First report of catheter associated Trichosporon pullulans breakthrough fungaemia in a cancer patient

Secondary hyperparathyroidism in chronic renal failure (CRF) is due to the increased activity of parathyroid gland. The negative feedback control exerted by the vitamin D metabolite 1,25 (OH)2 D3 is lacking due to the deficiency of this metabolite in CRF. We have studied whether alphacalcidol given orally as thrice weekly evening pulses lowers parathyroid hormone (PTH) levels of children with CRF. Alphacalcidol 0.5-3.0 micrograms was given thrice weekly orally to a total of 22 children (mean age 5.6 years) with CRF; the dosis was adjusted according to PTH, ionized calcium and phosphate concentration. Serum PTH decreased significantly from a pretreatment level of 393 +/- 81 to 122 +/- 34 ng/l after 12 months, and stabilized at this level. Mean vitamin D metabolite concentrations were within normal range. 1,25 dihydroxyvitamin D did not increase during therapy while PTH decreased. The estimated creatinine clearance remained nearly the same (20 +/- 3 and 21 +/- 6 ml/min/ 1.73 m2). Growth remained low normal and bone mineral density did not decrease. Oral alphacalcidol pulse therapy for hyperparathyroidism in uremic children seemed to be easy and effective. The response is even better in inhibiting potential autonomous parathyroid hyperplasia if this treatment was started early. We conclude that feedback regulation of PTH with oral alphacalcidol pulse therapy is efficient in the treatment of hyperparathyroidism in children with CRF prior to dialysis.     

Vitamin D metabolism: update for the clinician

Vitamin D3 must undergo two hydroxylation steps before it becomes fully active: 25-hydroxylation in the liver and 1- or 24-hydroxylation in the kidney. Parathyroid hormone, serum phosphate, and serum calcium are important in regulation of renal production of 1,25-dihydroxy vitamin D3 (1,25-[OH]2D3) and 24,25-dihydroxy vitamin D3. An enzyme involved in renal hydroxylation is deficient or defective in patients with chronic renal failure, the Fanconi syndrome, vitamin D-dependent rickets, hypoparathyroidism, and pseudohypoparathyroidism. Altered vitamin D metabolism also occurs in various hepatic diseases, postmenopausal osteoporosis, and anticonvulsant osteomalacia. Recently, 1,25-(OH)2D3 was approved for treatment of renal osteodystrophy. In physiologic doses, it predictably corrects many of the clinical and biochemical abnormalities associated with this disorder.     

Parathyroidectomy reduces 25-hydroxyvitamin D3-1 alpha-hydroxylase activity in the hypocalcemic vitamin D-deficient chick

To test the hypothesis that in the vitamin D-deficient state the activity of 25-hydroxyvitamin D3-1 alpha-hydroxylase (25-OHD3-1 alpha-hydroxylase) is modulated by parathyroid hormone and the plasma concentration of phosphate only in the presence of small amounts of 1,25-dihydroxyvitamin D3 (or some other metabolite of vitamin D), we measured the activity of this enzyme 24 h after parathyroidectomy (PTX) in frankly hypocalcemic, vitamin D-deficient chicks that were not supplemented with vitamin D or one of its metabolites. The otherwise predictable complications of PTX in this metabolic setting (hypocalcemia of increasing severity, tetany, moribundity, and death) were prevented by continuous intravenous administration of calcium (as a solution of calcium chloride/calcium gluconate 1:1) through a catheter in the external jugular vein placed at the time of PTX. The findings were as follows: (a) The activity of 25-OHD3-1 alpha-hydroxylase was significantly less in the parathyroidectomized group than in the sham-operated control chicks (P less than 0.001). (b) The reductive effect of PTX on the activity of this enzyme was significantly attenuated when hypophosphatemia was increased in severity by administration of glucose. (c) In the post-PTX state the activity of 25-OHD3-1 alpha-hydroxylase and plasma concentration of phosphate were significantly, inversely related (P less than 0.001). (d) In the sham-operated control group the activity of this enzyme and the plasma concentration of phosphate were not significantly correlated. These findings indicate that in the vitamin D-deficient state, both circulating parathyroid hormone and the plasma concentration of phosphate can significantly modulate the activity of 25-OHD3-1 alpha-hydroxylase in the absence of vitamin D or its metabolites. The findings also suggest that in the vitamin D-deficient state the plasma concentration of phosphate modulates the activity of this enzyme only when the concentration of circulating parathyroid hormone is not increased.     

Gastrectomy osteopenia in the rat: the role of vitamin B12 deficiency and the type of reconstruction of the digestive tract

1. The mechanisms underlying gastrectomy osteopenia are not yet clear. The gastrectomy-associated cobalamin (vitamin B12) deficiency may favour osteopenia and skeletal fractures. Also, the exclusion of the duodenum from the food passage may contribute to gastrectomy osteopenia. To investigate this, rats were gastrectomized and the passage of nutrients restored either with the duodenum excluded (Roux Y) or included (Longmire). Sham-operated rats served as controls. In half of the rats in each gastrectomy group the serum B12 levels were normalized by parenteral administration of B12.2. Four months post operation, both gastrectomy groups showed a similar degree of osteopenia. There was normal bone mineralization; serum levels of parathyroid hormone were normal, but decreased for 25-hydroxyvitamin D, and elevated for 1,25-dihydroxyvitamin D; in urine there was decreased pH and excessive hyperphosphaturia.3.B12 therapy had no influence on any of the essential bone and mineral metabolic parameters.4. We conclude that osteopenia in the gastrectomized rat (i) is not due to B12 or folic acid deficiency, calcium deficiency or secondary hyperparathyroidism; (ii) is independent of the type of anatomic reconstruction of the digestive tract; (iii) appears to be related to disturbed vitamin D, phosphorus and acid-base metabolism.     

Suppressive effect of calcium on parathyroid hormone release in adynamic renal osteodystrophy and secondary hyperparathyroidism

Serum parathyroid hormone (PTH) levels are markedly lower in patients with the adynamic lesion (AD) of renal osteodystrophy than in those with secondary hyperparathyroidism (2 degrees HPT), but serum PTH values are often moderately elevated in AD when compared to subjects with normal renal and parathyroid gland function (NL). To study the inhibitory effect of calcium on PTH release in AD and in 2 degrees HPT, the response to two-hour intravenous calcium infusions was examined in 6 patients with AD, in 31 patients with 2 degrees HPT and in 20 NL. Basal serum PTH levels were 88 +/- 51, 536 +/- 395, and 26 +/- 6 pg/ml, respectively, in AD, 2 degrees HPT and NL, whereas basal ionized calcium levels did not differ. When expressed as a percentage of pre-infusion values, PTH levels at the end of two-hour calcium infusions were higher both in AD (23.2 +/- 5.6%) and in 2 degrees HPT (27.8 +/- 12.3%) than in NL, (11.9 +/- 5.8%, P < 0.001). Both the amplitude of suppression (%) and the rate of decline (min-1) in serum PTH were less in AD and 2 degrees HPT than in NL, P < 0.05 for each parameter; corresponding values for each group, with 95% confidence intervals, were 77% (73 to 82) and 0.039 min-1 (0.030 to 0.048) in AD, 72% (68 to 76) and 0.031 min-1 (0.025 to 0.036) in 2 degrees HPT and 87% (84 to 89) and 0.070 min-1 (0.058 to 0.089) in NL. Neither variable differed between AD and 2 degrees HPT. Basal and nadir serum PTH levels were highly correlated: r = 0.95 and P < 0.05 in AD; r = 0.90 and P < 0.01 in 2 degrees HPT; r = 0.75 and P < 0.01 in NL. The slope of this relationship was less, however, both in AD and in 2 degrees HPT than in NL, P < 0.05 by analysis of co-variance. Thus, serum PTH levels fell below 20% of pre-infusion values in fewer subjects with AD (1 of 6) or 2 degrees HPT (9 of 31) than in NL (17 of 20) (chi 2 = 17.81, P < 0.005). The results indicate that the inhibitory effect of calcium on PTH release in vivo does not differ in AD and 2 degrees HPT despite marked differences in basal serum PTH levels. Variations in functional parathyroid gland mass rather than disturbances in calcium-sensing by the parathyroids probably account not only for the lower basal serum PTH levels in patients with AD compared to those with 2 degrees HPT, but also for the moderately elevated serum PTH values commonly seen in patients with AD.     

Two types of nutritional rickets in infants

In 100 infants with nutritional rickets, i.e., responsive to vitamin D therapy, we found a close inverse relationship between serum phosphorus, on the one hand, and serum alkaline phosphatase and the presence of radiological signs of rickets, on the other. There was no correlation between serum calcium and the severity of bone lesions. It is concluded that hypophosphatemia but not hypocalcemia is typical of rickets. Since hypophosphatemia and rickets can be produced experimentally by phosphate deficiency alone, we suggest our infants can be divided into two groups, one with true vitamin D deficiency that leads to hypocalcemia and no or mild bone lesions, and one with primary phosphate deficiency, resulting perhaps from a defect in phosphate transport, which leads to rickets and hypophosphatemia.     

Parathyroidectomy after renal transplantation: a retrospective analysis of long-term outcome

BACKGROUND: Advanced hyperparathyroidism refractory to active vitamin D continues to be a problem and frequently forces the nephrologist to resort to parathyroidectomy. One particular aspect is persisting advanced hyperparathyroidism after renal transplantation. Published information on this point is fragmentary. DESIGN: Retrospective analysis. PATIENTS: Between 1983 and 1995 a total of 456 patients with renal secondary hyperparathyroidism were subjected to parathyroidectomy (PTX) of whom 103 were transplanted or had at least a history of renal transplantation. The present analysis concerns 37 patients who had a functional renal graft at the time of PTX and were followed for up to 13 years. PTX was performed after an average of 36.7 months after renal transplantation. OUTCOME: Thirteen patients experienced rejection and became dialysis-dependent. Twenty-four patients had stable function of the renal graft. Seven patients died during follow-up. Hypoparathyroidism post-PTX developed in 4/37 patients, but could be overcome by replantation of cryoconserved parathyroid tissue. FREQUENCY ESTIMATE: A total of 2632 renal transplants were performed in the catchment area. As a minimum estimate 3.91% of patients with a functional graft required PTX. RECOMMENDATION: Parathyroidectomy should be considered early in cases with advanced secondary renal hyperparathyroidism, since renal transplantation does not necessarily guarantee reversibility of parathyroid overactivity.     

Influence of metabolic acidosis on serum 1,25(OH)2D3 levels in chronic renal failure

Metabolic acidosis has been shown to alter vitamin D metabolism. There is also evidence that calcium may modulate 1,25(OH)2D3 by a parathyroid hormone (PTH)-independent mechanism. To investigate the effect of rapid correction of chronic metabolic acidosis on serum 1,25(OH)2D3 levels by free calcium clamp in chronic renal failure, 20 patients with mild to moderate metabolic acidosis (mean pH 7.31 +/- 0.04) and secondary hyperparathyroidism (mean intact PTH 156.47 +/- 84.20 ng/l) were enrolled in this study. None had yet received any dialysis therapy. Metabolic acidosis was corrected by continuous bicarbonate infusion for 3-4 h until plasma pH was around 7.4, while plasma ionized calcium was held at the preinfusion level by calcium solution infusion during the entire procedure. The plasma pH, bicarbonate, total CO2, sodium, and serum total calcium levels were significantly increased while serum concentrations of alkaline phosphatase and albumin were significantly decreased after bicarbonate infusion. The plasma ionized calcium, potassium, serum magnesium, inorganic phosphorus, and 25(OH)D levels showed no significant change before and after bicarbonate infusion. The serum 1,25(OH)2D3 levels were significantly increased (38.66 +/- 11.77 vs. 47.04 +/- 16.56 pmol/l, p < 0.05) after correction of metabolic acidosis. These results demonstrate that rapid correction of metabolic acidosis raises serum 1,25(OH)2D3 levels in vitamin D-deficient chronic renal failure patients, and may underline the importance of maintaining normal acid-base homeostasis in the presence of secondary hyperparathyroidism in chronic renal failure.     

A novel nonsense mutation in the first zinc finger of the vitamin D receptor causing hereditary 1,25-dihydroxyvitamin D3-resistant rickets

Hereditary 1,25-dihydroxyvitamin D3 [1,25-(OH)2D3]-resistant rickets (HVDRR) is a rare autosomal recessive disorder resulting in target organ resistance to the active form of vitamin D [1,25-(OH)2D3]. Point mutations in the vitamin D receptor (VDR) gene have been identified in HVDRR. We investigated the molecular basis of HVDRR in a Brazilian family with two affected siblings. The propositus is a 12-yr-old boy born to first cousin parents who exhibited the classical pattern of the HVDRR, including early-onset rickets, total alopecia, convulsions, hypocalcemia, secondary hyperparathyroidism, and elevated 1,25-(OH)2D3 serum levels. His younger sister also developed clinical and biochemical features of HVDRR at 1 month of age and died at 4 yr of age. Genomic DNA was isolated from peripheral blood of the boy and from dried umbilical cord tissue of his affected sister. We amplified exons 2 and 3 of the VDR gene, which encode the zinc finger DNA-binding domain by PCR. Direct sequencing of the PCR products revealed a homozygous substitution of cytosine for thymine at nucleotide position 88 in exon 2 of the VDR gene in both affected siblings. This point mutation determined the substitution of a stop codon (TGA) for arginine (CGA) at amino acid position 30 at the first zinc finger of the DNA-binding domain of the VDR. This substitution generated a truncated receptor missing 397 residues. The parents and a normal sister were heterozygous for this mutation. In conclusion, we describe a novel nonsense mutation in the first zinc finger of the VDR that generated a severely truncated form of this receptor.     

Whole-body autoradiography of 123I-labelled islet amyloid polypeptide (IAPP). Accumulation in the lung parenchyma and in the villi of the intestinal mucosa in rats

The basal levels of cytosolic calcium ([Ca2+]i) in rats and/or humans with chronic renal failure (CRF) are elevated in many cells including brain synaptosomes, pancreatic islets, polymorphonuclear leukocytes, platelets and B and T cells. This rise in [Ca2+]i has been attributed to the state of secondary hyperparathyroidism of CRF. These observations have led to the proposition that CRF is a state of cellular calcium intoxication mediated by excess parathyroid hormone (PTH). The documentation of a high basal level of [Ca2+]i in other cells is needed to provide further support for this postulate. The present study evaluated the basal levels of [Ca2+]i of thymocyte, which are targets for PTH action, in normal, CRF, and CRF parathyroidectomized (CRF-PTX) rats. We also examined whether CRF affects the phenotype expression (Thy-1, CD4 and CD8) in thymocytes. The results showed that the basal levels of [Ca2+]i in thymocytes from CRF rats (81 +/- 3.7 nM) are significantly (p < 0.01) higher than those in normal animals (60 +/- 2.9 nM). PTX of CRF animals prevented the elevation in the basal levels of [Ca2+]i of thymocytes; in these animals, the levels were 59 +/- 2.8 nM. Neither CRF nor the elevation in [Ca2+]i of thymocytes affected their phenotype expression.     

Somatic mosaicism in the central nervous system in spinocerebellar ataxia type 1 and Machado-Joseph disease

Glucocorticoids (GC) are widely used for anti-inflammatory and immunosuppressive therapy. Thirty to 50% of GC-treated patients develop osteoporosis. Potential mechanisms of GC-induced osteoporosis (GC-OP) include abnormalities in calcium balance, vitamin D metabolism, parathyroid hormone release and activity, prostaglandin E2 and cytokine synthesis, interference with c-fos and p-53 expression in osteoblasts, and hypogonadism. Early diagnosis and detection of patients at risk are accomplished with rapid, safe and non-invasive bone density measurements. Preventive measures include maintaining a positive calcium balance, vitamin D supplementation (if indicated) and treatment of hypogonadism. The shortest duration and the smallest doses possible of GC for a particular condition are advisable. For high-risk patients and those with established GC-OP calcitonin or bisphosphonate therapy is recommended.     

Reduced expression of the renal calcium-sensing receptor in rats with experimental chronic renal insufficiency

Chronic renal insufficiency is associated with elevated serum parathyroid hormone (PTH) levels (2 degrees HPT), deficiency of 1,25-dihydroxyvitamin D (1,25(OH)2D), and hypocalciuria. In chronic renal insufficiency, the 2 degrees HPT may result from reduced expression of the parathyroid gland extracellular Ca(2+)-sensing receptor (CaSR). Since the CaSR was cloned from rat and human kidney, this study examined in rats whether expression of the renal CaSR is altered in experimental chronic renal insufficiency. Four weeks after chronic renal insufficiency was induced by 5/6 nephrectomy (Nx) in Sprague Dawley rats, the serum creatinine concentration was 0.96+/-0.06 mg/dl compared with 0.35+/-0.02 mg/dl in sham-operated animals (P < 0.05). The serum total Ca2+ and phosphorus concentrations were not different. In the Nx group, the serum concentration of amino-PTH was higher (65+/-8 pg/ml), and the concentration of 1,25(OH)2D was significantly lower (47+/-5 pg/ml) compared with 45+/-5 pg/ml and 61+/-4 pg/ml (P = 0.05) in the sham group, respectively. In a subset of rats studied, the Nx group was hypocalciuric (1.4+/-0.5 mg/kg per d) compared with the sham group (3.7+/-0.5 mg/kg per d) (P < 0.05). In the Nx rats, CaSR mRNA expression and CaSR protein levels were found to be reduced by 35 and 38%, respectively, than those observed in controls. These results suggest that reduced renal CaSR expression in chronic renal insufficiency may play a role in disordered mineral ion homeostasis, including hypocalciuria.     

Effectiveness of the elcatonin transdermal system for the treatment of osteoporosis and the effect of the combination of elcatonin and active vitamin D3 in rat

The efficacy of percutaneous elcatonin (EC), a hypocalcemic peptide, in the treatment of experimental osteoporosis in rats was evaluated in vivo. Additionally, the effect of the combined use of EC and active vitamin D3 (1,25(OH)2D3) for the treatment was compared with those of three other groups: 1,25(OH)2D3 alone, estradiol plus 1,25(OH)2D3, and a placebo, and low calcium diet (low Ca). The EC transdermal system and the EC plus 1,25(OH)2D3 system, applied to the rat abdominal skin 6 times for 48 h, significantly increased the ash weight and calcium content of the tibia in the rats, compared with those of placebo group (p < 0.05). The EC systems also slightly lowered the alkaline phosphatase activity in plasma of the morbid rats, without a difference in the plasma calcium content. These EC systems were superior to the 1,25(OH)2D3 system and the estradiol plus 1,25(OH)2D3 system in improving osteoporotic parameters. Thus, the EC systems were concluded to be an efficient drug delivery system for Paget's disease and osteoporosis.     

Bone mineral recovery after parathyroidectomy in patients with primary and renal hyperparathyroidism

Patients with hyperparathyroidism (HPT) generally display reduced bone mass due to excessive PTH activity. The effect of parathyroidectomy on bone mass changes in different types of HPT, however, is not well understood. Bone mineral density (BMD) was measured in the distal radius, total body, femoral neck, and lumbar spine by dual energy x-ray absorptiometry in four groups of patients with different hyperparathyroid conditions: primary symptomatic HPT (n = 54), primary asymptomatic (mild) HPT (n = 24), HPT associated with hemodialysis (n = 20), and HPT associated with renal transplant (n = 30). Subsets of patients with primary symptomatic HPT (n = 52), HPT associated with hemodialysis (n = 19), and HPT associated with renal transplant (n = 15) underwent parathyroidectomy, and bone density was measured longitudinally for 3 yr. Patients with primary asymptomatic (mild) HPT did not undergo surgery and were followed prospectively. Before surgery, all groups showed a greater reduction of bone mineral density in cortical bone (distal radius) than in predominantly trabecular bone (lumbar spine). In primary symptomatic HPT, the BMD z-score of the distal radius was -1.80 +/- 0.21 (+/-SEM), and the corresponding figures for the total body, femoral neck, and lumbar spine were -0.60 +/- 0.15, -0.54 +/- 0.14, and -0.53 +/- 0.18 compared with those of an age- and sex-matched reference group. In renal HPT BMD z-scores were -2.51 +/- 0.38 (hemodialysis patients) and -2.83 +/- 0.43 (renal transplant patients) for the distal radius and between -0.81 and -1.46 for the other measured sites. After parathyroidectomy, BMD increased by 1-8% at all sites in patients with primary symptomatic HPT and HPT associated with renal transplant. The largest increase in bone mass was observed in patients with HPT associated with hemodialysis, in whom the improvement amounted to 7-23%. In patients with primary HPT and HPT associated with hemodialysis, this increase in bone density resulted in virtual recovery from their preoperative bone loss. The majority of patients with asymptomatic primary HPT disease (n = 21) maintained their bone density during the follow-up period and have not shown evidence of increases in serum calcium or PTH levels, but three patients followed conservatively underwent parathyroidectomy due to progressive deterioration of BMD. We conclude that, regardless of the etiology, a large proportion of HPT patients show reduced bone density. In patients with primary symptomatic HPT and patients with HPT associated with hemodialysis, bone density increases after parathyroidectomy to an extent that largely restores the preoperative bone loss. However, no anabolic effect of parathyroidectomy on bone mass was observed in patients with HPT associated with renal transplant, probably because of their immunosuppressive therapy.     

Estrogen treatment for prevention and therapy of osteoporosis

Postmenopausal osteoporosis affects 30% of all women. Major risk factors include hereditary factors, deficiency of calcium and vitamin D in the diet, too little exercise, excessive alcohol consumption and a reduction in the amount or duration of sex hormone secretion (late menarche, early climacterium, etc.). Osteoporosis prophylaxis is of great importance. Since in the early stages, osteoporosis does not produce symptoms, an early diagnostic work-up involving osteodensitometry makes good sense in patients with individual risk factors. In addition to physical activity, basic countermeasures always include adequate calcium and vitamin D supplementation. Replacement therapy with estrogens (usually in combination with gestagens) is an effective and causal treatment of postmenopausal osteoporosis. However, the indication must be established individually on the basis of a benefit-risk consideration.     

Nutrition and osteoporosis: a nutritional analysis of women in postmenopause

In a cross-sectional study the effects of several nutritional factors on the manifestations of osteoporosis were investigated in 23 postmenopausal women aged 50 to 70 years. Twelve women (group 1) with osteoporosis and eleven healthy control subjects (group 2) were instructed to keep a seven-day nutritional record. Body mass index (BMI) was recorded, and radiological and bone mineral density investigations were undertaken. The daily total energy, protein, fat, carbohydrate, fiber, oxalic acid, calcium, magnesium, phosphorus, sodium, fluoride, zinc, copper, manganese, vitamin C, D, and K intake were analysed within the framework of a nutritional science program. No intergroup differences were observed with regard to total energy intake, nutritional components and BMI; however, age and years since the menopause differed significantly (p < 0.05). The results suggest that the manifestation of osteoporosis in women is influenced to a greater extent by age and years since the menopause than by the distribution of nutritional factors in a normal mixed diet. However, further studies are essential to evaluate the role of dietary composition on the manifestations of osteoporosis.     

Technetium 99m tetrofosmin parathyroid imaging. Results with double-phase study and SPECT in primary and secondary hyperparathyroidism

RATIONALE AND OBJECTIVES: The aim of our study was to evaluate the sensitivity, specificity, and positive predictive value (PPV) of technetium 99m (99mTc) tetrofosmin double-phase scintigraphy and single-photon emission computer tomography (SPECT) in preoperative localization of parathyroid adenoma in case of primary and secondary hyperparathyroidism (HPT). METHODS: Sixty-eight consecutive patients biochemically or sonographically suspected of parathyroid adenoma were included in our study. Apart from biochemical analysis of serum calcium, phosphate, and intact parathyroid hormone, double-phase scintigraphy was performed in each patient 5 and 45 minutes after injection of 370 MBq 99mTc tetrofosmin, followed by SPECT imaging. In consciousness of the scintigraphic results, ultrasound of the neck was performed as well to exclude false-positive results due to thyroid adenomas. RESULTS: Depending on the results of the biochemical analysis in combination with the results of the scintigraphic and ultrasound examination, the patients were classified retrospectively into three groups: group A with primary HPT (n = 35), group B with secondary HPT (n = 13), and group C without any biochemical suspicion of primary or secondary HPT (n = 20). In group A, double-phase study localized 25 of 36 (69.2%) parathyroid adenomas (one double adenoma) as against 34 of 36 (94.4%) with SPECT. Nine adenomas could be visualized only by SPECT. The reason for nonvisualization on planar scans was suspected to be an ectopic location in 2 cases (retrotracheal dislocation, retrovascular dislocation), a maximal diameter less than 15 mm (9-13 mm) in 6 cases, and oxyphilic-cell-poor cellularity in 1 case. Four false-positive retention (3 thyroid adenomas and 1 papillary thyroid carcinoma) were observed. SPECT showed a sensitivity of 94.4%, a specificity of 85%, and a PPV of 91.9% in biochemically suspected primary HPT. In group B, planar scintigraphy demonstrated 12 hyperplastic glands in 5 of 13 patients, and SPECT demonstrated 20 hyperplastic parathyroid glands in 8 out of 13 patients, which corresponds to a sensitivity of 38% and 61.5%, respectively. CONCLUSIONS: Technetium 99m tetrofosmin seems to be a promising alternative tracer with similar capabilities to 99mTc sestamibi in localization of parathyroid adenoma. SPECT showed clear advantages in terms of sensitivity over planar scintigraphy and should be used at least in cases with poor or no uptake in double-phase study. In endemic goiter areas, ultrasound of the neck should be performed to exclude false positive retention in thyroid adenomas. Technetium 99m tetrofosmin, like 99mTc sestamibi, is not ideal for localization of hyperplastic glands in secondary hyperparathyroidism because of low sensitivity.     

Alpha1-adrenergic and dopaminergic receptors are involved in the anoretic effect of corticotropin-releasing factor in goldfish

This study investigates the noradrenergic and/or dopaminergic receptors subtypes involved in the anoretic action of CRF in goldfish. Agonists and antagonists of alpha1- and alpha2-adrenoceptors, and D1- and D2-dopaminergic receptors were intracerebroventricularly (i.c.v.) administered alone or in combination with CRF in the case of antagonists. Food intake and hypothalamic content of catecholamines and their metabolites were measured at 2 h postinjection. On one hand, alpha1-adrenergic receptor antagonist, but not alpha2, blocked the anoretic effect of CRF. Moreover, we found a blockade of CRF-induced anoretic action by pretreatment with specific D1- and D2-dopaminergic antagonists. On the other hand, the i.c.v. administration of CRF reduced hypothalamic norepinephrine (NE) and dopamine (DA) content, without modifications in their metabolism. Thus, our results suggest that the anoretic effect of CRF appears to be mediated by alpha1-adrenergic and dopaminergic receptors in fish. Second, the reduction in hypothalamic NE and DA synthesis could be due to a direct effect of CRF treatment and/or a secondary effect of food intake reduction.     

Observations on pain and suffering

The researches on the mode of action of vitamin D have shown that vitamin D3 in animals is not utilized as such but after Hydrosylation of carbon 25 in the liver and of carbon 1 in the kidney. 1alpha,25-dihdroxycholecalciferol (1alpha,25-(OH)2D3) is the active on two target organis the intestin and bones, acting as a steroid hormone. In the intestin it controls the syntesis of a specific calcium binding protein (CaPB) responsable for calcium absorption. At the bone level it act on the deposition of calcium salts, and whenever necessary on its mobilization. Therefore 1alpha,25(OH)2D3 is active part of the calcium homeostatic system in the organism together with specific hormones such as parathyroid hormone and calcitonin.