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Biomedical subjects

J E Chappell

Publications and source records attributed to J E Chappell.

17 recordsLinked to original sources

Gunshot wounds to the hand: management and economic impact.

Low-velocity firearms represent the majority of civilian gunshot wounds to the hand, yet much of the literature is based on high-velocity injuries. The authors reviewed their treatment regimen for civilian gunshot wounds to the hand and offer a treatment algorithm that emphasizes early debridement and fracture stabilization. They also address the economic impact on society. The authors reviewed 121 fractures in 90 patients with gunshot wounds to the hand treated at an urban trauma center during the last 5 years. All patients were managed with irrigation and debridement, elevation, intravenous antibiotics, and early fracture stabilization. Sixty fractures were managed with rigid internal or external fixation: Kirshner wires (26%), miniplates (16%), and external fixation (8%). Fifty-six fractures were managed with closed reduction. Five fractures required amputation. There was one subsequent infection and two late amputations. The cost of hospitalization and operative care was more than $1.7 million. For gunshot wounds to the hand the authors advocate immediate irrigation and debridement, intravenous antibiotics, early fracture stabilization, and a low threshold for internal fixation. This regimen is supported by their low infection and complication rates.

Algorithms↗

Effect of hemodilution with diaspirin cross-linked hemoglobin on intracranial pressure, cerebral perfusion pressure, and fluid requirements after head injury and shock.

Hemodilution has been shown to increase cerebral blood flow (CBF) and reduce lesion volume in models of occlusive cerebral ischemia, but it has not been evaluated in the setting of head trauma and shock in which ischemia is thought to play a role in the evolution of secondary injury. In a porcine model of brain injury and shock the authors compared hemodilution with diaspirin cross-linked hemoglobin (DCLHb) to a standard resuscitation regimen using Ringer's lactate solution and shed blood. After creation of a cryogenic brain injury followed by hemorrhage, the animals received a bolus of either 4 ml/kg of Ringer's lactate solution (Group 1, six animals) or DCLHb (Group 2, six animals), followed by infusion of Ringer's lactate solution to restore mean arterial pressure (MAP) to baseline. Group 1 received shed blood 1 hour after hemorrhage (R1) in the form of packed red blood cells. Group 2 received shed blood only for an Hb count of less than 5 g/dl. The animals were monitored for 24 hours. At R1, Group 2 had a significantly greater cerebral perfusion pressure ([CPP] 88 +/- 5.7 vs. 68 +/- 2.4 mm Hg, p < 0.05). By 3 hours after hemorrhage (R3) Group 2 had a significantly lower Hb concentration (8.5 +/- 0.4 vs. 12.1 +/- 0.3 g/dl, p < 0.05) and a significantly lower intracranial pressure ([ICP] 9 +/- 0.8 vs. 14 +/- 0.6 mm Hg, p < 0.05). The total 24-hour fluid requirement was significantly less in Group 2 (10,654 +/- 505 ml vs. 15,542 +/- 1094 ml, p < 0.05) There was no difference between the groups regarding levels of regional CBF in the injured hemisphere. Cerebral O2 delivery was not significantly different between groups at any time. Lesion volume as determined at postmortem examination was not significantly different between the groups. The increased MAP and CPP and lower ICP observed in the Group 2 animals indicate that hemodilution with DCLHb may be beneficial in the treatment of head injury and shock.

Animals↗

Diaspirin cross-linked hemoglobin resuscitation improves cerebral perfusion after head injury and shock.

BACKGROUND: Shock associated with traumatic brain injury (TBI) doubles the mortality of TBI alone by inducing a secondary ischemic injury. Rapid correction of cerebral perfusion pressure (CPP) is thought to be essential to improving outcome. Diaspirin cross-linked hemoglobin (DCLHb) has been shown to improve cerebral blood flow, increase mean arterial pressure (MAP), and reduce lesion size in models of occlusive cerebral ischemia but has not been evaluated in a model of TBI combined with hemorrhagic shock. METHODS: We studied the effects of DCLHb resuscitation in a porcine model of cryogenic TBI and hemorrhagic shock (MAP = 50 mmHg). After combined insults, animals were randomized to receive a bolus of 4 mliters/kg of either lactated Ringer's solution (n = 5) or DCLHb (n = 6). Lactated Ringer's solution was then infused in both groups to maintain MAP at baseline. Shed blood was returned 1 hour after the initiation of resuscitation (R1). Animals were studied for 24 hours. RESULTS: DCLHb infusion resulted in a significantly greater MAP at R1 and R24 (95 +/- 4 vs. 82 +/- 2 and 99 +/- 3 vs. 85 +/- 3 mm Hg, respectively) and a significantly greater CPP at R1 and R24 (83 +/- 10 vs. 68 +/- 5 and 89 +/- 6 vs. 71 +/- 11 mm Hg, respectively). Intracranial pressure was lower in the DCLHb group, but this difference was not significant. There was no significant difference between the groups in cerebral oxygen delivery. DCLHb animals required less fluid to maintain MAP (12,094 +/- 552 vs. 15,542 +/- 1094 mliters, p < 0.05). CONCLUSION: These data suggest that DCLHb is beneficial in the early resuscitation of head injury and shock and that further investigation is warranted. Key Words: Diaspirin cross-linked hemoglobin, Head injury, Shock, Cerebral perfusion pressure.

Animals↗

Soluble and particulate phenylethanolamine N-methyltransferase in hypothalamus of diabetic rats.

Experimental diabetes increases total phenylethanolamine N-methyltransferase (PNMT) activity in the medulla-pons but not in the hypothalamus. In this study diabetes was induced with streptozotocin (65 mg/kg) in male Sprague-Dawley rats. Twenty-eight days after treatment there were no differences in soluble PNMT activity in the hypothalamus of diabetics and controls, but PNMT activity in a membrane-associated (particulate) fraction of hypothalamus was evaluated approximately twofold in tissues of diabetic animals compared with controls. A specific PNMT inhibitor, incubated with tissue extracts of control rats, abolished greater than 90% of particulate PNMT activity in the hypothalamus but reduced soluble PNMT activity in the hypothalamus by only 47%. These findings indicate that membrane-associated PNMT activity in rat hypothalamus differs from soluble hypothalamic PNMT in the in vitro response to an inhibitor and the in vivo response to diabetes and suggest the importance of separating subcellular hypothalamic fractions prior to assay of PNMT.

Animals↗

Fatty acid balance studies in premature infants fed human milk or formula: effect of calcium supplementation.

During the first 4 neonatal weeks, serial total fatty acid and individual fatty acid balance studies were completed in 35 healthy premature infants with appropriate weight for gestational age. Infants weighed less than 1500 gm at birth, were descriptively similar, and were receiving similar volumes of either preterm mothers' milk (PTM) or formula (S-M-A 20). Total fatty acid and major fatty acid contents of the two feeding regimens were similar. Total fecal output and total fatty acid excretion were higher, whereas subsequent total fat absorption and coefficient of absorption were significantly lower, in the group fed S-M-A 20 (P less than 0.001). Administration of oral calcium supplements fed as calcium lactate (1.5 to 2.0 mmol/kg/day) decreased total fatty acid absorption in both the PTM (P less than 0.01) and S-M-A 20 (P less than 0.001) groups. Furthermore, the effect of feeding (P less than 0.0001) and oral calcium (P less than 0.001) independently influenced coefficients of absorption for major fatty acids fed (C12:0, C14:0, C16:0, C18:0, and C18:1). Although the main indices for growth were similar in both feeding groups, infants with inefficient rates of total fatty acid absorption attained slower rates of weight gain and increased skinfold thickness. We conclude that oral calcium supplements significantly alter the efficiency of lipid absorption in enterally fed preterm infants.

Analysis of Variance↗

Prolactin binding protein in human milk.

Milk samples at day 16 of lactation were from six mothers delivering infants at 28-30 weeks of gestation and six mothers delivering normal full term infants. These early morning samples were used in a prolactin binding assay to determine whether 125I-labelled human prolactin was selectively bound to a soluble protein fraction. After Sephadex G-100 column chromatography, 7 samples contained a protein fraction which bound human prolactin. Binding was not apparent in the remaining 5 samples. Prior binding of maternal prolactin, total binding capacity and differing free prolactin levels may be significant factors responsible for these observations.

Carrier Proteins↗

Free fatty acid content of human milk: physiologic significance and artifactual determinants.

Analysis of human milk was conducted to determine if free fatty acids occur naturally or as a consequence of artifactual lipolysis after milk expression. Five mothers provided triplicate early morning milk samples on day 43 of lactation. Following extraction, lipid classes were separated by preparative thin layer chromatography and quantified by capillary gas liquid chromatography. Fresh milk samples collected with 20 volumes chloroform-methanol (1:1, v/v) were analogous in total free fatty acid level and profile of fatty acids to a duplicate sample collected with 0.4M EDTA and immediately frozen at -10 C. Low milk levels of free fatty acids appear to exist naturally. During days 4-37 of lactation, four serial milk samples from 15 mothers were collected and frozen with 0.4M EDTA. The concentration of free fatty acids in colostrum (0.03-0.5%, w/w) was lower than for subsequent days (0.3-2.5%, w/w). Additional samples were collected with and without a lipase inhibitor (0.4M EDTA) and subjected to routine collection and storage procedures. Significantly different fatty acid profile and higher levels of free fatty acids in milk collected without a lipase inhibitor added indicate that domestic freezing and/or thawing ruptures the fat globule membrane, allowing sn-1-stereospecific serum stimulated lipoprotein lipase contact with its triglyceride substrate. Standard procedures for collection of human milk for gavage fed infants appears to stimulate artifactual lipolysis of milk triglyceride and subsequent release of free fatty acids. The proposed relationship between dietary free fatty acids and prolonged, unconjugated hyperbilirubinemia in the newborn is discussed with regard to the significance of preintestinal lipolysis.

Fatty Acids, Nonesterified↗

Vitamin A and E content of human milk at early stages of lactation.

The influence of gestational age and lactational stage on carotene, retinol ester, alpha-tocopherol and gamma-tocopherol content of early human milk was studied. These nutrients were analyzed simultaneously using normal phase high-performance liquid chromatography. Serial samples of colostrum and early milk representative of complete early morning expressions were obtained during the first 6 weeks post-partum from mothers giving birth prematurely (PT) and at term (FT). Colostrum carotene content declined significantly during the first week of lactation. There was no apparent gestational age effect on milk carotene levels. The longitudinal pattern of change observed for milk retinol ester and alpha-tocopherol content was however, significantly different between PT and FT milk. Retinol ester levels were similar on days 1-2 postpartum reaching a maximal level on days 3-4 postpartum in FT milk. For PT milk the maximum retinol ester concentration occurred on days 6-7 postpartum. Retinol ester content decreased throughout lactation. The rate of decline was more marked for FT milk. The concentration of alpha-tocopherol in colostrum was higher in FT milk. On all subsequent days examined the level of alpha-tocopherol was greater in PT milk. For both FT and PT milk the alpha-tocopherol concentration was higher during the first week of lactation when compared with following weeks. gamma-Tocopherol levels were not influenced by gestational age or lactational stage. Levels of milk vitamin A and E did not appear to correlate with maternal intake. Colostrum levels of vitamin A and E may imply active sequestration by the mammary gland in compensation for limited placental transport. Early milk content of vitamin A and E appears to parallel mammary gland lipid synthesis.

Carotenoids↗

Trans fatty acids in human milk lipids: influence of maternal diet and weight loss.

Geometric and positional isomers of octadecanoic acid in milk expressed during the first 9 weeks of lactation were determined for mothers delivering prematurely (PT) and at term (FT). Total C18:1 concentration was lower in PT than FT milk. C18:1 trans (elaidic acid) content was higher in PT and FT colostrum compared with subsequent milk samples. No relationship was observed between C18:1 trans level in milk and oleic acid, linoleic acid, total fatty acid levels, or volume of milk expressed. While gestational age and lactational stage appeared to affect the trans fatty acid pattern, the overriding influence was rate of maternal postpartum weight loss. Effect of weight loss on milk trans fatty acid levels was independent of maternal diet. Trans fatty acid content of milk as a function of recent maternal fat intake was also demonstrated. This study indicates that infants receiving human milk ingest levels of trans fatty acids reflecting short and long term maternal diet.

Body Weight↗

Prostanoid content of human milk: relationships to milk fatty acid content.

Analysis of human milk was conducted to determine if transitions in milk lipid composition and thus the changes in fatty acid synthesis that occur during lactogenesis are related to levels of specific prostanoids present in milk lactated. Serial samples representative of a complete expression and reflecting varying concentrations of milk fatty acids were collected over the first 37 days of lactation. Milk from mothers delivering infants at term and mothers delivering premature infants of 28-33 weeks gestational age was compared to examine potential relationships between prostanoid concentration and gestational age effects on milk lipid content. Milk levels of prostaglandin E, prostaglandin F and the metabolite of prostacyclin--6-keto-prostaglandin F1 alpha were determined by radioimmunoassays. Transitions in fatty acid content for all milk lipid classes were determined by quantitative analysis of fatty acids by glass capillary gas liquid chromatography. During lactation the levels of prostaglandin E correlated with milk content of 6-keto prostaglandin F1 alpha. For term mothers, milk content of prostaglandin E, 6-keto prostaglandin F1 alpha, total fatty acids and medium chain fatty acids increased from early lactation when compared with subsequent days sampled. Levels of these milk constituents observed for early milk of preterm mothers were significantly different when compared with term mothers and in addition did not follow the same longitudinal pattern during subsequent days of lactation. Physiologically significant levels of prostaglandins in milk may reflect the balance between hormonal and subcellular controls over lactogenesis. It is also conceivable that the presence of these prostanoids in milk may influence gastrointestinal physiology and nutrient absorption in the neonate.

6-Ketoprostaglandin F1 alpha↗

Fatty acid utilization in perinatal de novo synthesis of tissues.

The fatty acid content of fetal tissues was utilized to estimate essential fatty acid accretion during intrauterine growth. These rates of essential fatty acid accretion were used to predict that 400 mg/kg of body weight for omega-6 fatty acids and 50 mg/kg of body weight for omega-3 fatty acids per day would be used for intrauterine de novo synthesis of tissues. For the high risk low birth weight infant of approx. 1300 g birthweight it can be calculated that extrauterine de novo tissue synthesis would utilize about 280 mg/kg of body weight for omega-6 fatty acids and about 35 mg/kg of body weight for omega-3 fatty acids based on projected growth rates that are similar in composition to intrauterine growth and amount to 17 g of gain per day. From fatty acid analysis of brown and white adipose tissue it was estimated that some 70 and 78% of these net whole body accretion rates for essential fatty acids represent omega-6 and omega-3 fatty acid accretion in the adipose organs. Fatty acid analysis of human milk at day 16 of lactation was utilized to estimate the low birth weight infants' daily intake of major essential and other fatty acids. For intake levels of 120 kcal/kg it was concluded that the essential fatty acid content of mothers' own milk provides 6650 +/- 345 mg of total fatty acids, 850 +/- 160 mg of omega-6 fatty acids and 140 +/- 17 mg of omega-3 fatty acids.

Adipose Tissue↗

Fatty acid accretion in the development of human spinal cord.

Lumbar and cervical segments of fetal and infant spinal cord were examined to determine the deposition rate of individual fatty acids in the spinal cord during the last trimester of fetal development and first 16 weeks of life. Fatty acid accretion rates were determined by regression analysis of spinal cord fatty acids at varying developmental ages. During the last trimester of fetal growth, accretion of major tissue fatty acids occurred earlier in cervical segments of spinal cord and at a greater rate than observed in lumbar regions. Postnatal accretion of fatty acids in cervical regions of spinal cord was minimal on a per gram of tissue basis with the exception of moderate increases in total omega-9 and saturated fatty acids, reflecting myelination. Significant postnatal accretion of fatty acids in lumbar regions of the spinal cord occurred some 4 weeks postnatally at rates significantly in excess of in utero rates. These developmental changes in fatty acid accretion are quantitatively relevant to estimates of fatty acid incorporation into spinal cord and parallel known processes of myelination and increasing neuro-motor activity in the developing infant.

Fatty Acids↗

Fatty acid accretion in fetal and neonatal liver: implications for fatty acid requirements.

The fatty acid content of liver was determined during the last trimester of infant growth and first 4 months of life in order to estimate fatty acid levels of developing liver and to assess minimal fatty acid requirements for tissue synthesis. Accretion rates were computed by regression analysis on fatty acid determinants of total liver lipid extracts from infants of varying developmental ages. During the last trimester of liver growth, accretion of most fatty acids paralleled increases in liver weight with the exception of C18:3, omega-3. This fatty acid remained at consistently low levels during the last trimester and represented less than 10% of total omega-3 fatty acids present in liver, even though significant accretion of longer chain omega-3 homologues occurred during the final trimester. For the term infants studied, significant increase in liver weight did not occur during the early weeks of life. However, liver levels of major fatty acids declined during the first five weeks of life apparently reflecting mobilization of saturated, omega-9 and omega-3 fatty acids from liver. During the first four months of life C18:2, omega-6 and total omega-6 fatty acid content of liver increased about 3.5- and 2-fold, respectively. After the initial 5 week lag net accretion of other fatty acid components also occurred in the developing liver. These developmental changes in fatty acid components of liver are quantitatively relevant to estimating the magnitude of the potential essential fatty acid reserve that may be present in liver of the developing human neonate.

Fatty Acids↗

Intrauterine fatty acid accretion rates in human brain: implications for fatty acid requirements.

Fatty acid components of infant brain were determined to assess fatty acid requirements for synthesis of structural lipids in brain tissue during the last trimester of development in the fetus. Quantitative fatty acid analysis of cerebellum, frontal and occipital brain lobes indicated rapid accretion of chain elongation and desaturation products during the last trimester of brain growth. Frontal and occipital brain lobes were similar in fatty acid content. Fatty acid accretion rates were determined by regression analysis of tissue fat components at varying gestational ages. Tissue accretion of saturated and omega-9 fatty acids, as well as total fatty acid content, paralleled increases in whole brain weight. Levels of linoleic (C18:2, omega-6) and linolenic (C18:3, omega-3) acids were consistently low in brain during the last trimester of development, while marked substantial accretion of long chain desaturation products, arachidonic (C20:4, omega-6) and docosahexaenoic (C22:6, omega-3) acids occurred. Accretion of individual fatty acids of cerebellum also reflected changes in tissue total fatty acid content, with exception of the levels of C18:3, omega-3 and its chain elongation products present in cerebellum during the last trimester. These developmental changes and estimates of fatty acid incorporation into whole brain and cerebellum are quantitatively relevant to estimation of fatty acid requirements of the low birth weight neonate.

Brain↗

Extrauterine fatty acid accretion in infant brain: implications for fatty acid requirements.

Total fatty acid content of infant brain was determined to assess minimal fatty acid requirements for synthesis of structural lipids in brain tissue during the first 13 weeks of life. Fatty acid accretion rates were determined by regression analysis of tissue fat components at varying postnatal ages. Quantitative fatty acid analysis indicated that postnatal accretion of long-chain polyenoic fatty acids in cerebellum, frontal and occipital brain lobes initially appeared to lag behind the rate of increase in brain weight and brain fat content. After a 4-week period total long-chain fatty acids increased at a rate similar to the increase in brain weight. Accretion of individual fatty acids in cerebellum also reflected changes in tissue total fatty acid content. These developmental changes in fatty acid components of whole brain and cerebellum are quantitatively relevant to estimation of the minimal extrauterine fatty acid requirements of the human neonate.

Brain↗