Increase In Serum Calcium Concentration Research Articles

Features of the state of bone tissue in children with cerebral palsy. Part 1. Etiological aspects. A literature review

BACKGROUND: The growth of the human body is the most significant period of development of the bone tissue, because it is during this period that the size, shape, and architectonics of bone are formed against the background of increasing body weight and increasing physical exertion. Considering a number of pathological factors of the underlying disease (alimentary, neurological, hormonal, stress, and physical), bone tissue in children with cerebral palsy grows and develops with deviations from the norm. АIM: To present up-to-date generalized information about the features of bone tissue in children with cerebral palsy to orthopedic traumatologists, neurologists, and physical therapy specialists. MATERIALS AND METHODS: Studies on the problem of bone tissue condition in patients with cerebral palsy were analyzed. Data published over the past 20 years were searched in the scientific databases PubMed, Google Scholar, Cochrane Library, Crossref, and eLibrary without language restrictions. RESULTS: In the last 20 years, the number of studies about pediatric osteoporosis has increased. The gold standard for determining the level of bone mineral density is dual-energy X-ray absorptiometry. However, its use in children has presented some difficulties and limitations. In children, the relationship between bone mineral density values and the risk of fractures has not been well studied, which does not allow us to discuss about osteoporosis based on densitometric bone mineral density data alone. In patients with cerebral palsy, a decrease in bone mineral density and bone mass during growth was found. Previous studies showed that the main factors associated with a decrease in bone mineral density in this group of patients include neuroendocrine causes due to growth retardation against the background of CNS damage, alimentary factors, decreased calcium and vitamin D concentrations, systemic use of glucocorticoids, intake of antiepileptic drugs, decreased motor activity, and low muscle mass. Increasing serum vitamin D concentrations does not have a positive effect on bone mass, although increasing serum calcium concentrations is associated with an increase in bone mineral density. CONCLUSIONS: Identifying and correcting factors leading to decreased bone mineral density in children with cerebral palsy can improve bone health in this group of patients. The absence of a relationship between bone mineral density values and the risk of fractures in children with cerebral palsy does not allow us to discuss about osteoporosis based only on bone mineral density densitometric data. There may be more factors leading to an increased risk of bone fractures in children with cerebral palsy that require further study.

What do we know about lithium associated hypercalcemia?

IntroductionLithium associated with hypercalcemia may mimic a psychiatric condition and be confused for a relapse of bipolar disorder. The etiology seems to be due to a reduced sensitivity of the parathyroid cells to calcium, altering the parathyroid hormone (PTH) response. Lithium as an essential monovalent cation has some structural similarity to calcium (Ca) and can interact with protein receptors. This leads to changes in the inhibitory configuration of PTH and increased serum calcium concentrations, rising the threshold necessary to suppress hormone secretion.Lithium-induced hyperparathyroidism (HIL) is the main cause of hypercalcemia in these patients.ObjectivesBased on a clinical case of lithium-associated hypercalcemia in a patient with bipolar disorder, review the existing literature and state the needs for periodic monitoring protocols.MethodsCase report and bibliographical review.ResultsA 38-year-old woman, diagnosed with bipolar affective disorder at the age of 18, has been treated with lithium during which she developed secondary tubulointerstitial nephropathy as an adverse effect. Recently, she requested medical evaluation for constitutional syndrome associated with deterioration of general condition with loss of strength and difficulty in walking. Analytically, mild hypercalcemia was detected, and the study was extended to include Ca and PTH.Chronic lithium therapy often develops mild hypercalcemia (approximately 10 to 20 percent of patients taking lithium), most likely due to increased secretion of PTH. Lithium can also unmask previously unrecognized mild hyperparathyroidism in patients with adenomas within a few years of starting therapy or induce parathyroid hyperplasia with a chronic use.The hypercalcemia usually, but not always, subsides when the lithium is stopped. Normalization of serum calcium is more likely to occur one to four weeks post-lithium withdrawal in patients with a relatively short duration of lithium use. It is less likely in patients receiving lithium for more than 10 years.Regarding the case to be presented, a review of the literature is carried out and the need to propose periodic calcium monitoring protocols is exposed.ConclusionsRecommendations include determination of serum calcium every 6 months, urinary calcium and creatinine every 12 months, and bone mineral density monitoring every 1 to 3 years. Regular analytical monitoring including total calcium, PTH and vitamin D, would identify patients with a tendency to hypercalcemia so that appropriate measures could be taken. So as chronic treatment with lithium can develop mild hypercalcemia, I consider it necessary to develop periodic monitoring protocols for this adverse effect.Disclosure of InterestNone Declared

Yeast Hydrolysate and Postmenopausal Osteoporosis

We used an ovariectomy (OVX) rat model to test whether yeast hydrolysate (YH) has therapeutic effects on postmenopausal osteoporosis-induced bone loss. The rats were separated into five treatment groups: the sham group (sham operation); the control group (no treatment after OVX); the estrogen group (estrogen treatment after OVX); YH 0.5% group (drinking water supplementation with 0.5% YH after OVX); and the YH 1% group (drinking water supplementation with 1% YH after OVX). In addition, the YH treatment restored serum testosterone concentration in the OVX rats up to the normal level. Further, YH treatment affected bone markers; a significant increase in serum calcium concentration was observed after adding YH to the diet. The levels of serum alkaline phosphatase, osteocalcin, and cross-linked telopeptides of type I collagen were reduced by YH supplementation, unlike those in the no-treatment control. Although not statistically significant, YH treatment in OVX rats improved trabecular bone microarchitecture parameters. These results show that YH may ameliorate the bone loss caused by postmenopausal osteoporosis because of the normalization of serum testosterone concentration.

Влияние элементного статуса детей 7–8 лет, проживающих в Хабаровском крае, на их физическое и когнитивное развитие

Objective. To evaluate the influence of changes in elemental status on the physical and cognitive development of children aged 7–8 years living in different biogeochemical regions of the Khabarovsk Territory. Patients and methods. Study design: observational, analytical, cross-sectional. Two groups of almost healthy children aged 7–8 years living in the central (n = 30) and northern areas (n = 30) of the Khabarovsk Territory were formed by random sampling. The quantitative analysis of elements (calcium, magnesium, zinc, copper, iron, selenium, mercury, lead, cadmium) in the hair and blood serum of children was carried out by inductively coupled plasma-mass spectrometry (ICP-MS). The concentration of iodine was determined in a first morning urine specimen using the cerium arsenite method. The evaluation of physical and cognitive development was performed according to standardized methods. Results. When assessing the influence of the content of elements in the body on children’s physical development, data were obtained on the involvement of calcium and selenium in the formation of the child’s growth: the most severe calcium and selenium deficiency corresponded to the lowest growth indicators (r = 0.45, r = 0.40, respectively, p < 0.05). The patterns of growth delay with decreased zinc and copper concentrations (r = 0.30, r = 0.35, respectively) and the effect of high iron serum levels (r = –0.30) were revealed. The comparison of children’s cognitive and elemental statuses showed a decreased level of verbal and logical reasoning in magnesium deficiency (r = 0.47, p < 0.05) and high iron levels (r = –0.48, p < 0.05). The higher the body was supplied with iodine and copper, the better the memory developed (r = 0.44, r = 0.41, respectively, p < 0.05). It was also found that an increase in serum calcium concentration improved the formation of conceptual and categorical apparatus (r = 0.37, p < 0.05) and voluntary attention in children (r = 0.34). Conclusion. This correlation analysis of the indicators of physical, cognitive, and elemental status of children demonstrates the important role of the optimal elemental status in the harmonious development of a child. Key words: elementary school children, cognitive abilities, elemental status, physical development

Hypercalcaemia in a dog with lymphoma without increases in parathyroid hormone, parathyroid hormone-related protein and vitamin D metabolites concentrations

Lymphoma is one of the most common causes of hypercalcaemia in dogs. Typically, the hypercalcaemic state is driven by ectopic production of parathyroid hormone-related protein by the malignant lymphoma cells....

OR07-03 Continuous Subcutaneous Delivery of RhPTH(1-84) by Pump in Adults with Hypoparathyroidism

More than 80,000 people in the United States have hypoparathyroidism, a disease of low or absent parathyroid hormone (PTH) leading to hypocalcemia and hyperphosphatemia. Conventional treatment with oral calcium and active vitamin D increases serum calcium concentrations but does not replace the physiologic functions of PTH. Once-daily subcutaneous injections of recombinant human (rh) PTH(1-84) were recently approved for the treatment of hypoparathyroidism, but are not consistent in correcting biochemical abnormalities and alleviating symptoms for all patients. In cases in which single or multiple daily injections of rhPTH(1-84) are insufficient for controlling symptoms, continuous subcutaneous infusion via insulin pump is used as a therapeutic alternative. Pump therapy with PTH(1-34) has some support in the literature as an effective form of treatment for hypoparathyroidism.1However, the effects of pump therapy with rhPTH(1-84) in patients with hypoparathyroidism have not been reported. Five women with chronic postsurgical hypoparathyroidism who received treatment at three different endocrine outpatient clinics in the United States were transitioned from multiple daily injections of rhPTH(1-84) to continuous delivery of rhPTH(1-84) using the Omnipod insulin pump. The patients’ ages ranged from 27 to 60 years old and all had had hypoparathyroidism for at least 5 years. All of the patients were transitioned from conventional therapy with oral calcium and calcitriol to subcutaneous injections of rhPTH(1-84), and then switched to continuous subcutaneous administration using an insulin pump. In all five patients, increased serum calcium concentrations and decreased serum phosphate concentrations were observed with increased frequency of PTH administration. Serum calcium concentrations were within the normal to high-normal range and serum phosphate concentrations were in the normal range on pump therapy. Urinary calcium was well-controlled (<250 mg/day) in four of the five patients. All of the women reported a decrease in symptoms while receiving pump-administered rhPTH(1-84), including a lower incidence of fatigue, brain fog, tingling, and muscle cramps compared to standard therapy and daily injections. This is the first report of patients with hypoparathyroidism on long-term therapy with continuously infused subcutaneous rhPTH(1-84) using a pump. Pump therapy improved key parameters of mineral metabolism; normalizing serum calcium in all patients and urinary calcium in four out of five patients. Clinical trials with larger cohorts are needed to confirm the efficacy of this promising mode of administration of rhPTH(1-84). Reference: 1. Winer KK. Advances in the treatment of hypoparathyroidism with PTH 1-34. Bone. 2019;120:535-541.

Effects of dietary menthol-rich bioactive lipid compounds on zootechnical traits, blood variables and gastrointestinal function in growing sheep

BackgroundThe present study aimed at investigating the influence of 90% menthol-containing plant bioactive lipid compounds (PBLC, essential oils) on growth performance, blood haematological and biochemical profile, and nutrient absorption in sheep. Twenty-four growing Suffolk sheep were allotted into three dietary treatments: Control (without PBLC), lower dose of PBLC (PBLC-L; 80 mg/d) and higher dose of PBLC (PBLC-H; 160 mg/d). Sheep in all groups were fed meadow hay ad libitum plus 600 g/d of concentrate pellets for 28 d.ResultsAverage daily gain was not affected by treatment. Feeding of PBLC increased hay and total feed intake per kg body weight (P < 0.05). Counts of total leucocytes, lymphocytes and monocytes were not different among treatments. However, neutrophil count decreased (P < 0.05) in PBLC-H with a similar trend in PBLC-L (P < 0.10). Concentrations of glucose, bilirubin, triglycerides, cholesterol, urea and magnesium in serum were not different among sheep fed different doses of PBLC. However, serum calcium concentration tended to increase in PBLC-H (P < 0.10) and serum concentrations of aspartate & asparagine (P < 0.01) and glutamate & glutamine (P < 0.05) increased linearly with increasing PBLC dose. In ruminal epithelia isolated from the rumen after killing, baseline conductance (Gt; P < 0.05) and short-circuit current (Isc; P < 0.01) increased in both PBLC groups. Ruminal uptakes of glucose and methionine in the presence of Na+ were not affected by the dietary PBLC supplementation. In the absence of Na+, however, glucose and methionine uptakes increased (P < 0.05) in PBLC-H. In the jejunum, Isc tended to increase in PBLC-H (P < 0.10), but baseline Gt was not affected. Intestinal uptakes of glucose and methionine were not influenced by PBLC in the presence or absence of Na+.ConclusionThe results suggest that menthol-rich PBLC increase feed intake, and passive ion and nutrient transport, the latter specifically in the rumen. They also increased serum concentrations of urea precursor amino acids and tended to increase serum calcium concentrations. Future studies will have to show whether some of these findings might be commonly linked to a stimulation of transient receptor potential (TRP) channels in the gastrointestinal tract.

Increased mortality and morbidity in patients with chronic hypoparathyroidism: A population-based study.

A population-based study was undertaken to determine the mortality and morbidity for people with hypoparathyroidism compared to the general population. In this study, patients identified with chronic hypoparathyroidism using data linkage from regional datasets were compared with five age- and gender-matched controls from the general population. Data from biochemistry, hospital admissions, prescribing and the demographic dataset were linked. Outcomes for mortality and specified conditions were examined for all patients and subdivided into post-surgical and non-surgical cases of hypoparathyroidism. All patients had an increased risk of epilepsy (HR 1.65 [95% CI 1.12-2.44]) and cataracts (HR 2.10 [1.30-3.39]) but no increased fracture risk. Only non-surgical hypoparathyroid patients also had increased mortality (HR 2.11 [1.49-2.98]), cardiovascular disease (HR 2.18 [1.41-3.39]), cerebrovascular disease (HR 2.95 [1.46-5.97]), infection (HR 1.87 [1.2-2.92]) and mental illness (HR 1.59 [1.21-2.11]). There was an increased risk of renal failure (HR 10.05 [95% CI 4.71-21.43]) during the first 2000days (5.5years) of follow-up. Renal failure and death were associated with increasing serum calcium concentrations. Patients with hypoparathyroidism have an increased risk of cataract and epilepsy. Non-surgical hypoparathyroidism is associated with increased mortality and additional morbidities.

Prepartum daylight exposure increases serum calcium concentrations in dairy cows at the onset of lactation.

In dairy cows, hypocalcemia is caused by the sudden calcium demand by the mammary gland at the onset of lactation. Calcitriol (1,25-dihydroxy vitamin D; 1,25-VitD) increases the intestinal calcium absorption and the renal calcium reabsorption. Daylight contributes to the formation of 1,25-VitD, as it transforms 7-dehydrocholesterol into cholecalciferol, a 1,25-VitD precursor. Calving pens are usually set in quiet places where cows can stay calm and relaxed before parturition. However, those pens often have poor lighting conditions and therefore cows may become vitamin D deficient because of inadequate daylight exposure. Therefore, we have tested the hypothesis that direct daylight exposure supports the synthesis of 1,25-VitD and consequently attenuates the decline of calcium concentrations at parturition. Twenty Holstein dairy cows were randomly assigned to 2 experimental groups (daylight group, DL; and control group). Beginning on d -10 before expected parturition, both groups were placed in a standard indoor calving pen from 1700 h to 800 h. From 800 h to 1700 h cows from the DL group were moved into a contiguous open pen with direct access to daylight whereas controls remained at the standard indoor calving pen. After parturition both groups were permanently placed in an indoor calving pen until the end of the experimental period (d 30 postpartum). Blood samples were collected daily from d -10 prior to expected parturition through d 7 postpartum with an additional sample on d 30 postpartum. Milk yield was recorded at each milking during the whole experimental period. In the DL group, 25-hydroxyvitamin D (25-VitD), 1,25-VitD and total calcium concentrations around parturition were higher than in the controls. Higher parathyroid hormone concentrations were observed in the control group compared to the DL group at parturition. Pyridinoline concentrations did not differ between groups on d 1, and therefore it is assumed that the intensity of calcium transfer from the bones to the bloodstream was not affected by the increased daylight exposure. The measured plasma metabolites (β-hydroxybutyrate, fatty acids and glucose) as well as milk yield were not affected by the increased daylight exposure. In conclusion, the increased daylight exposure before parturition increased 25-VitD and 1,25-VitD concentrations, preventing a considerable decline of total calcium concentrations around parturition.

Animal Models of Cancer-Associated Hypercalcemia.

Cancer-associated hypercalcemia (CAH) is a frequently-occurring paraneoplastic syndrome that contributes to substantial patient morbidity and occurs in both humans and animals. Patients with CAH are often characterized by markedly elevated serum calcium concentrations that result in a range of clinical symptoms involving the nervous, gastrointestinal and urinary systems. CAH is caused by two principle mechanisms; humorally-mediated and/or through local osteolytic bone metastasis resulting in excessive calcium release from resorbed bone. Humoral hypercalcemia of malignancy (HHM) is the most common mechanism and is due to the production and release of tumor-associated cytokines and humoral factors, such as parathyroid hormone-related protein (PTHrP), that act at distant sites to increase serum calcium concentrations. Local osteolytic hypercalcemia (LOH) occurs when primary or metastatic bone tumors act locally by releasing factors that stimulate osteoclast activity and bone resorption. LOH is a less frequent cause of CAH and in some cases can induce hypercalcemia in concert with HHM. Rarely, ectopic production of parathyroid hormone has been described. PTHrP-mediated hypercalcemia is the most common mechanism of CAH in human and canine malignancies and is recognized in other domestic species. Spontaneous and experimentally-induced animal models have been developed to study the mechanisms of CAH. These models have been essential for the evaluation of novel approaches and adjuvant therapies to manage CAH. This review will highlight the comparative aspects of CAH in humans and animals with a discussion of the available animal models used to study the pathogenesis of this important clinical syndrome.

69-Year-Old Woman With Confusion and Fatigue

Resident in Internal Medicine, Mayo School of Graduate Medical Education, Rochester, MN (H.M.K.); Advisor to resident and Consultant in Endocrinology, Diabetes, Metabolism, and Nutrition, Mayo Clinic, Rochester, MN (A.E.K.). A 69-year-old woman presented to her primary care physicianwith a 4-day history of fatigue and dizziness. She was 45 minutes late for her appointment because she had trouble driving to the office. She reported no motor or sensory deficits but had difficulty with coordination. Review of systems was positive for dysuria and urinary frequency. She did not have fever, chills, weight or appetite changes, respiratory, cardiac, or gastrointestinal symptoms, or recent head trauma. The patient’s medical history was remarkable for hypertension, hyperlipidemia, type 2 diabetes mellitus, osteoporosis, and gastroesophageal reflux disease. Medications included metoprolol tartrate, lisinopril with hydrochlorothiazide, lovastatin, cholecalciferol, and as-needed calcium carbonate. She had smoked half a pack of cigarettes per day for 40 years but had quit smoking 6 years previously. She didnot use alcohol or illicit drugs. On examination, the patient was afebrile with a blood pressure of 104/67 mm Hg, heart rate of 76 beats/min, respiratory rate of 17 breaths/min, oxygen saturation of 94% while breathing room air, and body mass index (calculated as weight in kilograms divided by height inmeters squared) of 39 kg/m. Shewas alert and oriented to person, place, and time. Her speech was dysarthric, and she had difficulty following simple commands. Her coordination was impaired with symmetric dysmetria on finger-to-nose testing, heel-kneeshin testing, and rapid alternating movements. Cranial nerves II through XII were intact. Results of motor and sensory examinations were within normal limits. Reflexes were symmetric. Lymph node, thyroid, cardiac, respiratory, gastrointestinal, musculoskeletal, and skin examinations identified no abnormalities.

Increased serum calcium levels and risk of type 2 diabetes in individuals at high cardiovascular risk.

Insulin resistance and secretion depend on calcium homeostasis. Cross-sectional studies have associated elevated serum calcium levels with markers of impaired glucose metabolism. However, only one prospective cohort study has demonstrated an increased risk of diabetes in individuals with increased serum calcium concentrations. The aim of the current study was to prospectively investigate the association between albumin-adjusted serum calcium concentrations and type 2 diabetes in subjects at high cardiovascular risk. Prospective assessment of participants from two Spanish PREDIMED study centers where serum calcium levels were measured at baseline and yearly during follow-up. Multivariate-adjusted Cox regression models were fitted to assess associations between baseline and changes during follow-up in serum calcium levels and relative risk of diabetes incidence. After a median follow-up of 4.78 years, 77 new cases of type 2 diabetes occurred. An increase in serum calcium levels during follow-up was related to an increased risk of diabetes. In comparison with individuals in the lowest tertile (-0.78 ± 0.29 mg/dL), the hazard ratio (HR) and 95% CI for diabetes incidence in individuals in the higher tertile of change (0.52 ± 0.13 mg/dL) during follow-up was 3.48 (95% CI 1.48-8.17; P for trend = 0.01). When albumin-adjusted serum calcium was analyzed as a continuous variable, per 1 mg/dL increase, the HR of diabetes incidence was 2.87 (95% CI 1.18-6.96; P value = 0.02). These associations remained significant after individuals taking calcium supplements or having calcium levels out of normal range had been excluded. An increase in serum calcium concentrations is associated with an increased risk of type 2 diabetes in individuals at high cardiovascular risk.

Vitamin D deficiency and its correction in children with sickle cell anaemia.

Vitamin D deficiency is common in sickle cell anaemia (SCA, HbSS), although its significance and optimal means of correction are unknown. We conducted an audit to assess the clinical significance of 25-hydroxy vitamin D (25-OHD) deficiency in children with SCA and to evaluate two methods of vitamin D supplementation. We audited 25-OHD levels in 81 children with SCA and looked for statistical associations with biochemical, haematological and clinical parameters. In a separate group of regularly transfused children with SCA, we compared changes in 25-OHD blood concentrations following treatment with either high-dose intramuscular ergocalciferol (n = 15) or 4 days of high-dose oral cholecalciferol (n = 64). Ninety-one percent of children with SCA had 25-OHD levels <20 μg/L. The 25-OHD levels were negatively correlated with increasing age (P < 0.001) but showed no significant relationship to laboratory measurements, transcranial Doppler velocities or hospital attendance. Both intramuscular ergocalciferol and oral cholecalciferol supplementations resulted in increases of 25-OHD blood concentration to normal levels. The mean dose of ergocalciferol was greater than that of cholecalciferol (7,729 versus 5,234 international units (IU)/kg, P < 0.001), but the increment in 25-OHD levels was significantly greater in the oral cholecalciferol group (6.44 versus 2.82 (ng/L)/(IU/kg), P < 0.001). Both approaches resulted in vitamin D sufficiency for about 120 days. Increased 25-OHD concentration was significantly associated with increased serum calcium concentration. Vitamin D deficiency is very common in SCA and can be effectively corrected with high-dose intramuscular ergocalciferol or 4 days of high-dose oral cholecalciferol. Prospective, randomised studies are needed to assess the clinical value of vitamin D supplementation.

AXT914 a novel, orally-active parathyroid hormone-releasing drug in two early studies of healthy volunteers and postmenopausal women

Antagonism of the calcium-sensing receptor in the parathyroid gland leads to parathyroid hormone (PTH) release. Calcilytics are a new class of molecules designed to exploit this mechanism. In order to mimic the known bone-anabolic pharmacokinetic (PK) profile of s.c. administered PTH, such molecules must trigger sharp, transient and robust release of PTH. The results of two early clinical studies with the orally-active calcilytic AXT914, a quinazolin-2ne derivative are reported. These were GCP-compliant, single and multiple dose studies of PK/PD and tolerability in healthy volunteers and postmenopausal women.The first study, examined single ascending doses (4 to 120mg) and limited multiple doses (60 or 120mgq.d. for 12days) of AXT914. The second study was a randomized, double-blind, active- and placebo-controlled, 4-week repeat-dose parallel group study of healthy postmenopausal women (45 and 60mg AXT914, placebo, 20μg Forteo/teriparatide/PTH(1–34) fragment).AXT914 was well tolerated at all doses and reproducibly induced the desired PTH-release profiles. Yet, 4weeks of 45 or 60mg AXT914 did not result in the expected changes in circulating bone biomarkers seen with teriparatide. However total serum calcium levels increased above baseline in the 45 and 60mg AXT914 treatment groups (8.0 % and 10.7%, respectively), compared to that in the teriparatide and placebo groups (1.3% and 1.0%, respectively). Thus the trial was terminated after a planned interim analysis due to lack of effect on bone formation biomarkers and dose-limiting effects on serum calcium.In conclusion, AXT914 was well tolerated but the observed transient and reproducible PTH-release after repeat oral administration of AXT914 which showed an exposure profile close to that of s c. PTH, did not translate into a bone anabolic response and was associated with a persistent dose-related increase in serum calcium concentrations.

Reprint of “Influence of analytical bias and imprecision on the number of false positive results using Guideline-Driven Medical Decision Limits”

BackgroundDiagnostic decisions based on decision limits according to medical guidelines are different from the majority of clinical decisions due to the strict dichotomization of patients into diseased and non-diseased. Consequently, the influence of analytical performance is more critical than for other diagnostic decisions where much other information is included. The aim of this opinion paper is to investigate consequences of analytical quality and other circumstances for the outcome of “Guideline-Driven Medical Decision Limits”. TermsEffects of analytical bias and imprecision should be investigated separately and analytical quality specifications should be estimated accordingly. Biological variation and analytical performanceUse of sharp decision limits doesn't consider biological variation and effects of this variation are closely connected with the effects of analytical performance. Such relationships are investigated for the guidelines for HbA1c in diagnosis of diabetes and in risk of coronary heart disease based on serum cholesterol. The effects of a second sampling in diagnosis give dramatic reduction in the effects of analytical quality showing minimal influence of imprecision up to 3 to 5% for two independent samplings, whereas the reduction in bias is more moderate and a 2% increase in concentration doubles the percentage of false positive diagnoses, both for HbA1c and cholesterol. Frequency of follow-up laboratory testsAn alternative approach comes from the current application of guidelines for follow-up laboratory tests according to clinical procedure orders, e.g. frequency of parathyroid hormone requests as a function of serum calcium concentrations. Here, the specifications for bias can be evaluated from the functional increase in requests for increasing serum calcium concentrations. Probability function for diagnosesIn consequence of the difficulties with biological variation and the practical utilization of concentration dependence of frequency of follow-up laboratory tests already in use, a kind of probability function for diagnosis as function of the key-analyte is proposed.

Effect of multispecies probiotic supplements on serum minerals, liver enzymes and blood pressure in patients with type 2 diabetes

Emerging evidence suggests that diabetes is associated with altering serum minerals, elevated liver enzymatic activity and blood pressures. This study was designed to determine the effects of multispecies probiotic supplements on serum minerals, liver enzymes and blood pressure in diabetic patients. This randomized double-blinded controlled clinical trial was performed among 58 diabetic patients aged 35–70 y. Subjects were randomly assigned to consume either multispecies probiotic supplements (N = 28) or the placebo group (N = 30) for 8 weeks. The multispecies probiotic supplement was consisted of seven viable and freeze-dried strains: Lactobacillus acidophilus (2 × 109 CFU), Lactobacillus casei (7 × 109 CFU), Lactobacillus rhamnosus (1.5 × 109 CFU), Lactobacillus bulgaricus (2 × 108 CFU), Bifidobacterium breve (2 × 1010 CFU), Bifidobacterium longum (7 × 109 CFU), Streptococcus thermophilus (1.5 × 109 CFU) and 100 mg fructo-oligosaccharide with lactose as carrier substances. Fasting blood samples were taken at baseline and after 8-week intervention to measure serum minerals, liver enzymes and total bilirubin. Consumption of the probiotic supplements, compared to the placebo, resulted in an increased serum calcium concentrations (0.21 vs. −0.83 mg/dL, P = 0.009) and a decreased serum alanine aminotransferase (ALT) levels (−2.46 vs. 4.62 mg/dL, P = 0.02). We did not find a significant difference in terms of effect on serum magnesium, zinc, iron, alkaline phosphatase (ALP), aspartate aminotransferase (AST) levels and blood pressures comparing the two groups. In conclusion, multispecies probiotic supplementation among diabetic patients had beneficial effects on serum calcium and ALT concentrations.

Influence of analytical bias and imprecision on the number of false positive results using Guideline-Driven Medical Decision Limits

BackgroundDiagnostic decisions based on decision limits according to medical guidelines are different from the majority of clinical decisions due to the strict dichotomization of patients into diseased and non-diseased. Consequently, the influence of analytical performance is more critical than for other diagnostic decisions where much other information is included. The aim of this opinion paper is to investigate consequences of analytical quality and other circumstances for the outcome of “Guideline-Driven Medical Decision Limits”. TermsEffects of analytical bias and imprecision should be investigated separately and analytical quality specifications should be estimated accordingly. Biological variation and analytical performanceUse of sharp decision limits doesn't consider biological variation and effects of this variation are closely connected with the effects of analytical performance. Such relationships are investigated for the guidelines for HbA1c in diagnosis of diabetes and in risk of coronary heart disease based on serum cholesterol. The effects of a second sampling in diagnosis give dramatic reduction in the effects of analytical quality showing minimal influence of imprecision up to 3 to 5% for two independent samplings, whereas the reduction in bias is more moderate and a 2% increase in concentration doubles the percentage of false positive diagnoses, both for HbA1c and cholesterol. Frequency of follow-up laboratory testsAn alternative approach comes from the current application of guidelines for follow-up laboratory tests according to clinical procedure orders, e.g. frequency of parathyroid hormone requests as a function of serum calcium concentrations. Here, the specifications for bias can be evaluated from the functional increase in requests for increasing serum calcium concentrations. Probability function for diagnosesIn consequence of the difficulties with biological variation and the practical utilization of concentration dependence of frequency of follow-up laboratory tests already in use, a kind of probability function for diagnosis as function of the key-analyte is proposed.

Association of calcium concentration with pulse pressure in older women: data from a large population-based multicentric study.

High arterial pulse pressure is a predictor of cardiovascular morbimortality. Mineral metabolism has been associated with blood pressure regulation. Our objective was to determine which variable among serum calcium, parathyroid hormone and 25-hydroxyvitamin D concentrations, was associated with pulse pressure among older adults. Cross-sectional study corresponding to the baseline assessment of the EPIDOS study. Five French cities including Amiens, Lyon, Montpellier, Paris and Toulouse. Randomized sample of 610 community-dwelling older women (mean age 80.2±3.5years) using no antihypertensive drugs. Serum calcium, parathyroid hormone and 25-hydroxyvitamin D concentrations; supine pulse pressure after 15 minutes of rest (hypertension defined as pulse pressure >50mmHg). Age, body mass index, the number of morbidities and of drugs daily taken, diabetes mellitus, dysthyroidy, the use of estrogenic drugs, smoking, alcohol consumption, practice of a regular physical activity, creatinine clearance, and the effects of season and study centers were used as potential confounders. Hypertensive participants (n=539) had higher calcium concentrations than normotensive ones (94.33±4.12mg/L versus 93.28±3.36mg/L respectively, P=0.040). There were no between-group differences for serum parathyroid hormone and 25-hydroxyvitamin D concentrations. The multiple logistic regressions examining the serum calcium, parathyroid hormone and 25-hydroxyvitamin D concentrations as predictors of hypertension found an association only with calcium (adjusted odds ratio=1.19, P=0.015), but not with parathyroid hormone (adjusted OR=1.01, P=0.349) or 25-hydroxyvitamin D concentration (adjusted OR=0.99, P=0.971). Increased serum calcium concentration was independently and positively associated with high pulse pressure in our study, possibly due to increased arterial stiffness. Interventions aimed at normalizing calcaemia may be attractive to prevent hypertension and cardiovascular risk in older adults.

Effects of dietary energy and calcium levels on performance, egg shell quality and bone metabolism in hens

This study investigated the effects of dietary energy and calcium levels on laying performance, eggshell quality and bone metabolism of layers. One hundred and sixty-two 19-week-old Hy-Line brown laying hens in 54 battery cages were allocated to one of nine dietary treatments with control, middle and high levels of energy (11.50, 12.68 and 13.37MJ/kg, respectively) and low, control and high levels of calcium (2.62%, 3.7% and 4.4%, respectively) for 60days, using a 3×3 factorial arrangement.Compared with the control energy diet, high- and middle-energy diets increased fat deposition and egg weight, decreased feed intake and bone quality and had no effects on eggshell quality. The high-energy diet reduced the serum phosphate concentration and elevated osteocalcin mRNA expression in the keel bone without increasing osteocalcin protein. Dietary calcium intake did not affect fat deposition, feed intake or egg weight. Low dietary calcium resulted in weaker eggshells and poorer bone quality than that from hens fed the control diet. High dietary calcium increased serum calcium concentration, osteoprotegerin mRNA and osteocalcin protein and inhibited serum alkaline phosphatase activity and decreased its mRNA compared with low or control dietary calcium. The high-energy and high-calcium diet significantly reduced egg production.Compared with the control energy diet, high- and middle-energy diets increased fat deposition but had negative effects on bone metabolic homeostasis. Dietary calcium did not influence fat deposition but a high-calcium diet benefited bone homeostasis, while a low-calcium diet was associated with poorer eggshell quality and bone homeostasis.

Treatment of cows with milk fever using intravenous and oral calcium and phosphorus

Fifteen cows with milk fever were treated with 500ml of 40 % calcium borogluconate (group A) administered intravenously. Fifteen other cows with milk fever received the same treatment, supplemented with 500ml of 10 % sodium phosphate administered intravenously, and 80g calcium as calcium lactate and 70g inorganic phosphorus as sodium phosphate administered orally in drinking water. The cows were monitored and blood samples collected for 3 days to measure the concentrations of total and ionized calcium, inorganic phosphorus and magnesium and the activity of creatine kinase. The two groups did not differ significantly with respect to the course of the disease. In each group 14 cows were cured. A rapid and significant increase in serum calcium concentration from the hypo- to the hypercalcaemic range occurred in both groups within 10min of the start of treatment, followed by a slow and steady decrease to the hypocalcaemic range. Calcium lactate did not prevent the calcium concentration from returning to the hypocalcaemic range, and the calcium profiles of the two groups did not differ significantly. As expected, treatment had little effect on the concentration of inorganic phosphorus in group A. In group B, treatment caused a rapid increase in the concentration of inorganic phosphorus to a maximum 20min after the start of treatment. This was followed by a slow decrease in the phosphorus concentration to the normophosphataemic range. Our findings confirmed that combined intravenous and oral administration of sodium phosphate in cows with periparturient paresis attributable to hypocalcaemia and hypophosphataemia results in a rapid and sustained increase in serum phosphorus, but not in serum calcium concentration. This modified therapy did not improve the success rate of milk fever treatment and further studies are needed to improve treatment of periparturient paresis.