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Gordon L Klein

Publications and source records attributed to Gordon L Klein.

12 recordsLinked to original sources
PubMed2006

Burn-induced bone loss: importance, mechanisms, and management.

OBJECTIVE: The purpose of this article is to familiarize the reader with the issue of bone loss that accompanies severe burn injury. Why is this important? How does it happen? How can we treat it? METHODS: The published findings on this subject are reviewed and integrated into a conceptual framework. RESULTS: Bone loss occurs quickly following a severe burn, is sustained, and increases the risk of postburn fracture. The likely mechanisms responsible are the increase in endogenous glucocorticoid production resulting from the stress response and resorptive cytokines resulting from the systemic inflammatory response and likely aggravated by progressive vitamin D deficiency. Calcium metabolism is also disrupted as the patients develop hypocalcemic hypoparathyroidism likely due to an upregulation of the parathyroid calcium-sensing receptor, possibly due to inflammatory cytokine stimulation. Treatment is achieved by use of anabolic agents and vitamin D supplementation. Studies of acute administration of the antiresorptive agent pamidronate are also promising. CONCLUSION: Postburn bone loss should be looked for in patients with a burn injury of 40% or greater total body surface area. The cause is inherent to the adaptive mechanisms following burn injury. Methods are available to treat this condition.

Journal Article↗
PubMed2005

Aluminum: new recognition of an old problem.

The aluminum problem is now over 25 years old, but has remained a neglected concern. Data indicate that aluminum contaminates much of the raw material used to manufacture solutions used for intravenous nutritional support of hospitalized and ambulatory patients, and that pharmaceutical manufacturers have only recently obtained the technology necessary to detect aluminum contamination of their products. As a result, aluminum bypassed normal barriers and entered the blood, accumulating in tissues such as bone, liver and the central nervous system with toxic consequences. Now that the FDA has finally issued a rule governing aluminum contamination in these solutions, manufacturers will need to develop methods to minimize such contamination; scientists should also realize that when data they obtain indicate a serious problem in the manufacturing sector they should be sure that the problem is properly addressed.

Aluminum↗
PubMed2005

Impaired zinc and copper status in children with burn injuries: need to reassess nutritional requirements.

Major burns are associated with impaired Zn and Cu status. These micronutrients are essential for bone matrix formation, linear growth, and wound healing. This study evaluated the status of Zn and Cu in burned children and assessed adequacy of supplementation. Six children, mean total body surface area (TBSA), 54+/-9% (S.D.), were recruited. Nutrient intakes, plasma, wound exudate, and 24h urine samples were collected and analyzed for Zn and Cu. Bone mineral content was assessed by dual energy X-ray absorptiometry. Dietary Zn and Cu were three times the dietary reference, and mean plasma concentrations of Zn and Cu were low at admission and discharge. Urinary Zn was elevated at admission, whereas Cu was elevated at both times. Wound Zn and Cu concentrations exceeded plasma concentrations, suggesting that inflammatory wound exudate was a primary route of loss. We demonstrate that burn injury in children results in low plasma levels of Zn and Cu that are inadequately compensated during hospitalization.

Adolescent↗
PubMed2004

The efficacy of acute administration of pamidronate on the conservation of bone mass following severe burn injury in children: a double-blind, randomized, controlled study.

Bone loss is a known complication of severe burn injury. It is, in part, due to increased endogenous glucocorticoids that contribute to the reduction in bone formation and osteoblast differentiation, hypercalciuria secondary to hypoparathyroidism, and vitamin D deficiency. In this study we attempted to prevent post-burn bone loss by acute intravenous administration of the bisphosphonate pamidronate. We enrolled 43 children, with burns of > 40% total body surface area, in a randomized, double-blind, placebo-controlled study, administering the study drug within 10 days of burn injury and again 1 week later. Dual energy X-ray absorptiometry was performed prior to drug therapy, at hospital discharge and at 6 months post-burn. Urine specimens were obtained at baseline and discharge for determination of calcium and free deoxypyridinoline. Blood was obtained along with the urine specimens for measurement of intact parathyroid hormone (iPTH) and ionized calcium (Ca) levels. Following doxycycline labeling, intra-operative iliac crest bone biopsies were obtained, and bone histomorphometry was determined. At time of discharge there were no differences in total body bone mineral content (BMC), but lumbar spine BMC was significantly higher in the pamidronate group (P < 0.005). By 6 months post-burn the differences in lumbar spine BMC persisted, but, now, total body BMC was significantly higher in the pamidronate group (P < 0.05). Bone histomorphometry and levels of urine Ca and free deoxypyridinoline failed to show significant increases in bone formation or decreases in bone resorption. Pamidronate did not exacerbate the hypocalcemia in burn patients. In summary, acute intravenous pamidronate administration following burns may help to preserve bone mass, perhaps by inhibiting the glucocorticoid-induced apoptosis of osteoblasts and osteocytes.

Absorptiometry, Photon↗
PubMed2004

Evidence supporting a role of glucocorticoids in short-term bone loss in burned children.

Children burned > or =40% total body surface area suffer acute bone loss. The reason(s) for this is uncertain. In order to determine whether high endogenous glucocorticoid production can contribute to the bone loss, we sequentially studied a total of 14 pediatric burn patients for bone histomorphometry; 7 of these patients and 4 controls were studied for characteristics of corticosteroid-induced bone loss, including decreased osteoblasts and down-regulation of the glucocorticoid receptor in bone. We then studied 4 of the burn patients and three controls for a decrease in markers of osteoblast differentiation, another feature of glucocorticoid toxicity. Bone biopsies were taken from each of the 14 burn patients a mean of 3 weeks post-burn. Histomorphometry was performed on one specimen ( n=7) and either glucocorticoid and mineralocorticoid receptor, collagen and alkaline phosphatase expression by RT-PCR ( n=7) or marrow stromal cell culture ( n=4) on the other. Patients were permitted a maximum of two biopsies for study. One biopsy was obtained intra-operatively from normal subjects during elective iliac crest alveolar bone grafting and compared with burn specimens for glucocorticoid receptors and marrow stromal cell culture. A 24 h urine specimen was obtained for free cortisol ( n=7). Histomorphometry revealed low osteoblast and osteoid surfaces and few detectable osteoblasts. Resorptive surfaces were also reduced. Glucocorticoid receptor alpha mRNA (GRalpha) was not decreased; however, there was a trend toward inverse relationships between urine free cortisol and GRalpha and type-1 collagen mRNA, r=-0.61 and -0.64, respectively, and a significantly lower mRNA for type-1 collagen in bone in burn vs control patients by the median test, lambda(2)=7.6 ( p<0.01). Markers of osteoblast differentiation, core-binding factor (cbf)a1, bone morphogenetic protein (BMP)-2, type-I collagen, and alkaline phosphatase were reduced in burn cell cultures compared with controls ( p<0.05). The eightfold elevation of urinary free cortisol excretion, low osteoblast number, decreased resorptive surface, and reduced markers of osteoblast differentiation are all consistent with an acute glucocorticoid effect on bone.

Adolescent↗
PubMed2004

Synthesis of vitamin D in skin after burns.

Severe burn injury is associated with vitamin D deficiency, low bone turnover, and abnormalities in calcium homoeostasis. Patients do not routinely receive vitamin D supplementation and sun exposure is currently not controlled. By analysis of skin biopsy samples for vitamin D3 precursors after exposure to ultraviolet B light we found that the conversion of 7-dehydrocholesterol to previtamin D3 was reduced in children a mean of 14 months after the burn. Low serum 25-hydroxyvitamin D concentrations were also found. We conclude that vitamin D supplementation is necessary after burn injury.

Adolescent↗
PubMed2004

Effects of long-term oxandrolone administration in severely burned children.

BACKGROUND: Severe burns cause exaggerated catabolism of muscle protein and inhibit bone deposition. Weakness and bony growth arrest interfere with rehabilitation. The purpose of this study was to determine whether oxandrolone administration for 1 year after the burn reverses muscle and bone catabolism in hypermetabolic pediatric burn patients. METHODS: Children with burns greater than 40% total body surface area were enrolled into a randomized controlled trial to receive oxandrolone as a long-term anabolic agent. All patients received similar clinical care. Subjects were studied at discharge (95% healed) and at 6, 9, and 12 months after the burn, after treatment with 0.1 mg/kg po bid or placebo. Serum hepatic transaminases were measured. Lean body mass (LBM), bone mineral content (BMC,) and bone mineral density (BMD) were measured by dual energy x-ray absorptiometry. Patients completed a safety questionnaire and were reviewed clinically at intervals. RESULTS: The groups were similar in age, weight, and total body surface area burned. LBM was significantly greater with oxandrolone at 6, 9, and 12 months after the burn (P < .001) and BMC at 12 months (P < .016). Age- and gender-matched BMD z scores were significantly better with oxandrolone (P < .039). Liver transaminases were unaffected. CONCLUSIONS: Long-term administration of oxandrolone safely improves LBM, BMC, and BMD in severely burned children.

Adolescent↗
PubMed2004

Burns.

Explore the source record for details and available documents.

Body Surface Area↗
PubMed2002

Hepatic osteodystrophy in chronic cholestasis: evidence for a multifactorial etiology.

Children with cholestatic liver disease have been thought to develop hepatic osteodystrophy resulting from vitamin D and calcium malabsorption, resulting in secondary hyperparathyroidism and osteomalacia or rickets. However, treatment with vitamin D has not always proven successful in improving the bone disturbance. The aim of our study was to determine the role of vitamin D deficiency in the pathogenesis of hepatic osteodystrophy. We studied five patients, three female and two male, ages 0.9-19 yr, with biopsy-proven chronic cholestatic liver disease and previously low serum levels of vitamin D despite oral intake of vitamin D preparations. Patients were admitted to the Clinical Research Center for 8 days for sunlight deprivation and ultraviolet light substitution and for determinations of serum 25-hyroxyvitamin D(25(OH)) D2 and -D3, osteocalcin, and type I collagen telopeptide (ICTP), the last two being markers of bone formation and resorption, respectively. Samples were taken on admission, at discharge, and 1 month later. Results demonstrated low serum levels of osteocalcin and normal circulating levels of ICTP. Admission serum 25(OH)D2 levels were uniformly low or undetectable and remained so. Admission levels of circulating 25(OH)D3 were normal or low and did not rise during ultraviolet light therapy or subsequent resumption of oral vitamin D therapy and remained low 1 month later. These results indicate that in the face of low-normal to low total 25(OH)D levels, the low osteocalcin and normal ICTP levels suggest that decreased bone formation and not increased bone resorption is the main determinant of bone loss in a subset of children with chronic cholestatic liver disease.

Adolescent↗
PubMed2002

Vitamin D depletion following burn injury in children: a possible factor in post-burn osteopenia.

BACKGROUND: Children burned > 40% total body surface area (TBSA) have chronically low bone mineral density (BMD) and increased risk for fractures and adult-onset osteoporosis. Because they are advised to avoid sunlight to prevent burn scar hyperpigmentation, we hypothesized that they develop vitamin D depletion, which could contribute to post-burn osteopenia. METHODS: We studied 24 children, ages 5-20 years, burned > or = 40% TBSA 7.1 +/- 3.8 (SD) years, range 1.9-13.3 years, previously (n = 12) and 2.0 +/- 0.2, range 1.4-2.1 years, previously (n = 12), of which half received recombinant human growth hormone during the first post-burn year. We measured lumbar spine BMD, serum 25-hydroxyvitamin D (25(OH)D), 1,25-dihydroxyvitamin D (1,25(OH)2D), intact PTH (iPTH), and osteocalcin. RESULTS: Serum 25(OH)D was low in 10/11 patients and 1,25(OH)2D was low in 5/11 at 7 years post-burn. Serum 25(OH)D was low in 10/12, while 1,25(OH)2D was low in 0/12 at 2 years; osteocalcin was low in 9/12 in the 7-year group; iPTH levels were in the lowest quartile in 5/12 patients at 7 years and 10/12 patients at 2 years. Serum 25(OH)D levels correlated with BMD z-scores, r = 0.53, p < 0.05, and inversely with iPTH levels, r = -0.66, p < 0.05, in the 7-year group. CONCLUSION: Burned children have low circulating levels of 25(OH)D which correlated with BMD z-scores, suggesting that post-burn vitamin D depletion may play a role in the chronically low bone density observed in these children.

Adolescent↗