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Biomedical subjects

K Burkhart

Publications and source records attributed to K Burkhart.

At least 19 recordsLinked to original sources
PubMed2006

[Shaft lengthening in hip replacement: experimental studies on bending stiffness].

BACKGROUND: Cortical atrophy of the proximal femur can be seen after wearing a total hip prosthesis for several years because loads are borne distally at the prosthesis tip. To achieve stable prosthesis implantation on the one hand and proximal bone regeneration on the other hand in hip revision arthroplasty, lengthening of the shaft component distributes loading forces to the femoral shaft first. It concentrates them to the proximal femur later through a higher elasticity. METHODS: In a three-point bending study the bending stiffness of an elastic slotted hip prosthesis shaft lengthening (HSL) was compared with that of the Synthes universal femoral nail (MN) and the unslotted HSL. RESULTS: The slotting of the elastic HSL has a significant influence on its bending stiffness; it lies 1,287 N/mm (76%) over that of the MN, but 1,855 N/mm (38%) under that of the unslotted HSL. Altogether the slotted HSL is rather more comparable to the MN than to the unslotted HSL regarding its bending conduct. CONCLUSION: The results confirm the elasticity of the slotted HSL in the style of conventional intramedullary nailing and encourage-above all in the context of previous clinical studies-its further use.

Biomechanical Phenomena↗
PubMed2005

Probability of porcine reproductive and respiratory syndrome (PRRS) virus infection as a function of exposure route and dose.

At the most elemental level, the design of effective strategies to control and/or eliminate porcine reproductive and respiratory syndrome (PRRS) virus depend on an accurate and comprehensive understanding of virus transmission. As a general rule, transmission is highly dependent on the route of exposure and the dose of virus. The objective of this study was to derive PRRS virus isolate VR-2332 dose-response curves for oral and intranasal routes of exposure, i.e., determine the probability that a specific virus dose would result in infection. Individually housed pigs approximately 21 days of age were exposed to specific doses of PRRS virus isolate VR-2332 by either oral or intranasal routes. Positive controls were intramuscularly inoculated with 10(2.2) 50% tissue culture infective dose (TCID50) of PRRS virus and negative controls were orally administered 100ml of diluent with no virus. Pigs were monitored for evidence of infection for 21 days following exposure, i.e., serum samples were collected on days 0, 7, 14, 21, and tested for virus and PRRS virus-specific antibodies. Dose-response curves and 95% confidence intervals for oral and intranasal routes of exposure were derived using logistic models (logit and probit). The infectious dose50 (ID50) for oral exposure was estimated to be 10(5.3) TCID50 (95% CI, 10(4.6) and 10(5.9)); the ID50 for intranasal exposure was estimated to be 10(4.0) TCID50 (95% CI, 10(3.0) and 10(5.0)). Given these estimates, it is worth noting that intramuscular exposure of animals to 10(2.2) TCID50 (positive controls) resulted in infection in all animals. Thus pigs were the most susceptible to infection via parenteral exposure.

Administration, Intranasal↗
PubMed1999

Intravenous midazolam for sedation of children undergoing procedures: an analysis of age- and procedure-related factors.

OBJECTIVE: This study was performed to determine the doses of midazolam used for sedation during procedures in children, and the frequency of adverse events. METHODS: We performed a retrospective analysis of data collected for a prospective study of flumazenil in children who had received midazolam for a procedure (n = 91, 1-17 years). RESULTS: Practitioners used a wide range of total midazolam doses (0.03-0.6 mg/kg); mean doses ranged from 0.09 +/- 0.06 mg/kg in adolescents to 0.26 +/- 0.13 mg/kg in toddlers (P < 0.001). Opioids were also used in 84% of patients. Twenty-six percent of children with normal lungs, most of whom had received relatively high opioid doses, developed decreased oxygen saturation (as low as 65%) after sedation. Other adverse events included airway obstruction (n = 3) and vomiting (n = 1). CONCLUSIONS: The frequent choice of midazolam, usually combined with an opioid, indicates its wide acceptance. Midazolam doses were inversely related to age. The presence of vomiting, airway obstruction, and decreased oxygen saturation underlines the importance of appropriate personnel, equipment, and monitors during sedation.

Adolescent↗
PubMed1999

Research fundamentals: V. The use of laboratory animal models in research.

Animal research has provided important information about many aspects of the pathophysiology of human disease. Well-performed animal studies can determine the potential benefit of many proposed therapeutic interventions, and experimental results from animal studies have served as the basis for many landmark clinical trials. Many animal research models are described in the research literature, and choosing the appropriate model to answer a research question can be a daunting task. Even more challenging is developing a new model when none of the existing systems are relevant to the proposed question. This article was prepared by members of the SAEM Research Committee to provide an overview of animal modeling. Important considerations in choosing, applying, and developing animal research models are outlined. Practical discussions of potential problems with animal models are also provided.

Animals↗
PubMed1998

Ceramide accumulation during oxidant renal tubular injury: mechanisms and potential consequences.

UNLABELLED: Ceramide is an important signaling molecule that is typically generated via sphingomyelinase (SMase)-mediated sphingomyelin (SM) hydrolysis. Although diverse forms of renal injury elicit ceramide accumulation, the molecular determinants of this change and its contribution to tissue damage are poorly defined. The present study uses iron (Fe/hydroxyquinoline)-mediated injury of cultured human proximal tubular (HK-2) cells to gain additional insights into these issues. A 4-h Fe exposure doubled ceramide levels in the absence of cell death. This was independent of de novo synthesis, since ceramide synthase inhibition (with fumonisin B1) had no effect. Oxidant stress directly suppressed, rather than stimulated, SMase activity by: (1) decreasing SMase levels; (2) depleting SMase-stimulating glutathione; and (3) increasing SM resistance to SMase attack. Fe suppressed cell sphingosine levels (3 to 4 times ceramide/sphingosine ratio increments), suggesting a possible ceramidase block. Fe did not directly affect HK-2 ceramidase levels. However, arachidonic acid (C20:4) accumulation, a consequence of oxidant-induced phospholipase A2 (PLA2) activation, markedly suppressed ceramidase and stimulated SMase activity. Exogenous C20:4, as well as PLA2 (in doses simulating Fe-induced deacylation) recapitulated Fe's ceramide-generating effect. Because C20:4 is directly cytotoxic, it was hypothesized that ceramide might offset some of C20:4's adverse effects. Supporting this possibility were the following: (1) C20:4 exacerbated Fe toxicity; (2) this was abrogated by ceramide treatment; and (3) ceramide blunted Fe-mediated cell death. CONCLUSIONS: (1) ceramide accumulation during acute cell injury can be an adaptive response to PLA2 activation/C20:4 generation; (2) C20:4-induced ceramidase inhibition, coupled with SMase stimulation, may trigger this result; and (3) these ceramide increments may exert a "biostat" function, helping to offset C20:4/PLA2- and "catalytic" iron-mediated tubular cell death.

Arachidonic Acid↗
PubMed1997

Safety and efficacy of flumazenil in the reversal of benzodiazepine-induced conscious sedation. The Flumazenil Pediatric Study Group.

OBJECTIVE: To determine the safety and efficacy of flumazenil when given for reversal of benzodiazepine-induced conscious sedation in children. DESIGN: Multicenter study conducted in emergency departments and pediatric endoscopy, bronchoscopy, or oncology suites. PATIENTS: One hundred seven children (median age, 6 years; range, 1 to 17 years) who received intravenous benzodiazepine for an invasive procedure. INTERVENTIONS: Flumazenil was given in increments of 0.01 mg/kg (0.2 mg maximum) at 1-minute intervals to a maximum total dose of 0.05 mg/kg (1.0 mg maximum). MEASUREMENTS: Clinical efficacy was assessed by the Clinical Global Impression Scale and Observer's Assessment of Alertness/Sedation Scale. The OAA/S, vital signs, lead II electrocardiogram, and clinical assessments were recorded at 0, 10, 30, 60, 90, and 120 minutes after flumazenil was given. RESULTS: All children received midazolam (mean total dose, 0.18 mg/kg) for sedation. One hundred (96%) patients achieved a complete or partial response to flumazenil by 10 minutes after its administration, on the basis of their CGIS scores (the mean dose of flumazenil administered at the time of the first complete response was 0.017 +/- 0.010 mg/kg). Seventy-one of 93 (76%) patients with a baseline OAA/S score < or = 3 (1 = deep sleep, 5 = alert) experienced an increase of > or = 2 points at 10 minutes after flumazenil administration, and 81 of 93 (87%) had a score of 4 or 5 after flumazenil administration. Seven patients, all within the 1- to 5-year age range, experienced resedation after initially responding to flumazenil. Thirty-seven of 107 patients (35%) experienced a total of 56 adverse events, most of which were considered to be unrelated to flumazenil administration. The most frequently occurring adverse events were abnormal crying, dizziness, nausea, fever, and headache. There were no clinically significant changes in vital signs or ECG tracings. No adverse events resulted in premature termination of drug administration. CONCLUSIONS: Flumazenil promptly and effectively reverses the central nervous system depressant effects of midazolam in children undergoing conscious sedation, with no significant adverse effects. Because of the potential for resedation, children who receive flumazenil should be monitored for 1 to 2 hours after its administration.

Adolescent↗
PubMed1997

Naja naja cobra bite.

Most venomous snakes in the United States are of the Crotalidae family. Another family of snakes, the Elapidae, are not so common, but their bites may be a threat to zoo keepers and persons who have exotic snakes as pets. Because Elapidae envenomation is not common, signs and symptoms of such envenomation may not be recognized. Elapidae venom, because of a curare-like property, can produce respiratory compromise followed by death within 10 minutes. Antivenin, cholinesterase inhibitors, and mechanical ventilation are treatments to consider in such envenomations. Unlike Crotalidae antivenin, Elapidae antivenin may not confer protection against species not used in its preparation. Identification of the involved snake, by family and specie, should be an early priority. Correct management of the envenomated patient is dependent on the prompt administration of the most specific antivenin available when indicated.

Adult↗
PubMed1997

Myoglobin toxicity in proximal human kidney cells: roles of Fe, Ca2+, H2O2, and terminal mitochondrial electron transport.

The purpose of this study was to gain direct insights into mechanisms by which myoglobin induces proximal tubular cell death. To avoid confounding systemic and hemodynamic influences, an in vitro model of myoglobin cytotoxicity was employed. Human proximal tubular (HK-2) cells were incubated with 10 mg/ml myoglobin, and after 24 hours the lethal cell injury was assessed (vital dye uptake; LDH release). The roles played by heme oxygenase (HO), cytochrome p450, free iron, intracellular Ca2+, nitric oxide, H2O2, hydroxyl radical (-OH), and mitochondrial electron transport were assessed. HO inhibition (Sn protoporphyrin) conferred almost complete protection against myoglobin cytotoxicity (92% vs. 22% cell viability). This benefit was fully reproduced by iron chelation therapy (deferoxamine). Conversely, divergent cytochrome p450 inhibitors (cimetidine, aminobenzotriazole, troleandomycin) were without effect Catalase induced dose dependent cytoprotection, virtually complete, at a 5000 U/ml dose. Conversely, -OH scavengers (benzoate, DMTU, mannitol), xanthine oxidase inhibition (oxypurinol), superoxide dismutase, and manipulators of nitric oxide expression (L-NAME, L-arginine) were without effect. Intracellular (but not extracellular) calcium chelation (BAPTA-AM) caused approximately 50% reductions in myoglobin-induced cell death. The ability of Ca2+ (plus iron) to drive H2O2 production (phenol red assay) suggests one potential mechanism. Blockade of site 2 (antimycin) and site 3 (azide), but not site 1 (rotenone), mitochondrial electron transport significantly reduced myoglobin cytotoxicity. Inhibition of Na, K-ATPase driven respiration (ouabain) produced a similar protective effect. We conclude that: (1) HO-generated iron release initiates myoglobin toxicity in HK-2 cells; (2) myoglobin, rather than cytochrome p450, appears to be the more likely source of toxic iron release; (3) H2O2 generation, perhaps facilitated by intracellular Ca2+/iron, appears to play a critical role; and (4) cellular respiration/terminal mitochondrial electron transport ultimately helps mediate myoglobin's cytotoxic effect. Formation of poorly characterized toxic iron/H2O2-based reactive intermediates at this site seems likely to be involved.

Antioxidants↗
PubMed1997

Decreased expression of mitochondrial-derived H2O2 and hydroxyl radical in cytoresistant proximal tubules.

Increased production of reactive oxygen metabolites (ROM) can contribute to the initiation phase of nephrotoxic and ischemic acute renal failure (ARF). However, whether altered ROM expression also exists during the maintenance phase of ARF has not been adequately assessed. Since diverse forms of tubular injury can initiate a "cytoresistant state," this study tested whether a down-regulation of ROM expression might develop in the aftermath of acute tubular damage, potentially limiting renal susceptibility to further attack. To test this hypothesis, rats were subjected to either mild myohemoglobinuria (glycerol injection) or bilateral ureteral obstruction and 24 hours later, cytoresistant proximal tubular segments (PTS) were isolated to assess ROM expression. PTS from sham operated rats were used to establish normal values. Both sets of cytoresistant PTS manifested approximately 75% reductions in H2O2 levels, as assessed by the phenol red/horseradish peroxidase technique (P < 0.01 to 0.001). A 40% reduction in hydroxyl radical (.OH) levels was also observed (salicylate trap method), thereby substantiating decreased oxidant stress in cytoresistant PTS. Catalase, glutathione peroxidase, and free iron levels were comparable in control and cytoresistant PTS, suggesting that decreased H2O2 production (such as by mitochondria) was the cause of the decreased oxidant stress. To test this latter hypothesis, H2O2 expression by control and cytoresistant PTS was assessed in the presence of respiratory chain inhibitors. Although site 1 and site 3 inhibition markedly suppressed H2O2 production in control PTS, they had no impact on H2O2 production in cytoresistant PTS, implying that production at these sites was already maximally suppressed. Correlates of the decreased mitochondrial H2O2 production were improvements in cell energetics (increased ATP/ADP ratios with Na ionophore treatment) and approximately 40 to 90% increases in PTS/renal cortical glutathione content. We conclude that: (1) proximal tubule H2O2/.OH expression can be downregulated during the maintenance phase of ARF; (2) this seemingly reflects a decrease in mitochondrial ROM generation; and (3) the associated improvements in glutathione content and/or cellular energetics could conceivably contribute to a post-injury cytoresistant state.

Animals↗
PubMed1997

Childhood poisoning involving transdermal nicotine patches.

OBJECTIVE: To describe the circumstances, medical complications, and outcomes of children exposed to a transdermal nicotine patch (TNP). DESIGN: Prospective case series; postmarketing surveillance study over a 24-month period. SETTING: Thirty-four United States poison centers. Patients. Children 0 to 15 years old exposed to a TNP. INTERVENTIONS: None. OUTCOME MEASURES: Exposure circumstances, symptoms and signs of toxicity, complications, disposition, and hospital length of stay. RESULTS: Reports were received concerning 36 exposures to TNP in children younger than 16 years old (mean: 3 years old). Eighteen of these TNP exposures were dermal; 18 additional children had bitten, chewed, or swallowed part of a patch. All four commercial brands of TNP were represented; no brand was associated with more symptoms or an increased severity of illness. Fourteen children (39%) developed symptoms, including gastrointestinal distress (nausea, vomiting, diarrhea, abdominal pain), weakness, dizziness, or localized rashes. Occurrence of symptoms after a dermal exposure to a TNP was associated with an estimated nicotine dose >/=.10 mg (>/=.01 mg/kg body weight). Ten children were seen in the emergency department; two were admitted overnight. All recovered fully. CONCLUSIONS: In this series, unintentional exposures to TNPs among young children usually involved used patches, were transient (<20 minutes duration), and required only skin decontamination and supportive care. Continued monitoring of inadvertent childhood exposures to TNPs is recommended to confirm these observations.

Abdominal Pain↗
PubMed1996

Phospholipase A2: a potentially important determinant of adenosine triphosphate levels during hypoxic-reoxygenation tubular injury.

During the course of O2 deprivation-induced proximal tubular injury, profound alterations in ATP homeostasis exist. This study sought to characterize direct cellular determinants of these abnormalities further. Mouse proximal tubular segments (PTS) were isolated and their adenine nucleotide profiles were determined during hypoxic-reoxygenation injury. The extent of oxidant stress, Ca2+ overload, cytoskeletal disruption, and phospholipase activity were experimentally manipulated by H2O2, Ca2+ ionophore, cytochalasin D, or PLA2 addition, respectively. Hypoxia induced the expected deterioration in adenylate profiles, and a persistent defect in ATP homeostasis was observed during reoxygenation (decreased ATP/ADP ratios and absolute ATP content). H2O2, Ca2+ ionophore, and cytochalasin D had no significant impact on adenylate profiles. However, doses of PLA2 that had no overt effect on normal tubules caused 50 to 75% reductions in both hypoxic and reoxygenation ATP/ADP ratios and absolute ATP content. This effect was completely reproduced by the addition of arachidonic acid (C20:4). No other test fatty acid (C16:0, C18:1, C18:3) reproduced this result. Despite its profound negative impact on hypoxic/reoxygenation ATP concentrations, PLA2 and C20:4 each decreased lethal cell injury (lactate dehydrogenase release), as previously reported. The reductions in ATP and lethal cell injury were not mechanistically linked, because C18:1 and C18:3 reproduced the protective action of C20:4 without altering adenine nucleotide profiles. Ouabain, mannitol, or plasma membrane fatty acid "scavenger" therapy (albumin) did not improve the posthypoxic/PLA2-induced depressions in ATP. The addition of C20:4 caused a modest decrease in posthypoxic tubule oxygen consumption, compared to controls. It was concluded that: (1) PLA2 can be a major determinant of ATP concentrations during both hypoxic and reoxygenation tubular injury; (2) this action is mediated via C20:4 release; (3) a primary defect in mitochondrial ATP production, rather than increased ATP consumption, is likely to be responsible for this action.

Adenosine Diphosphate↗
PubMed1996

Self-poisoning among adults using multiple transdermal nicotine patches.

OBJECTIVE: To investigate the characteristics and outcomes of poisoning cases involving the dermal application of multiple transdermal nicotine patches. DESIGN: Case series; prospective postmarketing surveillance over a 24 month period. SETTING: Telephone reports from 34 participating US poison centers. PATIENTS: Human poisonings involving more than one transdermal nicotine patch applied simultaneously. RESULTS: Nine cases of dermal exposure to 2-20 transdermal nicotine patches were reported. Cases resulted from either intentional misuse or suicide attempts and included concomitant exposure to other drugs in 7 of 9 cases. Mean age was 45 years; seven of nine patients were female. All suffered medical complications including seizures (3 subjects), other central nervous system changes (8 subjects), cardiovascular effects (6 subjects), and respiratory failure (4 subjects). Eight patients were hospitalized; all recovered. Plasma nicotine/cotinine concentrations did not correlate with the severity of illness. CONCLUSIONS: This case series demonstrated that simultaneous application of several transdermal nicotine patches can be implicated in adult suicide attempts. While signs of toxicity included gastrointestinal complaints, changes in level of consciousness, seizures and parasympathetic effects typical of nicotine poisoning, the frequent presence of co-intoxicants complicated the clinical course. As the accessibility of transdermal nicotine patches increases, increasing misuse of these products by suicidal adults is likely.

Administration, Cutaneous↗
PubMed1995

The myth of "captive subjects" in hospital-based nursing research.

The completion of data collection in an environment rich with potential subjects can be very challenging. The experience is somewhat like being thirsty and being surrounded by salt water. The strategies presented here represent the application of a wide range of strategies from the literature, peer consultation, and research team problem solving. These specific strategies can be adapted to a wide range of types of clinical research and clinical settings. The entire research team found solving each problem and obstacle as it arose to be challenging and rewarding. Sharing the work load and problem solving among the research team was both productive and enjoyable.

Breast Self-Examination↗
PubMed1988

Haemophilus influenzae type b anticapsular antibody responses to PRP-pertussis and PRP-D vaccines in Alaska native infants.

To evaluate immune responses in Alaska Native infants at high risk for invasive Haemophilus influenzae type b (Hib) disease, we studied PRP-pertussis and PRP-D conjugate vaccines in this population relative to responses in white infants in California and New York. Infants were immunized at two, four, and six months of age (both vaccines). In the PRP-pertussis trial, there were no significant differences in antibody levels at any age between Alaska Native infants and infants from California. Only 50% of the infants had a twofold or greater antibody rise after three doses. In the PRP-D trial, antibody levels at two months of age (presumably maternally acquired) were significantly higher for Alaska Native infants compared with infants from New York (P = .002). There were no significant differences in antibody levels after any of the three doses. Among Alaska Native infants there was no significant difference in antibody response based upon degree of ethnic purity.

Alaska↗