Effects of whole blood leukoreduction on platelet function and hemostatic parameters.

AIMS/OBJECTIVES: The aim of this study was to evaluate the hemostatic consequences of whole blood leukoreduction (LR). BACKGROUND: Whole blood is being used for trauma resuscitation in the military, and an increasing number of civilian trauma centres across the nation. The benefits of LR, such as decreased infectious and transfusion-related complications, are well established, but the effects on hemostatic parameters remain a concern. METHODS: Twenty-four units of whole blood were assigned to one of the four groups: non-leukoreduced (NLR), leukoreduced at 1 h and a height of 33 in. (LR-1), leukoreduced at 4 h and a height of 33 in. (LR-4(33)), or leukoreduced at 4 h and a height of 28 in. (LR-4(28)). Viscoelastic parameters, platelet aggregation, cell counts, physiological parameters and thrombin potential were evaluated immediately before and after LR, and on days 1, 7, 14 and 21 following LR. RESULTS: The viscoelastic parameters and thrombin generation potential were unchanged between the groups. Platelet aggregation was reduced in the LR-1 group compared with NLR after 7 days. The LR-4(28) group also showed a trend of reduced platelet aggregation compared with NLR. Aggregation in LR-4(33) was similar to NLR throughout the storage time. Physiological and electrolyte changes over the whole blood storage period were not affected by LR. CONCLUSION: Our study shows that whole blood can be LR at 4 h after collection and a height of 33 in. while maintaining platelet count and without altering platelet function and hemostatic performance.

Validation of the EORTC QLQ-GINET21 questionnaire for assessing quality of life of patients with gastrointestinal neuroendocrine tumours.

BACKGROUND: Quality of life is an important end point in clinical trials, yet there are few quality of life questionnaires for neuroendocrine tumours. METHODS: This international multicentre validation study assesses the QLQ-GINET21 Quality of Life Questionnaire in 253 patients with gastrointestinal neuroendocrine tumours. All patients were requested to complete two quality of life questionnaires - the EORTC Core Quality of Life questionnaire (QLQ-C30) and the QLQ-GINET21 - at baseline, and at 3 and 6 months post-baseline; the psychometric properties of the questionnaire were then analysed. RESULTS: Analysis of QLQ-GINET21 scales confirmed appropriate aggregation of the items, except for treatment-related symptoms, where weight gain showed low correlation with other questions in the scale; weight gain was therefore analysed as a single item. Internal consistency of scales using Cronbach's α coefficient was >0.7 for all parts of the QLQ-GINET21 at 6 months. Intraclass correlation was >0.85 for all scales. Discriminant validity was confirmed, with values <0.70 for all scales compared with each other.Scores changed in accordance with alterations in performance status and in response to expected clinical changes after therapies. Mean scores were similar for pancreatic and other tumours. CONCLUSION: The QLQ-GINET21 is a valid and responsive tool for assessing quality of life in the gut, pancreas and liver neuroendocrine tumours.

Femoroacetabular impingement and labral tears in the adolescent hip: diagnosis and surgical advances.

PURPOSE OF REVIEW: To identify several of the major trends and advancements in the diagnosis and care of the adolescent hip that have recently been responsible for reshaping the standard of care for this group of patients. RECENT FINDINGS: Recent research has provided an expanded understanding of hip mechanics and anatomy, improved imaging techniques and, in particular, produced a better appreciation of factors that predispose the hip to degenerative changes. It has led to the development and expansion of several treatment options, including hip arthroscopy, safe surgical dislocation of the hip and periacetabular rotational osteotomy. SUMMARY: An appreciation of emerging trends in the diagnosis and treatment of adolescent hip problems is important, as prompt recognition of and intervention for certain hip disorders may prevent ongoing injury and avoid or ameliorate chronic conditions associated with the development of degenerative joint changes and osteoarthritis.

Adrenergic blockade reduces skeletal muscle glycolysis and Na(+), K(+)-ATPase activity during hemorrhage.

BACKGROUND: Recent evidence suggests that hyperlactatemia in shock may reflect accelerated aerobic glycolysis linked to activity of the Na(+), K(+)-ATPase rather than hypoxia. Epinephrine stimulates glycolysis in resting muscle largely by stimulating Na(+), K(+)-ATPase activity. This study evaluates the effects of hemorrhagic shock, with and without combined alpha- and beta-adrenergic receptor blockade, on lactate production, glycogenolysis, Na(+)-K(+) pump activity, and high-energy phosphates in rat skeletal muscle. METHODS: Male Sprague-Dawley rats in four treatment groups were studied: unhemorrhaged control not receiving blockers (CN), controls receiving blockers (CB), shocked animals not receiving blockers (SN), and shocked rats receiving blockers (SB). Shocked rats (SN and SB) were bled to a MAP of 40 mm Hg, maintained for 60 min. Blocker groups (CB and SB) received propranolol and phenoxybenzamine. Arterial blood was drawn for plasma lactate, epinephrine, norepinephrine, and gas analysis. Lactate, glycogen, glucose 6-phosphate, ATP, phosphocreatine, and intracellular Na(+) and K(+) were determined in extensor digitorum longus and soleus muscles. For comparison, muscles were exposed to epinephrine and/or ouabain in vitro. RESULTS: With the exception of P(a)CO(2), HCO(3), and base excess in the SN group, no significant differences in arterial blood gas parameters were noted. Adrenergic blockade significantly reduced plasma lactate concentration. In shocked rats, adrenergic blockade significantly reduced muscle lactate and glucose 6-phosphate accumulation. Intracellular Na(+):K(+) ratio was decreased in SN rats, implying increased Na(+)-K(+) pump activity. Adrenergic blockade raised the intracellular Na(+):K(+) ratio in shocked animals, implying decreased pump activity. Epinephrine exposure in vitro stimulated muscle lactate production, raised glucose 6-phosphate content, and significantly reduced soleus phosphocreatine stores. CONCLUSIONS: Neither hypoxia nor defective oxidative metabolism appeared responsible for increased glycolysis during hemorrhagic shock. Adrenergic blockade concurrently reduced plasma lactate, muscle levels of lactate and glucose 6-phosphate, and muscle Na(+)-K(+) pump activity during shock. Rapid skeletal muscle aerobic glycolysis in response to increased plasma epinephrine levels may be an important contributor to increased glycolysis in muscle and increased plasma lactate during hemorrhagic shock.

Regulation of EGF signaling by cell polarity in MDCK kidney epithelial cells.

Although the presence of a dominant basolateral sorting signal ensures that the majority of newly synthesized epidermal growth factor (EGF) receptors are delivered directly to the basolateral surface in polarized epithelial cells, a fraction of the receptors are also delivered to the apical surface. Similar to most basolateral membrane proteins, the EGF receptor has an additional signal(s) that selectively targets molecules lacking a dominant basolateral signal to the apical surface. Although the physiological relevance of signal hierarchy is not known, alternative targeting may occur in different epithelial cell types or during development. The goal of this study, therefore, was to determine the effect of membrane domain location on EGF receptor function, focusing on EGF-induced MAP kinase signaling and DNA synthesis. Whereas ligand responsiveness was restricted to the basolateral domain in Madin-Darby canine kidney (MDCK) cells expressing a normal complement of receptors, apical ligand was effective if apical receptor density was increased by overexpression of an exogenous wild-type human gene. Unexpectedly, cells expressing apically localized, cytoplasmically truncated receptors, which behave as dominant negative mutations in other cell types, were also responsive to apical EGF. The cytoplasmically truncated molecules appear to have at least two effects: first, to increase the local concentration of ligand at the apical cell surface; and second, to facilitate activation of the relatively few native EGF receptors normally located at the apical surface. These results indicate that cell context is a critical determinant of receptor mutant protein phenotype.

Stimulation of both aerobic glycolysis and Na(+)-K(+)-ATPase activity in skeletal muscle by epinephrine or amylin.

Epinephrine and amylin stimulate glycogenolysis, glycolysis, and Na(+)-K(+)-ATPase activity in skeletal muscle. However, it is not known whether these hormones stimulate glycolytic ATP production that is specifically coupled to ATP consumption by the Na(+)-K(+) pump. These studies correlated glycolysis with Na(+)-K(+)-ATPase activity in resting rat extensor digitorum longus and soleus muscles incubated at 30 degrees C in well-oxygenated medium. Lactate production rose three- to fourfold, and the intracellular Na(+)-to-K(+) ratio (Na(+)/K(+)) fell with increasing concentrations of epinephrine or amylin. In muscles exposed to epinephrine at high concentrations (5 x 10(-7) and 5 x 10(-6) M), ouabain significantly inhibited glycolysis by approximately 70% in either muscle and inhibited glycogenolysis by approximately 40 and approximately 75% in extensor digitorum longus and soleus, respectively. In the absence of ouabain, but not in its presence, statistically significant inverse correlations were observed between lactate production and intracellular Na(+)/K(+) for each hormone. Epinephrine had no significant effect on oxygen consumption or ATP content in either muscle. These results suggest for the first time that stimulation of glycolysis and glycogenolysis in resting skeletal muscle by epinephrine or amylin is closely linked to stimulation of active Na(+)-K(+) transport.

Adrenergic antagonists reduce lactic acidosis in response to hemorrhagic shock.

BACKGROUND: Hemorrhagic shock is associated with lactic acidosis and increased plasma catecholamines. Skeletal muscle increases lactate production under aerobic conditions in response to epinephrine, and this effect is blocked by ouabain, a specific inhibitor of the cell membrane Na+/K+ pump. In this study, we tested whether adrenergic antagonists can block lactate production during shock. METHODS: Male Sprague-Dawley rats (250-300 g) were pretreated with phenoxybenzamine (2 mg/kg, i.v.) and/or propranolol (0.5 mg/kg, i.p.) before hemorrhaging to a mean arterial pressure of 40 mm Hg for 1 hour. Skeletal muscle perfusion, plasma lactate, and catecholamines were measured at baseline, 55 minutes after shock, and 1 hour after resuscitation. In a separate study, extensor digitorum longus and soleus muscles were incubated in Krebs buffer (95:5, O2:CO2) with 10 mmol/L glucose. One of each muscle pair was incubated in the absence or presence of epinephrine and of one or both adrenergic blockers. Medium lactate concentration was then measured. RESULTS: The combination of alpha- and beta-blockers significantly reduced plasma lactate levels during hemorrhage. In contrast, beta-blockade alone was associated with a significant increase in plasma lactate and epinephrine. None of the blockers altered tissue perfusion. Epinephrine stimulation of muscle lactate production in vitro was completely blocked by propranolol. CONCLUSION: Epinephrine release in response to hypotension is a primary stimulus for muscle lactate production in this model of hemorrhagic shock. Hypoxia alone does not explain the increased lactate levels because tissue perfusion was not altered by the adrenergic antagonists. These observations challenge the rationale behind lactate clearance as an end point for resuscitation after hemorrhagic shock.

Increased skeletal muscle Na+, K+-ATPase activity as a cause of increased lactate production after hemorrhagic shock.

BACKGROUND: Lactate production after hemorrhagic shock may be produced by aerobic glycolysis, which has been linked to activity of the Na+/K+ pump in smooth muscle and other tissues. We tested whether increased muscle Na+/K+ pump activity after shock was linked to increased lactate production. METHODS: Male Sprague-Dawley rats were subjected to 1 or 2 hours of hemorrhagic shock and then resuscitated with shed blood and normal saline. After 24 hours, pairs of extensor digitorum longus muscles were preincubated for 30 minutes in Krebs buffer (95:5, O2:CO2) with 10 mmol/L glucose. One muscle served as a control and was incubated in buffer alone; the other was incubated in buffer with 1 mmol/L ouabain, an inhibitor of the Na+, K+-ATPase. Lactate, ADP, ATP, glycogen, and creatinine-phosphate were determined. RESULTS: Under these well-oxygenated conditions, muscles from shocked rats produced about twice as much lactate as sham muscles. Inhibition of the Na+/K+ pump by ouabain significantly reduced lactate production. CONCLUSIONS: Hypoxia is unlikely to account for increased muscle lactate production after resuscitated hemorrhagic shock, because high lactate production persists under well-oxygenated incubation conditions. Inhibition of shock-induced lactate production by ouabain indicates energetic coupling of glycolysis to the Na+, K+-ATPase.

Examination of the role of nitric oxide synthase and renal kallikrein as candidate genes for essential hypertension.

1. Nitric oxide synthase and renal kallikrein are both involved in blood pressure regulation. Genes for these enzymes may, therefore, be considered candidates for hypertension pathogenesis. 2. In the present study, genotypes for nitric oxide synthase and renal kallikrein microsatellite markers were determined in a cross-sectional association analysis of hypertensive patients and normotensive control subjects. 3. Results from this study did not indicate an association of either of the candidate gene polymorphisms with essential hypertension. Hence, findings for this study do not support a role for these genes in human hypertension.

Medical coverage for multievent sports competition: a comprehensive analysis of injuries in the 1994 Star of the North Summer Games.

OBJECTIVE: To determine the incidence and type of requests for medical assistance and the treatment required in 21 sports at the 1994 Star of the North Summer Games and to develop a plan, based on these findings, for efficient allocation of medical supplies and staff. DESIGN: We reviewed our experience with a large multisport amateur athletic event and analyzed the pattern of injuries for participants in the various sports. MATERIAL AND METHODS: Injury evaluation forms and medical supply kits were given to the health-care volunteers, who received preliminary instructions on classifications and definitions of injuries and on appropriate completion of the forms. When a medical contact occurred, an evaluation form was completed. The data from these forms were subsequently compiled and analyzed. RESULTS: Of 6,243 athletes who participated in the 1994 Star of the North Summer Games, 55 (0.88%) received medical attention (2 officials also required medical assistance). The sports with the greatest number of medical contacts were soccer and track and field--31 and 16 contacts for medical assistance, respectively. The lower extremities were the anatomic site most frequently involved in injury (62% of the medical contacts). The most common types of injury were contusions, strains, and sprains. CONCLUSION: Because few injuries were sustained and most were of minor severity, basic medical supplies (such as ice bags and compression wraps) were sufficient. For locations with a scarcity of medical personnel, a triage system can be established in which athletic trainers or registered nurses manage the initial assessments and refer cases, as needed, to physicians for specialized care. An effective communication system can also considerably reduce volunteer hours.

Pancreatic denervation does not influence glucose-induced insulin response.

BACKGROUND: Pancreatic transplantation results in denervation and loss of splanchnic venous drainage and inflicts numerous metabolic abnormalities. However, it is unclear whether denervation or loss of splanchnic venous drainage is responsible for the observed metabolic abnormalities. METHODS: To discern denervation's role in these abnormalities, four mongrel dogs underwent extrinsic pancreatic denervation with preservation of splanchnic venous drainage. These animals, as well as four innervated control subjects, underwent standardized enteral and intravenous glucose tolerance testing. In addition, hyperglycemic clamps that maintained stable serum glucose elevations at either 2.8 or 8.3 mmol/L above basal were also performed. RESULTS: Prestimulated glucose (90.4 +/- 2.7 vs 92.6 +/- 4.9 mg/dl) and insulin levels (6.8 +/- 1.7 vs 8.5 +/- 1.4 muU/ml) did not differ between innervated and denervated groups. Integrated incremental enteral glucose (5320 +/- 1900 vs 7790 +/- 2000 mg/dl) and insulin (2565 +/- 350 vs 2836 +/- 598 muU/ml) levels did not differ between groups. Integrated incremental intravenous glucose (3680 +/- 400 vs 3950 +/- 1000 mg/dl) and insulin (741 +/- 70 vs 1053 +/- 326 muU/ml) levels also did not differ. During glucose clamp studies, time-weighted 60 to 120-minute insulin levels (2.8 mmol/L, 30 +/- 5.0 vs 24 +/- 4.8 muU/ml; 8.3 mmol/L, 57 +/- 5.9 vs 50 +/- 9.8 muU/ml) did not differ between groups. In addition, glucose disposal, cyclic insulin release, and insulin sensitivity indexes were unchanged by denervation. CONCLUSIONS: Extrinsic pancreatic neural elements are not necessary for cyclic insulin release in response to enteral or parenteral glucose challenge or physiologic and pharmacologic hyperglycemia. These findings suggest that the previously described posttransplantation glucose and insulin abnormalities are not attributable to denervation.

Gender differences in infirmary use at a residential summer camp.

Studies of health behavior in adults show that women report more morbidity and greater health service utilization than do men, despite lower mortality rates. Explanations involve social and biological gender differences in adult life. Infirmary utilization at a residential summer camp where parental influence is minimized was studied to determine whether these gender differences occur in the pediatric age group. Three hundred ninety-eight campers, 8 to 18 years old were studied. Girls were observed to make greater use of the infirmary than boys (p less than .01) and were especially likely to present with minor trauma, both musculoskeletal (p less than .05) and skin (p less than .01). No correlation was found between age and frequency of visits. Obvious morbidity was similar for boys and girls, in that no gender difference was observed in those visiting for definite medical indications alone or in those admitted. However, a difference was evident in those visiting for minor and trivial problems, particularly in those making three or more visits for minor and trivial problems (p less than .01). Although obvious morbidity was no different in campers, girls used the infirmary more than boys in a manner similar to that reported for adult health behavior. This suggests that gender differences occur earlier than suspected and are not simply related to adult social roles.

Gamma camera radionuclide images: improved contrast with energy-weighted acquisition.

An energy-weighted acquisition (EWA) technique has been developed that utilizes all scintillation events, weighting their contributions depending on their energy, to formulate a radionuclide image. Photopeak events from primary radiation contribute positively; scatter events contribute negatively, providing for scatter subtraction and improved image contrast. EWA is employed with an on-line weighted-acquisition module (WAM) as the data are acquired, rather than as a postprocessing technique. EWA was compared with normal window imaging in patients and in phantoms. For gallium-67 and thallium-201, contrast improved by as much as 40%. A much smaller improvement in contrast was observed with technetium-99m due to its ideal monoenergetic emissions. Single photon emission computed tomographic studies also showed improved contrast and were without artifact. EWA has great promise, and with further development quantitative scatter correction may be possible.

Adult human endothelial cell compatibility with prosthetic graft material.

We have developed a system for the in vitro evaluation of the interaction of human adult endothelial cells (HAEC) with prosthetic vascular graft material. HAEC, isolated from adult human iliac veins, proliferated vigorously in culture for approximately 70 population doublings. The large number of HAECs produced permitted high-density seeding of prosthetic grafts. Samples of prosthetic material were immobilized on a plastic ring and were used either untreated or coated with extracellular matrix, fibronectin, or plasma. HAEC were seeded at high density and adherence was evaluated by light and electron microscopy after a 2-hr incubation. While essentially no HAEC adhered to untreated grafts, treatment of grafts with either extracellular matrix, plasma, or fibronectin resulted in dramatic adherence of HAEC. The highest density of HAEC adherence was observed on collagen-coated Dacron grafts, and was equal to the cell density observed in confluent monolayers of HAEC grown on gelatin-coated tissue culture plastic. This study demonstrates a method capable of determining HAEC-graft biocompatibility prior to the use of an in vivo system.