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Hypomagnesemia in infants of diabetic mothers: perinatal studies.

Fifty-six diabetic mothers and their infants were studied prospectively from birth. Twenty-one of 56 IDM had serum Mg less than or equal to 1.5 mg/dl, on at least one occasion during the first 3 days. Serum Mg in these hypomagnesemic infants did not demonstrate the normal increase with postnatal age that was present in normomagnesemic infants. Decreased neonatal serum Mg was related to increased severity of maternal diabetes, young mothers, mothers for lower gravidity, and prematurity. Decreased serum Mg, alone or with decreased ionized or total Ca, did not correlate with neuromuscular irritability in the infants. Decreased serum Mg in IDM was associated with decreased maternal serum Mg, decreased neonatal ionized and total Ca, increased serum P, and decreased parathyroid function. Serum Mg was not related to dietary P intake, or urinary Ca or P excretion. Thus, transitory neonatal hypomagnesemia occurs in IDM; it is speculated that factors causing HM might include maternal HM or neonatal hyperphosphatemia, and that the HM is related to the hypocalcemia and functional hypoparathyroidism of IDM.

Blood↗

Transient congenital hypoparathyroidism: possible association with anomalies of the pulmonary valve.

Transient congenital hypoparathyroidism was observed in four neonates who also had congenital cardiac defects. Severe hypocalcemia and hyperphosphatemia were noted at 2 or 3 weeks of age, but resolved by 2 to 4 months of age with minimal treatment (oral calcium alone). Parathyroid hormone, measured with a highly sensitive, homologous antiserum, was initially borderline detectable and became easily detectable as the hypocalcemia resolved. Immune function was normal in each patient. The congenital cardiac defects in each case involved the pulmonary valve. These patients might be regarded as having either a partial form of the DiGeorge syndrome or a separate syndrome in which congenital pulmonary valve lesions are linked to delayed maturation of parathyroid function by an as yet obscure mechanism.

Age Factors↗

Autosomal dominant hypoparathyroidism with variable, age-dependent severity.

Hypoparathyroidism (hypocalcemia, hyperphosphatemia, mild hypomagnesemia, and inappropriately low serum C-terminal parathyroid hormone concentration) was found in six members of a family representing three successive generations. No patient had aortic arch or conotruncal malformations, lymphopenia, or features of type I or type II autoimmune polyglandular syndromes. Two individuals had transient neonatal seizures without further difficulties despite persistent hypocalcemia. None of the four affected adults has had major complications of hypoparathyroidism (mental retardation, cataracts, or seizures). We believe that persistence of hypoparathyroidism after resolution of neonatal hypocalcemic seizures should prompt a survey of the family for hypoparathyroidism.

Adult↗

Renal osteodystrophy in children undergoing continuous ambulatory peritoneal dialysis.

Fifteen children undergoing continuous ambulatory peritoneal dialysis for 0.3 to 2.4 years were evaluated longitudinally for renal osteodystrophy. Immunoreactive parathyroid hormone, 25-OHD, total and ionized calcium, inorganic phosphate, and alkaline phosphatase levels were measured regularly. Skeletal radiographic studies were performed at the onset and conclusion of CAPD and at six-month intervals during therapy. All children received 1,25(OH)2D3 and aluminum hydroxide, and nine received supplemental calcium. Plasma 25-OHD concentrations were normal to elevated, and calcium increased steadily to high normal levels despite a trend to persistent hyperphosphatemia. The increased calcium levels suppressed parathyroid hormone overactivity in only one patient. At the onset of CAPD, nine patients had hyperparathyroid bone disease seen radiographically, three of whom also had rachitic lesions. At the end of CAPD, the hyperparathyroid lesions had improved in four patients, completely resolved in three, and deteriorated in two. Rachitic lesions had completely healed in two patients and improved in the third. However, among the six children without radiographically evident lesions at onset of CAPD, hyperparathyroid bone lesions developed in two and rachitic lesions in two others during CAPD. Although CAPD and appropriate therapy benefited most patients with renal osteodystrophy, the benefits were not uniform, and bone lesions deteriorated in some.

Adolescent↗

Effects of oral calcium carbonate on control of serum phosphorus and changes in plasma aluminum levels after discontinuation of aluminum-containing gels in children receiving dialysis.

Orally administered calcium carbonate was evaluated as a phosphate binding agent in 15 children, ages 0.6 to 17.2 years, receiving maintenance dialysis. Changes in plasma aluminum concentration were assessed after discontinuation of treatment with aluminum-containing gels. The mean daily dose of calcium carbonate was 5.1 +/- 2.5 gm (384 +/- 315 mg/kg/day), and correlated inversely with body weight (r = 0.72, P less than 0.01) and age (r = 0.71, P less than 0.01). Mean serum calcium, phosphorus, and bicarbonate values were unchanged throughout the study. Plasma aluminum concentration fell from 90 +/- 51 to 34 +/- 22 micrograms/L (P less than 0.005). Dietary phosphorus intakes were 44 +/- 21 and 42 +/- 19 mg/kg/day during the control period and at the end of the study, respectively. Transitory hypercalcemia was the only side effect in 92% of the patients. In none of the patients did uncontrolled hyperphosphatemia, metabolic alkalosis, diarrhea, or symptoms or signs of hypercalcemia develop. Our data indicate that calcium carbonate is an effective phosphate binding agent in children receiving dialysis, and should be used in lieu of aluminum-containing gels in young children with renal failure.

Adolescent↗

Five years' experience with continuous ambulatory or continuous cycling peritoneal dialysis in children.

In 93 children, end-stage renal disease was treated with the new dialytic methods of continuous ambulatory peritoneal dialysis (CAPD) or continuous cycling peritoneal dialysis (CCPD) over 5 years. Modality survival rates at 36 months with CAPD, CCPD, or both were 20%, 93%, and 87%, respectively. Use of CCPD as the primary dilaytic method increased during the study period. The peritonitis rate was one episode per 11.8 patient treatment months and was similar with both CAPD and CCPD. Gram-positive organisms were cultured in 34% of these episodes of peritonitis. Staphylococcus aureus peritonitis was associated with a recurrence rate of 40% and led to catheter replacement in 45% of the episodes. Peritoneal membrane failure necessitating switching to hemodialysis was related to peritonitis in three patients. Of the 74 peritoneal catheters that required replacement, 70% were infected. Serial serum levels of urea nitrogen, potassium, calcium, phosphorus, albumin, and alkaline phosphatase remained stable, whereas serum creatinine level rose slightly over time. Episodes of hyperkalemia, hypercalcemia, and hyperphosphatemia were observed at a frequency of one episode per 12.2, 4.6, and 2.5 treatment months, respectively. Blood transfusions were required in once per 1.5 and 3.3 treatment months in seven anephric patients and in 35 patients with their own kidneys, respectively (P = 0.05). In prepubertal patients who received CAPD or CCPD for greater than 1 year, little or no improvement in growth occurred in relationship to either chronologic or bone age.

Adolescent↗

Parathyroid gland hemorrhage in perinatally lethal osteogenesis imperfecta.

In four neonates with perinatally lethal osteogenesis imperfecta (OI) who survived for more than 9 days after birth, vascular congestion and acute hemorrhage were found in 10 of 11 parathyroid glands; in one neonate, all four parathyroid glands, including the only gland without acute hemorrhage, contained abundant deposits of stainable iron. One neonate had hypocalcemia, and one had both hyperphosphatemia and hypocalcemia. In four neonates with OI who died within 72 minutes of birth, all 10 parathyroid glands demonstrated were free of hemorrhage and hemosiderin deposition. Only minor foci of acute hemorrhage were seen in three of 170 glands in 113 comparison neonates and infants. We conclude that parathyroid gland hemorrhage is common in perinatally lethal OI with survival beyond the immediate period of birth, and is otherwise rare. We speculate that parathyroid hemorrhage may be related to difficulty in maintaining postnatal calcium homeostasis in the absence of adequate calcium reserves in bone. Acute parathyroid gland hemorrhage causes fluctuations in serum calcium levels that have on occasion proved fatal, and parathyroid hemorrhage may be a proximate cause of death in some neonates with OI.

Female↗

Hypoparathyroidism in a patient with long-chain 3-hydroxyacyl-coenzyme A dehydrogenase deficiency caused by the G1528C mutation.

Mitochondrial trifunctional protein (MTP), an enzyme complex participating in fatty acid beta-oxidation, is the potential site of two documented defects: long-chain 3-hydroxyacyl-coenzyme A dehydrogenase (LCHAD) and MTP deficiencies. LCHAD deficiency usually manifests as hypoglycemia, with hepatopathy, hypotonia, cardiomyopathy, and retinopathy. Hypoparathyroidism has been detected in a patient with MTP deficiency. We now report on a patient with LCHAD deficiency and hypoparathyroidism, evidenced by hypocalcemia, hyperphosphatemia, and a low level of parathyroid hormone, in whom the parathyroid glands could not be located after death.

3-Hydroxyacyl CoA Dehydrogenases↗

Time of day improves efficacy and reduces adverse reactions of vitamin D3 in 5/6 nephrectomized rat.

Time-dependent differences in adverse reactions and efficacy by a repeated administration of 1,25(OH)2 vitamin D3 (vit D, 0.3 microg/Kg/day for 12 weeks) were examined in 5/6 nephrectomized rats under a condition of 12-hour light-dark cycle. The 5/6 nephrectomy increased serum concentrations of phosphate, osteocalcin and PTH, and urinary excretions of phosphate and deoxypyridinoline (DPD) while the maneuver reduced serum Ca concentration and its urinary excretion. Animals with a dosing of the drug at 2 hours after light on (HALO) had more grade of hypercalcemia and hyperphosphatemia than those at 14 HALO. Reduction of serum intact PTH and increase of serum vit D were observed in both groups with a similar extent. Increase of osteocalcin by the drug was greater in 14 HALO trial. Urinary excretion of DPD was not influenced by the treatment. The increase in bone density of femur was greater in 14 HALO than in 2 HALO trials. These results suggest that adverse reactions of vit D were ameliorated and its efficacy was enhanced after the repeated dosing of the drug at 14 HALO. Time-dependent variation in the sensitivity of the drug to osteoblast was involved in the mechanism of these events, while the roles of pharmacokinetic alteration and renal response were small, if any.

Amino Acids↗

Diagnosis and management of bone disorders in chronic renal failure and dialyzed patients.

Renal osteodystrophy is multifactorial. Decreased calcium absorption from the GI tract, secondary to low calcitriol levels; hyperphosphatemia; skeletal resistance to the action of parathormone; and aluminum deposition on the surface of the bones are its main pathogenetic mechanisms. Its biochemical features include abnormalities in serum calcium, phosphate, alkaline phosphatase, parathormone, calcitriol, and aluminum concentration. Radiographic methods are of little use in the characterization of the type of osteodystrophy present, but they may be of help in assessing mineral loss from the skeleton. Clinical manifestations are from bones (pain, deformities, fractures) or from metastatic calcifications. Bone biopsy is the definitive means of diagnosis. The main histologic types of osteodystrophy include osteitis fibrosa, osteomalacia, mixed form (with features of both osteitis fibrosa and osteomalacia), and aluminum osteodystrophy (presenting as either osteomalacia or aplastic lesion). The management of renal osteodystrophy should address all the pathogenetic mechanisms. Correction of the abnormalities in calcium and phosphate metabolism and prevention of aluminum osteodystrophy are the cardinal rules of management. Specific measures (parathyroidectomy, chelation of aluminum) have clear-cut indications and usually require a bone biopsy.

Aluminum↗

Recurrent osseous metaplasia of the cervix after loop electrosurgical excision.

BACKGROUND: Osseous metaplasia of the uterus is a rare pathologic entity usually affecting the endometrial cavity without cervical extension. It has been reported after abortion, in cases of chronic endometritis, and as a result of metabolic disorders as hypervitaminosis D, hyperparathyroidism, hypercalcemia, and hyperphosphatemia. CASE: A woman developed osseous metaplasia of the cervix shortly after loop electrosurgical excision procedure (LEEP) for severe cervical dysplasia. Normal transvaginal ultrasonograms before the LEEP, and failure to detect osseous metaplasia after histologic review of the tissue obtained from that procedure indicate that the osseous metaplasia had been induced by the LEEP. The heterotopic bone formation rapidly recurred after initial removal. Her serum calcium, phosphorus, and vitamin D levels were normal. CONCLUSION: LEEP may result in healing with metaplastic bone formation.

Adult↗

Renal hypertension in children.

Preliminary results of this retrospective-prospective analysis of renal hypertension in 110 children indicate that hypertension may be secondary to a wide variety of acute progresive, and chronic renal diseases which may be either congenital or acquired. Affected children may be detected at any time from infancy through adolescence. Symptoms usually associated with acute glomerulonephritis (i.e., headache, swelling, nausea, vomiting, anorexia, fatigue, dizziness, and fever) occur in both acute and chronic renal diseases associated with hypertension. Headache and swelling are the most common symptoms in this series. Peripheral edema, rales, and increased heart size were found in between 10 and 25% of these children. Differential diagnosis may be approached by a consideration of causes of acute and chronic hypertension. The child with chronic renal disease usually presents with a long history of fatigability, poor growth, and pallor, and laboratory tests reveal elevation of the creatinine and BUN along with anemia, hypocalcemia, and hyperphosphatemia. In contrast, the child with acute renal disease and hypertension presents with a history of prior good health followed by the abrupt onset of signs and symptoms of renal disease; laboratory tests usually reveal modest elevations of creatinine and BUN, anemia is unusual, an abnormal urinalysis is common, and serum calcium and phosphorous levels are usually normal. Renovascular and asymmetric renal parenchymal disease represent uncommon but important conditions because surgery may be curative. Treatment may be surgical, medical, or combined. Surgical conditions include renal trauma, hydronephrosis, asymmetric renal disease, and renal arterial disease. Adequate blood pressure control without medication can be expected following surgery in instances of unilateral involvement with a normal contralateral kidney. Meticulous assessment of the contralateral kidney is needed to determine that it is normal. If surgery is unsuccessful or is not indicated, pharmacologic therapy is initiated with a stepwise regimen starting with the mildest agent (e.g., thiazides) and then adding additional antihypertensive drugs when adequate blood pressure control has not yet been achieved. The goal of therapy is the lowest, safest, tolerated blood pressure levels. Long-term, carefully designed studies of antihypertensive agents for children with renal hypertension are not available. The need for collection and critical analysis of data concerning the clinical course of children with renal hypertension is evident from a review of the literature and from the preliminary data presented in this series. The presentation of such information and a critique of outcome variables will provide a basis for program planning for affected children and improvement in patient care where indicated.

Adolescent↗

Tumor lysis syndrome.

Tumor lysis syndrome (TLS) is a constellation of metabolic disturbances observed in tumors with high cell turnover. It is associated with significant morbidity and mortality. TLS is characterized by the increased release of intracellular contents (uric acid, potassium, phosphorus) into the extracellular compartment, which can overwhelm the body's capacity for clearance. TLS is usually caused by response to chemotherapy; however, it may also occur spontaneously. Because uric acid, potassium, and phosphorus are excreted primarily by the kidneys, TLS can lead to hyperuricemia, hyperkalemia, and hyperphosphatemia with accompanying renal compromise. The pathophysiology of TLS-associated acute renal failure is probably multifactorial. Potential etiologies include intravascular volume depletion, urinary precipitation of nucleic acid metabolites and calcium phosphate, and malignancy-associated nephrotoxins. Despite prophylactic therapy with allopurinol and volume repletion, patients may still develop TLS with acute renal failure. While reducing the risk of uric acid precipitation, allopurinol and alkalinization increase the risk of xanthine and calcium phosphate crystals, respectively. Aggressive hydration might lead to volume overload, specifically in older patients. Novel approaches in the management of TLS include the use of urate oxidase, which can provide effective treatment with an acceptable safety profile.

Allopurinol↗

Urate oxidase in the prophylaxis or treatment of hyperuricemia: the United States experience.

Nonrecombinant urate oxidase (Uricozyme, Sanofi-Synthélabo, Inc, Paris, France) is a highly effective uricolytic agent, but its use is associated with hypersensitivity reaction manifested mainly by bronchospasm in approximately 5% of patients. Recently, several multi-institutional studies have evaluated the efficacy and safety of a recombinant urate oxidase (rasburicase). In a phase I/II study, all 131 patients with newly diagnosed acute lymphoblastic leukemia (ALL) or stage III/IV non-Hodgkin's lymphoma (NHL) experienced rapidly decreased plasma uric acid concentrations after receiving recombinant urate oxidase. Serum creatinine levels also decreased significantly. Toxicity was negligible, and none of the patients required dialysis. In a phase III trial, children with newly diagnosed ALL or stage III/IV NHL were stratified and randomized to receive recombinant urate oxidase or allopurinol. Results showed that the 27 patients who received recombinant urate oxidase had a significantly lower plasma uric acid concentration and a more rapid decline in serum creatinine level than did the 25 who took allopurinol. One patient in the recombinant urate oxidase group had hemolysis of unknown cause, and one in the allopurinol group required hemofiltration for hyperphosphatemia. To further assess the safety profile of recombinant urate oxidase, the data on 245 patients (173 children and 72 adults) who received this agent in a compassionate-use program were reviewed retrospectively. The drug produced dramatic decreases in uric acid concentrations in all patients. Nine patients (four children and five adults) had mild adverse reactions that were drug-related or of unknown etiology. These data suggest that recombinant urate oxidase is safe and effective in the prophylaxis and treatment of hyperuricemia associated with malignancy or chemotherapy.

Allopurinol↗

Hyperparathyroidism associated with renal disease. Pathogenesis, natural history, and surgical treatment.

Hyperparathyroidism associated with renal failure is due to chronic parathyroid stimulation by hypocalcemia, which, in turn, results from hyperphosphatemia and low circulating 1,25(OH)2D3. If prophylactic measures and medical treatment of hyperparathyroidism fail, parathyroidectomy should be performed to prevent the progression of bone disease. Resolution of renal hyperparathyroidism is often seen after kidney transplantation, but some hypercalcemic patients require prophylactic or therapeutic parathyroidectomy. Hypocalcemia is the most common complication after parathyroidectomy. Our long-term results with subtotal parathyroidectomy are satisfactory. Total parathyroidectomy plus parathyroid autograft should be used in selected cases.

Female↗

Calcinosis--calcinogenic plants.

The calcinogenic plants are among the most noxious plants to animals in the world. The pathological and biochemical effects of calcinogenic plants in cattle, sheep, goats, pigs, horses, buffalo and laboratory animals have been determined. The chemical nature of the toxic agents and the precise mechanism by with the calcinogenic plants induces calcinosis have been defined. Most of the active principle present as steroidal glycoside is hydrolyzed in intestine, rumen and other tissues or by the bacterial flora releasing the steroidal fragment, in most cases 1,25(OH)(2)D(3). The excess of vitamin D stimulates CaBP synthesis and calcium and phosphate absorption, producing hypercalcemia and/or hyperphosphatemia. The excessively absorbed mineral cannot be physiologically accommodated, and the deposition in soft tissues results in calcinosis. The different means of treatment of calcinosis and control of calcinogenic plants are discussed with regards to their effectiveness. A number of potential uses of calcinogenic plants have been suggested but none has been exploited on a large scale. The understanding of the mechanisms involved with calcinosis contributed enormously to the compression of vitamin D mechanism. Research methods were developed and improved but a lot is to be done in this fascinating subject.

Animals↗

Metabolic abnormalities associated with phosphoric acid ingestion.

A 64-year-old man ingested a phosphoric acid solution in a suicide attempt. He subsequently developed hyperphosphatemia, hypocalcemia, and systemic metabolic acidosis. Local caustic effects of the acid were mild. The patient recovered and was lost to follow-up.

Aluminum Hydroxide↗

Clinical and psychological aspects of restless legs syndrome in uremic patients on hemodialysis.

BACKGROUND: The pathogenesis of restless legs syndrome (RLS) is still unclear. The purpose of this study is to determine relationships of the presence of RLS in uremic patients regularly undergoing hemodialysis (HD) with demographic, clinical, and psychological factors. METHODS: In 490 uremic patients on HD therapy in Japan, RLS was diagnosed based on diagnostic criteria established by the International Restless Legs Syndrome Study Group. Data were compared between patients with and without RLS. RESULTS: There were univariately significant (P < 0.05) differences in serum phosphorus levels, anxiety levels determined using the Hospital Anxiety and Depression Scale, and degrees of emotion-oriented and avoidance-oriented coping determined using the Coping Inventory for Stressful Situations. In multivariate analyses, low hemoglobin levels, high serum phosphorus levels, high anxiety levels, and a great degree of emotion-oriented coping were independently related to the presence of RLS in uremic patients on HD therapy, with statistical significance (P < 0.05). CONCLUSION: Hyperphosphatemia, anxiety, and a great degree of emotion-oriented coping with stress were independently related to the presence of RLS in uremic patients on HD therapy. The pathogenesis of RLS seems to involve more than one mechanism, which leads to restless legs as the final common pathway. These findings may provide new clues to the pathogenesis of RLS.

Adaptation, Psychological↗