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PubMed2001

Influence of nitrogen and phosphorous availability and ozone stress on Norway spruce seedlings.

Four-year-old Norway spruce (Picea abies L. (Karst.)) seedlings were exposed to ambient and elevated (1.5 x ambient in 1997 and 1.6 x ambient in 1998) ozone concentrations [O3] and three nitrogen (N) and two phosphorus (P) availabilities: "optimal" values (control); 70% of the control N and P values (LN and LP); and 150% of the control N value (HN). Treatments were applied in an open-field ozone fumigation facility during the 1997 and 1998 growing seasons. Effects on growth, mineral and pigment concentrations, stomatal conductance and ultrastructure of needles were studied. The HN treatment increased growth significantly, whereas elevated [O3] had a slight or variable impact on growth and biomass allocation in all N treatments. Although there were no significant effects of the LP treatment on plant growth during the second year, there was a reduction in 1-year-old shoot dry mass in the elevated O3 + LP treatment at the end of the experiment. There were no significant treatment effects on mineral concentrations of current-year and 1-year-old needles at the final harvest. In response to the HN treatment, chlorophyll a and b and carotenoid concentrations increased significantly in current-year needles. Chlorophyll a/b ratio decreased in response to elevated [O3] alone, but increased in seedlings in the O(3) + LP treatment. Stomatal conductance of current-year needles decreased with increasing N availability, but increased in response to elevated [O3]. However, the O3-induced increase in stomatal conductance was less in the LN and LP treatments than in the control treatment. In chloroplasts of current-year needles, increased N availability decreased mean starch grain area, but increased the number of plastoglobuli. We conclude that Norway spruce seedlings are relatively tolerant to slightly elevated [O3], and that nitrogen and phosphorus imbalances do not greatly affect the influence of O3 on this species when the exposure lasts for two growing seasons or less.

Minerals↗

PubMed2003

Acclimation of shoot and needle morphology and photosynthesis of two Picea species to differences in soil nutrient availability.

To investigate morphological acclimation to differences in nutrient availability, we compared shoot and needle morphology of Picea glehnii (Friedr. Schmidt) M. T. Mast. and Picea jezoensis (Siebold & Zucc.) Carrière trees growing on nutrient-poor volcanic ash and nutrient-rich, brown forest soil. Trees of both species were shorter and had more open canopies when growing on volcanic ash than when growing on brown forest soil. Nutrient-poor conditions limited height growth less in P. glehnii than in P. jezoensis. In both species, trees growing on volcanic ash had shorter annual increments in the previous year and more needles per shoot length and, hence, a smaller shoot silhouette area (SSA) relative to needle dry mass (NDM) than trees growing on brown forest soil. Soil type had less effect on shoot projected needle area (PNA). Total needle area (TNA) of P. glehnii shoots was similar between soil types, whereas TNA of P. jezoensis was lower in trees growing on volcanic ash than in trees growing on brown forest soil. For both species, low SSA in response to nutrient-poor conditions resulted in low shoot SSA/PNA ratios, indicating high within-shoot self-shading. Shoot SSA/TNA of P. glehnii was lower in trees growing on volcanic ash than in trees growing on brown forest soil, indicating that needles were sun-acclimated. In contrast, shoot SSA/TNA of P. jezoensis was higher in trees growing on volcanic ash than in trees growing on brown forest soil. The contrasting response of TNA to low nutrient availability was associated with species-specific differences in needle morphology. Needles of P. glehnii growing on volcanic ash were slightly shorter, wider, thicker and heavier than those of trees growing on brown forest soil, indicating morphological acclimation to high irradiance. Needles of P. jezoensis growing on volcanic ash were shorter than those of trees growing on brown forest soil, but did not show morphological acclimation to high irradiance in width, thickness or mass. For both species, nutrient-poor conditions decreased maximum photosynthetic rate (Amax) per NDM. However, when expressed per PNA, the decrease in Amax was reduced, and when expressed per SSA, Amax was higher in trees growing on volcanic ash than in trees growing on brown forest soil. On volcanic ash, Amax per NDM was lower for P. glehnii than for P. jezoensis. However, morphological changes at the shoot and needle levels reversed this trend when Amax was expressed per SSA or per PNA. The species-specific differences in morphological response to differences in soil nutrient availability suggest that P. glehnii is more tolerant of nutrient-poor conditions, whereas P. jezoensis is better at exploiting nutrient-rich soils.

Acclimatization↗

PubMed2004

Effects of temperature and nutrient availability on plasma membrane lipid composition in Scots pine roots during growth initiation.

We studied the effects of root zone temperature (RZT) and nutrient availability on free sterols and phospholipids in the plasma membrane (PM) and on PM-ATPase activity in roots of 1-year-old Scots pine (Pinus sylvestris L.) seedlings during growth initiation in the spring. Seedlings were grown for 6 weeks in hydroponic cultures with low (0.5 mM N; LN) or high (3 mM N; HN) nutrient availability. The root zone was subjected to slow warming (SW) and fast warming (FW) treatments while maintaining similar air temperatures in both treatments. Decreases in the amount of phospholipids and in the phospholipid/free sterol ratio, an increase in the degree of saturation of phospholipid fatty acids and changes in free sterol composition were observed during root growth initiation. Changes in lipid composition of the PM associated with the cold deacclimation process were detected at RZTs above 9 degrees C. Nutrient availability affected the lipid composition of the PM only when RZT was increased slowly. When RZT increased from 4 to 6 degrees C in the SW treatment, the degree of saturation of phospholipid fatty acids decreased, especially in HN seedlings. The sitosterol/stigmasterol ratio remained higher in HN seedlings than in LN seedlings. After an RZT of 9 degrees C had been reached in the SW treatment, HN caused increases in the saturation of phospholipid fatty acids and root PM-ATPase activity, and a decrease in the phospholipid/free sterol ratio. Possible effects of changes in PM lipid composition on root growth and PM-ATPase activity are discussed.

Adenosine Triphosphatases↗

PubMed2004

Cardiac myocyte-specific HIF-1alpha deletion alters vascularization, energy availability, calcium flux, and contractility in the normoxic heart.

At a resting pulse rate the heart consumes almost twice-as much oxygen per gram tissue as the brain and more than 43 times more than resting skeletal muscle (1). Unlike skeletal muscle, cardiac muscle cannot sustain anaerobic metabolism. Balancing oxygen demand with availability is crucial to cardiac function and survival, and regulated gene expression is a critical element of maintaining this balance. We investigated the role of the hypoxia-inducible transcription factor HIF-1alpha in maintaining this balance under normoxic conditions. Cardiac myocyte-specific HIF-1alpha gene deletion in the hearts of genetically engineered mice caused reductions in contractility, vascularization, high-energy phosphate content, and lactate production. This was accompanied by altered calcium flux and altered expression of genes involved in calcium handling, angiogenesis, and glucose metabolism. These findings support a central role for HIF-1alpha in coordinating energy availability and utilization in the heart and have implications for disease states in which cardiac oxygen delivery is impaired. Heart muscle requires a constant supply of oxygen. When oxygen supply does not match myocardial demand cardiac contractile dysfunction occurs, and prolongation of this mismatch leads to apoptosis and necrosis. Coordination of oxygen supply and myocardial demand involves immediate adaptations, such as coronary vasodilatation, and longer-term adaptations that include altered patterns of gene expression (2-4). How the expression of multiple genes is coordinated with oxygen availability in the heart and the impact of oxygen-dependent gene expression on cardiac function are insufficiently understood. Further elucidating these relationships may help clarify the molecular pathology of various cardiovascular disease states, including ischemic cardiomyopathy and myocardial hibernation (5, 6).

Animals↗

PubMed2026

Low Carbohydrate Availability in Energy Balance Alters Bone Turnover and Muscle Proteomic Response With Limited Endocrine Disruption.

Training with low carbohydrate availability (LCA) has been proposed as an independent determinant of physiological perturbations commonly attributed to low energy availability (LEA) and to increase skeletal muscle oxidative machinery, yet the effects of LCA in isolation from LEA remain unclear. We examined whether short-term carbohydrate restriction under energy balance alters endocrine and metabolic markers associated with LEA and skeletal muscle proteomic response. In a randomized crossover design, eight trained males completed 4 days of either a low-carbohydrate high-fat diet (LOW; 12% carbohydrate, 69% fat, 19% protein) or a normal-carbohydrate diet (NORM; 62% carbohydrate, 19% fat, 19% protein), while undertaking daily cycloergometer exercise (15 kcal kg FFM-1 day-1) and maintaining energy availability at 45 kcal kg FFM-1 day-1. LOW induced a clear metabolic shift consistent with LCA, evidenced by elevated circulating free fatty acids, glycerol and β-hydroxybutyrate, in fasting conditions and fat oxidation at rest and during exercise, alongside reduced exercise glucose concentrations. Despite these responses, LOW did not alter insulin, testosterone, triiodothyronine, leptin, hepcidin, or P1NP. In contrast, β-CTX increased and IGF-1 decreased relative to NORM. Muscle glycogen concentration decreased only in LOW (40% ± 14%). Proteomic analysis identified 671 proteins; 57 differentially expressed in LOW relative to NORM were limited to fatty acid metabolism pathways and suppression of ribosomal, sarcomeric, and extracellular matrix proteins. These findings indicate that isolated LCA exerts limited endocrine disruption but may selectively compromise bone turnover and muscle anabolic response, suggesting that without acute LEA, LCA has limited influence on muscle oxidative phenotype.

Male↗

PubMed1997

Emergency room visits despite the availability of primary care: a study of high risk inner city infants.

Very low birth weight preterm infants randomized to receive comprehensive primary care in an ongoing clinical trial were prospectively evaluated to determine the cause of frequent emergency room use despite the availability of a primary healthcare provider and specific social services. Mothers were interviewed to assess knowledge of available resources, when to seek medical attention, and the perception of problems that limit access to health care. The healthcare provider was not called before 49% of the emergency room visits and mothers often did not recall what infant signs needed medical attention. Seventy-nine percent of emergency room visits were delayed more than 10 hours; and 15 of 62 (24%) emergency room visits resulted in admittance to the hospital. We conclude that in high-risk populations, the mere availability of primary care does not assure that it will be used. New strategies to help parents know when and how to use services are needed to increase the delivery of primary care.

Emergency Medical Services↗

PubMed1996

Effects of availability of patient-related charges on practice patterns and cost containment in the pediatric intensive care unit.

OBJECTIVE: To investigate the effects of the availability of daily patient-related charges to healthcare providers on practice patterns and cost containment in the pediatric intensive care unit (ICU) setting. DESIGN: Prospective, nonrandomized, controlled trial. SETTING: Pediatric ICU. PATIENTS: All patients admitted to the pediatric ICU during the study period. This number included a prospective control group (n=325) and an intervention group (n=273). These 598 patients spent 2,274 patient days in the pediatric ICU. INTERVENTIONS: The daily itemized patient charges related to diagnostic studies ordered in the pediatric ICU were made available to healthcare providers during the intervention period of the study. MEASUREMENTS AND MAIN RESULTS: Information was collected prospectively on patients in the control group before the intervention period. This information included data on demographics, daily severity of illness measures, daily resource consumption, intensity of nursing and medical interventions, and daily patient-related charges. Outcome information on survival and length of pediatric ICU stay was also collected. The same data were collected prospectively during the intervention period of the study. Measurements on quality assurance and morbidity were made to ensure that there was no compromise in patient care. There were no significant differences in patient demographics and diagnoses between the control and intervention groups. There was a reduction in the average daily laboratory (16.7%), radiology (9.1%) computerized axial tomography (8.5%), and pharmacy (25.1%) charges in the intervention group as compared with controls. The decreases in laboratory and pharmacy charges were statistically significant (p<.0001). The decreases in laboratory and pharmacy charges remained significant even after adjustment for severity of illness. CONCLUSIONS: The availability of patient-related charges to healthcare providers can result in changes in practice patterns, producing a decrease of patient charges and an improvement in cost containment in the pediatric ICU.

Analysis of Variance↗

PubMedDate not supplied

Increasing manager availability: a retention strategy.

The availability of a manager can significantly assist the personal and professional growth of nurses and increase retention. Successful use of availability is done by a manager who understands both the concept of availability and its possible limitations.

Communication↗

PubMed1996

Benzodiazepine use in Chile: impact of availability on use, abuse, and dependence.

This study tested the hypothesis whether over-the-counter benzodiazepine availability influenced patterns of benzodiazepine use, abuse, and dependence in Chile. If over-the-counter availability represents a major risk factor leading to benzodiazepine substance use disorders, rates of abuse, and dependence would be significantly higher among over-the-counter benzodiazepine users than among prescription drug users. The study was a household survey of a stratified sample (N = 1,500) of the Santiago (Chile) population performed by trained interviewers. Data were collected by structured questionnaires on demographic characteristics, drug use, psychoactive substance use disorders, and other psychosocial variables. Past-year prevalence of benzodiazepine use was 31.4%, daily use of benzodiazepines for > or = 12 months, 5.9%, and subjects who met DSM-III-R criteria for dependence, 3.3%. Seventy-four percent of subjects obtained the benzodiazepine over-the-counter (always 45%; sometimes 29%). No subject acknowledged recreational benzodiazepine use or met criteria for benzodiazepine abuse. Use, long-term use, and dependence occurred equally frequently among both over-the-counter and prescription benzodiazepine users. Results suggest that although over-the-counter availability increases benzodiazepine use, it is not a major risk factor that leads to benzodiazepine abuse and/or dependence.

Adolescent↗

PubMed1990

Should safety concerns with available ulcer treatment influence drug selection?

With the identification of the parietal cell receptors for gastric acid secretion coupled with the introduction of cimetidine in 1977, treatment of acid-peptic diseases was transformed from empiric therapy to an approach based on a clearer understanding of human physiology. Today, physicians are confronted with an array of antiulcer agents that differ within their drug class (e.g., the H2-receptor antagonists) as well as in their mechanisms of action (e.g., neutralize acid, alter mucosal defensive factors, or suppress acid secretion). With minor exceptions, the clinical efficacy of the available antiulcer drugs can be regarded as comparable. Thus, the safety profile becomes the next consideration when choosing among similarly effective drug products. Of the available antiulcer agents, the H2-receptor antagonists as a class have an excellent safety profile, as indicated by more than 25 years of cumulative clinical experience and postmarketing surveillance. Important safety issues with currently available antiulcer drugs, i.e., H2-receptor antagonists, sucralfate, prostaglandin E analogues, and the newest antiulcer agent, omeprazole, are reviewed to place them into perspective for the clinician.

Antacids↗

PubMed1998

Effects of human milk pasteurization and sterilization on available fat content and fatty acid composition.

BACKGROUND: Human milk is frequently heat treated in hospitals to reduce bacterial contamination, particularly in banked milk fed to preterm infants. Pasteurization and sterilization may induce oxidative losses of unsaturated lipids and vitamins and may inactivate enzymes and immunologic factors. This study was designed to examine the effects of pasteurization and sterilization on milk fat content available to the recipient infant and on fatty acid composition. METHODS: In fresh, pasteurized (62.5 degrees C for 30 minutes), and sterilized (120 degrees C for 30 minutes) milk samples (5 ml) of 12 mothers (days 5-35 of lactation), fat content was determined gravimetrically and the contribution of 30 fatty acids was determined by gas-liquid chromatography. RESULTS: The coefficients of variation for measurements of milk fat content were 0.7% and of fatty acids accounting for more than 0.09% of weight, 0.1-3.0%. Available fat content was 3.1+/-1.4 g/dl (mean +/- SD) in fresh human milk and 3.1+/-1.4 g/dl (not significant) in pasteurized human milk. Fat content declined to 2.7+/-1.1 g/dl (p < 0.001 vs. fresh) in sterilized human milk, because of increased fat adherence to the container surface after sterilization. The percentage composition of saturated, monounsaturated, and polyunsaturated fatty acids of the n-6 (C18:3, C20:2, C20:3, and C22:4) and the n-3 series (C18:3 C20:5, C22:5, and C22:6) was not affected by thermal treatment. Milk sterilization caused a slight decrease of linoleic (-0.7% vs. fresh milk; p = 0,006) and arachidonic (-2,6%; p = 0.045) acids. CONCLUSIONS: Pasteurization of human milk does not influence fat content and composition, but sterilization may reduce available fat content by more than 10%, whereas there are only slight changes in fatty acid composition.

Arachidonic Acid↗

PubMed1988

Alterations in cerebral availability of metabolic substrates after severe head injury.

Cerebral and systemic metabolism of oxygen, glucose, lactate, pyruvate, beta-hydroxybutyrate, acetoacetate, and amino acids were studied in 27 comatose patients during the first 7 days after a head injury. Systemic oxygen consumption was elevated initially and gradually returned toward normal over the week of study. In contrast, cerebral oxygen consumption was depressed and decreased further over the week of study. Cardiac output and cerebral blood flow were increased with respect to systemic and cerebral metabolic requirements, and remained elevated for the entire week of study. Systemic hyperglycemia and lactic acidosis were present. The injured brain often made a sizeable contribution to the lactic acidosis. The arterial concentrations of pyruvate, beta-hydroxybutyrate and acetoacetate were low. The early postinjury arterial amino acid profile was typically an increased level of alanine, taurine, glutamic acid, and a reduced concentration of valine, leucine, isoleucine, threonine, serine, ornithine, and arginine. At 3-4 days postinjury, as the early abnormalities were returning toward normal, glutamine, lysine, phenylalanine, tyrosine, and methionine became elevated. These late increases in amino acids occurred at the time of the peak in plasma catecholamine concentrations. The net cerebral flux of amino acids followed the same general pattern of evolution over time as did the arterial concentration of amino acids. On days when the availability of the individual amino acid was increased, the net cerebral flux tended to be positive; when the availability was decreased, the net cerebral flux was zero or there was a net efflux of the amino acid. There was a significant linear relationship between the arterial concentration and the net flux of 13 of the 17 amino acids studied. Unlike the fasting state in normal man, in which beta-hydroxybutyrate and acetoacetate are important metabolic substrates, cerebral metabolism after head injury is almost totally dependent upon the aerobic and anaerobic metabolism of glucose. This is at least in part due to injury-induced limitations in the variety of substrates that are available for the brain to extract.

Adolescent↗

PubMed1998

A geographic relation between alcohol availability and gonorrhea rates.

BACKGROUND AND OBJECTIVES: The availability of alcohol measured as alcohol outlet density is associated with numerous alcohol-related outcomes in small area analysis. A number of studies suggest that high-risk sexual behavior should also be considered an alcohol-related outcome. GOAL OF THIS STUDY: To assess the geographic relationship between alcohol availability and high-risk sexual behavior at the neighborhood level. STUDY DESIGN: Ecological analysis of the geographic relation between off-premise, on-premise, and total alcohol outlet density and reported gonorrhea rates among 155 urban residential census tracts in New Orleans during 1995. RESULTS: All alcohol outlet density variables were positively related to gonorrhea rates. Off-premise outlets per square mile was most strongly related to gonorrhea rates (beta +/- SE) (beta = 0.582+/-0.073), accounting for 29% of the variance in gonorrhea rates. Interpreted as an elasticity, a 10% increase in off-sale alcohol outlet density accounts for a 5.8% increase in gonorrhea rates. Including the covariates percent black and percent unemployed to the model reduced but did not remove the effect of off-sale outlet density (beta = 0.192+/-0.047). CONCLUSIONS: These results indicate there is a geographic relationship between alcohol outlet density and gonorrhea rates at the census tract level. Although these results cannot be interpreted causally, they do justify a public health intervention as a next step in defining the relation between alcohol availability and high-risk sexual behavior.

Alcohol Drinking↗

PubMed1993

Limited availability of medications for cancer patients.

We surveyed both chain and independent pharmacies within 10 counties of central South Carolina to determine the availability of certain medications that are often prescribed for patients during cancer treatment. One hundred twenty (59%) of the 202 surveys distributed were returned. Results indicate that many of the 65 products included in the survey are not stocked on a regular basis by the majority of the pharmacies that responded. Limited availability of these medications not only may prevent a patient from receiving timely drug therapy, but may exacerbate the anxieties and frustrations experienced by patients as they deal with their disease as well. This limited accessibility to medications could directly influence patient compliance. Therefore, patients need to be informed that availability is often limited, and that prescribed medications may require special ordering by their pharmacist. Awareness of this potential problem and increased communication among physicians, nurses, pharmacists, and patients could alleviate delays in drug therapy and improve the continuity of patient care.

Analgesics↗

PubMed2001

Dose-dependent toxicity of a commercially available demineralized bone matrix material.

STUDY DESIGN: A relative risk assessment was performed to determine the safety of three commercially available Grafton demineralized bone matrix quantities used in athymic rats. OBJECTIVE: To evaluate the possible dose-dependent adverse effects of a commercially available demineralized bone matrix containing glycerol. SUMMARY OF BACKGROUND DATA: Commercially available Grafton demineralized bone matrix contains glycerol. The toxic effects of glycerol leading to acute renal failure have been documented. The toxicity of this glycerol-containing substance in higher doses has not been reported. METHODS: Three doses of Grafton putty were implanted in the upper hind limb muscles of athymic nude rats. The rats were observed for adverse effects and early death. Histologic studies were performed. RESULTS: All eight of the rats implanted with the highest dose of Grafton putty (0.008 mL/g) died, five of them within 12 hours of implantation and three in 48 to 72 hours. One rat with the intermediate dose (0.004 mL/g) died within 12 hours of implantation. By 72 hours after implantation, three of the six rats (50%) with the intermediate dose had died. All six of the rats receiving the lowest dose (0.002cc/g) survived. The median lethal dose of Grafton putty in athymic rats was estimated to be 0.00469 mL/g body weight. Histologic analysis of the animals that received the high dose showed acute tubular necrosis, probably secondary to rhabdomyolysis. CONCLUSIONS: In athymic rats, large amounts of Grafton putty lead to death in a dose-dependent manner. Because the median lethal doses of Grafton putty (0.00469 mL/g) and glycerol (0.00442 mL/g) are comparable, a potential source of toxicity is the glycerol contained in the material. The results of this study suggest that high doses have the potential to cause acute renal failure. The authors suggest that clinical usage of Grafton putty in humans should be limited to no more than 2 mL/kg body weight of this material.

Animals↗

PubMed2001

Survey of intensive care units and availability of drug assays in Australasia.

The availability of drug assays, toxicologic screens, or both can play a significant role in the clinical decision-making processes affecting comatose patients with brain injury, including the decision to continue life support. However, with the widespread trend to reduce such comprehensive laboratory services down to core routine drugs, many clinical staff are finding it increasingly difficult to obtain such assay results in a time-frame relevant to the clinical needs of their patients and families. The authors have surveyed the intensive care units in Australasia to assess their perspectives in this area. The results from 53% of units responding showed there was insufficient clinical pharmacologic support available. Whereas the majority of centers had ready access to the standard immunoassays and urine drug screens, few had access to more complex assays, especially in the time-frame that was required. Interestingly, there was wide variability between centers as to the time to terminate life support in the absence of other indices (e.g., 4-vessel angiography). The use of basic pharmacokinetic principles including drug half-life was practiced in some centers, albeit probably inappropriately in this patient subpopulation. There is generally insufficient availability of specialized drug assay laboratories to meet clinical demands, primarily because of reduction in services and financial constraints in the public hospital system.

Australia↗

PubMed1993

Choosing an alternative bone marrow donor among available family members.

PURPOSE: Bone marrow transplantation (BMT) can be curative for patients with hematological malignancies, marrow failure syndromes, and certain metabolic disorders. However, fewer than half of the patients who could benefit have a donor who is either an HLA-matched sibling or a phenotypically similar unrelated volunteer. PATIENTS AND METHODS: The opportunity for allogeneic bone marrow transplantation is significantly increased by the use of partially mismatched, haploidentical related donors. The likelihood of finding a donor within the family is dependent on the acceptable degree of mismatch on the unshared chromosome. The degree of mismatch is expected to be approximately 10% for a one-antigen mismatch, 20-30% for a two-antigen mismatch, and > 95% for a three-antigen mismatch. Improvements in transplant techniques designed to enhance engraftment and to prevent the development of severe acute and chronic graft-versus-host disease have increased the feasibility of utilizing this readily available donor pool. Obviously, the ability to use a three-antigen mismatched related donor would make bone marrow transplantation available for almost every patient. RESULTS: Recent studies combining in vitro and in vivo immunomodulation of donor lymphocytes have resulted in consistent engraftment and control of acute graft-versus-host disease. CONCLUSIONS: These findings provide encouragement that there may need be no restriction on the availability of allogeneic marrow transplants as a therapeutic option for appropriate candidates.

Bone Marrow Transplantation↗

PubMed2006

Intervariability and intravariability of bone morphogenetic proteins in commercially available demineralized bone matrix products.

STUDY DESIGN: Enzyme-linked immunosorbent assay was used to detect bone morphogenetic proteins (BMPs) 2, 4, and 7 in 9 commercially available ("off the shelf") demineralized bone matrix (DBM) product formulations using 3 different manufacturer's production lots of each DBM formulation. OBJECTIVES: To evaluate and compare the quantity of BMPs among several different DBM formulations (inter-product variability), as well as examine the variability of these proteins in different production lots within the same DBM formulation (intra-product variability). SUMMARY OF BACKGROUND DATA: DBMs are commonly used to augment available bone graft in spinal fusion procedures. Surgeons are presented with an ever-increasing variety of commercially available human DBMs from which to choose. Yet, there is limited information on a specific DBM product's osteoinductive efficacy, potency, and constancy. METHODS: There were protein extracts from each DBM sample separately dialyzed 4 times against distilled water at 4 degrees C for 48 hours. The amount of BMP-2, BMP-4, and BMP-7 was determined using enzyme-linked immunosorbent assay. RESULTS.: The concentrations of detected BMP-2 and BMP-7 were low for all DBM formulations, only nanograms of BMP were extracted from each gram of DBM (20.2-120.6 ng BMP-2/g DBM product; 54.2-226.8 ng BMP-7/g DBM). The variability of BMP concentrations among different lots of the same DBM formulation, intra-product variability, was higher than the variability of concentrations among different DBM formulations, inter-product variability (coefficient of variation range BMP-2 [16.34% to 76.01%], P < 0.01; BMP-7 [3.71% to 82.08%], P < 0.001). BMP-4 was undetectable. CONCLUSIONS: The relative quantities of BMPs in DBMs are low, in the order of 1 x 10(-9) g of BMP/g of DBM. There is higher variability in concentration of BMPs among 3 different lots of the same DBM formulation than among different DBM formulations. This variability questions DBM products' reliability and, possibly, efficacy in providing consistent osteoinduction.

Biological Products↗