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Biomedical subjects

D Honeycutt

Publications and source records attributed to D Honeycutt.

8 recordsLinked to original sources

Synteny and regional marker order assignment of 26 type I and microsatellite markers to the horse X- and Y-chromosomes.

The hypothesis that the conservation of sex-chromosome-linked genes among placental mammals could be extended to the horse genome was tested using the UCDavis horse-mouse somatic cell hybrid (SCH) panel. By exploiting the fluorescence in-situ hybridization (FISH) technique to localize an anchor locus, X-inactivation-specific transcript (XIST) on the horse X chromosome, together with the fragmentation and translocation of the X- and Y-chromosome fragments in a somatic cell hybrid panel, we regionally assigned 13 type I and 13 type II (microsatellite) markers to the horse X- and Y-chromosomes. The synteny groups that correspond to horse X- and Y-chromosomes were identified by synteny mapping of sex-specific loci zinc finger protein X-linked (ZFX), zinc finger protein Y-linked (ZFY) and sex-determining region Y (SRY) on the SCH panel. A non-pseudoautosomal gene in the human steroid sulfatase (STS) was identified in both X- and Y-chromosome-containing clones. The regional order of the X-linked type I markers examined in this study, from Xp- to Xq-distal, was [STS-X, the voltage-gated chloride channel 4 (CLCN4)], [ZFX, delta-aminolevulinate synthase 2 (ALAS2)], XIST, coagulation factor IX (F9) and [biglycan (BGN), equine F18, glucose-6-phosphate dehydrogenase (G6PD)] (precise marker order could not be determined for genes within the same brackets). The order of the Y-linked type I markers was STS-Y, SRY and ZFY These orders are the same arrangements as reported for the human X- and Y-chromosomes, supporting the conservation of genomic organization between the human and the horse sex chromosomes. Regional ordering of X-linked type I and microsatellite markers provides the first integration of type I and type II markers in the horse X chromosome.

Animals↗

Pentafraction for superior resuscitation of the ovine thermal burn.

OBJECTIVE: To determine if a new hydroxyethyl starch, pentafraction, will cause better capillary retention of fluid in thermally burned and nonburned tissues when compared with some currently used volume expanders. DESIGN: Randomized, controlled, experimental study. SETTING: University research laboratory. SUBJECTS: Twenty-one healthy adult range ewes. INTERVENTIONS: Sheep, surgically prepared for chronic study, were randomly assigned to one of three colloid groups for the resuscitation of thermal injuries: a) ovine fresh-frozen plasma group; b) pentastarch group; and c) pentafraction group. Twenty-one sheep were subjected to a 40% total body surface, third-degree flame burn under anesthesia (1.5% to 2% halothane). When awakened, the sheep received 15 mL/kg of one of the above colloids, and then lactated Ringer's solution (2 mL/hr/kg). All animals survived and were killed at 48 hrs after burn injury. MEASUREMENTS AND MAIN RESULTS: We found that cardiac index decreased and systemic vascular resistance increased in the pentastarch and plasma groups. However, cardiac index increased in the pentafraction group, while systemic vascular resistance increased by only half as much as in the other two groups. Cardiac index in the plasma group decreased significantly for the first 8 hrs, and did not return to the baseline value for 48 hrs. Systemic vascular resistance increased significantly for the first 8 hrs in both the plasma and pentastarch groups. Prefemoral lymph flow was significantly more increased in the pentastarch group, while the lung lymph/plasma oncotic gradient was maintained only by the pentafraction group. CONCLUSIONS: Pentafraction is as good, or even superior, for volume resuscitation in the burn patients, when compared with pentastarch and plasma. This conclusion is made most evident by the attenuated changes in systemic vascular resistance and cardiac index. Pentafraction decreases the fluid flux and potential subsequent edema significantly in burned tissues and effectively maintains the pulmonary microvascular integrity.

Animals↗

Heterozygote ornithine transcarbamylase deficiency presenting as symptomatic hyperammonemia during initiation of valproate therapy.

Ornithine transcarbamylase is a mitochondrial urea cycle enzyme. Women with heterozygous ornithine transcarbamylase deficiency may have no symptoms or have episodic, symptomatic hyperammonemia, which can be fatal. We report a previously undiagnosed heterozygote ornithine transcarbamylase-deficient patient who had symptomatic hyperammonemia during initiation of valproate therapy. This is the second such patient reported. Symptomatic hyperammonemia during valproate therapy may indicate ornithine transcarbamylase deficiency. Since valproate inhibits ureagenesis and can be toxic to mitochondria, it should be used extremely cautiously, or not at all, in ornithine transcarbamylase-deficient patients.

Adult↗

Effect of exogenous growth hormone on whole-body and isolated-limb protein kinetics in burned patients.

The effect of growth hormone on protein kinetics was assessed in burned patients during the hyperdynamic phase using N15 lysine and balance data across the leg. Levels of resting energy expenditure and cardiac index were comparably elevated in all patients, but leg blood flow was greater in the patients receiving growth hormone. Growth hormone therapy (0.2 mg/kg per day) significantly stimulated protein synthesis in the whole body and in the studied leg. A hyperinsulinemic clamp, which raised the insulin concentration to more than 1435 pmol/L of blood, caused comparable stimulation of leg protein synthesis in patients not receiving growth hormone, but did not further increase protein synthesis in the growth hormone-treated patients. These results suggest that administration of exogenous growth hormone may limit the peripheral protein wasting in severely injured patients by a mechanism similar to that of insulin.

Adolescent↗

Effect of exogenous growth hormone on glucose utilization in burn patients.

The treatment of burn patients with recombinantly derived human growth hormone (rHGH) appears effective in counteracting protein catabolism. However, exogenous growth hormone is frequently associated with hyperglycemia, an aspect which may limit its usefulness. Therefore, to assess the affect of rHGH on glucose utilization, 13 severely burned patients (65% +/- 4 TBSA burn; mean +/- SEM) began receiving on admission either placebo or rHGH (0.2 mg/kg.d) in a double-blind randomized fashion. While hypermetabolic (percentage REE/predicted REE 1.41 +/- 0.11) fasting oxygen consumption and CO2 production were measured using indirect calorimetry prior to and then during a hyperinsulinemic euglycemic clamp. This experiment demonstrated that rHGH significantly reduced glucose uptake and inhibited glucose oxidation compared to the placebo patients. Since the decreases in glucose oxidation and uptake were proportional, glucose utilization (percentage glucose uptake oxidized) remained similar in both patient groups. Furthermore, the hyperinsulinemic clamp lowered the plasma amino acid concentrations in the control patients while rHGH-treated patients had no significant alterations. In conclusion, exogenous growth hormone therapy induces an insulin resistance in burn patients. Furthermore, since the glucose utilization did not change, it is likely that the mechanism of insulin resistance is due to a deficiency in glucose transport.

Amino Acids↗

Propranolol diminishes extremity blood flow in burned patients.

Beta adrenergic blockade diminishes the catecholamine-mediated elevations in heart rate and myocardial contractility that characterize postburn hypermetabolism. To examine how these alterations in cardiac performance affect peripheral perfusion, indirect calorimetry and leg blood flow were measured before and then after a 2-hour intravenous propranolol infusion. Five severely burned patients (55% + 7% total burn surface area), given propranolol at 8 micrograms/kg/minute, had a significant reduction in cardiac index and heart rate with an increased leg vascular resistance resulting in a decrease in extremity perfusion. Four healthy volunteers were given propranolol at 5 micrograms/kg/minute, resulting in a comparable decrease in heart rate, yet there was no change in leg vascular resistance or extremity perfusion. In both patient groups, propranolol decreased the plasma lactate concentration. This suggests that in hypermetabolic patients, beta adrenergic blockade reduces peripheral perfusion and that peripheral perfusion is not a principal determinate of plasma lactate levels. Rather adrenergic blockade appears to decrease lactate concentration as a consequence of the inhibition of lipolysis.

Adult↗

Cold stress response in patients with severe burns after beta-blockade.

Adrenergic receptor blockade has been shown to be of benefit in the treatment of adverse cardiovascular changes in patients with burns during the hypermetabolic phase. This article examines the stress response to cold exposure in adults and children with 33% to 95% total body surface area burns with and without beta-blockade. Resting energy expenditures were measured by indirect calorimetry; the test subjects were exposed to mean temperatures of 27.5 degrees C (room temperature) or 24.6 degrees C (cold). The mean resting energy expenditure at ambient room temperature in patients with burns without beta-blockade was 1411 +/- 70 kcal/m2/day (mean +/- SEM). This value was 142% of that predicted for normal control subjects without burns. When placed in a cold temperature, patients with burns significantly increased their resting energy expenditures by 160% of predicted values, whereas patients with similar burns and beta-blockade increased their resting energy expenditures by 156%. Adults with septic burns had a mean resting energy expenditure 198% of the predicted value. These patients did not significantly increase their resting energy expenditures when they were exposed to cold either with or without beta-blockade. Data suggest that patients with septic burns already have a maximal metabolic response and that cold stress does not further increase this response. Males, ages 17 to 54 years, were found to increase their resting energy expenditures by 11.4 kcal/m2/day for each percent total body surface area burn. We conclude that beta-blockade with propranolol in therapeutic doses may be used in patients with burns without adversely affecting the cold stress response.

Adrenergic beta-Antagonists↗