Multiple neurological abnormalities in mice deficient in the G protein Go.

The G protein Go is highly expressed in neurons and mediates effects of a group of rhodopsin-like receptors that includes the opioid, alpha2-adrenergic, M2 muscarinic, and somatostatin receptors. In vitro, Go is also activated by growth cone-associated protein of Mr 43,000 (GAP43) and the Alzheimer amyloid precursor protein, but it is not known whether this occurs in intact cells. To learn about the roles that Go may play in intact cells and whole body homeostasis, we disrupted the gene encoding the alpha subunits of Go in embryonic stem cells and derived Go-deficient mice.

Preschool hearing screening: evaluation of a parental questionnaire.

Objective: To evaluate the validity of a parental questionnaire used to screen preschool children for persistent hearing impairment.

Methodology: Six-hundred and eighty-five children aged 4-5 years from a Metropolitan area of Adelaide, Australia, were enrolled. Each parent completed a questionnaire aimed at detecting parental concerns about hearing impairment.

Comparison of lumbar and thoracic epidural narcotics for postoperative analgesia in patients undergoing abdominal aortic aneurysm repair.

Objective: To determine whether there is an advantage of thoracic over lumbar epidural narcotics for postoperative analgesia in patients undergoing abdominal aortic aneurysm repair.

Design: A prospective randomized study.

Setting: Subjects were inpatients at an academic medical center.

Alpha 2-adrenergic receptor subtypes in rat dorsal root and superior cervical ganglion neurons.

To determine which alpha 2-adrenergic receptor subtypes are present in primary afferent and sympathetic postganglionic neurons we have performed in situ hybridization and immunohistochemistry experiments on rat dorsal root and superior cervical ganglia. Reverse transcriptase polymerase chain reaction was used as a preliminary screen for the presence of mRNA encoding alpha 2-adrenergic subtypes in dorsal root and superior cervical ganglia; polymerase chain reaction primers amplified distinct regions of the rat alpha 2A-(RG20), alpha 2B-(RNG) and alpha 2C-(RG10) adrenergic receptor subtypes in mRNA extracted from lumbar dorsal root and superior cervical ganglia. To localize receptors to cell types in the ganglia, in situ hybridization was performed on cryosections of dorsal root and superior cervical ganglia with oligonucleotide probes designed to distinguish between mRNA encoding for alpha 2-adrenergic receptor subtypes.

Emergency surgery in hematologic patients.

Patients at risk for clinically significant bleeding and who require urgent or emergent surgical procedures are encountered. Usually local causes are responsible, but a generalized hematologic defect may be uncovered. Quickly and effectively distinguishing the cause may be critical to rapid treatment and survival.

Selective attenuation of mu-opioid receptor-mediated effects in rat sensory neurons by intrathecal administration of antisense oligodeoxynucleotides.

To test the hypothesis that the expression of specific proteins on peripheral terminals of primary afferents can be attenuated by intrathecal administration of antisense oligodeoxynucleotides (ODNs), we administered ODNs antisense to the mu-opioid receptor to male Sprague-Dawley rats via chronically implanted intrathecal cannulae. Antisense but not mismatch ODN treatment significantly decreased peripheral (D-Ala2, N-Me-Phe4, Gly5-ol)-enkephalin (DAMGO) inhibition of prostaglandin E2 (PGE2) hyperalgesia. Antisense treatment affected neither the magnitude of PGE2 hyperalgesia nor the antinociception produced by a peripherally administered adenosine A1-agonist.

DAMGO inhibits prostaglandin E2-induced potentiation of a TTX-resistant Na+ current in rat sensory neurons in vitro.

We have tested the hypothesis that the mu-opioid agonist, [D-Ala2,N-Me-Phe4,Gly5-ol]enkephalin (DAMGO), inhibits prostaglandin E2 (PGE2)-induced modulation of a tetrodotoxin-resistant voltage-gated Na+ current (TTX-R INa) in putative nociceptors in vitro. Patch-clamp electrophysiological techniques were used on cultured dorsal root ganglion neurons from the adult rat. PGE2 (1 microM) induced a 103 +/- 22.

Characterization of six voltage-gated K+ currents in adult rat sensory neurons.

1. Previously three voltage-gated K+ currents were described in neurons from mammalian sensory ganglia: two transient and one sustained. Because there is considerable variability in the gating properties of these three currents, we have investigated the possibility that this variability reflects the presence of additional currents in sensory neurons.

Role of a Ca(2+)-dependent slow afterhyperpolarization in prostaglandin E2-induced sensitization of cultured rat sensory neurons.

To determine if inhibition of a Ca(2+)-dependent slow afterhyperpolarization (AHPslow) contributes to prostaglandin E2 (PGE2)-induced sensitization of DRG neurons, we have used patch-clamp electrophysiological techniques on cultured dorsal root ganglion (DRG) neurons from the adult rat. In support of a role for AHPslow in sensitization of DRG neurons, we demonstrate that: (1) AHPslow expression is restricted to a subpopulation of putative nociceptors; (2) burst duration is controlled by AHPslow in these neurons; and (3) in some neurons, PGE2 decreases AHPslow and produces a concomitant increase in the number of action potentials generated in response to depolarizing current injection. However, our results also demonstrate that AHPslow modulation is not sufficient to explain PGE2-induced sensitization in the majority of DRG neurons because: (1) the size of the population of DRG neurons expressing AHPslow is less than half the size of the population of DRG neurons sensitized by PGE2; (2) PGE2 produces a decrease in action potential threshold as well as an increase in the number of action potentials in response to current injection, while inhibition of AHPslow has little effect on threshold; and (3) the sensitizing effects of PGE2 are dissociated from its effects on AHPslow in more than half of neurons tested.

Co-expression of nociceptor properties in dorsal root ganglion neurons from the adult rat in vitro.

The cell body of sensory neurons in vitro has been used as a model to study the electrophysiological properties of afferent terminals. A limitation of this approach has been the ability to identify the function of the neuron studied. In the present study, we have tested the hypothesis that a putative nociceptor can be identified in vitro based on the expression of properties associated with nociceptors in vivo.

Hyperalgesic agents increase a tetrodotoxin-resistant Na+ current in nociceptors.

Sensitization of primary afferent neurons underlies much of the pain and tenderness associated with tissue injury and inflammation. The increase in excitability is caused by chemical agents released at the site of injury. Because recent studies suggest that an increase in voltage-gated Na+ currents may underlie increases in neuronal excitability associated with injury, we have tested the hypothesis that a tetrodotoxin-resistant voltage-gated Na+ current (TTX-R INa), selectively expressed in a subpopulation of sensory neurons with properties of nociceptors, is a target for hyperalgesic agents.

Inhibition of unstimulated exocrine pancreatic secretion by peptide YY in the rat.

Peptide YY is an ileocolonic peptide known to inhibit postprandial and cholecystokinin-induced pancreatic exocrine secretion. It has also been shown to increase intestinal water and electrolyte absorption. These findings implicate PYY as being potentially useful for controlling watery diarrhea.

Catecholamine-induced mechanical sensitization of cutaneous nociceptors in the rat.

C-Fiber mechanoheat (C-MH) nociceptors from the saphenous nerve were studied, in control rats and in rats that underwent surgical sympathectomy. Intradermal injection, alone, of either norepinephrine (NE) or the calcium ionophore, A23187, did not affect mechanical threshold. The combination of A23187 and NE, however, significantly decreased mechanical threshold.

Criminal activity and crack addiction.

The association of crack and criminal activity is commonly believed but not well documented or characterized in any systematic studies of crack addicts. In this survey of 200 crack addicts, daily use of crack correlated more with illicit, criminal activities to obtain a supply of crack than to demographic features. Correspondingly, felony and cocaine dealing was associated with total dollars spent on cocaine but not to other demographic features such as level of property or affluence.

Dissociation of "conscious desire" (craving) from and relapse in alcohol and cocaine dependence.

Treatment of withdrawal and postabstinence craving has yielded mixed results in eliminating drug and alcohol use, improving outcomes, and reducing relapse in those patients addicted to alcohol and drugs. To assess the role of "conscious desire" (or craving) for drugs/alcohol during abstinence and withdrawal in continued addictive drug and alcohol use, we analyzed data from 1626 patients voluntarily admitted to a primary rehabilitation center in Minnesota. Eighty-one percent and 71% of all patients completed surveys at 6 and 12 months following discharge.

The effect of lumbar epidural and general anesthesia on plasma catecholamines and hemodynamics during abdominal aortic aneurysm repair.

Twenty-four patients undergoing abdominal aortic aneurysm (AAA) repair were studied to compare the effects of lumbar epidural anesthesia (LEA) and general anesthesia (GA) on plasma catecholamine levels and hemodynamics before and during infrarenal aortic cross-clamping. Patients received either a high dose of opioid anesthetic (GA group, n = 12), or lumbar epidural anesthesia to T4 sensory level with a light general anesthetic (LEA group, n = 12). Systemic vascular resistance (SVR) and norepinephrine (NE) and epinephrine (E) levels were measured before anesthetic induction (before epidural activation in the LEA group, and before general anesthesia induction in the GA group), 15 min before cross-clamping, and 1,5, and 10 min after cross-clamping.

Peptide YY ameliorates cerulein-induced pancreatic injury in the rat.

Peptide YY (PYY), a known inhibitor of both pancreatic secretion and the release of cholecystokinin (CCK), may play a role in the pathophysiology of acute pancreatitis (AP). Supramaximal stimulation of the pancreas with CCK, or its analogue cerulein, induces edematous AP. We previously documented significant decreases in plasma PYY in sodium taurocholate-induced AP in the anesthetized pig, with exogenous PYY suppressing plasma amylase activity.

The effect of epidural/general and cervical plexus block anesthesia on activated clotting time in patients undergoing vascular surgery.

The effect of anesthetic induction and surgical incision on activated clotting time (ACT) was determined in patients undergoing vascular surgery. Patients undergoing carotid endarterectomy (CAE) (n = 50) and abdominal aortic aneurysm repair (AAA) (n = 45) were studied. Patients in the CAE group had cervical plexus block anesthesia, whereas patients in the AAA group had a combination of epidural and general anesthesia.

A neurochemical basis for alcohol and other drug addiction.

There are major clinical observations in alcohol and other drug addicts and neurochemical studies in animals and humans that support the hypothesis for a common neurochemical basis for alcohol and other drug addiction. The common occurrence of concurrent alcohol and multiple drug dependence in clinical and general populations, family history and genetic studies, and basic and clinical research in the neurochemistry of addictive behavior provide evidence for a common genealogical vulnerability to combined alcohol and other drug addiction. Clinical neurochemical models for addictive behaviors can be derived from neurochemical pathways for the initiation and sustenance of addictive disorders.