Risk of infection from needle reuse at a phlebotomy center.

OBJECTIVES: This study determined infection risk for HIV, hepatitis B virus (HBV), and hepatitis C virus (HCV) from needle reuse at a phlebotomy center that possibly exposed 3810 patients to infection. METHODS: We used a model for the risk of infection per blood draw, supplemented by subsequent testing results from 1699 patients. RESULTS: The highest risk of transmission was for HBV infection: 1.1 x 10(-6) in the best case and 1.2 x 10(-3) in the (unlikely) worst case. Subsequent testing yielded prevalence rates of 0.12%, 0.41%, and 0.88% for HIV, HBV, and HCV, respectively, lower than National Health and Nutrition Examination Survey III prevalence estimates. CONCLUSIONS: The infection risk was very low; few, if any, transmissions are likely to have occurred.

The cost-effectiveness of expanded HIV counselling and testing in primary care settings: a first look.

OBJECTIVE: To estimate the cost-effectiveness of approaches to expanded HIV counselling and testing. DESIGN: A cost-effectiveness analysis. SETTING: Primary care practices in the USA. PARTICIPANTS: New patient visits. INTERVENTIONS: Two approaches were examined: (i) requesting all patients to complete an HIV-risk screening instrument, with counselling as well as testing offered only to patients disclosing risk factors ('risk histories' option); and (ii) routine offering of voluntary testing to all patients, with consent obtained but no pre-test counselling ('routine testing'). MAIN OUTCOME MEASURES: The primary outcome was the cost per infection identified. We also examined: (i) the costs and numbers of infections averted if individuals change their risk behaviours; and (ii) the additional years of life and quality-adjusted life years (QALY) gained as a result of earlier HIV testing and treatment for infected individuals. RESULTS: Routine testing is the most cost-effective approach to identifying infected individuals at an incremental cost of US$4200 per infection identified. Although using risk histories is more costly and less effective than routine testing, it becomes similarly cost-effective using plausible ranges for sensitivity analyses. If at least 10% of HIV-positive individuals change their behavior, both routine testing and using risk histories would save money. If testing identifies infected individuals one year earlier than they otherwise would have been diagnosed, routine testing would cost US$22000 per QALY gained. CONCLUSION: Routine testing is the most cost-effective approach to identifying new HIV infections. However, using risk histories may be similarly cost-effective under various assumptions. Both routine testing and using risk histories are more cost-effective than current practices.

Use of preventive services by managed care enrollees: an updated perspective.

We examined whether enrollees in managed care plans received more preventive services than enrollees in non-managed care plans did, by conducting an updated literature synthesis of studies published between 1990 and 1998. We found that 37 percent of comparisons indicated that managed care enrollees were significantly more likely to obtain preventive services; 3 percent indicated that they were significantly less likely to do so; and 60 percent found no difference. Enrollees in group/staff-model health maintenance organizations (HMOs) were more likely to receive preventive services, but there was little evidence, outside of Medicaid managed care, that managed care plans are worse at providing preventive services. However, most of the evidence is equivocal: Provision of preventive services was neither better nor worse in managed versus non-managed care plans. Because of the blurred distinctions among types of health plans, more research is needed to identify which plan characteristics are most likely to encourage appropriate utilization.

Central and systemic kappa-opioid agonists exacerbate neurobehavioral response to brain injury in rats.

The endogenous opioid peptide dynorphin has been implicated in the pathophysiology of secondary tissue injury after central nervous system (CNS) trauma. The detrimental effects of dynorphin appear to be mediated through both opioid receptors (probably kappa-receptors) and nonopioid mechanisms. However, both kappa-opioid agonists and antagonists have been reported to improve outcome in models of CNS trauma. To attempt to clarify this controversy, we examined the effects of centrally or systemically administered kappa-opioid agonists on neurological recovery after experimental fluid-percussion brain injury in the rat. Agonists included dynorphin A-(1-17) [Dyn A-(1-17)], which has actions at both kappa 1- and kappa 2-sites, and the selective kappa 1-agonists U-50,488H and U-69,593. des-Tyr-dynorphin A-(2-17) [Dyn A-(2-17)], which is inactive at opioid receptors, was also used. Microinjection of Dyn A-(1-17), but not Dyn A-(2-17) or U-50,488H, into the lateral ventricle 15 min before brain injury significantly worsened motor deficits over a 2-wk period. However, systemic administration of high doses of the kappa-agonists U-50,488H and U-69,593 also significantly worsened neurological outcome. These results fail to demonstrate any protective actions of kappa 1-agonists in this model of experimental traumatic brain injury and suggest that the opioid-related pathophysiological actions of dynorphin may be mediated by kappa 2-opioid receptors.

Myoblasts transferred to the limbs of embryos are committed to specific fibre fates.

In the limb bud of the 5-day-old avian embryo, when primary muscle fibre formation is beginning and before specific muscles appear, differences in the expression of fast and slow myosin heavy chain genes can be detected among primary fibres of the premuscle masses. Myoblasts that form colonies of fibres of specific types can be isolated from these limb buds. To assess the role of myoblast commitment in specifying fibre types during embryonic development, we cloned myoblasts of specific types from embryonic and adult muscles, transfected them with a reporter gene, and transferred them into developing limb buds. After transfer, cloned myoblasts formed fibres in the limb with the same patterns of myosin heavy chain gene expression as the fibres they formed in cell culture. These results demonstrate that initial skeletal muscle fibre type diversity during avian limb development can originate, in part, from the commitment of distinct myoblast types to the formation of specific fibre types.

Beneficial effect of the nonselective opiate antagonist naloxone hydrochloride and the thyrotropin-releasing hormone (TRH) analog YM-14673 on long-term neurobehavioral outcome following experimental brain injury in the rat.

Neurobehavioral dysfunction following traumatic brain injury results, in part, from delayed biochemical changes initiated by the traumatic insult. Endogenous opioid peptides have been implicated as one type of neurochemical factor involved in the delayed pathological sequelae of central nervous system (CNS) injury, including brain trauma. Both opiate antagonists and thyrotropin-releasing hormone (TRH) and its analogs, which antagonize the physiologic effects of endogenous opioids, have been shown to improve cardiovascular, cerebrovascular, metabolic, and neurologic status following both traumatic and ischemic CNS injury. The present study evaluated the ability of the opiate antagonist naloxone hydrochloride to improve posttraumatic neurologic motor function following experimental fluid-percussion brain injury in the rat, and compared the therapeutic effectiveness of naloxone to the long-acting, centrally active TRH analog YM-14673. Thirty minutes following fluid-percussion brain injury of moderate severity, animals received an intravenous bolus of either naloxone (2.0 mg/kg with constant infusion of 1.7 mg/kg/h, n = 8), YM-14673 (1.0 mg/kg, n = 8), or saline (n = 8). Although naloxone caused a modest and nonsignificant increase in mean arterial blood pressure (MAP); YM-14673 significantly increased MAP within 5 min of administration (p < 0.05), an effect that continued up to 4 h postinjury. Postinjury administration of both naloxone and YM-14673 caused a significant improvement in neurobehavioral outcome which persisted up to 4 weeks postinjury. These results suggest that endogenous opioid peptides may be involved in the pathologic response to traumatic CNS injury and that pharmacotherapies directed at antagonizing opioid peptides may enhance neurobehavioral recovery after brain injury.

Almitrine mimics hypoxic vasoconstriction in isolated rat lungs.

The effect of almitrine bimesylate or the solvent malic acid on pulmonary vascular perfusion pressure was assessed in isolated rat lungs and on the contractile behavior of rat aorta and main pulmonary artery rings. Addition of almitrine to the lung perfusate during normoxia caused a dose-dependent, transient increase in pulmonary artery pressure with no change of the lung microvascular pressure. In systemic or pulmonary conduit arteries, the contractile tension was unaffected by almitrine. This indicates a precapillary locus of drug action. We also examined almitrine's effect on hypoxic pulmonary vasoconstriction (HPVC) in isolated lungs perfused with blood or with physiological salt solution (PSS). Low-dose almitrine potentiated hypoxic vasoconstriction in blood- but not in PSS-perfused lungs. However, a high dose of almitrine reduced hypoxic vasoconstriction dose dependently. When almitrine was added to the lung perfusate during hypoxia- or cyanide-induced (NaCN, 5 x 10(-5) M) pulmonary vasoconstriction, almitrine caused no further vasoconstriction. However, when the pulmonary perfusion pressure was elevated by KCl (20 mM) to the same magnitude as by alveolar hypoxia or cyanide, almitrine elicited a pressor response comparable to that observed during normoxia. Almitrine-induced pulmonary vasoconstriction resembled hypoxic vasoconstriction in that agents known to enhance hypoxic vasoconstriction (phorbol myristate acetate, vanadate, and 4-aminopyridine) enhanced, and known inhibitors of HPVC (the Ca2+ entry blocker nifedipine and hypothermia) inhibited, the almitrine-induced vasoconstriction. These findings lead us to speculate that almitrine also affects the oxygen-sensing limb of the hypoxic pressor response, not simply the effector (contractile apparatus of the vascular muscle cell).

Induction of heat shock protein 72-like immunoreactivity in the hippocampal formation following transient global ischemia.

Global ischemia was produced in adult rats by combining bilateral carotid artery occlusions with systemic hypotension for 5 or 10 minutes. Induction of the 72 kD heat shock protein (HSP72) in the hippocampus was examined immunocytochemically 18-24 hours later. Several patterns of HSP72-like immunoreactivity (HSP72LI) were observed. Five minutes of ischemia induced HSP72 in isolated columns of CA1a pyramidal neurons, or throughout CA1 pyramidal neurons and dentate hilar neurons. Ten minutes of ischemia induced marked HSP72LI in CA3 pyramidal neurons, moderate HSP72LI in dentate granule cells, and minimal HSP72LI in CA1 pyramidal, dentate hilar neurons, and hippocampal glia. Two hippocampi subjected to 10 minutes of ischemia exhibited marked HSP72LI in capillary endothelial cells but no neuronal or glial HSP72LI. It is proposed that (a) the induction of HSP72 in hippocampal sectors correlates with their vulnerability to global ischemia (CA1 greater than hilus greater than CA3 greater than dentate gyrus); (b) the induction of HSP72 in hippocampal cells correlates with their vulnerability to global ischemia in that mild ischemia induced HSP72 only in neurons, moderate ischemia in neurons and glia, and severe ischemia only in capillary endothelial cells; (c) the failure to induce HSP72 in hippocampal neurons in 2 cases of 10 min ischemia may be related to severe injury causing disruption of protein synthesis in these cells.

Beneficial effect of a platelet-activating factor antagonist, WEB 2086, on endotoxin-induced lung injury.

We tested the hypothesis that platelet-activating factor plays an important role in promoting endotoxin-induced lung injury by studying the effect of WEB 2086, a specific platelet-activating factor receptor antagonist, on lung vascular leak in endotoxin-treated rats. Intraperitoneal injection of Salmonella enteritidis endotoxin (2 mg/kg) increased the extravascular leakage of 125I-labeled albumin in perfused lungs at 30 min, 2 h, 6 h, and 48 h. Treatment with WEB 2086 (10 mg/kg ip) either 20 min before or 30 min after endotoxin injection significantly reduced lung injury at 2 h after endotoxin (leak index: control 0.74 +/- 0.03, endotoxin 1.79 +/- 0.14, endotoxin + pretreated WEB 1.23 +/- 0.09, endotoxin + posttreated WEB 1.21 +/- 0.13). In addition, posttreatment with WEB 2086 starting at 90 min after endotoxin injection markedly reduced lung leak at 6 h (control 0.74 +/- 0.03, endotoxin 1.29 +/- 0.14, endotoxin + WEB 0.71 +/- 0.06). The protective effect of WEB 2086 was not the result of cyclooxygenase blockade because the release of thromboxane B2 by endotoxin-treated lungs was not affected by WEB 2086. Furthermore, neither pretreatment nor posttreatment with WEB 2086 significantly reduced the endotoxin-induced increase in plasma glutathione disulfide, a marker of in vivo oxidative stress. In rats given a lethal dose of endotoxin (20 mg/kg ip), posttreatment with WEB 2086, starting at 2 h after endotoxin, significantly improved survival compared with vehicle treatment. We conclude that WEB 2086 ameliorated endotoxin-induced lung injury without reducing oxidative stress in the rat and suggest that blockade of platelet-activating factor receptor may be an important therapeutic consideration in sepsis-induced acute lung vascular injury.

Traumatic brain injury in the rat: characterization of a lateral fluid-percussion model.

Experimental fluid-percussion models produce brain injury by rapidly injecting saline into the closed cranium. In the present study we characterize the physiological, histopathological and neurological responses to mechanical brain injury in the rat produced by lateral fluid-percussion injury of graded severity. Physiological experiments (n = 105) demonstrated that all levels of injury produced an acute and transient systemic hypertension and bradycardia. Acute hypertension followed by significant hypotension occurred at higher magnitudes of injury. Post-injury suppression of electroencephalographic amplitude was related to the severity of injury. An increase in slow wave (delta/theta) electroencephalographic activity with a concomitant decrease in alpha/beta electroencephalographic activity were observed only at moderate and high magnitude of injury and were correlated with a worsened neurological outcome (r = 0.84; P less than 0.05) and increased mortality (r = 0.66; P less than 0.05). Alterations in brainstem auditory-evoked potentials were also observed only at the higher levels of injury. Histopathological analysis revealed that the extent of post-injury hemorrhage, cavitation and vascular disruption (as measured by extravasation of Evans Blue dye) was greater at the higher magnitudes of injury. Neurological scoring performed over a 4-week post-injury period demonstrated that lateral fluid-percussion brain injury produces a chronic neurological deficit that is directly related to the severity of injury. Survival was also significantly reduced at the higher magnitudes of injury. These data demonstrate that the lateral model of fluid-percussion injury in the rat reproduces many of the features of head injury observed in other models and species and may therefore be a useful experimental model for the study of the pathophysiology of traumatic brain injury.

Endogenous opioids, opiate receptors and traumatic brain injury.

The present study examined the role of endogenous opioid peptides in the pathophysiological sequelae of fluid percussion head injury in the cat. Two hours following injury, tissue concentrations of dynorphin-like immunoreactive material (ir-Dyn) were significantly elevated in specific brain regions where injury, as evidenced by histological examination, was most severe. Changes in ir-Dyn but not beta-endorphin-like immunoreactive material (ir-End) were significantly correlated with a fall in regional cerebral blood flow (CBF) that occurred 2 h following injury. Administration of the opiate antagonist WIN44,441-3 (with enhanced activity at kappa-receptors) stereospecifically increased cerebral blood flow to the injured regions.