Applications of Metabolomics in Calcium Metabolism Disorders in Humans.

The pathogenesis of the disorders of calcium metabolism is not fully understood. This review discusses the studies in which metabolomics was applied in this area. Indeed, metabolomics could play an essential role in discovering biomarkers and elucidating pathological mechanisms. Despite the limited bibliography, the present review highlights the potential of metabolomics in identifying the biomarkers of some of the most common endocrine disorders, such as primary hyperparathyroidism (PHPT), secondary hyperparathyroidism (SHPT), calcium deficiency, osteoporosis and vitamin D supplementation. Metabolites related to above-mentioned diseorders were grouped into specific classes and mapped into metabolic pathways. Furthermore, disturbed metabolic pathways can open up new directions for the in-depth exploration of the basic mechanisms of these diseases at the molecular level.

Calcium Metabolic Disorders in Pregnancy: Primary Hyperparathyroidism, Pregnancy-Induced Osteoporosis, and Vitamin D Deficiency in Pregnancy.

Physiologic changes during pregnancy include calcium, phosphate, and calciotropic hormone status. Calcium metabolic disorders are rare in pregnancy and management with close calcium and vitamin D control and supplementation. Primary hyperparathyroidism is mostly asymptomatic and does not affect conception or pregnancy. It requires control of plasma calcium levels. Surgical intervention may be indicated. Data on severe cases are missing. Osteoporosis in or before pregnancy is rare but usually diagnosed from fractures. Medical treatment other than supplementation is contraindicated. Vitamin D deficiency is common and may affect conception and increase complications. Current evidence does not prove vitamin D supplements effective in improving outcomes.

Resultados del tratamiento quirúrgico del hiperparatiroidismo primario en un país en vías de desarrollo / Outcomes of Primary Hyperparathyroidism Surgical Treatment in a Low-Middle Income Country

Introducción: El hiperparatiroidismo primario es una enfermedad común y con una distribución similar en todo el mundo. El propósito del estudio fue establecer si la presentación clínica y bioquímica, así como los resultados de su tratamiento quirúrgico, difieren en un país en vías de desarrollo, que no cuenta con todos los recursos diagnósticos y terapéuticos recomendados actualmente. Metodología: Análisis retrospectivo de pacientes operados por un mismo equipo, entre 1992 y 2015. Se obtuvo información sobre presentación clínica, resultados de estudios preoperatorios, procedimientos quirúrgicos, diagnóstico histopatológico y evolución postoperatoria. Resultados: Se operaron 55 pacientes con edad promedio de 45 años, 78% mujeres. El 65% eran sintomátcos. El valor promedio preoperatorio de calcio sérico fue 11.2 mg/dl, PTH 167.1 pg/ml, fósforo 2.6 mg/ dl, 25-hidroxi vitamina D 17.3 ng/ml y calcio urinario de 24 horas 294.7 mg. Al 59% se realizó estudios de localización preoperatoria. La sensibilidad del ultrasonido fue 57.14% y 75% para centellografa con tecnecio sestamibi. La positividad de los estudios de localización determinó el tipo de exploración quirúrgica (p=0.02). Se practcaron 27 (49%) exploraciones unilaterales y 28 (51%) bilaterales, resecando 47 (85.5%) adenomas solitarios y 3 ½ glándulas en 7 (12.7%) casos de hiperplasias. En 27 (36%) coexista patología tiroidea. Las tasas de curación, persistencia y recurrencia fueron 94.5%, 5.5% y 3.6% respectivamente. Conclusiones: La mayoría de nuestros pacientes operados son jóvenes y sintomátcos. La estrategia quirúrgica fue condicionada por los estudios de localización. Nuestras tasas de curación, persistencia y recurrencia son comparables a las reportadas.

Background: Primary hyperparathyroidism (HPTP) is a common disease with widespread distribution around the world. The aim of this study was to establish if clinical and biochemical disease characteristics and long term results differ in patents with HPTP in a low-middle income country without all recommended diagnostc and therapeutc resources. Methods: Retrospective collection of clinical diagnosis, biochemical, operative details, histology and long term results of all surgically treated patents with HPTP, from 1992 to 2015, by the same surgical team. Results: 55 patents with HPTP were analyzed. Average age is 45 years old with 78% of female patents. Sixty five percent were symptomatic. The mean preoperative serum calcium level was 11.2 mg/dl, PTH 167.1 pg/ml, phosphorus 2.6 mg/ dl, vitamin D 17.3 ng/ml and 24 hour urinary calcium 294.7 mg. Fifty nine percent of the patents had preoperative imaging. Ultrasound and sestamibi scan sensitivity was 57.1% and 75% respectively. Unilateral localization in preoperative imaging determined surgical exploration (p=0.02). Unilateral approach was used in 27 (49%) patents and bilateral in 28 (51%); 47 (85.5%) solitary adenomas and 7 (12.7%) 3 ½ gland resections of hyperplastic glands were performed. Thyroid pathology co-existed in 27 (36%) patients. Cure, persistence and recurrence rates were 94.5%, 5.5% y 3.6% respectively. Conclusions: In this study most of the patents were young and symptomatc. Surgical strategy was determined by preoperatve imaging. Cure, persistence and recurrence rates were comparable to published literature.

Reversal of uremic tumoral calcinosis by optimization of clinical treatment of bone and mineral metabolism disorder.

Tumoral calcinosis is an uncommon type of extraosseous calcification characterized by large rubbery or cystic masses containing calcium-phosphate deposits. The condition prevails in the periarticular tissue with preservation of osteoarticular structures. Elevated calcium-phosphorus products and severe secondary hyperparathyroidism are present in most patients with uremic tumoral calcionosis (UTC). Case report of an obese secondary to chronic glomerulonephritis, undergoing continuous ambulatory peritoneal dialysis (CAPD) reported the appearance of painless tumors in the medial surface of fifth finger and left arm. Tumoral calcinosis was confirmed by left biceps biopsy. Poor adherence to CAPD. The patient was transferred to the "tidal" modality of peritoneal dialysis and after was treated by hemodialysis, despite the persistence of severe hyperparathyroidism progressive reduction of UTC until near to its complete disappearance. Nowadays, one year after patient received deceased-donor kidney transplantation, he presents with an improvement in secondary hyperparathyroidism. UTC should be included in the elucidation of periarticular calcification of every patient on dialysis. Relevant laboratory findings such as secondary hyperparathyroidism and elevated calcium- phosphorus products in the presence of periarticular calcification should draw attention to the diagnosis of UTC.

Reversal of uremic tumoral calcinosis by optimization of clinical treatment of bone and mineral metabolism disorder / Reversão da calcinose tumoral urêmica pela otimização do tratamento clínico da desordem do metabolismo ósseo e mineral

Abstract Tumoral calcinosis is an uncommon type of extraosseous calcification characterized by large rubbery or cystic masses containing calcium-phosphate deposits. The condition prevails in the periarticular tissue with preservation of osteoarticular structures. Elevated calcium-phosphorus products and severe secondary hyperparathyroidism are present in most patients with uremic tumoral calcionosis (UTC). Case report of an obese secondary to chronic glomerulonephritis, undergoing continuous ambulatory peritoneal dialysis (CAPD) reported the appearance of painless tumors in the medial surface of fifth finger and left arm. Tumoral calcinosis was confirmed by left biceps biopsy. Poor adherence to CAPD. The patient was transferred to the "tidal" modality of peritoneal dialysis and after was treated by hemodialysis, despite the persistence of severe hyperparathyroidism progressive reduction of UTC until near to its complete disappearance. Nowadays, one year after patient received deceased-donor kidney transplantation, he presents with an improvement in secondary hyperparathyroidism. UTC should be included in the elucidation of periarticular calcification of every patient on dialysis. Relevant laboratory findings such as secondary hyperparathyroidism and elevated calcium- phosphorus products in the presence of periarticular calcification should draw attention to the diagnosis of UTC.

Resumo A calcinose tumoral é um tipo raro de calcificação extraóssea caracterizada por grandes massas císticas e elásticas contendo depósitos de fosfato de cálcio. A condição é mais prevalente no tecido periarticular e preserva estruturas osteoarticulares. A elevação do produtos cálcio-fósforo e o hiperparatireoidismo secundário grave estão presentes na maioria dos pacientes com calcinose tumoral urêmica (UTC). O relato de caso em questão refere-se a um homem de 22 anos, branco, obeso, com doença renal crônica secundária à glomerulonefrite crônica, em diálise peritoneal ambulatorial contínua (CAPD), que apresentou aparecimento de tumores indolores na face medial do quinto quirodáctilio e braço esquerdo. A calcinose tumoral foi confirmada por biópsia do bíceps esquerdo. O paciente apresentava baixa adesão à CAPD. Foi transferido para a modalidade de diálise peritoneal e depois iniciou tratamento por hemodiálise. Apesar da persistência do hiperparatireoidismo grave, houve redução progressiva da UTC, com resolução próxima do seu desaparecimento completo. Há 1 ano o paciente foi submetido a transplante renal, doador falecido, e apresentou melhora do hiperparatiroidismo secundário. A UTC deve ser incluída na elucidação de calcificação periarticular de pacientes em diálise. Os achados laboratoriais relevantes, tais como hiperparatiroidismo secundário e elevação dos produtos cálcio-fósforo na presença de calcificação periarticular, devem chamar a atenção para o diagnóstico da UTC.

[Research progress on pharmacotherapy of calcific aortic valve disease].

With the population aging and declining incidence of rheumatic heart disease, calcific aortic valve disease (CAVD) has become the most frequent valve disease and the common cause of aortic valve replacement. Patients with CAVD need to cope with a deteriorating quality of life and valve replacement is the only effective clinical option for the patients. Therefore, early pharmacotherapy is of great significance in prevention or slow-down of the progression of CAVD. For years CAVD was considered to be a passive wear and tear process of valves, but now it is recognized as an active and multi-factorial process. Histopathologic studies have revealed that inflammation, disorder of calcium and phosphorus metabolism and dyslipidemia are involved in the process of CAVD. Clinical trials of CAVD pharmacotherapy have been carried out based on those histopathologic studies. Statin, renin-angiotensin inhibitors and anti-osteoporosis drug are well studied in recent years. This article reviews the recent research progress of the pharmacotherapy for CAVD.

Disordered myocardial Ca(2+) homeostasis results in substructural alterations that may promote occurrence of malignant arrhythmias.

We aimed to determine the impact of Ca(2+)-related disorders induced in intact animal hearts on ultrastructure of the cardiomyocytes prior to occurrence of severe arrhythmias. Three types of acute experiments were performed that are known to be accompanied by disturbances in Ca(2+) handling. Langedorff-perfused rat or guinea pig hearts subjected to K(+)-deficient perfusion to induce ventricular fibrillation (VF), burst atrial pacing to induce atrial fibrillation (AF) and open chest pig heart exposed to intramyocardial noradrenaline infusion to induce ventricular tachycardia (VT). Tissue samples for electron microscopic examination were taken during basal condition, prior and during occurrence of malignant arrhythmias. Cardiomyocyte alterations preceding occurrence of arrhythmias consisted of non-uniform sarcomere shortening, disruption of myofilaments and injury of mitochondria that most likely reflected cytosolic Ca(2+) disturbances and Ca(2+) overload. These disorders were linked with non-uniform pattern of neighboring cardiomyocytes and dissociation of adhesive junctions suggesting defects in cardiac cell-to-cell coupling. Our findings identified heterogeneously distributed high [Ca(2+)](i)-induced subcellular injury of the cardiomyocytes and their junctions as a common feature prior occurrence of VT, VF or AF. In conclusion, there is a link between Ca(2+)-related disorders in contractility and coupling of the cardiomyocytes pointing out a novel paradigm implicated in development of severe arrhythmias.

Hypochlorhydria-induced calcium malabsorption does not affect fracture healing but increases post-traumatic bone loss in the intact skeleton.

Efficient calcium absorption is essential for skeletal health. Patients with impaired gastric acidification display low bone mass and increased fracture risk because calcium absorption is dependent on gastric pH. We investigated fracture healing and post-traumatic bone turnover in mice deficient in Cckbr, encoding a gastrin receptor that affects acid secretion by parietal cells. Cckbr-/- mice display hypochlorhydria, calcium malabsorption, and osteopenia. Cckbr-/- and wildtype (WT) mice received a femur osteotomy and were fed either a standard or calcium-enriched diet. Healed and intact bones were assessed by biomechanical testing, histomorphometry, micro-computed tomography, and quantitative backscattering. Parathyroid hormone (PTH) serum levels were determined by enzyme-linked immunosorbent assay. Fracture healing was unaffected in Cckbr-/- mice. However, Cckbr-/- mice displayed increased calcium mobilization from the intact skeleton during bone healing, confirmed by significantly elevated PTH levels and osteoclast numbers compared to WT mice. Calcium supplementation significantly reduced secondary hyperparathyroidism and bone resorption in the intact skeleton in both genotypes, but more efficiently in WT mice. Furthermore, calcium administration improved bone healing in WT mice, indicated by significantly increased mechanical properties and bone mineral density of the fracture callus, whereas it had no significant effect in Cckbr-/- mice. Therefore, under conditions of hypochlorhydria-induced calcium malabsorption, calcium, which is essential for callus mineralization, appears to be increasingly mobilized from the intact skeleton in favor of fracture healing. Calcium supplementation during fracture healing prevented systemic calcium mobilization, thereby maintaining bone mass and improving fracture healing in healthy individuals whereas the effect was limited by gastric hypochlorhydria. © 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 34:1914-1921, 2016.

[Cognitive Function and Calcium. The link between dementia and bone and calcium metabolism disorders].

Bone and calcium metabolism disorders are closely linked with dementia. Screening for dementia is important since chronic hypercalcemia and hypocalcemia resulting from parathyroid function abnormalities can become a cause of dementia onset. In recent years, it has become clear that vitamin D deficiencies inducing cardiovascular disease and other factors are involved in the pathogenesis of various diseases that in turn become risk factors in dementia, especially Alzheimer's disease. Moreover, osteoporosis and dementia both commonly occur among the elderly. Treating dementia patients for osteoporosis is important since fragility fractures, especially femoral neck fractures, resulting from osteoporosis greatly affect the prognosis of patients with dementia.

[Disorders of calcium metabolism]. / Störungen des Kalziumstoffwechsels.

The majority of clinical complaints derive from disorders of calcium metabolism and are associated with a wide variety of clinical symptoms caused by numerous diseases with entirely different types of pathophysiology. The prognosis varies from favorable to fatal depending on the pathophysiology of the underlying disorder of calcium metabolism; therefore, the diagnostic work-up aims to quickly identify the underlying disease causing the disturbance in calcium homeostasis. Every clinical situation with a diminished state of calcium absorption is treated with calcium and vitamin D in varying doses whereas every disorder with an increased calcium absorptive or resorptive state is treated with improved diuresis in addition to antiresorptive drugs, such as bisphosphonates. In many situations the management of a disturbed calcium balance requires an interdisciplinary approach in order to treat the underlying disease in parallel with correction of the calcium homeostasis.

Calcificaciones esclerocoroideas asociadas a hipovitaminosis D / Sclerochoroidal calcification associated with hypovitaminosis D

CASO CLÍNICO: Mujer de 69 años que presenta en una exploración funduscópica rutinaria unas lesiones subretinianas blanco-amarillentas en la periferia media temporal superior de ambos ojos. Ecográficamente eran hiperecogénicas, situándose a nivel esclerocoroideo. Se realizó una tomografía axial computarizada que mostró calcificaciones esclerocoroideas posterolaterales. El estudio metabólico reveló una deficiencia severa de vitamina D sin otros hallazgos significativos. Discusión: Las calcificaciones esclerocoroideas son lesiones poco frecuentes que se producen como consecuencia del depósito de calcio a nivel de la esclera y la coroides. Tienen un aspecto clínico característico y en la mayor parte de los casos son idiopáticas. En ocasiones se asocian a enfermedades que cursan con alteraciones del metabolismo del calcio y fósforo, por lo que es necesario realizar un estudio metabólico completo. Se presenta un caso de calcificaciones esclerocoroideas bilaterales asociadas a una hipovitaminosis D de grado severo sin otros hallazgos metabólicos

CASE REPORT: A 69 year-old woman was referred for a routine visit, during which funduscopy revealed white-yellow subretinal lesions in the superotemporal mid-periphery of both eyes. A and B scan ultrasound showed hyperechogenic lesions located at scleral and choroidal level. Computed tomography revealed posterolateral sclerochoroidal calcifications. Metabolic studies showed a severe vitamin D deficiency with no other remarkable findings. Discussion: Sclerochoroidal calcifications are an infrequent finding that occur as a result of calcium deposit at scleral and choroidal level. They have a characteristic clinical picture and are idiopathic in most cases, but may be associated with some systemic diseases, such as calcium and phosphorous metabolic disorders; this fact warrants a thorough metabolic study. We report a case of bilateral sclerochoroidal calcifications associated with severe vitamin D deficiency with no other significant metabolic findings

Litiasis renal cálcica y densidad mineral ósea. Importancia del metabolismo óseo en la litiasis urinaria / Calcium Renal Lithiasis and Bone Mineral Density. Importance of Bone Metabolism in Urinary Lithiasis

Contexto: La litiasis renal cálcica es una enfermedad multifactorial, en la que intervienen en su fisiopatología diferentes factores minerales y metabólicos que pueden encontrarse alterados, entre ellos el metabolismo óseo y fosfocálcico. Objetivo: Establecer la evidencia científica y demostrar la relación existente entre litiasis renal cálcica y pérdida de densidad mineral ósea, mediante el uso de marcadores de remodelado óseo y metabolitos urinarios y séricos. Adquisición de la evidencia: Se realiza una revisión bibliográfica en PubMed utilizando diferentes MeSHTerms como Nephrolithiasis, Bone mineral density, Urinary stones, Calcium, Bone resorption y Bone formation, usando diferentes combinaciones. Se seleccionan únicamente los trabajos con resúmenes en inglés o español y se descartan casos clínicos y trabajos con estudio estadístico inapropiado. Se seleccionan un total de 40 publicaciones. Síntesis de la evidencia: En los diferentes estudios analizados se observa que los pacientes con hipercalciuria presentan una mayor pérdida de densidad mineral ósea con respecto a los normocalciúricos. Entre los pacientes con litiasis cálcica, tanto los que tienen normocalciuria como los que tienen hipercalciuria presentan pérdida de densidad mineral ósea, siendo más evidente en estos últimos. Esta pérdida de densidad mineral está acentuada y es importante en los pacientes con litiasis recidivante. El aumento de los marcadores calcio/creatinina en ayunas y β-crosslaps son los más determinantes de litiasis y pérdida de densidad mineral en estos pacientes. Conclusión: Se recomienda solicitar marcadores de remodelado óseo y calcio/creatinina en ayunas en pacientes con litiasis cálcica recidivante por la importante presencia de pérdida de densidad mineral ósea, con un nivel de evidencia III (AU)

Context: Calcium Nephrolithiasis is a multifactorial disease; in its pathophysiology is involved various minerals and metabolic factors that may be altered, including bone and phosphor-calcium metabolism. Objective: To establish the scientific evidence and demonstrate the relationship between calcium nephrolithiasis and bone mineral density loss, through the use of bone turnover markers, serum and urinary metabolites. Evidence acquisition: We performed a PubMed literature review using different MeSH Terms like «Nephrolithiasis» «Bone mineral density»,«Urinary stones», «Calcium», «Bone resorption» and «Bone formation», with different combinations. We only selected articles with abstracts in English or Spanish and discarded clinical cases and articles with inappropriate statistical study. A total of 40 articles were selected. Evidence synthesis: In different studies reviewed have been observed that patients with hypercalciuria have a higher bone mineral density loss with respect to normocalciuric. Among patients with calcium stones (normocalciuric or hypercalciuric), there is loss of bone mineral density, being more evident in patients with stones and hypercalciuria. This mineral density loss is marked and important in patients with recurrent calcium stones. Increased markers like fasting calcium/creatinine and β-CrossLaps are determinant of nephrolithiasis and mineral density loss in these patients. Conclusion: We recommend perform markers of bone turnover and fasting calcium/creatinine in patients with recurrent calcium stones by the significant presence of bone mineral density loss, with a level of evidence III (AU)

Disturbances in calcium metabolism and cardiomyocyte necrosis: the role of calcitropic hormones.

A synchronized dyshomeostasis of extra- and intracellular Ca(2+), expressed as plasma ionized hypocalcemia and excessive intracellular Ca(2+) accumulation, respectively, represents a common pathophysiologic scenario that accompanies several diverse disorders. These include low-renin and salt-sensitive hypertension, primary aldosteronism and hyperparathyroidism, congestive heart failure, acute and chronic hyperadrenergic stressor states, high dietary Na(+), and low dietary Ca(2+) with hypovitaminosis D. Homeostatic responses are invoked to restore normal extracellular [Ca(2+)](o), including increased plasma levels of parathyroid hormone and 1,25(OH)(2)D(3). However, in cardiomyocytes these calcitropic hormones concurrently promote cytosolic free [Ca(2+)](i) and mitochondrial [Ca(2+)](m) overloading. The latter sets into motion organellar-based oxidative stress, in which the rate of reactive oxygen species generation overwhelms their detoxification by endogenous antioxidant defenses, including those related to intrinsically coupled increments in intracellular Zn(2+). In turn, the opening potential of the mitochondrial permeability transition pore increases, allowing for osmotic swelling and ensuing organellar degeneration. Collectively, these pathophysiologic events represent the major components to a mitochondriocentric signal-transducer-effector pathway to cardiomyocyte necrosis. From necrotic cells, there follows a spillage of intracellular contents, including troponins, and a subsequent wound healing response with reparative fibrosis or scarring. Taken together, the loss of terminally differentiated cardiomyocytes from this postmitotic organ and the ensuing replacement fibrosis each contribute to the adverse structural remodeling of myocardium and progressive nature of heart failure. In conclusion, hormone-induced ionized hypocalcemia and intracellular Ca(2+) overloading comprise a pathophysiologic cascade common to diverse disorders and that initiates a mitochondriocentric pathway to nonischemic cardiomyocyte necrosis.

Presencia y severidad de calcio coronario: su relación con la aparición de eventos coronarios agudos / Presence and severity of coronary calcium: its relationship with acute coronary events

Fundamento: La detección de calcio en las arterias coronarias confirma la presencia de aterosclerosis y ha demostrado ser una herramienta útil para estratificar el riesgo cardiovascular. Objetivo: determinar la relación entre la presencia y severidad de calcio coronario con la aparición de eventos coronarios agudos.Métodos: se realizó un estudio observacional, descriptivo, prospectivo, tipo serie de casos, en el Hospital Universitario Dr Gustavo Aldereguía Lima de Cienfuegos, entre enero y diciembre de 2008. La serie estuvo conformada por 137 pacientes, en los que se estudió: sexo, antecedentes patológicos personales, cifras de glucemia en ayunas, creatinina, colesterol total y triglicéridos. Los pacientes fueron seguidos durante dos años para evaluar la aparición de eventos coronarios agudos.Resultados: La edad media fue de 53,2±7,4 años, con predominio del sexo masculino (52,5 por ciento). El mayor porciento de pacientes clasificados como de alto riesgo, según la cuantificación del calcio coronario (16,8 por ciento) perteneció al sexo masculino, predominando en los mayores de 70 años. La diabetes se relacionó de forma significativa con la severidad del puntaje de calcio. El infarto agudo del miocardio fue más frecuente en pacientes con puntaje de calcio mayor de 400 unidades Agatston.Conclusiones: la aparición de eventos coronarios agudos fue más frecuente en los pacientes de alto riesgo según cuantificación del calcio coronario(AU)

Background: Calcium detection in coronary arteries confirms the presence of atherosclerosis and has proved to be a useful tool for risk stratification. Objective: To determine the relationship between the presence and severity of coronary calcium with the onset of acute coronary events. Methods: An observational, descriptive, prospective, case series study was conducted at the Dr. Gustavo Aldereguía Lima University Hospital of Cienfuegos, between January and December 2008. The series consisted of 137 patients who were studied according to: sex, personal medical history and record of fasting blood glucose, creatinine, total cholesterol and triglycerides. Patients received follow-up for two years in order to assess the occurrence of acute coronary events. Results: Average age was 53.2 ± 7.4 years, with predominance of males (52.5 percent). The greatest percentage of patients classified as high risk according to the quantification of coronary calcium (16.8 percent) were males, predominantly those over 70 years old. Diabetes was significantly associated with severity of calcium scores. Myocardial infarction was more frequent in patients with calcium scores above 400 Agatston units. Conclusions: The occurrence of acute coronary events was more frequent in patients at high risk according to coronary calcium quantification(AU)

Is plasma calcium concentration implicated in the development of critical illness polyneuropathy and myopathy?

INTRODUCTION: This prospective study investigated whether plasma ionized calcium concentration abnormalities and other electrolyte disturbances represent risk factors for the development of critical illness polyneuromyopathy (CIPNM) in ICU patients. METHODS: One hundred and ninety consecutive adult critically ill patients with prolonged ICU stay (longer than 7 days) were prospectively evaluated. Patients with acute weakness and/or weaning difficulties were subjected to extensive electrophysiological measurements in order to establish the diagnosis of CIPNM. All recognized and/or possible risk factors for development of CIPNM were recorded. RESULTS: The diagnosis of CIPNM was confirmed in 40 patients (21.05%). By applying a logistic regression model, hypocalcemia (P = 0.02), hypercalcemia (P = 0.01) and septic shock (P = 0.04) were independently associated with the development of CIPNM in critically ill patients. CONCLUSIONS: We found that septic shock and abnormal fluctuations of plasma Ca²âº concentration represent significant risk factors for the development of CIPNM in critically ill patients.

[Clinical significance of disturbed calcium metabolism].

The authors present literature data on the role of Ca-P metabolism and its regulators in the development of bone and cardiovascular pathology, intrauterine development, organogenesis, cell growth and differentiation. A large number of agents are currently available to modify Ca-P metabolism. (calcium and vitamin Dpreparations, PTH, calcitonin, stimulators of Ca-sensitive receptors, calcitriol receptor ligands, etc.) although their application is hampered by the dificulty of laboratory control and the lack of basic knowledge. It is maintained that raising awareness among practitioners about these issues may improve diagnostics of Ca-P metabolic disorders (in the first place, calcium and vitamin D deficiency, secondary hyperthyroidism) and promote their medicamental and non-medicamental therapy.

Results of medical treatment and metabolic risk factors in children with urolithiasis.

Data on conservative treatment in children with urolithiasis are limited. The aim of the study was to determine the metabolic etiology and results of conservative treatment in children with urolithiasis. We evaluated the clinical presentation and metabolic features of 112 children with urolithiasis. The mean age at diagnosis of urolithiasis was 3.9 (range 0.1-18) years, and follow-up duration was 16.7 (range 1-36) months. The most common presenting symptoms were flank or abdominal pain and restlessness (25%). Urine analysis revealed metabolic abnormalities in 92% of cases, including hypocitraturia (42%), hyperoxaluria (32.1%), hypercalcuria (25%), hyperuricosuria (9.8%), and cystinuria (2.7%). Patients who had metabolic risk factors were treated according to underlying metabolic abnormalities. About half of these patients were stone free or stones were diminished in size. These results showed that early recognition and treatment of urinary metabolic abnormalities will reduce the number of invasive procedures and renal damage in children with urolithiasis.