Search PubMed⌕ Search

Biomedical subjects

M S Gold

Publications and source records attributed to M S Gold.

At least 55 records · Page 3Linked to original sources
PubMed1996

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. 2. Using whole cell patch-clamp techniques, we provide evidence for the existence of six voltage-gated K+ currents in cultured dorsal root ganglion (DRG) neurons from the adult rat. The six currents were identified on the basis of distinct biophysical and pharmacological properties; three currents are transient (IAf, IAht, and IAs), and three are sustained (IKi, IKlt, and IKn). 3. In addition to possessing distinct biophysical and pharmacological properties, four of the six currents are differentially expressed among subpopulations of DRG neurons. IAht is selectively expressed in small-diameter neurons. IKi is expressed more frequently in neurons with an action-potential shoulder, and both IAht and IAs are selectively coexpressed in neurons that respond to the algogenic agent capsaicin. IAf is selectively expressed in large-diameter neurons and is the only current expressed more frequently in neurons without an action-potential shoulder. 4. It is likely that much of apparent variability in the properties of the three voltage-gated K+ currents reported previously in vertebrate sensory neurons can be accounted for by the existence of at least three additional voltage-gated K+ currents described in this report.

4-Aminopyridine↗
PubMed1994

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. In the presence of the alpha 2-adrenergic antagonist, yohimbine, or the cyclooxygenase inhibitor, indomethacin, C-MHs were not sensitized by the combination of NE + A23187. One week after surgical sympathectomy, the number of C-MHs sensitized by NE + A23187 was significantly reduced. In summary, NE appears to sensitize nociceptors indirectly. These data are compatible with the suggestion that a sympathetic postganglionic neuron-dependent release of prostaglandins mediates the sensitization. NE appears to act at an alpha 2-adrenergic receptor, only in the presence of an increased intracellular Ca2+.

Action Potentials↗
PubMed1994

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. There was a large (P < 0.05) increase in NE and E in the GA group by 15 min before aortic cross-clamping, but NE and E levels in the LEA group did not increase. The GA group had significantly higher levels of NE and E than the LEA group 15 min before cross-clamping and also after clamping. NE levels in the LEA group increased after cross-clamping, and NE levels in the GA group remained constant. E levels remained stable in both groups after cross-clamping. After clamping, SVR increased in both groups, but the increase occurred after 1 min in the GA group and took 5 min to become significant in the LEA group. There was no significant correlation between changes in NE or E and changes in SVR in either group. This study shows that epidural anesthesia to T4 prevents NE and E increases in response to abdominal surgery.(ABSTRACT TRUNCATED AT 250 WORDS)

Anesthesia, Epidural↗
PubMed1994

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. Forty-two percent were diagnosed as alcohol dependent (AD) alone, 28% as alcohol and drug dependent (ADD) other than cocaine, and 25% as cocaine dependent (CD). At 6 months following discharge, the CD group had the lowest abstinence rate for drugs, at 83%, compared to the AD group, at 99%, and for alcohol, at 76%, compared to the AD group, at 75%. The AD group had the best outcomes and the least slippage from 6 to 12 months for drugs and alcohol. In all groups craving was not a major self-reported cause of relapse. For the CD subgroup, impulsive action with no known cause was the most common reason for relapse, while the AD group cited depression. These data agree with other reports in the literature suggesting that relapse is not commonly related to conscious craving. Our experience suggests that craving is rarely the first reason given for relapse. Drug seeking and use are such highly ritualized, automatic behaviors that the addict may appear not to require the intervention of conscious thoughts or distinct craving states to use.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1994

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. Moreover, the majority of crack addicts in this sample used cocaine intranasally before starting crack use. The mean age from onset of crack use to seeking help for cocaine addiction is less than 3 years. Severity of crack use and addiction as measured by daily use was associated with psychosocial consequences more than other demographic features.

Adolescent↗
PubMed1993

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. We hypothesized that PYY may ameliorate cerulein-induced pancreatic injury in a conscious animal model. Thirty-two male Sprague-Dawley rats underwent chronic cannulation of the jugular vein and carotid artery for drug infusion and blood sampling. The animals were allowed to recover from anesthesia for a minimum of 16 hours, after which they were randomized to one of four (n = 8) treatment groups (cerulein 10 micrograms/kg/h, PYY 400 pmol/kg/h, cerulein+PYY, and control-saline 2 mL/kg/h). All treatments were administered by intravenous infusion over the first 6 hours of the experiment. Blood samples were taken prior to infusion and at 1, 3, 6, 9, and 24 hours into the study; the rats were then killed and the pancreata removed for weighing and histologic examination. All pancreatic specimens were graded in a blinded fashion for vacuolization, edema, inflammation, and necrosis. The mean basal plasma amylase level for all animals was 1,171 +/- 100 U/L and was not significantly different between groups. Infusion of cerulein resulted in significant increases in plasma amylase levels at 3, 6, 9, and 24 hours (4,827 +/- 1,022 U/L at 24 hours). In the group receiving both cerulein and PYY, the hyperamylasemia was attenuated with a return to basal values at 24 hours (1,206 +/- 103 U/L). There was significant pancreatic weight gain (1.99 +/- 0.07 g versus 1.03 +/- 0.07 g) and a worsened histologic picture in cerulein-treated animals compared with control animals (worsened edema, necrosis, and vacuolization). The addition of PYY to cerulein resulted in significantly lower pancreatic weight (1.27 +/- 0.11 g) than in the non-PYY-treated rats receiving cerulein. Pancreatic weight was not significantly different in this group compared with the control group. In addition, pancreatic histologic findings were significantly improved in those rats receiving PYY (decreased vacuolization and necrosis). Amylase levels, pancreatic weight, and morphologic findings were not significantly changed compared with basal values in the control or PYY alone treated groups. e conclude that as an inhibitor of pancreatic exocrine secretion, PYY ameliorates cerulein-induced pancreatic injury in the conscious rat.

Amylases↗
PubMed1993

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. The ACT was measured 1) before induction of anesthesia, 2) 5 min after induction, 3) 5 min after incision, 4) 5 min after heparinization, and 5) at the onset of skin closure. Heparin was reversed with protamine only if the ACT after revascularization was > 200 s. Reversal was considered adequate if the ACT was < 200 s and the surgeon felt that hemostasis was adequate. The ACT decreased by 12.26 +/- 1.23 (mean +/- SE) (P = 0.006) in the CAE group and by 12.47 +/- 1.01 (P = 0.002) in the AAA group with induction of anesthesia. There was a further decrease of 5.06 +/- 0.62 (P = 0.26) in the CAE group and 5.17 +/- 0.83 (P = 0.22) in the AAA group with incision. There was a significant difference in ACT in both groups from postinduction and postincision to skin closure (higher at skin closure). No patient in either group required additional protamine or clotting factors post-operatively, or return to the operating room for excessive bleeding. This study demonstrates that anesthetic induction with cervical block or epidural/general anesthesia decreases ACT.(ABSTRACT TRUNCATED AT 250 WORDS)

Anesthesia, Epidural↗
PubMed1993

Cocaine dependence: alcohol and other drug dependence and withdrawal characteristics.

In this study, a cocaine abstinence syndrome is confirmed. Moreover, the cocaine withdrawal syndrome was found to be medically and psychiatrically benign and required no medication for detoxification in this inpatient setting. The 150 patients who underwent cocaine withdrawal did not show the three distinct phases of the abstinence symptomatology previously described. No patients required pharmacological intervention for cocaine withdrawal, and the dropout rate was 8% of the 150 cocaine dependents. The common symptoms of acute cessation of cocaine were transient craving, hyperactivity, slight tremor, insomnia and apprehension. The diagnosis of cocaine dependence alone without an additional drug or alcohol diagnosis was unusual in this study at 5%, as is the solitary use of cocaine also uncommon according to other studies. Studies clearly document that the concurrent and simultaneous use and dependence on multiple drugs and alcohol is present in the majority of treatment populations and common in the general population. As many as 54% of cocaine dependents qualified for alcohol dependence in this study, and many were dependent on alcohol prior to their cocaine dependence. Cocaine dependence appears to be yet another diagnosis in the spectrum of the multiple drug and alcohol dependent.

Adolescent↗
PubMed1993

Hypothesized neurochemical models for psychiatric syndromes in alcohol and drug dependence.

Exploration of the neurochemistry of psychiatric and substance use disorders in dual diagnosis patients may help explain the greater than chance comorbidity of these disorders and lead to advances in treatment. This paper will focus on the hypothesized neurochemical changes associated with primary substance use disorders which might lead to secondary psychiatric disorders by mimicking the hypothesized neurochemical changes of primary psychiatric disorders. For example, hypothesized serotonergic deficits in alcoholism, endorphin deficits in opioid dependence, and dopamine depletion in cocaine dependence all might predispose to depression. A vicious cycle of cocaine dependence and depression and a vicious cycle of alcohol and drug dependence and panic anxiety are reviewed as models for hypothesized alcohol or drug withdrawal related neurochemical changes predisposing to continued chemical dependency. Exploration of the neurochemistry of dual diagnosis patients reinforces the need for treatment approaches that take into account both aspects of illness.

Alcoholism↗
PubMed1993

A hypothesis for a common neurochemical basis for alcohol and drug disorders.

Research findings clearly support a uniform theory for a neurochemical basis of drug and alcohol addiction. Data are available that document final common pathways for addictive behaviors in the limbic system in which neurotransmitters modulate the drive states, mood, and instinctual behaviors. The specific areas in the brain implicated in the loss of control inherent in the addictive use of multiple drugs and alcohol are the ventral tegmentum, nucleus accumbens, locus ceruleus, dorsal raphe nuclei, and the periaquaductal grey area. These sites contain cell bodies and receptors for dopamine, norepinephrine, serotonin, and endogenous opiates respectively, where multiple drugs and alcohol can often produce their effects. The acquired drive of addiction that arises spontaneously, repetitively, and relentlessly is manifested in the addictive behaviors of preoccupation, compulsivity, and relapse to drugs and alcohol.

Alcoholism↗
PubMed1993

Opiate addiction and the locus coeruleus. The clinical utility of clonidine, naltrexone, methadone, and buprenorphine.

Detoxification from opiate addiction has been a medical problem for as long as opiate drugs have been available. Treatment before the discovery of clonidine involved giving another opioid drug with less dangerous consequences of chronic use, such as the long-acting and orally administered once a day methadone, for another opioid mu agonist like heroin, which must be taken intravenously many times a day, thus making rehabilitation, work, and avoidance of hepatitis, HIV, and other illnesses difficult. Although methadone has proved to be very beneficial, it still has significant abuse potential. Naltrexone, because it blocks the effects of all opiates, has facilitated the transformation from addiction to a drug-free state for many recovering addicts. By alleviating withdrawal symptoms and by lessening the detoxification period, clonidine similarly has improved the prospect of recovery from opiate addiction. Relapse, whether withdrawal is treated with clonidine or other new agents or not, occurs with great regularity because repeated opiate use can induce a new acquired drive state--the drive for opiates. In addition, with powerful withdrawal symptoms during abstinence, opiate relapse is difficult to prevent without an adequate treatment program. The efficacy of clonidine and other medical magic bullets for withdrawal distress needs to be given as part of a long-term recovery program which not only allows the brain to re-establish normal homeostatic changes in the drug-free state but also provides sufficient motivation for new approaches to achieving and sustaining pleasurable existence.

Animals↗
PubMed1992

The pharmacologic treatment of alcohol and cocaine abuse. Integration of recent findings into clinical practice.

The clinical evidence available to date does not yet support the routine use of pharmacologic interventions in the majority of cases of alcohol or cocaine abuse. The available data suggest, however, that interventions should be considered, especially in patients who relapse or drop out of treatment, in more difficult cases, and in instances in which there are associated psychiatric disorders. Education and prevention should be reconsidered as the important "treatments" they are today.

Adolescent↗
PubMed1992

Perioperative fluid management.

The physiologic effects of surgery as well as anesthesia on fluid balance have been discussed. Detailed discussions of some types of surgery and patient populations were included to clarify situations in which fluid management may be unusually difficult. Principles derived from the examination of these situations should make fluid management during the perioperative period easier.

Anesthesia↗
PubMed1991

Periaqueductal gray stimulation produces a spinally mediated, opioid antinociception for the inflamed hindpaw of the rat.

The objective of the present study was to characterize stimulation-produced antinociception from the periaqueductal gray matter (PAG) in rats with unilateral hindlimb inflammation induced by an intraplantar injection of Freund's complete adjuvant. Rats were chronically implanted with a bipolar stimulating electrode in the PAG. Nociception was assessed using a paw pressure test. Prior to inflammation, PAG stimulation significantly increased paw pressure threshold in both paws compared to non-stimulated controls. Following inflammation, PAG stimulation inhibited nociception in the inflamed, but not the non-inflamed paw. Systemic administration of naloxone blocked antinociception from ventral, but not dorsal PAG stimulation sites. Intrathecal, but not subcutaneous, administration of quaternary naltrexone completely blocked stimulation-produced antinociception from the PAG. The known increased levels of endogenous opioids occurring in the spinal cord ipsilateral to the site of inflammation suggest a mechanism for the selective antinociceptive effect of ventral PAG stimulation seen for the inflamed paw.

Analysis of Variance↗