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P Weinstein

Publications and source records attributed to P Weinstein.

At least 73 records · Page 4Linked to original sources

Modulation of glutamate-induced intracellular energy failure in neonatal cerebral cortical slices by kynurenic acid, dizocilpine, and NBQX.

The severity and rapidity of acute, glutamate-induced energy failure were compared in live cerebral cortical slices. In each experiment 80 live cerebral cortical slices (350 microns thick) were obtained from neonatal Sprague-Dawley rats, suspended and perfused in a nuclear magnetic resonance (NMR) tube, and studied at 4.7 T with interleaved 31P/1H NMR spectroscopy. NMR spectra, obtained continually, were determined as 5-min averages. Slices were perfused for 60 min with artificial cerebrospinal fluid (ACSF) containing either glutamate alone or glutamate mixed with one of three glutamate-receptor antagonists: kynurenate, dizocilpine (MK-801), and 2,3-dihydroxy-6-nitro-7-sulfamoylbenzo(F)quinoxaline (NBQX). Dose-dependent decreases in high-energy phosphates were studied during glutamate exposure (0.5 to 10 mM), with and without antagonist protection. Energy recovery after glutamate exposures was measured during a 60-min washout with glutamate-free, antagonist-free ACSF. Reversible and irreversible energy failures were characterized by changes in intracellular pH, and by changes in relative concentrations of ATP, phosphocreatine (PCr), and inorganic phosphate. No changes were observed in intracellular levels of N-acetylaspartate and lactate. Some special studies were also done using R-(-)-2-amino-5-phosphonovaleric acid (100 microM) and tetrodotoxin (1 mM) to examine glutamate receptor specificity in this tissue model. Dizocilpine (150 microM) best ameliorated the energy failure caused by 2.0 mM glutamate. With dizocilpine the maximum ATP decrease was only 6 +/- 5%, instead of 35 +/- 7%.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine Triphosphate↗

Human copper-zinc superoxide dismutase transgenic mice are highly resistant to reperfusion injury after focal cerebral ischemia.

BACKGROUND AND PURPOSE: We have demonstrated in a previous study that superoxide radicals play a role in the pathogenesis of cerebral infarction, using a transgenic mouse model of distal middle cerebral artery occlusion, permanent ipsilateral cerebral carotid artery occlusion, and 1-hour contralateral cerebral carotid artery occlusion that produced infarction only in the cortex. However, the role of superoxide radicals in reperfusion injury in transgenic mice overexpressing superoxide dismutase (SOD) is unknown. Using a mouse model of intraluminal blockade of middle cerebral artery that produced both cortical and striatal infarction, we now further examined the role of superoxide radicals in ischemic cerebral infarction after reperfusion in transgenic mice overexpressing human CuZn-SOD activity. METHODS: Transgenic mice of strain Tg HS/SF-218, carrying human SOD-1 genes, and nontransgenic littermates were anesthetized with chloral hydrate (350 mg/kg IP) and xylazine (4 mg/kg IP). Physiological parameters were maintained at a normal range using a 30% O2/70% N2O gas mixture inserted via an inhalation mask. Body temperature was maintained at 37 +/- 0.5 degrees C by using a heating pad throughout the studies. The middle cerebral artery occlusion was achieved with a 5-0 rounded nylon suture placed within the internal cerebral artery for 3 hours followed by the removal of the suture to allow reperfusion for another 3 hours. Cerebral infarct size in brain slices and infarct volume, neurological deficit, cortical blood flow, and glutathione levels were measured in both transgenic and nontransgenic mice. RESULTS: Compared with the nontransgenic mice, the infarcted areas were significantly decreased in coronal slices from transgenic mice. The infarct volume (in cubic millimeters) was reduced by 26% in transgenic mice after ischemia and reperfusion. This decrease in the infarct volume in transgenic mice closely paralleled the reduced neurological deficits. Introduction of the suture to block blood supply to the middle cerebral artery territory produced a rapid decrease in the relative surface blood flow in the ipsilateral core and the peri-ischemic (penumbra) areas. There were no significant differences in the local cerebral blood flow in the ischemic core or the penumbra areas between the transgenic and nontransgenic groups. However, the level of reduced glutathione in the penumbra area was significantly higher in transgenic mice than in nontransgenic mice, whereas there was no difference in the reduced glutathione levels in the ischemic core between these two groups. CONCLUSIONS: Our study demonstrated that superoxide radicals play a major role in the pathogenesis of cerebral infarction in reperfusion injury after a focal stroke. The reduction in infarct volume and neurological deficits is not dependent on the changes in cerebral blood flow but rather correlate with reduced oxidative stress in the ischemic brain tissue, which was indicated by the relatively high levels of endogenous reduced glutathione in transgenic mice.

Animals↗

Topical anesthesia: differentiating the pharmacological and psychological contributions to efficacy.

Pain can be influenced by both pharmacologic and psychologic factors. The purpose of this study was to investigate the pharmacologic and psychologic factors. The purpose of this study was to investigate the pharmacologic and psychologic processes that may play a role when topical anesthesia is used to reduce the pain of dental injections. Subjects were assigned to one of two belief manipulation conditions: one-half of the subjects were led to believe they would receive a placebo, while the remaining subjects were told they would receive the active agent. In reality, all subjects received two separate injections at contralateral sites, one preceded by a placebo and the other by a 20% benzocaine gel. The order in which injections were given was associated with differences in pain report. Second injections were more painful than first injections. Whether injections were preceded by an active or placebo agent did not alter subjects' experienced pain. Likewise, the belief manipulation did not affect the pain report. However, subjects who believed they would receive the active agent anticipated significantly less pain than subjects who thought they would receive placebo. The widespread belief that topical anesthetics are effective at reducing injection pain may serve to reduce the anticipatory anxiety associated with an impending dental injection, thus making the injection experience less aversive.

Administration, Topical↗

Opioid receptor antagonist nalmefene stereospecifically inhibits glutamate release during global cerebral ischemia.

The opioid receptor antagonist nalmefene improves cellular bioenergetics and attenuates the reduction in tissue glutamate levels after global cerebral ischemia/reperfusion. The latter finding suggests that nalmefene might inhibit glutamate release during ischemia. To test this hypothesis, we used microdialysis techniques to examine the effect of nalmefene pretreatment on extracellular excitatory amino acid levels during global cerebral ischemia in rats. Saline, (-)-nalmefene (20, 100 or 500 micrograms/kg) or the inactive nalmefene enantiomer (+)-nalmefene (100 micrograms/kg) were given 15 min prior to induction of ischemia using a multi-vessel occlusion model. Pretreatment with (-)-nalmefene decreased peak dialysate glutamate in a dose-dependent fashion as compared to saline-treated controls, whereas (+)-nalmefene had no effect. These results suggest that opioid receptors may modulate glutamate release during ischemia and that inhibition of excitatory amino acid release may contribute to the protective actions of opioid receptor antagonists in cerebral ischemia.

Animals↗

Cryptosporidial diarrhoea in South Australia. An exploratory case-control study of risk factors for transmission.

OBJECTIVE: To identify risk factors for transmission of cryptosporidiosis in South Australia. DESIGN: Case-control study of 51 cases of laboratory confirmed cryptosporidiosis and 51 age and sex matched controls. SETTING: Subjects from greater Adelaide, with cases notified by local pathology laboratories to the Communicable Disease Control Unit, South Australian Health Commission, during the summer of 1990/1991. PARTICIPANTS: One in 10 cases was selected systematically from 479 laboratory notifications, and permission was obtained from the treating physicians to contact the patients. Subjects nominated age and sex matched controls living in the same area. METHODS: By means of a structured questionnaire, participants were asked by telephone about exposure to possible risk factors in the two weeks preceding the illness/interview. The risk factors included those most commonly cited in the literature as resulting in zoonotic, waterborne and person-to-person infection. The number and percentage of cases and controls exposed was recorded for each risk factor. The probability of having been exposed to selected risk factors was compared between cases and controls by the exact test for matched pairs. RESULTS: The proportion of cases and controls exposed was similar for all risk factors except water sources. Controls were more likely to have consumed only rain water than were cases (P < 0.005). Cases tended more than controls to have consumed only spring water (P = 0.06) or only mains water (P = 0.09). CONCLUSIONS: The consumption of spring water or mains water contaminated with cryptosporidial oocysts may be the mode of transmission of cryptosporidiosis in South Australia. The advent of specific methods for detecting Cryptosporidium sp. in water will allow this hypothesis to be tested.

Adolescent↗

Physicians' practice patterns in pediatric electrodiagnosis.

The medical literature contains contradictory reports and recommendations regarding pediatric patients' pain and distress during electrodiagnosis. We surveyed 117 pediatric neurologists and physiatrists regarding their practice patterns in pediatric electrodiagnosis; 84 (72%) responded, of whom 44 (52%) regularly perform electrodiagnosis on children (mean = 85 per year, representing 3,667 examinations per year). Respondents reported extreme behavioral distress (eg, screaming, flailing, requiring additional restraint, or attempting to leave the examination table) in 35% of examinations, most often among 2- to 6-year-olds. Pain medications are never prescribed by 45%, occasionally by 48%, and always by 2%; general anesthesia is never administered by 75%, occasionally by 21%. Only 32% reported that any psychological intervention is routinely offered to enhance child coping. Wide variability was found in physicians' preferences about parental presence, order of examinations, demonstration of procedures, and other aspects of electrodiagnosis.

Adolescent↗

The safety and efficacy of outpatient midazolam intravenous sedation for oral surgery with and without fentanyl.

This study examined midazolam and midazolam plus fentanyl in a placebo-controlled, double-blind clinical trial. It tested the hypothesis that combined drug therapy results in significantly poorer safety but no difference in efficacy compared to the single drug approach. Subjects were among 207 mildly anxious young adults having their third molars removed. Fentanyl had a significant depressant effect on respiration. Fifty of 79 (63%) subjects who received a midazolam-fentanyl combination became apneic, while only two of 78 (3%) who received midazolam alone were apneic (Fisher's Exact Test, P < 0.001). Two subjects (2.5%) in the combination group and none in the midazolam alone group had oxygen saturations drop below 90%. About twice as many subjects in the combination group had end-tidal carbon dioxide (EtCO2) levels greater than 25% above baseline. While these results are consistent with those for apnea, contingency analyses of the oxygen saturation and EtCO2 results were not statistically significant. Subjects in the combination group were more than four times as likely to have excellent versus good, fair, or poor sedation at a given level of intraoperative pain, and behavioral (movement and verbalization) but not cognitive measures of anxiety were attenuated.

Adolescent↗

The effect of instruction on dentists' motivation to manage fearful patients.

This study assesses the effect of the pre-doctoral and continuing behavioral education on dentists' efforts to treat fearful patients. A mail survey consisting of a booklet of 27 questions was sent to the 1988 and 1989 graduates of the Universities of Washington (UW), Kentucky (UK), and British Columbia (UBC). Graduates from UW and UK who received predoctoral instruction and some UBC graduates who received continuing education on the behavioral approach to caring for fearful patients were compared with UBC graduates who received only a primarily pharmacological oriented education. The overall response rate was 80.4 percent (164/204). Results indicate the average proportion of fearful patients seen was greater for those receiving behavioral instruction. Dentists who received behavioral instruction also reported greater effort addressing fear during patient's initial contact with the practice; however, they perceived the costs of the behavioral approach to be greater. No differences were found between groups for the remaining effort measures.

Adaptation, Psychological↗

Dental fears in general practice: new guidelines for assessment and treatment.

Dental fear is a world-wide problem and universal barrier to oral health care services. Fears acquired in childhood through direct experience with painful treatment or vicariously through parents, friends or siblings, may persist into adulthood. Symptomatic treatment and lack of trust and control exacerbate fears. Coexisting psychiatric conditions further complicate treatment. Treatment steps recommended in this paper include careful assessment of fears, application of dental and psychological management techniques to enhance trust, feelings of control, and the development of coping skills, and appropriate and targeted use of pharmacological agents. Prevention of fear development through the use of effective behavioural child management techniques combined with preventive dentistry should be a fundamental part of general dental practice throughout the world.

Adaptation, Psychological↗

Paradoxical effects of nitrous oxide on human memory.

Using the method of adjusted learning, subjects learned number-noun pairs while breathing either placebo or 30% nitrous oxide. Subjects breathing nitrous oxide required more acquisition trials to attain a learning criterion than did subjects breathing placebo. Two weeks later, half of the subjects from each group were administered either placebo or nitrous oxide and were asked to recall the noun that had accompanied each number cue. Results showed that: 1) nitrous oxide inhalation can decrease the accessibility of to-be-recalled material and 2) nitrous oxide administered during the acquisition of material can paradoxically improved the recall of that material 2 weeks later. The additional number of acquisition trials subjects received during nitrous oxide inhalation could potentially account for this paradoxical enhancement of delayed recall; however, correlational analyses suggest this was not the case. No evidence for any state-dependent effects of nitrous oxide on cued recall were found.

Adolescent↗

Adolescent dental fear and control: prevalence and theoretical implications.

This study examined the prevalence and etiology of dental fear in a large, representative sample of Singapore adolescents. Participants completed a questionnaire regarding fear of the dentist, dental beliefs and their most recent dental visit. The population prevalence of high dental fear was 115 fearful children per 1000 population (SE = 0.02). Children who reported painful treatment and perceived lack of control at the dentist were 13.7 times more likely to report high fear and 15.9 times less likely to be willing to return to the dentist or dental nurse. The etiology of severe clinical fear appears strongly related to direct conditioning in the presence of pain and vulnerability.

Adaptation, Psychological↗

Exploration of variables related to children's behavioral distress during electrodiagnosis.

To investigate variables potentially related to children's distress during electromyography/nerve conduction studies (EMG/NCS), mothers of 39 children ages two to 17 years reported the child's gender, experience with EMG/NCS, previous negative medical/dental experiences, general response to painful procedures, information-seeking style prior to procedures, health care fears, and information about the mothers' own health care fears and their anxiety regarding EMG/NCS. Physicians who performed the studies completed a behavioral distress checklist for each child. Results indicated that children exhibiting more behavioral distress were younger, had been uncooperative with previous painful procedures, were more likely to have had more negative medical/dental experiences, and had mothers who themselves reported greater fear and anxiety about undergoing EMG/NCS. Regression analyses indicated that previous negative medical/dental experiences accounted for additional variance in distress beyond that attributed to the child's age. Significant positive correlations between children's distress and specific previous negative medical/dental experiences were found.

Adolescent↗

Dental fear in Japan: Okayama Prefecture school study of adolescents and adults.

A total of 3,041 students and staff in middle school in Okayama Prefecture, Japan, were surveyed regarding dental fear. Over 88% reported fear, with 42.1% classified as having high fear. Almost 70% reported acquiring dental fear prior to junior high school. A majority reported being hurt at the last appointment. Delay of dental work was also reported for over 50% of the sample. Coping, pattern of physiological upset, nondental fears, and sex and age differences were also reported. Results suggest intervention is needed to address the major dental public health problems associated with dental fear.

Adolescent↗