Osteogenic response to marrow aspiration: increased serum osteocalcin and alkaline phosphatase in human bone marrow donors.

It has been shown recently in experimental animals that regeneration of bone marrow after ablation is associated with enhanced osteogenic growth factor activity and a systemic increase in bone formation. To assess the possible occurrence of a similar phenomenon in humans, serum markers of bone formation, osteocalcin and alkaline phosphatase, were measured in marrow donors before the aspiration of large amounts of iliac marrow and 1 day to 5 weeks thereafter. Both osteocalcin and alkaline phosphatase showed significant increases, with peak values 1-3 and 2-4 weeks postaspiration, respectively. The absolute maximal increase in osteocalcin was significantly higher in adolescent and child donors than in adults. When evaluated together with studies on systemic changes during fracture healing and marrow regeneration, these findings suggest that marrow aspiration in humans evokes a systemic osteogenic response.

Effect of swimming on prednisolone-induced osteoporosis in elderly rats.

We investigated the possible ameliorating and preventive effect of swimming on prednisolone-induced osteoporosis in elderly rats. A total of 48 female Sabra strain rats were randomly assigned to the following groups and treatments: (1) control (C), (2) swimming (S), (3) prednisolone-treated (CP), and (4) swimming + prednisolone (SP). An additional 8 rats were sacrificed and examined at the onset of the study. Groups C and S were sham injected; groups CP and SP were injected with prednisolone (Ultracorten), 80 mg/kg three times per week for 10 weeks. Groups S and SP swam 1 h daily, 5 days per week for 10 weeks. SP rats swam simultaneously with prednisolone administration. At the end of the swimming period, in vivo bone mineral content (BMC) measurements were performed on rat vertebrae L4-5 by single-photon absorptiometry. Later, the humerus and femur were removed for the following measurements: morphometric, bone density (BD) by Compton scattering technique, bone ion content by atomic absorption, and hydration fraction by proton magnetic resonance (PMR). We found that the humeral BD of S rats was greater by 14% for group S over C and 3% greater for group SP over CP (P less than 0.05). Vertebral BMC was higher by 15% in group S over C and 11% higher for group SP over CP (P less than 0.05). Femoral calcium (mg/g dry bone) ion content was higher by 5% in group S over C and 8% in group SP over CP group (P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Tryptophan deficiency and picolinic acid: effect on zinc metabolism and clinical manifestations of pellagra.

In five experiments, rats were fed tryptophan (Tryp)-deficient diets with 6-12 micrograms/g zinc (Zn) and, in one experiment, a Zn-deficient diet to test the effect on clinical manifestations, plasma and bone Zn, and ability of picolinic acid (PA) or extra (12 micrograms/g) Zn to compensate. Tryp deficiency caused classical manifestations of pellagra although niacin intake was in excess of normal requirements. At marginal Zn intakes, oral PA caused a significant increase of plasma Zn and, compared with Tryp-adequate controls, Tryp deficiency resulted in lower plasma Zn and plasma:bone Zn ratios. Extra Zn (total 24 micrograms/g) was ineffective. Subcutaneous PA showed a tendency to lower plasma Zn. PA had no effect on clinical manifestations. We conclude that a Tryp metabolite other than nicotinic acid is necessary in the prevention of pellagra. Our hypothesis links this finding with the observed Tryp and PA effect on Zn metabolism.

Correlation of fetal kidney and testis congenic graft survival with reduced major histocompatibility complex burden.

Prolonged survival was enjoyed by fetal and postnatal testis and midgestational renal grafts transplanted beneath the renal capsule of adult congenic mice, confirming previous findings in nonimmunosuppressed outbred rats (3,5). The strategies that enable immature tissues to escape rejection in a graft survival assay were studied by comparing expression of major histocompatibility class I and class II protein and messenger ribonucleic acid (mRNA) in each tissue at different ages. In general, graft survival was best when class I and II expression was low. After transplantation, surviving kidney and testis grafts both showed marked induction of class I and II mRNA measured using donor and recipient-specific oligonucleotide probes. Immunohistochemically detected protein of both classes, however, could not be found in the kidney and was minimal in the testis. Fetal tissues appear to express lower levels of protein and mRNA--and, although invading lymphocytes may induce expression of class I and II mRNA after transplantation, protein was not inducible. The failure of these tissues to express significant levels of transplantation antigens may explain the prolonged survival of these immature grafts.

Definitive treatment of Hirschsprung's disease in the newborn with a one-stage procedure.

BACKGROUND: The purpose of this study was to review our experience and early follow-up with 15 one-stage pull-through procedures performed at the time of diagnosis in neonates and infants with Hirschsprung's disease. METHODS: Historic chart review of all patients with the new diagnosis of Hirschsprung's disease seen at the C.S. Mott Children's Hospital at the University of Michigan, Ann Arbor, between June 1989 and June 1992 was performed. Progress notes, operative and anesthetic records, pathology reports, and outpatient follow-up notes were used for data collection. RESULTS: Operative technique included a modified endorectal pull-through after determining the presence of ganglion cells by frozen section. No colostomies were performed before or after operation. Three patients had affected family members. All infants were born at term. Operation was performed within 24 hours of diagnosis and as early as 48 hours of age. Twelve patients had standard rectosigmoid disease, two had total colonic disease, and another had long-segment disease. Bowel function returned within 4 days of operation, and feeding was instituted by postoperative day 6 in all patients. All of the patients with rectosigmoid disease are doing well. Patients with long-segment or total colonic disease had more problems but are currently at home and doing well. Morbidity included two postoperative bowel obstructions and three patients with postoperative enterocolitis. CONCLUSIONS: A single definitive operation may be used to treat Hirschsprung's disease diagnosed in the newborn. Long-term follow-up in these patients is required.

An oral zinc loading test in psoriasis.

Changes of zinc in body fluids were evaluated in 12 patients with extensive psoriasis and compared with those of 11 healthy volunteers, using an oral zinc loading test. Plasma zinc levels and urinary zinc excretion were measured by atomic absorption spectrophotometry. No significant difference was found between plasma zinc levels and urinary zinc excretion following an overnight fast. Both groups showed extensive increases in urinary zinc excretion following the loading test. The peak levels of plasma zinc were significantly lower in the psoriatic patients two and four hours after zinc ingestion (P less than .01 and P less than .02, respectively).

Normal zinc and iron concentrations in mice after early exposure to phenobarbital.

Zinc and iron levels were studied in mice with early (pre/neonatal) exposure to phenobarbital, as the levels of these trace metals are known to be correlated with specific behaviors shown in our previous and present experiment to be affected by early phenobarbital administration. Mice were exposed to phenobarbital prenatally or neonatally. At adulthood they showed marked reduction from control in all parameters of eight-arm maze performance (P less than 0.001). Since zinc is known to be correlated with this behavior, it was subsequently studied in barbiturate exposed animals. The differences between barbiturate exposed and control offspring for zinc levels in plasma, brain and hippocampus did not reach statistical significance. Our previous studies have shown that the number of dopamine receptors and the resulting apomorphine-induced climbing behavior is altered after early exposure to phenobarbital. The effect of iron level on dopamine receptors is now well established. Subsequently, a group of mice were tested for iron levels in their brain and liver. No significant differences were found. It is suggested that deficits in the hippocampal behaviors, mainly eight-arm maze, after early exposure to phenobarbital are not related to changes in zinc levels. Similarly, early phenobarbital-induced alternation in dopamine receptors and the resulting dopaminergic behaviors are not related to changes in iron levels.

Modern treatment modalities for neonatal and pediatric respiratory failure.

BACKGROUND: Respiratory failure secondary to a variety of causes remains a significant cause of morbidity and mortality in the pediatric population. Newer therapies are appearing frequently in an attempt to decrease the number of deaths from this disease state. We briefly review the current literature on some of the newer modalities including: high-frequency ventilation, surfactant, liquid ventilation, and nitric oxide. We then present our experience from the past 11 years in the most invasive, yet successful, therapy for acute respiratory failure-extracorporeal membrane oxygenation (ECMO). METHODS: Retrospective review of all patients treated with ECMO from September 1983 to December 1994 was undertaken. Data were collected from bedside ECMO flow sheets and the standardized data entry forms submitted to the Extracorporeal Life Support Organization. All statistical analyses were performed using a standard statistical software program. RESULTS: During the study period, 194 neonates and 47 pediatric patients were treated with ECMO. The survival rate in the neonatal population is 82% and in the pediatric population it is 40%. The neonatal patients required an average of 153 hours of support while the pediatric patients required 220 hours (P = 0.008). CONCLUSIONS: While the newer treatment modalities discussed may have an important role in treating neonatal and pediatric respiratory failure in the near future, ECMO remains a cornerstone of the modern treatment modalities. Although somewhat invasive, ECMO is effective therapy with increasing survival rates each year.

Effect of valproic acid therapy on zinc metabolism in children with primary epilepsy.

The effect of long-term treatment with valproic acid (VPA) on zinc (Zn) metabolism was studied in 15 children with absence seizures. During treatment with VPA the erythrocyte Zn content was significantly lower than that found in controls matched for sex and age. Plasma and urine values of Zn and of copper were within normal limits. It is suggested that the anticonvulsive action of VPA may be mediated through its effect on the metabolism of Zn in the brain and the concomitant changes in the activity of the enzymes glutamic acid decarboxylase and carbonic anhydrase.

Calcium homeostasis, bone metabolism and safety aspects during long-term treatment with a GnRH agonist.

Thirty-five women with symptomatic fibroids were treated with monthly injections of 3.2 mg microcapsulated D-Trp-6-LHRH for 6 months. During treatment serum 17 beta-oestradiol levels decreased, falling to castration levels associated with a reduction in the volume of the fibroids. In 16 patients a complete calcium homeostasis and bone metabolism work-up was carried out during treatment and subsequently for a 6-month follow-up period. Bone mineral content (BMC) and Compton bone densitometry readings remained unchanged. There were significant increases in serum calcium phosphate and alkaline phosphatase concentrations. A slight although not significant increase was observed in osteocalcin and parathyroid hormone (PTH) serum levels. Serum 1,25(OH)2D3 values decreased significantly after 3 months of treatment. Urinary hydroxyproline/creatinine and calcium/creatinine ratios as well as 24-h urinary calcium values increased significantly during the treatment period but decreased rapidly to pretreatment values after 3 months in the follow-up period. The endocrine changes induced by the GnRH-agonist treatment were associated with reversible biochemical signs of increased bone turnover and no significant changes in bone mass, suggesting that the treatment can be administered safely for a period of 6 months in patients with oestrogen-dependent diseases.

Peripheral and central venous access.

Peripheral venous access is indicated for the administration of fluids, drugs, or if nutrients when other routes are unavailable. Central venous access is indicated if peripheral access is unsuccessful or if hypertonic, irritant, or vasoconstrictor solutions are used. Because of anatomical variations, different peripheral cannulation sites are more appropriate in different age groups. The preferred sites for long-term central venous access in infants and children are the external jugular, facial, internal jugular, saphenous veins at the groin, and subclavian veins. The practical aspects of peripheral and central venous access and the complications are discussed.

Fluids and electrolytes in infants and children.

The fluid and electrolyte management of the surgical neonate must take into account the acute transition to extrauterine life superimposed on the gradual changes associated with fetal and neonatal maturation and growth. With this transition, there are acute changes in body water distribution, and a striking increase in evaporative losses from the skin and respiratory tract. These changes, as well as those in renal function and sodium balance in the preterm and full-term infant are discussed.

Low erythrocyte zinc content in acquired aphasia with convulsive disorder (Landau-Kleffner syndrome).

Abnormal zinc metabolism in a 6-year-old male patient with Landau-Kleffner syndrome (acquired aphasia and convulsive disorder) is the subject of our report. We describe a significant decrease of erythrocyte and plasma zinc levels in the patient as compared with normal. Red blood cell zinc content is normally 38.5 +/- 2.7 micrograms/g hemoglobin v 16.5 micrograms/g hemoglobin found in the patient. Plasma zinc level is 94.6 +/- 10.4 micrograms/dL in normal in comparison with 50.4 micrograms/dL in the patient. Normal oral zinc tolerance test performed on the patient precludes altered zinc absorption or increased urinary loss. The possible connection between abnormal zinc metabolism and the pathophysiology of Landau-Kleffner syndrome is discussed.

Inflammatory bowel disease.

Inflammatory bowel disease in children encompasses at least two forms of intestinal inflammation: ulcerative colitis and Crohn's disease. These two disease processes are differentiated based on clinical presentation, radiologic findings, endoscopic findings, histologic evaluation, and exclusion of alternative causes. The treatment and operative interventions are reviewed.

Utility of sonography in the diagnosis of bronchopulmonary sequestration.

Sonography in six patients with pulmonary sequestration demonstrated findings associated with and indicative of that diagnosis. The most useful feature, which was seen in three cases and is diagnostic of sequestration, is the identification of an anomalous systemic artery arising from the aorta.