Postanginal sepsis following infectious mononucleosis.

During a five-year period, three patients were seen with postanginal sepsis occurring within ten days of the onset of infectious mononucleosis. Postanginal sepsis was not diagnosed in other hospitalized patients during this period. These cases demonstrate that postanginal sepsis can be a complication of infectious mononucleosis.

Acute illnesses in the 2 weeks after hospitalization for bacterial meningitis.

The hospital records of 118 2-month-old to 3-year-old children who had been treated for bacterial meningitis were reviewed. Within 2 weeks after hospitalization, one fourth of the patients sought medical attention for an acute illness, but only one was treated for the possible relapse or recurrence of meningitis. Because only five of the 113 patients with available follow-up information required a diagnostic lumbar puncture procedure, it is not recommended that a lumbar puncture be performed following treatment of bacterial meningitis to provide end-of-treatment baseline information.

Haemophilus influenzae type b meningitis: occurrence in three siblings over a two-year period.

Haemophilus influenzae type b meningitis occurred in all three siblings in one family over a 24-month period. Investigations of the organisms involved and immunologic studies of the family revealed low percentages of E-rosette-forming cells (T-cells) in both surviving children and in the father. This report suggests that host susceptibility to H influenzae is genetically controlled and that T-cell functions, as yet undetermined, may be involved.

Febrile infants at low risk for serious bacterial infection--an appraisal of the Rochester criteria and implications for management. Febrile Infant Collaborative Study Group.

OBJECTIVE: Prospective studies were conducted to test the hypothesis that infants unlikely to have serious bacterial infections (SBI) can be accurately identified by low risk criteria. METHODS: Febrile infants (rectal T > or = 38 degrees C) < or = 60 days of age were considered at low risk for SBI if they met the following criteria: 1) appear well; 2) were previously healthy; 3) have no focal infection; 4) have WBC count 5.0-15.0 x 10(9) cells/L (5000-15,000/mm3), band form count < or = 1.5 x 10(9) cells/L (< or = 1500/mm3), < or = 10 WBC per high power field on microscopic examination of spun urine sediment, and < or = 5 WBC per high power field on microscopic examination of a stool smear (if diarrhea). The recommended evaluation included the culture of specimens of blood, cerebrospinal fluid, and urine for bacteria. Outcomes were determined. The negative predictive values of the low risk criteria for SBI and bacteremia were calculated. RESULTS: Of 1057 eligible infants, 931 were well appearing, and, of these, 437 met the remaining low risk criteria. Five low risk infants had SBI including two infants with bacteremia. The negative predictive value of the low risk criteria was 98.9% (95% confidence interval, 97.2% to 99.6%) for SBI, and 99.5% (95% confidence interval, 98.2% to 99.9%) for bacteremia. CONCLUSIONS: These data confirm the ability of the low risk criteria to identify infants unlikely to have SBI. Infants who meet the low risk criteria can be carefully observed without administering antimicrobial agents.

Five years of experience with the exclusive use of amikacin in a neonatal intensive care unit.

From November 1, 1980, to December 31, 1985, 3959 infants were admitted to the neonatal intensive care unit and 2385 infants (60%) received 2791 courses of aminoglycoside therapy. Aminoglycoside use totaled 16,279 patient days of which 16,070 (98.7%) were with amikacin. From November 1, 1980, to January 31, 1983, 1017 pairs of pre- and posttreatment endotracheal or pharyngeal specimens yielded 318 Gram-negative bacteria isolates. From November 1, 1980, to December 31, 1985, Gram-negative bacteria were isolated from 381 clinical specimens. Of the 318 surveillance and 380 clinical isolates tested, 285 (90%) and 358 (94%), respectively, were susceptible to amikacin. Amikacin resistance did not increase during the study. Amikacin-resistant organisms were isolated more frequently from patients receiving multiple courses than those receiving single courses of amikacin and resistant organisms were not usually found before the administration of amikacin. None of the 15 amikacin-resistant isolates made 6'-N-aminoglycoside acetyltransferase and 3 isolates took up only small amounts of radiolabeled amikacin, suggesting that resistance was due to decreased permeability. The extensive use of amikacin in a neonatal intensive care unit for over 5 years did not result in an increase of amikacin-resistant Gram-negative bacteria.

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)

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.

The role of serotonergic receptors in the effects of mu opioids in squirrel monkeys responding under a titration procedure.

This experiment was conducted to determine whether drugs acting on brain serotonin modulate the effects of the mu opioid, morphine, as measured by the squirrel monkey shock titration procedure and, if so, whether serotonergic modulation is mediated via specific 5HT receptor subtypes. Under this procedure, electric shock was delivered to the monkey's tail and scheduled to increase once every 15 s from 0.01 to 2.0 mA in 30 steps. Five responses on a lever during the 15-s shock period terminated the shock for 15 s, after which the shock resumed at the next lower intensity. The intensity below which monkeys maintained shock 50% of the time (median shock level or MSL) and rate of responding (RR) in the presence of shock were determined under control conditions and after administration of morphine alone and in combination with various serotonergic compounds. Morphine increased median shock level and decreased rate of responding in a dose-dependent manner. These effects of morphine was attenuated by the 5HT1A receptor agonists, 8-OH-DPAT [(+)-8-hydroxy-2(di-n-propylamino tetralin HBr] and ipsapirone. The effects of morphine were not altered by the 5HT1A receptor antagonist, NAN-190 [1-(2-methoxyphenyl-4-[4-(2-phthalimido) butyl] piperazine HBr], and 5HT2 receptor antagonist, ketanserin, the 5HT3 receptor antagonist, MDL 72222 [3-tropanyl-3,5-dichlorobenzoate], the alpha 2 adrenergic antagonist, yohimbine, or the alpha2 adrenergic agonist, clonidine. These results suggest that 5HT1A receptors may be involved in the effects of morphine in the shock titration procedure, whereas 5HT2, 5HT3 and alpha 2 adrenergic receptors do not appear to play a role in morphine's effects in this procedure.

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)

Antinociceptive effects of the kappa opioid, U50,488: lack of modulation by 5-HT2 antagonists.

The kappa opioid, U50,488, was examined alone and in combination with the 5HT2 antagonists, ketanserin, pirenperone and LY 53857. Squirrel monkeys responded under a shock titration procedure in which shock intensity increased every 15 s from 0.01 to 2.0 mA in 30 steps. Five responses terminated the shock for 15 s, after which the shock resumed at the next lower intensity. The level at which the monkeys kept the shock 50% of the time (median shock level/MSL) was determined. U50,488 alone produced dose-dependent increases in median shock level whereas none of the 5-HT2 antagonists altered responding under this procedure. When ketanserin (0.032-5.6 mg/kg) was administered in combination with U50,488, very high doses of ketanserin (3.2-5.6 mg/kg) shifted the U50,488 dose-effect curve to the left. Neither pirenperone (0.032-10.0 micrograms/kg) nor LY53857 (0.01-0.32 mg/kg) altered the U50,488 dose-effect curve in any monkey. Taken together, these data do not support a role for the 5-HT2 system in kappa-induced antinociception in the primate.

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.

Differential antagonism of the rate-decreasing effects of kappa-opioid receptor agonists by naltrexone and norbinaltorphimine.

Eight kappa-opioid receptor agonists were examined for their effects in squirrel monkeys responding under a fixed interval 3-min schedule of stimulus termination. Six of these kappa-opioid receptor agonists decreased dose-dependently the total number of responses and with an order of potency consistent with kappa-opioid receptor interaction. Three of these kappa-opioid receptor agonists, bremazocine, U69,593 [[(5a,7a,8b)-(+)-N-[7-(1-pyrrolidinyl)-1-oxaspiro(4,5)dec-8-yl)] benzeneacetamide] and enadoline, were evaluated following pretreatment with 1.0 mg/kg of naltrexone or 3.0 mg/kg of norbinaltorphimine. The effects of the three agonists were antagonized significantly by naltrexone, but only those of bremazocine and U69,593 were antagonized significantly by norbinaltorphimine. Statistical analysis of the data averaged over six monkeys revealed that naltrexone was significantly more potent than norbinaltorphimine at antagonizing enadoline and U69,593, but naltrexone and norbinaltorphimine were equipotent at antagonizing bremazocine. Moreover, naltrexone was 8-fold more potent at antagonizing U69,593 and enadoline than at antagonizing bremazocine. These results suggest that under these conditions the effects of U69,593 and enadoline may be mediated, in part, by a different receptor population, perhaps a subtype of kappa-opioid receptors, from the one that mediates the effects of bremazocine.

An in vitro investigation of the penetrating efficacy of BIS-GMA resin pit and fissure coatings.

The frequency of complete penetration of two commercial BIS-GMA resin pit and fissure coating materials into wide and constricted fissures was assessed from photomicrographs. It was found that 334 of the 390 wide fissures examined were completely filled by the coating materials. However, in contrast, only 28 of the 650 constricted fissures examined were completely filled by these resins.

Effect of stannous fluoride treatments on the progression of initial lesions in approximal surfaces of permanent posterior teeth.

Bite-wing radiographs were used to determine the effect of three forms of topical SnF2 therapy on the progression of initial lesions in the approximal surfaces of permanent posterior teeth. Radiographs were taken annually over a four-year period. The subjects were schoolchildren, aged 12-14 yr, living in a low fluoride area. The professional application of a 10% SnF2 solution for 30 s, semi-annually for two yr, had no discernible effect on the development of the initial lesions. However, the home use of a SnF2 dentifrice did inhibit caries progression appreciably at all but one of the four time intervals in the study. The professional application of a 10% SnF2 solution for 30 s, semi-annually for two yr, combined with the home use of a SnF2 dentifrice, was the most effective treatment in retarding lesion development. Even without topical fluoride therapy, the rate of progression of initial approximal lesions was generally quite slow. In view of these findings, it would seem sound clinical practice to treat all initial lesions in approximal surfaces with topical fluoride therapy and delay placement of restorations until there is radiographic evidence of lesions reaching dentin.

Parametric evaluation of the development of sensitization to the effects of morphine on locomotor activity.

Animals repeatedly administered drugs of abuse often become more sensitive to their effects. It has been proposed that this behavioral sensitization may serve as a useful model for changes that may underlie the etiology and maintenance of drug-seeking behavior. This study was designed to determine systematically some of the conditions of drug exposure under which sensitization occurs to morphine-induced stimulation of locomotor activity. Groups of rats (n=8 per group) were exposed to a regimen of intermittent morphine or saline injections for 1--4 days and tested at later time points with morphine or saline. The amount of behavioral sensitization observed was related to the number of drug exposures, but not to the dose of morphine used during drug exposures. Sensitization to morphine persisted for as long as 3 months and was completely blocked when naltrexone was administered with the test dose of morphine after the final morphine exposure. Administration of naltrexone with morphine during the exposure regimen did not alter the development of behavioral sensitization. These results indicate a robust behavioral sensitization to morphine that appears to be influenced in an orderly manner within a narrow window of the drug exposure conditions.

Serotonin involvement in the discriminative stimulus effects of mu and kappa opioids in rats.

The role of serotonin (5-HT) in the discriminative stimulus effects of opioids was examined using a two-lever, food-reinforced drug discrimination procedure. The effects of the 5-HT(1A) full agonist 8-OH-DPAT, the 5-HT(1A) partial agonist buspirone and the 5-HT(2) antagonist ketanserin were evaluated in rats trained to discriminate the mu opioid agonist morphine, or the kappa opioid agonist U50, 488 from saline. In rats trained to discriminate 5.6mg/kg of morphine from saline, morphine dose-dependently substituted (produced >/= 80% morphine-appropriate responding) for the morphine stimulus. In contrast, U50,488, 8-OH-DPAT and ketanserin did not substitute for morphine, and buspirone produced only a small degree of substitution (approx. 40% morphine-appropriate responding). When administered in combination with morphine, 8-OH-DPAT, but not buspirone and ketanserin, attenuated the discriminative stimulus effects of higher doses of morphine. In rats trained to discriminate 5.6mg/kg of U50, 488 from saline, U50, 488 dose-dependently substituted for the U50, 488 stimulus. When administered alone, 8-OH-DPAT and buspirone partially substituted (produced between 40% and 79% U50, 488-appropriate responding) for the U50,488 stimulus, whereas morphine and ketanserin did not substitute for U50,488. The opioid antagonist naltrexone failed to antagonize the effects of 8-OH-DPAT and buspirone suggesting that the effects of these drugs in U50,488-trained rats were not mediated by opioid receptors. When administered in combination with U50,488, 8-OH-DPAT, but not buspirone or ketanserin, attenuated the discriminative stimulus effects of the training dose of U50,488. These results suggest that the 5-HT system is involved in the discriminative stimulus effects of both morphine and U50,488, although the exact nature of this 5-HT involvement is not clear.

Modulation of the discriminative stimulus effects of d-amphetamine by mu and kappa opioids in squirrel monkeys.

It has been reported that the discriminative stimulus effects of cocaine in squirrel monkeys can be potentiated by mu opioid agonists and attenuated by kappa opioid agonists. The purpose of this study was to extend these observations by examining the effects of mu and kappa opioids agonists on the discriminative stimulus effects of d-amphetamine (AMPH). Five squirrel monkeys were trained to discriminate 0.3 mg/kg of AMPH (i.m.) from saline using a stimulus termination/avoidance task. AMPH and cocaine substituted dose dependently for the AMPH training stimulus in all five monkeys. The AMPH training dose was completely antagonized by 0.1 mg/kg of the D1 dopamine antagonist SCH 39166. When administered alone, the kappa agonist U69,593 substituted partially or completely for AMPH in four of five monkeys, the kappa agonist enadoline substituted completely for AMPH in two of five monkeys, and morphine substituted completely for AMPH in one monkey. In all five monkeys, pretreatment with some doses of U69,593 or enadoline attenuated the discriminative stimulus effects of AMPH; however, some doses of U69,593 and enadoline also potentiated the effects of AMPH in at least two monkeys. Morphine pretreatment potentiated the discriminative stimulus effects of AMPH in three monkeys and either attenuated or did not alter these effects in two monkeys. Morphine pretreatment did not significantly alter the discriminative stimulus effects of cocaine except in one monkey. These data indicate large individual differences in the abilities of mu and kappa opioid agonists to alter the discriminative stimulus effects of AMPH.

Lack of NMDA receptor involvement in caffeine-induced locomotor stimulation and tolerance in rats.

The involvement of NMDA-type glutamate receptors in caffeine's locomotor stimulant effects and the development of tolerance to these effects was examined in rats. Caffeine and the noncompetitive NMDA receptor antagonists, MK-801 and phencyclidine (PCP), were examined alone and in combination. Caffeine produced a biphasic dose-effect curve. Both MK-801 and PCP increased locomotor activity at the highest doses tested. MK-801 and PCP shifted the caffeine curve upward, but only with the highest doses that increased locomotor activity when given alone. For the tolerance experiment, osmotic pumps containing either MK-801 or nothing at all and were implanted in rats that were given either caffeinated or drug-free tap water to drink. All rats drinking caffeine showed tolerance to its locomotor stimulant effects, whereas rats drinking drug-free tap water did not. Chronic infusion of MK-801 (0.1 and 0.3 mg/kg/day) failed to block the development of tolerance to caffeine. The 0.3 mg/kg/day infusion of MK-801 appeared to slightly delay the development of tolerance to caffeine, but this effect was probably due to the locomotor stimulant effects of this infused dose of MK-801 alone. These data provide no evidence that NMDA-type glutamate receptors play a crucial role in mediating caffeine's locomotor stimulant effects or tolerance to these effects.

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.

The role of dopamine in the locomotor stimulant effects and tolerance to these effects of caffeine.

Current evidence indicates that the acute locomotor stimulant effects of caffeine involve dopamine (DA) receptor activation; however, few studies have investigated the role of DA receptors in mediating the development of tolerance to caffeine. Therefore, the present study was designed to determine the degree to which DA receptors mediate the development of tolerance to the locomotor stimulant effects of caffeine. Caffeine was examined alone and in combination with haloperidol (HAL), GBR 12909, nisoxetine and fluoxetine. HAL dose-dependently and completely blocked the acute effects of caffeine on locomotor activity, and the highest dose of GBR 12909 enhanced the effects of caffeine. Neither nisoxetine nor fluoxetine altered the effects of caffeine. HAL was infused via osmotic pumps (0.1 mg/kg/day) during a 14-day regimen of chronic caffeine administered in a caffeinated drinking solution ( approximately 136 mg/kg/day). HAL did not block the development of tolerance to the locomotor stimulant effects of caffeine, but did impair the recovery from tolerance following withdrawal of caffeine. [3H]SCH 23390 (DA D(1)) binding sites were downregulated in the nucleus accumbens and striatum and were upregulated in the prefrontal cortex of caffeine-treated vs. control rats; however, the affinity of [3H]SCH 23390 for these binding sites was unaltered. There were no differences between the caffeine-treated and control rats in number or affinity of [3H]spiperone (DA D(2)) binding sites. These results suggest that, although HAL did not alter the development of tolerance to caffeine, changes in DA D(1) receptors could be one component of the mechanism underlying caffeine-induced tolerance.