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Biomedical subjects

J L Blumer

Publications and source records attributed to J L Blumer.

At least 73 records · Page 4Linked to original sources
PubMed1994

Single-dose pharmacokinetics of piperacillin and tazobactam in infants and children.

The pharmacokinetics of piperacillin and tazobactam were assessed after single-dose administration to 47 infants and children. Study subjects ranging in age from 2 months to 12 years were randomized to receive one of two different doses of a piperacillin-tazobactam combination (8:1): a low dose (n = 23) of 50 and 6.25 mg of piperacillin and tazobactam per kg of body weight, respectively, or a high dose (n = 24) of 100 and 12.5 mg, respectively. The pharmacokinetic behavior of tazobactam was very similar to that observed for piperacillin, supporting the use of these two agents in a fixed-dose combination. No differences in the pharmacokinetics of piperacillin or tazobactam were observed between the two doses administered. The elimination parameters half-life and total body clearance decreased and increased, respectively, with increasing age, whereas volume parameters (volume of distribution and steady-state volume of distribution) remained relatively constant for both compounds. The primary metabolite of tazobactam, metabolite M1, was measurable in the plasma of 18 of the 47 study subjects; 17 of these 18 subjects received the high doses. More than 70% of the administered piperacillin and tazobactam doses were excreted unchanged in the urine over a 6-h collection period. These data combined with the known in vitro susceptibilities of a broad range of pediatric bacterial pathogens indicate that a dose of 100 mg of piperacillin and 12.5 of mg tazobactam per kg of body weight administered as a fixed-dose combination every 6 to 8 h would be appropriate to initiate clinical efficacy studies in infants and children for the treatment of systemic infections arising outside of the central nervous system.

Child↗
PubMed1994

Catecholamine and blood lactate responses to incremental rowing and running exercise.

Ten collegiate rowers performed discontinuous incremental exercise to their tolerable limit on two occasions: once on a rowing ergometer and once on a treadmill. Ventilation and pulmonary gas exchange were monitored continuously, and blood was sampled from a venous catheter located in the back of the hand or forearm for determination of blood lactate ([La]) and plasma epinephrine ([Epi]) and norepinephrine ([NE]) concentrations. Thresholds for lactate (LT), epinephrine (Epi-T), and norepinephrine (NE-T) were determined for each subject under each condition and defined as breakpoints when plotted as a function of O2 uptake (VO2). For running, LT (3.76 +/- 0.18 l/min) was lower (P < 0.05) than Epi-T (4.35 +/- 0.14 l/min) and NE-T (4.04 +/- 0.19 l/min). For rowing, LT (3.35 +/- 0.16 l/min) was lower (P < 0.05) than Epi-T (3.72 +/- 0.22 l/min) and NE-T (3.70 +/- 0.18 l/min) and was lower (P < 0.05) than LT for running. Within each mode of exercise, Epi-T and NE-T did not differ. Because LT occurred at a significantly lower VO2 than either Epi-T or NE-T, we conclude that catecholamine thresholds, per se, were not the cause of LT. However, for both modes of exercise LT occurred at a plasma [Epi] of approximately 200-250 pg/ml (rowing, 221 +/- 48 pg/ml; running, 245 +/- 45 pg/ml); these concentrations are consistent with the plasma [Epi] reported necessary for eliciting increments in blood [La] during Epi infusion at rest. Plasma [NE] at LT differed significantly between modes (rowing, 820 +/- 127 pg/ml; running, 1,712 +/- 217 pg/ml).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1994

Mechanical ventilators optimized for pediatric use decrease work of breathing and oxygen consumption during pressure-support ventilation.

OBJECTIVES: a) To investigate whether the patient work of breathing needed to trigger inspiration is affected by the type of ventilator delivering pressure-support ventilation for mechanically ventilated pediatric patients. b) To determine whether changes in oxygen consumption (VO2) trend with changes in work of breathing and would thus be helpful in tracking work of breathing. DESIGN: Prospective study. SETTING: Pediatric intensive care unit at a university hospital. PATIENTS: Nine mechanically ventilated patients (2 to 75 months of age). INTERVENTIONS: While maintaining a constant pressure-support ventilation level, patients were alternately supported with the Siemens Servo 900C, the Bird VIP, and the Newport Wave E200 ventilators in random order. MEASUREMENTS AND MAIN RESULTS: Work of breathing, defined as the integral of the pressure-volume curve corresponding to negative pressure, was calculated with a pulmonary monitoring system. VO2 was measured with a metabolic cart. Patient distress levels were assessed using the COMFORT scale, a behavioral scoring system. Mean values (20 breaths/patient) for measured variables with each ventilator were compared using analysis of variance and Scheffé tests, with p < .05 indicating statistical significance. The lowest VO2 (103 +/- 35 mL/min/m2) and work of breathing (24 +/- 15 g.cm/m2) were achieved with the Bird VIP ventilator and were significantly (p < .05) lower than those values obtained with either the Siemens Servo 900C (VO2 147 +/- 33 mL/min/m2; work of breathing 49 +/- 18 g.cm/m2) or the Newport Wave E200 (VO2 122 +/- 33 mL/min/m2; work of breathing 35 +/- 15 g.cm/m2). Also, the values of work of breathing and VO2 obtained using the Newport Wave E200 were significantly (p < .05) lower than those values obtained using the Servo 900C. No change in behavioral distress occurred when the ventilators were changed. In all patients, there was a clear similarity in the trends of VO2 and work of breathing. CONCLUSIONS: We conclude that VO2 and work of breathing may be reduced significantly using the latest generation of mechanical ventilators optimized for infant and pediatric use. Because work of breathing is less with the Bird VIP than the other two ventilators tested, leading to a corresponding decrease in VO2, we suggest that the Bird VIP better adapts the patient to the ventilator and may facilitate weaning from ventilatory support. We also suggest that changes in VO2 might be helpful in tracking changes in work of breathing.

Analysis of Variance↗
PubMed1993

Pediatric intensive care sedation: survey of fellowship training programs.

Children hospitalized in a pediatric intensive care unit are frequently distressed. The purpose of this study was to identify the patterns of use of sedative agents in pediatric critical care patients. A questionnaire survey was mailed to 45 directors of Pediatric Critical Care Fellowship Training Programs listed in Critical Care Medicine, January 1989. The response rate was 75.6% (34 questionnaires). The most commonly identified goals of sedation were reduced patient discomfort or distress and fewer unplanned extubations. The agents most frequently employed for this purpose were opioids (morphine or fentanyl), chloral hydrate, or benzodiazepines. Although conventional doses are used, opioids and benzodiazepines are often given hourly or by continuous infusion. Satisfaction with the efficacy and safety of commonly used opioids was greater (most common response "very satisfied") than for the benzodiazepines ("somewhat satisfied"). The physician's or nurse's clinical impression was reported to be the "most important" criterion for deciding when a patient required a dose of sedative; objective criteria were selected as less important. The majority of patients (65.7%) in the surveyed units were ideally "sedated to the point of no distress with as-needed medication." The majority of respondents (76.4%) identified efficacy as the major problem with sedation. Drug withdrawal was considered to be the major problem with sedative use by only a minority of respondents (6.9%). Although withdrawal is seen in 61.8% of units, it is generally treated when recognized, rather than prevented by routine tapering of sedation. Optimal sedation of pediatric intensive care unit patients is considered problematic, despite the use of frequent doses of many sedatives. Systematic investigation of pharmacodynamic response to these agents in the pediatric critical care population is indicated.

Attitude of Health Personnel↗
PubMed1992

Application of an organic solvent extraction to the determination of catechol-O-methyltransferase activity by high-performance liquid chromatography in human mononuclear cells.

We report here a method for measuring mononuclear cell catechol-O-methyltransferase (COMT) activity which is ideally adapted to clinical studies. The method measures the O-methylation of dopamine to 3-methoxytyramine and 4-methoxy-3-hydroxyphenethylamine. Whole mononuclear cell sonicate is incubated with saturating concentrations of dopamine, S-adenosyl-L-methionine and magnesium chloride in sodium-potassium phosphate buffer at pH 7.3. An organic solvent extraction using ethyl acetate is then used for product separation, followed by high-performance liquid chromatography with electrochemical detection for product separation and quantification. This method allows both O-methylated products, 3-methoxytyramine and 4-methoxy-3-hydroxyphenethylamine, to be isolated and quantified separately. The apparent Michaelis constants for dopamine and S-adenosyl-L-methionine using this method are similar to values reported previously (0.51 and 14 microM, respectively). The optimal concentration of magnesium chloride is eight to ten times higher than previously reported. No endogenous inhibitors were apparent using this assay. The within-day coefficient of variation using this method is 7% when measuring 3-methoxytyramine and 5% when measuring 4-methoxy-3-hydroxyphenethylamine. The between-day coefficient of variation is 11%. Mononuclear cell COMT activity can be detected using protein concentrations as low as 0.75 mg/ml, corresponding to 2-3 ml of whole blood. The small amount of blood required per sample allows multiple sample analysis from a single patient, including infants.

Adult↗
PubMed1992

Determination of platelet monoamine oxidase activity by high-performance liquid chromatography with electrochemical detection.

A procedure for determining human platelet monoamine oxidase (MAO) with dopamine (DA) as substrate is described. High-performance liquid chromatography (HPLC) with electrochemical detection (ED) was used to separate and detect components of the reaction mixture. The method for platelet preparation was also improved and only 2 ml of blood were required. Following a 10-min incubation of the platelet preparation with DA in 0.1 M Tris buffer (pH 9.0), excess DA substrate was removed by adsorption on a cation-exchange resin. The reaction product, 3,4-dihydroxyphenylacetaldehyde, was adsorbed on acid-washed alumina, eluted with 0.1 M perchloric acid and analyzed by HPLC. Simple, clean chromatograms were obtained with good reproducibility using 3,4-dihydroxybenzylamine as an internal standard. The within-sample, between-samples and between-day relative standard deviations were 0.9, 3.7 and 6.1%, respectively. The apparent Michaelis constant and maximum velocity were 0.10 mM and 0.37 nmol/min.mg protein, respectively. This HPLC-ED method offers a good alternative to methods using radioactivity.

Blood Platelets↗
PubMed1992

Cephalexin and penicillin in the treatment of group A beta-hemolytic streptococcal throat infections.

OBJECTIVE: To determine whether cephalexin or penicillin is more effective in the treatment of group A beta-hemolytic streptococcal tonsillopharyngitis in children. DESIGN: Randomized, double-blind, crossover study conducted from 1981 to 1984. SETTING: Seven pediatric practices in the United States, including private offices and pediatric clinics. PARTICIPANTS: Of the 654 patients, 525 children and adolescents with clinical evidence of tonsillitis or pharyngitis and throat cultures positive for group A beta-hemolytic streptococcal infection were evaluable. Eighty percent of patients completed the study; none were withdrawn because of adverse reaction. SELECTION CRITERIA: Children and adolescents who had acute illness suggestive of group A beta-hemolytic streptococcal infection were enrolled in the study. Treatment was continued if the throat culture was positive for group A beta-hemolytic streptococcal infection. INTERVENTIONS: Four doses of cephalexin and penicillin (27 mg/kg per day) were prescribed to be taken on an empty stomach for 10 days. MEASUREMENTS/MAIN RESULTS: Symptomatic clinical failure occurred in 8% of penicillin-treated patients and in 3% of cephalexin-treated patients. Bacteriologic failure rates were 11% in the penicillin treatment group and 7% in the cephalexin treatment group. The combined treatment failure rate of clinical relapse plus asymptomatic bacteriologic failure was 19% in the penicillin treatment group and 10% in the cephalexin treatment group. Paired antistreptolysin-O titer increased significantly in 62.3% of penicillin-treated patients and in 64.2% of cephalexin-treated patients. Similarly, anti-DNase B titers rose 52.2% in penicillin-treated patients and 52.4% in cephalexin-treated patients. CONCLUSION: Cephalexin is a more effective drug than penicillin in the treatment of group A beta-hemolytic streptococcal throat infection in children.

Adolescent↗
PubMed1992

Assessing distress in pediatric intensive care environments: the COMFORT scale.

Managing psychological distress is a central treatment goal in Pediatric Intensive Care Units (PICUs), with medical and psychological implications. However, there is no objective measure for assessing efficacy of pharmacologic and psychological interventions used to reduce distress. Development of the COMFORT scale is described, a nonintrusive measure for assessing distress in PICU patients. Eight dimensions were selected based upon a literature review and survey of PICU nurses. Interrater agreement and internal consistency were high. Criterion validity, assessed by comparison with concurrent global ratings of PICU nurses, was also high. Principal components analysis revealed 2 correlated factors, behavioral and physiologic, accounting for 84% of variance. An ecological-developmental model is presented for further study of children's distress and coping in the PICU.

Adaptation, Psychological↗
PubMed1991

Management of nutritional and infectious complications of postoperative chylothorax in children.

Postoperative chylothorax may occur following any intrathoracic surgical procedure in children. From January 1979 through February 1987, 18 children aged 1 month to 9 years had chylothorax listed among their discharge diagnoses. Initial therapy for all patients consisted of chest tube placement for pleural space drainage and nutritional support with either enteral formulas enriched with medium-chain triglycerides or total parenteral nutrition. Both total parenteral nutrition and medium-chain triglyceride-enriched enteral regimens provided adequate nutritional support in these children. Five of the 18 experienced lymphopenia secondary to chylous lymphocyte loss. Infections were diagnosed in 5 patients during hospitalization; one was a fatal viral pneumonitis. No correlation between infectious complications and lymphocyte count could be demonstrated.

Bacterial Infections↗
PubMed1991

Influence of infusion pumps on the pharmacologic response to nitroprusside.

OBJECTIVE: To compare the relationship between variability in nitroprusside delivery from five infusion pumps and the resulting variability in mean arterial pressure (MAP). DESIGN: Randomized, crossover study design. SETTING: A pediatric ICU in a university hospital. PATIENTS: Informed parental consent was obtained for six patients who were hemodynamically stable and receiving a continuous nitroprusside infusion for a clinical application. Subjects ranged in age from 11 months to 9 yr. INTERVENTIONS: All of the subjects were administered nitroprusside using selected infusion pumps, which included Abbott (Micro), 3M/AVI (210), IMED (965), IVAC (565), and Kendall McGaw (MicroRate). MEASUREMENTS AND MAIN RESULTS: After an initial equilibration interval for each device, MAP was measured and recorded at 10-sec intervals for greater than or equal to 90-min intervals using a computerized data collection technique. Variation in nitroprusside administration (flow continuity) for each infusion pump was determined in vitro using a computerized gravimetric technique. Variation in both MAP and flow continuity was mathematically expressed as the coefficient of variance (CV) of the measured values for each of the respective infusion pumps. For the Abbott, IMED, 3M/AVI, IVAC, and Kendall McGaw, infusion pumps, mean +/- SD continuity CV values were 85 +/- 31%, 39 +/- 26%, 19 +/- 8%, 17 +/- 3%, and 12 +/- 3%, respectively, and MAP CV values were 18 +/- 21%, 15 +/- 11%, 8 +/- 2%, and 16 +/- 10%, respectively. CONCLUSIONS: An apparent direct relationship between MAP variability and flow continuity was observed. We speculate that variation in effect of potent short-acting drugs may, in part, be due to infusion pump operation.

Blood Pressure↗
PubMed1991

Comparative trial of cefprozil vs. amoxicillin clavulanate potassium in the treatment of children with acute otitis media with effusion.

A total of 137 children with acute otitis media with effusion were randomly allocated to treatment with cefprozil (30 mg/kg/day divided into two equal doses), an investigational cephalosporin or amoxicillin clavulanate potassium (40 mg/kg/day divided into three equal doses) for 10 days. The most common pathogens obtained from middle ear cavities by tympanocentesis were Streptococcus pneumoniae (33%), Haemophilus influenzae (19.6%) and Moraxella catarrhalis (8.3%). Patients were scheduled for follow-up visits at midtreatment, at end of therapy and at 30 days. Of the 137 children 122 were evaluable. Five of 60 patients (8.3%) treated with cefprozil and 14 of 62 patients (22.5%) treated with amoxicillin clavulanate potassium were considered therapeutic failures because of persistence of symptoms and/or isolation of the original pathogen or superinfection (P = 0.05). Rates of relapse, reinfection and persistent middle ear effusion as documented by tympanogram were comparable in both groups. When persistent middle ear effusion was analyzed by pneumatic otoscopy, 64 of 103 affected ears (62.1%) treated with cefprozil and 80 of 105 affected ears (76.1%) treated with amoxicillin clavulanate potassium were abnormal (P = 0.04). Loose stools were more common in children treated with amoxicillin clavulanate potassium than in children treated with cefprozil (P = 0.0004). Based on the efficacy results from this study, the lower gastrointestinal side effects and the convenience of twice-a-day dosing, we believe that cefprozil in a dosage of 30 mg/kg/day divided every 12 hours represents a potential alternative for the treatment of acute otitis media with effusion in children.

Acute Disease↗
PubMed1991

Single-dose pharmacokinetics of ceftibuten (SCH 39720) in infants and children.

Ceftibuten (CFB), a new broad-spectrum cephalosporin for oral administration, possesses potent activity in vitro against a wide range of gram-negative and certain gram-positive pathogens frequently encountered in pediatric patients. Its antimicrobial spectrum and dosage formulation suggest a use for CFB in the treatment of otitis media and upper and lower respiratory and urinary tract infections in infants and children. To assess the pharmacokinetic characteristics of CFB in pediatric patients, we completed a multicenter investigation of 49 children (26 females) between the ages of 6 months and 17 years who had normal hepatic and renal functions and no evidence of chronic disease. Pharmacokinetic parameters were determined from repeated blood samples (n = 12) and, when possible, quantitative urine collections (n = 7) obtained over a 12- to 24-h period following a single oral CFB dose of either 4.5 or 9.0 mg/kg of body weight. CFB was quantitated from plasma and urine samples by using a sensitive, microanalytical high-pressure liquid chromatography method. The drug was rapidly absorbed (mean time to maximum concentration in serum = 140 min) and produced apparent peak concentrations in plasma (Cmax) ranging from 5.0 to 19.0 mg/liter. Average CFB pharmacokinetic parameters (+/- standard deviations) were as follows: apparent elimination half-life, 2.0 +/- 0.5 h; mean residence time, 3.9 +/- 1.1 h; apparent steady-state volume of distribution, 0.4 +/- 0.2 liter/kg; and apparent total plasma clearance (CL/F), 2.5 +/- 0.9 ml/min/kg. No significant differences in any of the pharmacokinetic parameters were observed between the two dosing groups. Significant (P < 0.05) negative correlations were found between patient age and CFB elimination half-life and CL/F and between the estimated creatinine clearance and renal clearance and CL/F. Apparent age dependence of CFB disposition was also reflected by a greater CL/F in children from 0.5 to less than or equal 5 years of age (3.1 +/- 1.1 ml/min/kg) than in children > 10 years of age (2.0 +/- 0.6 ml/min/kg; P < 0.005). The increased CL/f for CFB (3.0 +/- 0.5 ml/min/kg) was corroborated by a validation study performed with 11 infants (1.0 +/- 0.5 ml/min/kg) with CL/F for 19 subjects suggested that appreciable nonrenal clearance (1.3 +/- 0.6 ml/min/kg) of CFB occurred in children, a finding different from preliminary data for adults.

Adolescent↗
PubMed1991

Phenothiazine-associated apnea in two siblings.

A two-month-old white girl presented to our facility with increasing lethargy and new onset apnea and bradycardia following a week of upper respiratory tract infection symptoms. The patient had been receiving a cough syrup containing promethazine hydrochloride during the previous five days, which was temporally correlated with the onset of lethargy and apneic episodes. Upon further investigation, it was discovered that the patient's older sibling also may have experienced phenothiazine-associated apnea after receiving a combination of meperidine hydrochloride, promethazine hydrochloride, and chlorpromazine as a premedication prior to an endoscopic examination. In addition to the presentation of these cases, the literature pertaining to phenothiazine-associated apnea is reviewed.

Apnea↗
PubMed1991

Ceftizoxime disposition in neonates and infants during the first six months of life.

The single-dose pharmacokinetics of ceftizoxime sodium were studied in 52 neonates and infants between 0.1 and 189 days of age. Subjects received ceftizoxime 25 or 50 mg/kg iv over 15-30 minutes. The drug was administered q8-12h for five days to permit tolerance evaluation on repetitive dosing. No differences were observed in ceftizoxime pharmacokinetic parameter estimates relative to dose. However, marked differences were observed in ceftizoxime pharmacokinetic characteristics relative to infant age; ceftizoxime half-life and mean residence time decreased, whereas body clearance increased with infant age. Ceftizoxime volume of distribution remained relatively constant over infant age. No adverse effects associated with ceftizoxime administration were observed. These data suggest that ceftizoxime 50 mg/kg q12h be used for infants less than or equal to 2 weeks of age (less than or equal to 40 weeks postconceptional age) and that 50 mg/kg q8h be administered for older infants.

Aging↗
PubMed1991

Opioids and other analgesics. Adverse effects in the intensive care unit.

Analgesics are an important component of care for critically ill patients. The agents available--opioids, anesthetics, and NSAIDs--are efficacious, but each is capable of inducing a variety of adverse effects. Many adverse effects associated with opioid use can be minimized with the use of anticipatory measures. Anesthetic agents and NSAIDs offer less effect on cardiovascular and respiratory function than opioids, but are not without adverse effects. A thorough understanding of analgesic-associated adverse effects and drug interactions, as well as methods for anticipating and monitoring them, can help to minimize their effect on the ICU patient.

Analgesics↗
PubMed1990

Comparison of acellular and whole-cell pertussis-component DTP vaccines. A multicenter double-blind study in 4- to 6-year-old children.

An acellular pertussis-component combined diphtheria and tetanus toxoids, and pertussis (APDT) vaccine adsorbed was compared with a licensed whole-cell pertussis-component combined diphtheria and tetanus toxoids, and pertussis (DTP) vaccine adsorbed for reactogenicity and immunogenicity when given as the fifth DTP immunization to eighty-two 4- to 6-year-old children. The reaction rates with both vaccines were low; APDT vaccine recipients had significantly less pain and warmth at the injection site than did DTP vaccine recipients. Antibody responses to pertussis antigens (lymphocytosis-promoting factor, filamentous hemagglutinin, and agglutinogens) and to diphtheria and tetanus toxoids were all brisk. The APDT vaccine recipients had a more marked response in antibodies to filamentous hemagglutinin and a less marked response in agglutinins than whole-cell vaccine recipients. On the day after immunization, both APDT and DTP vaccine recipients had an increase in mean leukocyte and neutrophil counts. This APDT vaccine is immunogenic and less reactogenic than a DTP vaccine with a whole-cell pertussis component when administered as a booster to 4- to 6-year-old children.

Agglutinins↗