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Biomedical subjects

K R Powell

Publications and source records attributed to K R Powell.

At least 19 recordsLinked to original sources
PubMed1992

Hemolytic uremic syndrome due to Escherichia coli O157: H7 in a child with multiple infections.

Hemolytic uremic syndrome (HUS) is characterized by hemolytic anemia, thrombocytopenia, and uremia; it is a common cause of acute renal failure in children. Although many microbial agents have been associated with HUS, only Escherichia coli O157: H7 has been clearly demonstrated to be a major cause of this illness. A case is presented of a healthy 4-year-old boy who had a recent varicella infection; when evaluated for HUS his blood and stool cultures both grew Salmonella montevideo and blood cultures grew group A beta-hemolytic streptococci. A stool cultured on MacConkey-sorbitol agar also grew E. coli O157: H7. An eightfold rise in serum antibodies to E. coli O157: H7 lipopolysaccharide was also demonstrated. The child recovered completely and was healthy 3 years later. Although this child had several infectious agents anecdotally associated with HUS, appropriate culture of stool showed that he also had E. coli O157: H7 infection. Previous cases thought to be due to other pathogens may similarly have been caused by co-infection with E. coli O157: H7.

Antibodies, Bacterial↗
PubMed1992

Intermediate efficacy mu opioids: examination of their morphine-like stimulus effects and response rate-decreasing effects in morphine-tolerant rats.

The present study examined the effects of morphine, the intermediate efficacy mu opioids (-)-pentazocine, (-)-metazocine, proxorphan, levallorphan, (-)-NANMY (N-allylnormetazocine) and (-)-cyclazocine, and the mu antagonist naloxone 1) in rats responding under a FR (fixed-ratio) 30 schedule before, during and after a chronic morphine regimen, and 2) in rats trained to discriminate 10.0 [10-MS (morphine sulfate)] or 3.0 mg/kg (3-MS) of morphine from saline. Under the FR30 schedule, chronic administration of morphine produced tolerance to morphine's rate-decreasing effects and conferred cross-tolerance to (-)-metazocine, proxorphan and (-)-pentazocine. However, the effects of these intermediate efficacy mu opioids could be differentiated from those of morphine on the basis of their 1) shallow dose-effect curves, and 2) large differences in the degree to which tolerance developed in individual rats. In the drug discrimination procedure, (-)-metazocine, proxorphan and (-)-pentazocine produced high levels of substitution for the 3-MS stimulus and intermediate levels for the 10-MS stimulus. In contrast to the pattern of substitution observed with morphine in the 10-MS group, the effects of these drugs were characterized by 1) shallow dose-effect curves, 2) large individual differences in the lowest dose of each drug that substituted completely for the 10-MS stimulus and 3) the failure to obtain complete substitution for the 10-MS stimulus in all of the rats tested. The behavioral profile obtained with the intermediate efficacy mu opioids (-)-NANM, levallorphan and (-)-cyclazocine was indicative of opioids with intrinsic efficacy lower than that of (-)-pentazocine, (-)-metazocine and proxorphan. Under the FR30 schedule, chronic administration of morphine produced an enhanced sensitivity to the rate-decreasing effects of (-)-NANM and levallorphan but not (-)-cyclazocine. In the drug discrimination procedure, (-)-NANM, levallorphan and (-)-cyclazocine produced high levels of substitution for the 3-MS stimulus and low levels for the 10-MS stimulus. Like naloxone, these drugs produced a dose-related attenuation of the 10-MS stimulus. The results of the present study suggest that the relative order of intrinsic efficacy among the opioids tested is: morphine > (-)-metazocine = (-)-pentazocine = proxorphan > (-)-cyclazocine = levallorphan = (-)-NANM > naloxone.

Animals↗
PubMed1991

Differential cross-tolerance to mu and kappa opioid agonists in morphine-tolerant rats responding under a schedule of food presentation.

If different populations of opioid receptors mediate the actions of mu and kappa opioid agonists, then tolerance induced by the chronic administration of a mu agonist should confer cross-tolerance to other mu agonists but not necessarily to those compounds whose effects are mediated by the kappa receptor. This hypothesis was evaluated in the present investigation by examining the effects of the mu agonists morphine, l-methadone and fentanyl, the kappa agonists U50,488 and bremazocine, and the mixed kappa/mu agonist ethylketocyclazocine in rats responding under a fixed-ratio 30 schedule of food presentation before, during and after exposure to a regimen of chronic morphine administration. For comparison, naloxone was evaluated as a representative mu antagonist and the phenothiazine chlorpromazine as a control drug. During all phases of the experiment, each of these compounds produced dose-related decreases in rate of responding. During the daily administration of 40 mg/kg morphine, tolerance developed to the rate-decreasing effects of morphine, l-methadone and fentanyl, and an enhanced sensitivity to the effects of naloxone. In contrast to the effects obtained with these mu opioids, there was no evidence that chronic morphine administration produced tolerance or enhanced sensitivity to the rate-decreasing effects of U50,488, bremazocine, ethylketocyclazocine and chlorpromazine. The present findings demonstrate that the chronic administration of morphine results in the selective development of tolerance to other mu agonists.(ABSTRACT TRUNCATED AT 250 WORDS)

3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cycloh↗
PubMed1991

Autoradiographic analysis of the in vivo distribution of 3H-imipramine and 3H-desipramine in brain: comparison to in vitro binding patterns.

Using high resolution autoradiographic techniques, the distribution of radioactivity in forebrain and brainstem was assessed after IV injection of 3H-impramine or 3H-desipramine. Results were compared with regional binding of the drugs to brain sections in vitro. Similar topographic binding of 3H-imipramine and 3H-desipramine was observed in vitro among brain regions, except in the paraventricular nucleus of the hypothalamus and locus coeruleus, where binding was greater for 3H-desipramine. For both 3H-desipramine and 3H-imipramine, some brain regions that exhibited high binding in vitro also showed high accumulation after in vivo injection. However, certain regions that contained high densities of binding sites for the antidepressant drugs as measured by in vitro binding showed very low accumulation of radioactivity after in vivo treatment. Such regions included the dentate gyrus of the hippocampus, layer 1 of piriform cortex, caudate-putamen, pontine and midbrain central gray, and cerebellar granular layer. Compared to in vitro binding of the drugs, the distribution of imipramine and desipramine in vivo appears more anatomically selective. For imipramine, primary sites of action in vivo, as indicated by the topographic distribution in brain, appear to be the locus coeruleus, hippocampus, lateral septal nucleus, and amygdala. For desipramine, the greatest accumulation in vivo was found in the locus coeruleus, paraventricular nucleus of the hypothalamus, and anterior thalamic nuclei.

Animals↗
PubMed1991

Evaluation of the effects of PD 134308 (CI-988), a CCK-B antagonist, on the punished responding of squirrel monkeys.

Lever pressing of squirrel monkeys was maintained by a fixed-interval 3-min schedule of food presentation during which every 30th response also produced a brief electric shock. Lever pressing was suppressed during this stimulus (conflict or punishment) compared to that occurring prior to the introduction of shock or, with some monkeys, during an alternate stimulus in which punishment did not occur. PD 134308 (CI-988), administered i.m. (0.03-3.0 mg/kg), increased punished responding but had no effect on non-punished responding. Peak increases of 150% of control occurred at 3.0 mg/kg. There was no indication of sedation at the highest dose of PD 134308 (10.0 mg/kg). By comparison, chlordiazepoxide (1.0-10 mg/kg, i.m.) produced similar effects, except the magnitude of increases in punished responding reached approximately 200% of control performance levels and the higher doses reduced non-punished response rates. PD 134308 produces anxiolytic-like effects in this animal model of anxiety that would suggest potential clinical efficacy in humans of a novel class of compounds with actions at or modulated by cholecystokinin receptors.

Animals↗
PubMed1991

Relevance of common tests of cerebrospinal fluid in screening for bacterial meningitis.

This study tests the hypothesis that if cerebrospinal fluid (CSF) has a nucleated blood cell count (NucBC) of less than 6/mm3, CSF tests other than bacterial culture need not be performed to exclude the diagnosis of bacterial meningitis in patients not receiving antimicrobial agents. The results of tests performed on the first specimen of CSF obtained for a given hospital visit from children younger than 3 years of age, exclusive of newborn infants admitted to the hospital on their date of birth, were analyzed. Of 3356 CSF specimens evaluated, 122 were from patients with bacterial meningitis; 460 specimens were analyzed separately because the erythrocyte count was greater than 1000/mm3. A negative CSF screening test result was defined as a CSF NucBC less than 6/mm3. In facilitating the diagnosis of bacterial meningitis, this screening test had a sensitivity of 98.4%, a specificity of 75.2%, and a negative predictive value of 99.9%. The other CSF tests varied widely in screening effectiveness: a Gram-stained smear had a sensitivity of 53% and a specificity of 97%. Receiver operating characteristic curve analysis was used to assess the screening relevance of CSF tests. The CSF NucBC and CSF segmented NucBC performed indistinguishably and superiorly compared with the CSF protein or glucose concentration and the ratio of CSF glucose to serum glucose concentration. Logistic regression analysis showed that the NucBC alone is superior to any combination of the other CSF tests. In a prospective study of 215 children younger than 3 years of age undergoing a lumbar puncture in our emergency department, 85% had empiric criteria identifying them as appropriate for an abbreviated CSF evaluation. The CSF NucBC was less than 6/mm3 in 70% of the 181 patients who would have been eligible for an abbreviated CSF evaluation. These data suggest that a strategy for the sequential testing of CSF could be adopted that would exclude unnecessary determinations and thereby save time, effort, and health care dollars.

Blood Glucose↗
PubMed1991

The changing spectrum of group B streptococcal disease in infants: an eleven-year experience in a tertiary care hospital.

Risk factors, clinical syndromes and the case-fatality rates associated with Group B Streptococcus (GBS) infections in infants managed at the University of Rochester Medical Center during 1979 to 1989 were reviewed. Overall 92 episodes of early onset disease (EOD) and 54 of late onset disease (LOD) were diagnosed in 143 infants (3 infants with EOD presented later with LOD). About one-third of patients with EOD and controls were non-white compared with two-thirds of patients with LOD that occurred in racial minority groups. Prematurity and low birth weight were significantly more common in patients with invasive GBS disease than in controls. Eighty-three of 92 (90%) cases of EOD were detected during the first day of life and 10 of 54 (19%) cases of LOD occurred in infants older than 3 months of age. At the time of diagnosis 4% of infants with EOD were asymptomatic, 54% had respiratory disease, 27% had sepsis without a focus, 15% had meningitis and 1% had urinary tract infection or omphalitis. Among infants with LOD 46% had sepsis, 37% meningitis, 7% urinary tract infection, 6% osteomyelitis and/or septic arthritis and 4% cellulitis or pneumonia. Leukopenia and shift to the left were observed in 43 and 61% of episodes of EOD and in 28 and 57% of episodes of LOD, respectively. All infants were promptly treated with antibiotics and vigorous supportive therapy. The case-fatality rate was 13% in EOD and 0 in LOD.(ABSTRACT TRUNCATED AT 250 WORDS)

Female↗
PubMed1990

Opioid agonists/antagonists in morphine-tolerant squirrel monkeys.

The mu-opioid agonist morphine, the opioid antagonist naloxone and the isomers of the mixed action opioids, cyclazocine, n-allylnormetazocine, and pentazocine were examined in squirrel monkeys responding under a fixed-ratio 30 schedule of food presentation. Dose-effect curves for all drugs were obtained prior to, during, and following a chronic regimen in which monkeys received 6 mg/kg/day of morphine. When compared to the dose-effect curves obtained prior to the chronic regimen, the morphine dose-effect curve obtained during the chronic regimen was shifted to the right 0.5-1.0 log unit, whereas the naloxone dose-effect curve shifted over 3 log units to the left. No changes were observed between the prechronic and chronic dose-effect curves for (+)-cyclazocine, (+)-n-allylnormetazocine, and (+)- or (-)-pentazocine. The (-) isomers of n-allylnormetazocine and cyclazocine shifted 0.6-1.7 log units to the left. These results suggest that the (-) isomers of cyclazocine and n-allylnormetazocine have mu antagonist properties which are revealed during chronic morphine administration.

Analgesics, Opioid↗
PubMed1990

Normalization of plasma arginine vasopressin concentrations when children with meningitis are given maintenance plus replacement fluid therapy.

We hypothesized that plasma arginine vasopressin (AVP) concentrations in children with meningitis are appropriate for the children's degree of hypovolemia, even though the concentrations were higher than expected for the serum osmolality. A randomized study was conducted to compare the effect on plasma AVP concentrations of giving maintenance fluid requirements plus replacement of any deficit versus restricting fluids to two thirds of maintenance requirements for 24 hours. Plasma AVP concentrations and serum osmolality were measured before fluid therapy was begun and again after 24 hours. Nineteen children, 2 months to 17 years of age, were studied; 13 had bacterial meningitis (12 with Haemophilus influenzae type b). Ten children (seven with bacterial meningitis) received a mean of 1.42 times the calculated maintenance fluid requirements, and nine (six with bacterial meningitis) were restricted to a mean of 0.65 times maintenance. Children in the maintenance group also received significantly more sodium (mean = 6.3 mEq/kg/24 hr) than children in the fluid-restricted group (mean = 2.0 mEq/kg/24 hr). The two groups were comparable for plasma AVP concentration and serum osmolality before fluid therapy was begun. The plasma AVP concentration was significantly lower after 24 hours of maintenance plus replacement fluids than after fluid restriction (p = 0.005), and the change in AVP concentration correlated with the amount of sodium given (p less than 0.02). This study supports the hypothesis that serum AVP concentrations are elevated in patients with meningitis because of hypovolemia and become normal when sufficient sodium is given to facilitate reabsorption of water by the proximal tubule of the kidney. Patients with meningitis can be given maintenance plus replacement fluids but should be monitored for the development of the syndrome of inappropriate secretion of antidiuretic hormone.

Adolescent↗
PubMed1990

Outpatient management of selected infants younger than two months of age evaluated for possible sepsis.

Previously healthy infants younger than 2 months of age without evidence of soft tissue or musculoskeletal infection who had white blood cell counts between 5000 and 15,000/mm3, band form counts less than or equal to 1500/mm3, urinalysis less than or equal to 10 white blood cells/high power field (spun sediment) and stool less than or equal to 5 white blood cells/high power field (if diarrhea) were considered at low risk for a serious bacterial infection. Infants meeting these criteria whose parents were judged to be adequate observers and had a telephone and automobile were eligible for outpatient management. Infants were given ceftriaxone to cover the possibility that the low risk criteria might miss more infants with serious bacterial infections than was predicted. From Jan. 1, 1987 to May 31, 1989, 86 infants younger than 2 months were enrolled. There were no serious complications in these infants. Twelve had transient problems possibly related to the intramuscular ceftriaxone therapy. One low risk infant was hospitalized for Neisseria meningitidis bacteremia and five other infants were hospitalized for medical or social reasons. All six hospitalized infants had short admissions and did well. This study supports the continued use of the low risk criteria to distinguish infants unlikely to have a serious bacterial infection. Furthermore, in a selected group of low risk infants, outpatient management may be an acceptable alternative to inpatient therapy.

Ambulatory Care↗