15-3 assays in relation to adjuvant chemotherapy as well as the earlier detection and treatment of metastatic disease.

CA 15-3 Serum Levels in Ovarian Cancer

Serum levels of CA 15-3, an antigen expressed by human breast carcinoma cells, were measured in 58 ovarian cancer patients, 24 patients with benign ovarian tumor and 62 patients with benign gynecological conditions. Abnormally high serum CA 15-3 levels were found in 41 of 58 patients (71%) with ovarian cancer. The percentage of CA 15-3 positivity correlated with tumor stage. Elevated serum CA 15-3 levels were found in 5 of 24 patients (20%) with benign ovarian tumor. None of the patients with benign gynecological conditions had increased serum CA 15-3 levels. Serial measurements showed CA 15-3 concentrations to be correlated with the clinical behavior of disease in 21 of 25 patients (84%). CA 15-3 serum levels were also found to be correlated with findings on second look. These results suggest that CA 15-3 may represent a useful tumor marker in ovarian cancer.