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Biomedical subjects

K M Johnson

Publications and source records attributed to K M Johnson.

At least 91 records · Page 5Linked to original sources
PubMed1996

Patients and family members: the role of knowledge and attitudes in cancer pain.

Cancer pain theoretically comprises sensory, affective, and cognitive dimensions, implying that patients and family members perceive and report cancer pain based on these factors. The study reported here investigated the relationship between specific knowledge and attitudes (cognitive factors), and patients' and family members' reports of pain due to cancer. The relationship between cognitive factors and reports of cancer pain was investigated in interviews with 122 patients and their family members. Pain was measured using the Brief Pain Inventory; knowledge and attitudes were measured using a form previously developed by the authors. Patients' and family members' reports of patient pain and performance status were highly correlated, although family members consistently reported more pain and disability. Using regression analysis, cognitive factors were strongly related to family reports of patients' pain (R2 = 0.27), but contributed little to explaining pain reported by patients themselves (R2 = 0.06). Improved understanding of patients' pain assessments depends on further investigation of other cognitive factors and of sensory and affective factors. Family members' assessments of pain are significantly related to appropriate knowledge and attitudes.

Adult↗
PubMed1996

Material properties, biocompatibility, and wear resistance of the Medtronic pyrolytic carbon.

Pyrolytic carbon is the material of choice for components in the majority of heart valves available today. Many manufacturers have vertically integrated their manufacturing capabilities to include their own carbon manufacturing facilities. Medtronic is no exception. Because of the critical nature of pyrolytic carbon to the success of a valve design, a series of in vitro tests were conducted to determine the relative equivalence of Medtronic and CarboMedics, Inc. (CMI) pyrolytic carbon based on the Medtronic HallTM design. Correlation between in vivo and in vitro pyrolytic carbon wear is provided based on an analysis of explanted Medtronic Hall discs manufactured by CMI. Material, physical, chemical, and biocompatibility proprieties for Medtronic carbon were determined using standardized techniques. Structural integrity of the discs was evaluated by accelerated cyclic testing to determine depth of wear characteristics. Explanted valves were subjected to identical depth of wear analysis. No statistical difference was found between CMI and Medtronic pyrolytic carbon discs based on mechanical and physical properties and depth of wear on both inflow and outflow disc surfaces. Furthermore, evaluation of CMI discs after explant from human subjects confirms similar wear characteristics with a half life in excess of the 570 years projected from the in vitro experiments. In summary, material properties, structural integrity and biocompatibility testing conducted on heart valve discs made by Medtronic showed results virtually identical to those from testing of discs made by CMI.

Biocompatible Materials↗
PubMed1995

Voltage-dependent calcium channel involvement in NMDA-induced activation of NOS.

We have previously shown that N-methyl-D-aspartate (NMDA) increases nitric oxide synthase (NOS) activity in rat frontal cortex; however, the actual mechanism of this activation has not been addressed. Tetrodotoxin (TTX; 0.05 microM) inhibited NMDA-activated NOS, suggesting that TTX-sensitive Na+ channels are interposed between the NMDA receptors and the NOS cellular compartment. The NMDA response was also blocked by voltage-dependent Ca2+ channel (VDCC) blockers including Cd2+, Co2+, funnel web spider toxin (FTX) and omega-Aga IVa, but not by nifedipine or omega-conotoxin. These data suggest that Ca2+ flux through P- and/or Q-type VDCC subsequent to NMDA-induced depolarization may be at least as important for NOS activation as Ca2+ entry through the NMDA receptor.

Animals↗
PubMed1995

Basal and scopolamine-evoked release of hippocampal acetylcholine following traumatic brain injury in rats.

This study employed in vivo microdialysis in awake, freely-moving Sprague-Dawley rats to examine acetylcholine (ACh) release in the dorsal hippocampus at 14 days following lateral controlled cortical impact. Extracellular levels of ACh were measured prior to and after an intraperitoneal administration of scopolamine (1 mg/kg), which evokes ACh release by blocking autoreceptors. At 14 days post injury there were no differences in basal ACh levels. However, injury produced a significant reduction in scopolamine-evoked ACh release. The data suggest that cholinergic neurotransmission remains chronically compromised, and thus may contribute to previously documented post traumatic spatial memory deficits.

Acetylcholine↗
PubMed1995

Chemistry and biology of the 2 beta-alkyl-3 beta-phenyl analogues of cocaine: subnanomolar affinity ligands that suggest a new pharmacophore model at the C-2 position.

A series of 2 beta-alkyl-3 beta-phenyltropanes (i.e., the 2 beta-alkyl analogues of the WIN series) were prepared as analogues of cocaine and tested for their ability to displace [3H]mazindol binding and to inhibit high-affinity dopamine uptake into striatal nerve endings (synaptosomes). These 2 beta-alkyl analogues were readily prepared in optically pure form starting from cocaine by proceeding through the 2 beta-phenyl-bearing aldehyde 6 as a key intermediate. Wittig reaction of 6 with the appropriate phosphorane and hydrogenation delivered the final products. All new compounds with the exception of 8e were found to exhibit nanomolar or subnanomolar affinity for the cocaine binding site in the rat striatum. These results are in apparent opposition to the binding model previously proposed which suggests a hydrogen bond donor-acceptor interaction to be present in the vicinity of the C-2 substituent. Taken together with our previous reports and recent findings from other laboratories, we suggest a new pharmacophore model in which 2 beta-substituents lacking H-bond acceptors enhance affinity to the binding site through hydrophobic interactions. The new SAR data contained herein may be relevant to the design of possible cocaine antagonists.

Animals↗
PubMed1995

Seasonal respiratory viral infections. Impact on infants with chronic lung disease following discharge from the neonatal intensive care unit.

OBJECTIVE: To determine the frequency and severity of acute respiratory infections in infants with bronchopulmonary dysplasia following discharge from the neonatal intensive care unit. DESIGN: A prospective cohort study of 30 oxygen-dependent children who were younger than 2 years (mean age, 9.8 months; range, 3 to 24 months) were studied from September 1990 through April 1991. MEASUREMENTS/RESULTS: During the study, 101 (90.2%) of 112 visits for illness were prompted by new or worsening respiratory symptoms. Diagnoses included upper respiratory tract infection (30.4%), otitis media (26.0%), pneumonia (11.1%), acute exacerbation of bronchopulmonary dysplasia (10.4%), reactive airway disease (9.6%), and bronchiolitis (5.9%). Among these children, an increase in the fraction of inspired oxygen was necessary during 43% of visits. Ten children were hospitalized on 25 occasions for a mean of 37.6 hospital days per child (range, 1 to 107 days), and mean length of stay for each hospitalization was 15 days (median, 6 days). Five children were admitted to the pediatric intensive care unit. Respiratory viruses isolated included respiratory syncytial virus (n = 7), parainfluenza 3 virus (n = 3), and adenovirus (n = 2). No isolates of influenza A or B were detected. Anthropometrics at study entry and study end were converted to z scores as descriptors of weight for age, height for age, and weight for height. Growth improved during the 8 months of the study; however, overall, the children were leaner at study end than at study entry. CONCLUSIONS: In children with bronchopulmonary dysplasia, respiratory viral infections led to significant morbidity, which included long and frequent hospitalizations during the peak of the respiratory viral season. Although weight and linear growth increased throughout the study, patients were leaner at study conclusion than at study entry.

Bronchopulmonary Dysplasia↗
PubMed1995

Polymyxin B prevents increased sympathetic activity and alveolar macrophage tumor necrosis factor release in parenterally fed rats.

OBJECTIVE: To determine the effects of polymyxin B sulfate in rats fed by total parenteral nutrition on norepinephrine excretion, macrophage tumor necrosis factor production, and bacterial translocation. DESIGN: Randomized animal study. SETTING: A university teaching hospital in Seattle, Wash. MATERIALS AND METHODS: Three groups of rats were studied: chow plus intravenous saline, total parenteral nutrition, or total parenteral nutrition supplemented with polymyxin B sulfate. After 5 days, urinary excretion of norepinephrine and epinephrine was calculated, peritoneal and alveolar macrophages were cultured, and their spontaneous and lipopolysaccharide-stimulated tumor necrosis factor production was measured. Mesenteric lymph nodes were cultured for bacteria. RESULTS: Rats fed by total parenteral nutrition had increased urine norepinephrine excretion (33%) and alveolar macrophage tumor necrosis factor production (80%) and trends for increased epinephrine excretion and bacterial translocation compared with rats fed chow. Alveolar but not peritoneal macrophage tumor necrosis factor production was significantly related to norepinephrine excretion (r = .5, P < .01). The addition of polymyxin B to total parenteral nutrition decreased weight gain (P < .05), urinary norepinephrine excretion (P < .01), and alveolar macrophage tumor necrosis factor production (P < .05) compared with rats fed by total parenteral nutrition. Polymyxin B also tended to decrease the magnitude of bacterial translocation. CONCLUSIONS: Alveolar macrophage tumor necrosis factor production appears to be influenced by sympathetic nervous activity. Total parenteral nutrition-induced endotoxemia may indirectly alter macrophage function by stimulating sympathetic nervous activity.

Animals↗
PubMed1995

Physician knowledge and attitudes about cancer pain management: a survey from the Minnesota cancer pain project.

The purposes of the study were to determine the knowledge and attitudes about cancer pain management (CPM) among practicing physicians in six Minnesota communities and to determine the physician-related barriers to optimal CPM. Eligible community physicians were surveyed by telephone. The study analyzed responses of 145 physicians (response rate, 87%). The majority of the physicians were primary care specialists (73%). Significant knowledge deficits were identified in nine of 14 CPM principles, but inappropriate attitudes were found in only two of nine CPM concepts. Medical specialty had the strongest influence on knowledge and attitudes, with primary care physicians having significantly better outcomes than surgeons or medical subspecialists. Effective education strategies must address knowledge deficits, attitudes, and motivations of the relevant peer group influencing physicians, as well as those of individual physicians. The Minnesota Cancer Pain Project is testing strategies to enhance CPM by physicians and improve patient outcomes.

Clinical Competence↗
PubMed1995

The Minnesota Cancer Pain Project: design, methods, and education strategies.

The Minnesota Cancer Pain Project (MCPP) is a community-based research project to test various innovative education strategies for improving cancer pain management (CPM) in Minnesota. The main hypothesis is that community-based, multidisciplinary and integrated education programs can improve CPM and change knowledge, attitudes, and behaviors regarding CPM in cancer patients, their families, and community physicians and nurses. The specific aim of the MCPP is to demonstrate effective methods to improve CPM in communities. The MCPP design is a randomized trial with before- and after-intervention assessments of cancer pain and CPM knowledge, attitudes, and behaviors among cancer patients and their families, physicians, and nurses. The unit of randomization and study is the community, with six Minnesota communities participating in the MCPP. This paper describes the hypotheses, design, methods, and education strategies of the MCPP. Baseline data from the participating communities and the cancer patient sample are reported.

Family↗
PubMed1995

Regulation of striatal cyclic-3',5'-adenosine monophosphate accumulation and GABA release by glutamate metabotropic and dopamine D1 receptors.

In this study, the regulation of striatal cyclic-3',5'-adenosine monophosphate (cAMP) formation and GABA release by dopamine D1 and metabotropic glutamate receptors (mGluR) was studied in brain slices. In the absence of adenosine A2 receptor blockade, the mGluR agonist, 1-aminocyclopentane-1S,3R-dicarboxylic acid (1S,3R-ACPD) stimulated cAMP accumulation through a pertussis toxin-insensitive mechanism that could be blocked by L-serine-o-phosphate, but not by L(+)-2-amino-3-phosphonopropionic acid. However, in the presence of the adenosine antagonist, 3-isobutyl-1-methylxanthine, 1S,3R-ACPD had no significant effect on basal cAMP, but it inhibited cAMP formation stimulated by the D1 agonist, SKF 38393. This inhibitory response was prevented by pertussis toxin pretreatment and mimicked by L(+)-2-amino-3-phosphonopropionic acid, but it was unaffected by L-serine-o-phosphate. Thus, 1S,3R-ACPD was determined to activate distinct mGluRs in the striatum that mediate either inhibition or activation of cAMP accumulation, with the latter effect being dependent on the activation of adenosine A2 receptors. A potential physiological role for the interaction between the D1 and adenosine-dependent stimulatory metabotropic receptor was sought by examining this interaction on striatal GABA release. SKF 38393 and 1S,3R-ACPD together were found to potentiate striatal GABA release induced by 15 mM K+. The potentiation was blocked by the D1 antagonist, SCH 23390. However, this effect was only partially mimicked by a high concentration of forskolin (100 microM) and was not blocked by L-serine-o-phosphate, thereby suggesting that the stimulatory mGluR does not mediate this potentiation.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1995

Characterization of nitric oxide generator-induced hippocampal [3H]norepinephrine release. II. The role of calcium, reverse norepinephrine transport and cyclic 3',5'-guanosine monophosphate.

The mechanisms by which two nitrogen monoxide (NO) generators, hydroxylamine and S-nitroso-L-cysteine (NO-CYS), induce hippocampal [3H]norepinephrine ([3H]NE) release was investigated. Neither hydroxylamine- nor NO-CYS-induced release was affected by the guanylate cyclase inhibitors, methylene blue or LY 83,583. The effect of hydroxylamine was completely dependent on extracellular Ca++ and reduced by 40% in the presence of omega-conotoxin GVIA, an N-type Ca(++)-channel antagonist; however it was unaffected by Ni++, nifedipine, caffeine or thapsigargin. The stimulatory effect of hydroxylamine on hippocampal cyclic GMP formation was not significantly affected by removal of extracellular Ca++, indicating that Ca(++)-dependent release is not due to inhibition of NO formation from hydroxylamine. However, the response to NO-CYS was reduced by 35 to 50% in either nominally Ca(++)-free or 10 mM MgSO4-containing buffer. Interestingly, buffer containing ethylene glycol bis(beta-aminoethyl ether)-N,N'-tetraacetic acid dramatically enhanced the formation of NO from NO-CYS and potentiated the NO-CYS response. Both NO-CYS- and hydroxylamine-induced [3H]NE release was inhibited by NE transport blockers, indicating a prominent role for reverse transport. NO-CYS completely inhibited synaptosomal uptake of [3H]NE (IC50 approximately, 300 microM). NO generator-induced [3H]NE release has a glutamate-dependent component (see accompanying article). Inhibition of glutamate-evoked [3H]NE release by mazindol, an inhibitor of NE transport, suggests that the glutamate-dependent component also involves reversal of the NE transporter. These data suggest that NO produced from hydroxylamine or NO-CYS evoke both vesicular and nonvesicular release of hippocampal [3H]NE. Putative NO target molecules and the role of extracellular Ca++ are discussed.

Animals↗
PubMed1995

Characterization of nitric oxide generator-induced hippocampal [3H]norepinephrine release. I. The role of glutamate.

In this study we compared the effects of two nitrogen monoxide (NO) generators, hydroxylamine and S-nitroso-L-cysteine (NO-CYS), on hippocampal [3H]norepinephrine ([3H]NE) release. A 10-min incubation with hydroxylamine (3-3,000 microM) or NO-CYS (30-10,000 microM) induced a concentration-dependent increase in the basal [3H]NE efflux with EC50 values of approximately 100 microM and 1 mM, respectively. Reduced hemoglobin, a NO scavenger, blocked both hydroxylamine- and NO-CYS-evoked [3H]NE release. Long-term exposure (> or = 25 min) to 100 microM hydroxylamine, or to millimolar concentrations of NO-CYS, evoked a tetrodotoxin-insensitive [3H]NE release. However, a 10-min stimulation with either 100 microM hydroxylamine or 300 microM NO-CYS was sensitive to 0.5 microM tetrodotoxin, a voltage-sensitive sodium channel blocker. This suggested that under these conditions hydroxylamine and NO-CYS induce [3H]NE release indirectly in part, perhaps via releasing an excitatory neurotransmitter. Indeed, kynurenate, a nonselective ionotropic glutamate receptor antagonist, produced an 80% inhibition of the NO generator-evoked [3H]NE release. CGS 19755, a N-methyl-D-aspartate receptor antagonist, had no significant effect, whereas the alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid/kainate receptor antagonists, CNQX and GYKI 52446, inhibited the hydroxylamine response by 50%. In synaptosomes, a preparation in which synaptic interactions are nonsignificant, NO-CYS induced a dose-dependent release of both [3H]NE and [3H]glutamate. These data suggest that, in hippocampal slices, NO generators evoke [3H]NE release both directly from noradrenergic terminals and indirectly via releasing glutamate.

Animals↗
PubMed1995

Can cavitation bubbles generated by mechanical heart valves be detected by transcranial Doppler?

Increasingly, transcranial Doppler (TCD) systems are being considered as potential tools to determine the thrombogenicity of herat valve prostheses and/or to serve as early warnings of impending thromboembolic strokes. TCD is thought to detect the presence of intracranial arterial microemboli based on high intensity signals (HITS). While the exact cause of these HITS is not known, it has been theorized that they are due in part to mechanical valve induced cavitation. To determine if this is correct, in vitro experiments were conducted to find if TCD could detect mechanical valve induced cavitation bubbles. An in vitro flow system was developed in which 29mm Medtronic Hall, St. Jude Medical and Medtronic Intact valves, one each, were simultaneously subjected to validated non-cavitation and cavitation generating conditions. Polystyrene particles as well as air bubbles were infused into the flow system to provide controls for comparison. The flow field proximal to each valve was interrogated using TCD sample volumes located 2.5 cm proximal to, 1.3 cm proximal to, and at the valvular inflow surface. The TCD system accurately detected both infused air bubbles and polystyrene particles at all sample volume locations. Under known cavitation generating conditions without infused air bubbles, the TCD failed to register HITS at any sample volume location. Even though cavitation at the valve surface might have been masked by a "system generated artifact", cavitation formed bubbles must persist and pass through the two proximal sample volumes if they were to be captured intracranially. These data suggest that the TCD is unable to detect mechanical valve induced cavitation bubbles either because the bubbles are too small, too few, or too short lived. It is therefore probable that clinically recorded HITS associated with mechanical valves are from origins other than valve induced cavitation bubbles.

Algorithms↗
PubMed1994

Traumatic brain injury reduces hippocampal high-affinity [3H]choline uptake but not extracellular choline levels in rats.

Hippocampal cholinergic hypofunction may contribute to memory deficits following experimental traumatic brain injury. These studies examined two important factors in acetylcholine synthesis: choline availability and neuronal uptake. No reductions in basal extracellular choline levels, using microdialysis, were observed 2 weeks after cortical impact injury. However, studies of high affinity [3H]choline uptake in the hippocampus, measured in a synaptosomal preparation, found a reduction in the maximum velocity of choline uptake (Vmax), while no differences in affinity constants (Km) were found. The results suggest that post-traumatic cholinergic deficits are not attributable to decreased availability of choline, but may be associated with either a decreased ability of cholinergic neurons to take up choline and/or a loss of cholinergic neurons.

Acetylcholine↗
PubMed1994

Structure-activity relationship studies of N-sulfonyl analogs of cocaine: role of ionic interaction in cocaine binding.

Six new N-sulfonylated analogs of cocaine have been prepared, and these compounds have been evaluated for their ability to inhibit [3H]mazindol binding and [3H]dopamine uptake into striatal synaptosomes. The N-sulfonyl compounds still inhibited binding and uptake at low micromolar concentrations despite the neutral character of the tropane nitrogen, thus suggesting that the binding of cocaine to the dopamine transporter may not require protonation of its nitrogen and ionic interaction with its recognition site.

Animals↗
PubMed1994

Regulation of nitric oxide synthase activity in cortical slices by excitatory amino acids and calcium.

Nitric oxide synthase (NOS) activity was determined in adult rat frontal cortex and hippocampus by measuring the conversion of L-[3H]arginine to L-[3H]citrulline. N-methyl-D-aspartate (NMDA), but not kainate or alpha-amino-3-hydroxy-5-methylisoxazole-4-propionate (AMPA), stimulated NOS activity. This effect was concentration dependent (EC50 approximately 30 microM) and was inhibited by tetrodotoxin, EGTA, N omega-nitro-L-arginine (NOARG), Mg2+, phencyclidine, and (cis)-4-phosphonomethyl-2-piperidine carboxylate (CGS 19755), but not by 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX). NOS activity was increased to an even greater extent by the calcium ionophores ionomycin and A23187 and by depolarization with 50 mM K+. Interestingly, neither caffeine nor 1-aminocyclopentane-1,3-dicarboxylic acid (1S,3R-ACPD), drugs that would be expected to increase intracellular Ca2+ concentration by release of Ca2+ from intracellular ryanodine- and inositol-1,4,5-trisphosphate-sensitive stores, respectively, had any significant effect on NOS activity. It is concluded that NOS can be activated by NMDA binding to a classic NMDA glutamate receptor subtype as well as by depolarization or other agents that increase the influx of extracellular Ca2+. The paradoxical lack of effect of caffeine, as well as the inhibitory effect of tetrodotoxin, are discussed.

Amino Acid Oxidoreductases↗