Prospective validation of a transcriptomic severity classifier among patients with suspected acute infection and sepsis in the emergency department.

Background And Importance: mRNA-based host response signatures have been reported to improve sepsis diagnostics. Meanwhile, prognostic markers for the rapid and accurate prediction of severity in patients with suspected acute infections and sepsis remain an unmet need. IMX-SEV-2 is a 29-host-mRNA classifier designed to predict disease severity in patients with acute infection or sepsis.

Nonparathyroid hormone-mediated calcium resorption in a rat model of immune glomerulonephritis.

Skeletal demineralization is a frequent accompaniment of chronic renal disease and is likely multifactorial. We studied the role of inflammation in stimulating bone resorption in a rat model of glomerulonephritis (GN). Three-week-old Sprague-Dawley rats received either saline (n = 8) or horse spleen apoferritin and lipopolysaccharide (HSA/LPS, n = 8) by intraperitoneal injection, for 6 weeks; afterward, they were observed for either an additional 3 weeks (9 weeks total; n = 4 from each group) or 14 weeks (20 weeks total; n = 4 from each group).

Angiotensin II reduces calcium uptake into bone.

Children with neonatal Bartter syndrome (NBS) have hypercalciuria, nephrocalcinosis, and osteopenia. A complex of basic-fibroblast growth factor (b-FGF) and a naturally occurring glycosaminoglycan has been identified in the serum and urine of NBS patients. This complex increases bone resorption in a bone disc bioassay system.

In vivo and in vitro effects of a pulsed electromagnetic field on net calcium flux in rat calvarial bone.

Although PEMF's have been found to promote fracture healing and to modulate the activity of bone cells in vitro, effects on bone metabolism are largely unexplored. A bioassay using neonatal rat calvarial bone was used to determine the early effects of a pulsing electromagnetic field (PEMF) exposure in vivo and in vitro on bone metabolic calcium exchange. Bone discs taken from whole body exposed animals (0-4 hours) show a log exposure time-dependent average increase in net Ca uptake in the 0-50% range (r2 = 0.

Conjunctive effects of fibroblast growth factor and glycosaminoglycan on bone metabolism in neonatal bartter syndrome.

The calciotropic activity of urine from a subject with neonatal Bartter syndrome (NBS) has been partially purified using ion-exchange and gel chromatographic techniques. A bioassay using bone disks from rat calvaria was used to estimate calciotropic activity, which in the urine of the subject with NBS appears to be due to basic fibroblast growth factor (bFGF) bound to a glycosaminoglycan susceptible to heparitinase digestion. The calciotropic activity is eluted from DEAE-Sephacel and Sepharose CL-6B in a narrow band in association with metachromatic material and is destroyed by heparitinase and blocked by an antibody to bFGF.

Melatonin: the dark force.

Although the pineal gland was described 2,300 years ago, its functions remained obscure and productive research was limited until 1958, when Lerner and associates defined melatonin. In 1965 Wurtman and Axelrod advanced the "melatonin hypothesis," according to which the pineal gland acts as a transducer responding to changes in circumambient light by changing its rates of melatonin output. Sites and mechanisms of melatonin action are still poorly understood.

Humoral factor in children with neonatal Bartter syndrome reduces bone calcium uptake in vitro.

The neonatal Bartter syndrome (NBS) is associated with a complex disorder of mineral metabolism in children, including hypercalciuria, nephrocalcinosis, and diminished bone mineral density. Although cyclooxygenase inhibition usually brings about improvement in these findings, there is a variable component which is resistant to such therapy in many children. The factor mediating this disorder has not been identified.

Interleukin 1beta mediated calciotropic activity in serum of children with juvenile rheumatoid arthritis.

Objective: To detect the presence and source of calciotropic activity in the serum of children with juvenile rheumatoid arthritis (JRA).

Methods: Metabolic evaluation of an adolescent with polyarticular JRA and hypercalcemia/hypercalciuria included testing with a bone disc bioassay. The bioassay detects calciotropic activity (increased bone resorption or reduced bone formation) in serum.

Protamine and acute depletion of magnesium limit bone response to parathyroid hormone.

The effect of protamine on calcium homeostasis was studied in nine pediatric patients undergoing cardiopulmonary bypass. Total serum calcium decreased from 8.44 mg/dL to 7.

Calcium kinetics in the hyperprostaglandin E syndrome.

Metabolic investigations, including the use of stable isotopes of calcium, were used to study calcium kinetics in three children with the hyperprostaglandin E syndrome. The studies were performed both during indomethacin treatment and in the absence of therapy. Off therapy, each child had hypercalciuria (mean urinary calcium excretion 0.

Pineal and adrenal effects on calcium homeostasis in the rat.

In human infants and newborn rats, white light at the intensity used to treat hyperbilirubinemia lowers serum calcium concentration. Occipital shielding or (in newborn rats) exogenous melatonin prevents this effect. Propranolol, by inhibiting melatonin synthesis, also causes hypocalcemia, which is preventable by melatonin.

Hypercalciuria with Bartter syndrome: evidence for an abnormality of vitamin D metabolism.

Some children with Bartter syndrome have hypercalciuria. To determine the mechanism for this phenomenon, we studied tubular function and calcium metabolism in six such children. All patients had hypokalemic alkalosis, normotension, hyperreninemia, growth retardation, low fractional distal chloride reabsorption (4/5), and elevated urinary prostaglandin E2 excretion (5/6).

The cardiopulmonary effects of calcium infusion in infants with persistent pulmonary hypertension of the newborn.

Low blood ionized calcium levels have been reported previously in association with alkalosis in infants undergoing hyperventilation for persistent pulmonary hypertension. We investigated the effect of acute calcium infusions on the cardiopulmonary status of 10 hypocalcemic, hyperventilated infants with persistent pulmonary hypertension. Acid-base status, arterial partial pressure of oxygen, vital signs, and echocardiographically determined right and left systolic time interval ratios and left ventricular shortening fractions were obtained before and after rapid infusions of calcium gluconate or saline.

Calcemic responses to photic and pharmacologic manipulation of serum melatonin.

Phototherapy of newborn rats (NBR) resulted in a decrease in serum calcium and melatonin levels. Transcranial light penetrance in NBR increased with wavelength. Below 640 nm (penetrance = 6.

Stimulation of calcium uptake in rat calvaria by prostacyclin.

Treatment of newborn rat calvaria discs with a variety of unsaturated fatty acids led to a 50% enhancement of calcium uptake. Arachidonic acid was effective at lower concentrations than cis-vaccenic or oleic acid, while trans-vaccenic acid and saturated fatty acids did not enhance calcium uptake. Cyclooxygenase inhibitors indomethacin and acetylsalicylic acid abolished the enhancement of calcium uptake seen in response to cis-vaccenic acid and inhibited calcium uptake by otherwise untreated bones.

Effect of hyperventilation on total calcium, ionized calcium, and serum phosphorus in neonates.

The effect of alkalosis (pH greater than 7.55) on total calcium, ionized calcium, and serum phosphorus was studied in seven infants with persistent pulmonary hypertension (PPH) before, during, and after hyperventilation. Hyperventilation-induced alkalosis resulted in marked decreases in total calcium, phosphorus, and ionized calcium.

Phototherapy-induced hypocalcemia in newborn rats: prevention by melatonin.

When young rats are exposed to white fluorescent light the concentration of calcium in their serum decreases. This effect is prevented by shielding the occiput, by inhibiting corticosterone synthesis, and by exogenous melatonin. Furthermore, the expected hypocalcemic response to cortisol injection is prevented by melatonin.

Glucagon-induced hypocalcemia in the rat: effects of maturation and insulin.

In adults of several species including man, a small transient decrease in serum calcium concentration follows glucagon administration in doses of 1 to 10 mg/kg. The effects of maturation and insulin on this phenomenon were assessed by comparing the response of newborn and adult rats to equivalent doses of glucagon with and without prior insulin administration. After injection of 1 microgram/g of glucagon, the decrease in serum calcium concentration at 60 min was significant in the newborn rats (-1.