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Biomedical subjects

G Koren

Publications and source records attributed to G Koren.

At least 559 records · Page 31Linked to original sources
PubMed1989

A high-performance liquid chromatographic method for the measurement of deferoxamine in body fluids.

A high-performance liquid chromatography method for the analysis of deferoxamine (DFO) in 100 microliters of serum or plasma is described. The procedure involves the addition of the internal standard ciprofloxacin to the sample, followed by ultrafiltration to remove protein. The ultrafiltrate is then directly injected into the chromatography system. Separation is achieved using a reverse-phase mu Bondapak C18 column and a ternary solvent system (sodium phosphate:acetonitrile:methanol) running at 2.0 ml/min. Assay time is 10 min, and chromatograms show no interference from coadministered drugs during this period of time. Coefficients of variation were found to be less than 5%, and analytical recovery of DFO was 85%. Validation experiments in an experimental dog model and in patients with iron overload demonstrate that the method is appropriate for studying the pharmacokinetics of DFO in thalassemic patients receiving drug for the treatment of chronic iron overload.

Adolescent↗
PubMed1989

Interpretation of elevated postmortem serum concentrations of digoxin in infants and children.

The relationship between excessive postmortem digoxin concentrations (greater than 6.4 nmol/L) and administered dose, and antemortem levels and time of sampling after death were determined in 27 digitalized children who died in our hospital between March 24, 1981 and September 1, 1983. In all 27 cases, postmortem concentrations were higher than antemortem levels (9.5 +/- 2.5 nmol/L and 3.12 +/- 1.72 nmol/L, respectively). In none of these patients was there clinical or electrocardiographic evidence of digitalis toxicity. There was a significant correlation between antemortem and postmortem determinations, and between time of sampling after death and postmortem concentration. Positive correlation existed between antemortem or postmortem concentrations and dose per kilogram. The degree of elevation in digoxin levels was uniform in most cases, and the likelihood of elevation falling in the range 3.5 to 7.0 nmol/L was 66%. If the estimated concentration of digoxin at the time of death was taken as baseline, in 75% of cases the subsequent elevation was between 5.3 and 8.3 nmol/L (mean, 6.5 +/- 1.1 nmol/L). Digoxin concentrations measured in newborn infants not receiving digoxin were significantly higher after death (1.5 +/- 0.3 nmol/L) than in age-matched living infants not receiving digoxin (0.5 +/- 0.3 nmol/L). These data indicate that the size of antemortem dose, the time of sampling after death, and existence of endogenous digoxinlike factors affect postmortem readings of digoxin levels. Consequently, excessive postmortem determinations cannot be directly interpreted as proof of toxic antemortem levels.

Child, Preschool↗
PubMed1989

Topical skin anesthesia for venous, subcutaneous drug reservoir and lumbar punctures in children.

A new topical anesthetic ointment (EMLA, "eutectic mixture of prilocaine and lidocaine was studied in a double-blind, placebo-controlled trial to evaluate its efficiency in alleviating pain associated with venous, subcutaneous drug reservoir and lumbar punctures in children. Pain intensity was scored by the children themselves, using a visual analogue scale in which 0 corresponded to absence of sensation and 10 to the worst imaginable painful sensation. Venipunctures were performed on 18 children (6.1 to 12.2 years of age) equally divided in the study and control groups; EMLA cream was associated with lesser pain scores than those with placebo (means +/- SD: 2.8 +/- 2.4 vs 6.8 +/- 2.1, P less than .01). A crossover trial was used in the studies of subcutaneous drug reservoir and lumbar punctures, eight children (6.1 to 15.1 years of age) were tested for subcutaneous drug reservoir punctures; pain induced by this procedure was rated at 3.9 +/- 2.2 with placebo compared with 1.2 +/- 1.8 with EMLA cream (P less than .04). In lumbar punctures (14 children studied, 5.5 to 15.3 years of age), EMLA cream was again associated with less pain (1.9 +/- 1.9) than was placebo (5.6 +/- 3.0, P less than .01). It was concluded that the use of EMLA cream substantially reduces pain caused by venous, subcutaneous drug reservoir, and lumbar punctures in children and may therefore be offered to young patients, particularly those repeatedly submitted to such procedures.

Adolescent↗
PubMed1989

Pregnancy outcome following first trimester exposure to cocaine in social users in Toronto, Canada.

Studies of drug-dependent women reveal high rates of adverse fetal effects of cocaine. However, no data are available on the effect of the chemical in social users who discontinue cocaine upon realizing they are pregnant. We report the results of the first phase of a prospective study examining the outcome of pregnancy in women seeking counseling from the Motherisk Program in Toronto. Of 25 women seen in our clinic for 1st trimester cocaine exposure, 92% reported use of less than 10 g of cocaine and 36% reported marijuana use. Other illicit drug use was rare; cigarette and alcohol use was common. The study group did not experience adverse pregnancy outcome above the rate expected in the general population. There were 23 single births 1 pair of twins, and 1 spontaneous abortion. Birth weight and gestation were within normal limits. Only 1 child had a major malformation, syndactyly. Infant development was within normal limits, as measured by developmental milestones. All children are scheduled for assessment using the Bayley Scales of Infant Development. The results of the BSID will be compared to results from a cannabis-exposed control group and a no-drug control group.

Canada↗
PubMed1988

The use of infants in drug research when there is no direct benefit to them: a survey of Canadian health care professionals serving on ethics committees.

Canadian health care professionals and lawyers serving on ethics committees were questioned about their views on pharmacokinetic research in newborn infants who are not likely to benefit directly from the results. Of the 50 respondents 13 felt that blood samples should be taken only for therapeutic reasons; 10 of the 13 argued that additional blood samples should not be taken, because there is no direct benefit to the infant; and 8 felt that proxy consent cannot be given for invasive nontherapeutic research. Four of the five participating lawyers would not permit additional blood samples to be taken. Of the 37 respondents who would permit additional blood samples to be taken, 27 felt that the number of samples taken should depend on the researcher's justification for that number of samples; only 7 of the respondents had a clear idea of what the "upper limit" of the number of blood samples should be.

Anti-Bacterial Agents↗
PubMed1988

The dissociation between aminoglycoside serum concentrations and nephrotoxicity.

Using newborn and adult rats we tested the correlation between aminoglycoside dose, resultant serum and renal cortical concentrations and nephrotoxicity evidenced by creatinine in serum and urine, N-acetylglucosaminidase and beta 2 microglobulins in urine and sphingomyelinase in renal cortical tissue. Our data reveal that aminoglycoside nephrotoxicity is clearly more evident in adult rats despite significantly lower drug serum concentrations and in the presence of substantially higher renal cortical concentrations. These data indicate that high aminoglycoside serum concentrations are not causing nephrotoxicity but rather reflect secondary body accumulation of the drug associated renal damage.

Acetylglucosaminidase↗
PubMed1988

Determinants of low serum concentrations of salicylates in patients with Kawasaki disease.

The mechanisms leading to the previously reported difficulties in achieving therapeutic serum concentrations of salicylates in Kawasaki disease were studied in eight children, once during the acute (febrile) phase and again during the nonfebrile (subacute) phase of the disease. Salicylate bioavailability was impaired during the acute phase of the disease (47.7% +/- 6.6%), and increased significantly thereafter to 75.1% +/- 9.3%. During the febrile phase there was a significant correlation between salicylate bioavailability and steady-state serum concentrations. Salicylate renal clearance was significantly higher during the febrile phase (14.45 +/- 2.5 mL/kg.h), compared with the nonfebrile phase (7 +/- 1.6 mL/kg.h, P less than 0.05). The change in salicylate clearance could be explained by decreased protein binding in the acute phase (82.5% +/- 1.9%) with substantially more free salicylates caused by significantly lower serum albumin concentrations. Changes in urine metabolites during the acute and subacute phases were consistent with the changes in dose administered (100 mg/kg in the acute phase vs 10 mg/kg in the subacute phase). The pattern of metabolites excreted in the urine of children with Kawasaki disease receiving 100 mg/kg was similar to that in children with juvenile rheumatoid arthritis receiving the same dose.

Arthritis, Juvenile↗
PubMed1988

Vitamin C-induced erythrocyte damage in premature infants.

This study was undertaken after the observation in a premature infant of a hemolytic anemia with Heinz bodies that appeared to result from administration of a multivitamin preparation. In vitro incubation of erythrocytes of premature infants with sodium ascorbate (0.1 mg/ml) for 3 hours significantly raised the number of Heinz body-containing cells from 17.6 +/- 5.7% to 27.2 +/- 8.2% (mean +/- SE). Erythrocytes of term infants and those of adults developed Heinz bodies after exposure to higher sodium ascorbate concentrations (1.0 mg/ml). Erythrocytes of adult and newborn guinea pigs were similarly affected by sodium ascorbate. Daily intraperitoneal injections of 500 mg of sodium ascorbate, given for 7 days to four adult guinea pigs, caused significant Heinz body formation. These studies indicate that the erythrocytes of premature infants are uniquely sensitive to the development of Heinz bodies after exposure to sodium ascorbate. The levels required to produce Heinz bodies in vitro are in the range of those found in vivo after routine administration of vitamin C to premature infants. The significance of these observations in the development of hyperbilirubinemia in premature infants and in the safety of vitamin C remains to be determined.

Adult↗
PubMed1988

Anticoagulation with sodium warfarin in children: effect of a loading regimen.

To assess dose requirements of warfarin in children, we analyzed retrospectively the treatment of 26 patients with the drug. Subsequently we treated 15 children, prospectively, with a regimen derived from our retrospective analysis (0.2 mg/kg/day for 2 days). In the retrospective analysis we found the prothrombin time (PT) at day 2 to correlate significantly with the dose given on day 0 (p less than 0.001) and with the cumulative dose on days 0 and 1 (p less than 0.001), but the standardized loading regimen resulted in a wide range of PTs independent of age, weight, or body surface area. The warfarin dose contributes only 40% of the variability in PT; an individual child's response to warfarin cannot be predicted accurately on the basis of the usual morphometric measurements.

Child↗
PubMed1988

Pharmacokinetics and adverse effects of amphotericin B in infants and children.

The pharmacokinetics and safety of amphotericin B infusion were studied in 13 infants and children (age range 3 weeks to 18 years; median age 11 years) treated with the drug for proved (n = 11) or suspected (n = 2) fungal infections. The dose during the first day was 0.5 mg/kg, followed by a daily dose of 1 mg/kg for the rest of the treatment period in most patients. The drug was infused over 4 to 6 hours. During the first day, serum concentrations were above the target therapeutic level of 0.3 microgram/ml in all patients at 2 and 6 hours from the start of the infusion, in 12 of 13 patients at 12 hours, but in only 6 of 13 patients at 24 hours. On the third day, all concentrations were greater than 0.3 microgram/ml throughout the 24-hour period, and in 12 of 13 patients were greater than 0.5 microgram/ml. The same kinetic profile prevailed on days 7 to 10 of therapy, with a tendency for increasing concentrations. Elimination half-life was 9.93 +/- 1.5 hours (mean +/- SEM), clearance rate 26 +/- 5 ml/kg.hr, and distribution volume 378 +/- 25 ml/kg. The half-life inversely correlated with patient's age. Pharmacokinetic values calculated during the first day were not different from those calculated on day 3. Significant decreases in hemoglobin, platelets, and serum potassium concentration were recorded along with significant increases in serum creatinine, urea, and aspartate transaminase values. Because of the large pharmacokinetic variability and the high rate of serious adverse effects, individualized dosing of amphotericin B based on therapeutic drug monitoring should be considered.

Adolescent↗
PubMed1988

Physician compliance and relapse rates of acute lymphoblastic leukemia in children.

We studied the prescription patterns of maintenance therapy for children with acute lymphoblastic leukemia and their association with duration of complete remission. Both 6-mercaptopurine and methotrexate (MTX) were prescribed in doses significantly lower than those recommended (75 mg/m2 daily 6-mercaptopurine; 20 mg/m2 weekly MTX) during maintenance therapy. Of 212 evaluated patients, patients who had relapses (n = 101) received significantly less MTX compared with patients who did not have relapses (n = 111) during the first 2 years of maintenance therapy. In the group of standard-risk patients who received the same induction therapy (n = 92), 11 of 17 who received less than 50% of the recommended MTX dose (64%) and 28 of 75 who received greater than 50% of the dose (37%) had relapses (P less than 0.05). The two groups had comparable periods of interruption of MTX therapy. Further analysis revealed that the lower maintenance dose stemmed from a continuous low prescribed dose and not from more frequent interruption of therapy in relapse. Physicians' inability or failure to adhere to the recommended protocol was associated with a higher relapse rate of acute lymphoblastic leukemia. Improved physicians' compliance may improve the prognosis of the disease.

Administration, Oral↗
PubMed1988

An unusual skin exposure to copper; clinical and pharmacokinetic evaluation.

Skin exposure to copper is rare and has been described only with copper sulfate. A case of skin exposure to copper after an explosion of copper azide is presented. The amount of copper absorbed by this route was estimated to be 7.7 mg. Calculated distribution volume was 2.02 I/kg, half-life was 167.4 days and clearance was 0.0058 ml/min/kg. The authors also demonstrated metallic copper to be radiopaque, in contrast to copper salts. It is suggested that copper may be absorbed from the skin even if it is in the metal form. Careful clinical follow up as well as serial determinations of serum copper should guide the need for chelation therapy.

Accidents, Occupational↗
PubMed1988

Analgesic and respiratory effects of epidural sufentanil in patients following thoracotomy.

Immediately following thoracotomy, 22 patients were entered into a randomized, double blind study comparing the effects of three lumbar epidural doses of sufentanil on postoperative pain and respiratory pattern. Patients were given either 30 micrograms (group I), 50 micrograms (group II), or 75 micrograms (group III) of epidural sufentanil in 20 ml N saline. Repeat doses were given on request for the 24-h study period. Linear analogue pain score (PS), heart rate (HR), and mean arterial pressure (MAP) were measured at 15-min intervals after each dose. Respiratory depression was assessed by the presence of: 1) slow respiratory rate (SRR--less than 10 breaths per minute for greater than 5 min), 2) apnea (AP--cessation of tidal ventilation for greater than 15 s), and 3) increased PaCO2 in arterial blood gases (ABG) drawn at regular intervals. SRR and AP were measured using respiratory inductive plethysmography (RIP). A further group of ten patients (group IV) underwent preoperative RIP monitoring during sleep and in the absence of any drug. Maximum analgesia was achieved within 15 min after a dose of sufentanil for all groups. Analgesia was not significantly prolonged by increasing the dose of sufentanil. SRR occurred in all four groups (group I: 2/9; group II: 2/6; group III: 7/7; group IV: 2/10 P less than 0.05 I, IV:II, I, IV:III, II:III). The number of episodes of SRR/hr was highest in group II (group I: 0.6 +/- 0.8, group II: 4.12 +/- 0.6, group III: 1.8 +/- 2.0, group IV: 0.5 +/- 0.2) (NS).(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1988

High-frequency oscillation in the rescue of infants with persistent pulmonary hypertension.

High-frequency oscillatory ventilation (HFOV) was used to treat 41 infants with persistent pulmonary hypertension of the newborn (PPHN). Of the 37 patients who showed early improvement on HFOV, three died. The remaining 34 patients demonstrated, within one hour of the switchover to HFOV, a rise in mean arterial/alveolar oxygen tension ratio (PaO2/PaO2) from 0.093 +/- 0.041 (SD) to 0.132 +/- 0.051 (p less than .001), and a fall in mean PaCO2 from 42 +/- 10 to 34 +/- torr 9 (p less than .01). Mean airway pressure (Paw) fell significantly (p less than .01) within 12 h. The mean duration of conventional mechanical ventilation before starting HFOV was longer in 13 patients who developed bronchopulmonary dysplasia (BPD) than in 21 non-BPD patients (44.7 +/- 32.3 vs. 19.1 +/- 15.6 h, p less than .002), as was the duration of exposure to Paw greater than 15 cm H2O during that treatment mode (31.8 +/- 21.3 vs. 9.5 +/- 6.0 h, p less than .001). HFOV is often effective in the treatment of patients with PPHN, and early initiation of this type of mechanical ventilation may be associated with a reduced incidence of BPD.

Birth Weight↗
PubMed1988

Agonal elevation in serum digoxin concentrations in infants and children long after cessation of therapy.

In 11 of 15 profoundly sick, digitalized infants and children, elevation in serum digoxin concentration could be detected long after cessation of therapy. This phenomenon concurred with a rapid deterioration of renal function. Because death of a digitalized child may be attributed to the glycoside itself, it is important to recognize that elevation in serum concentration to a potentially toxic level is a common pathophysiologic pattern.

Child↗
PubMed1988

Pharmacokinetic interaction between nifedipine and propranolol.

In 8 healthy volunteers, single-dose nifedipine pharmacokinetics were compared with and without the coadministration of propranolol. An elevation of the mean Cmax was found, from 73.9 +/- 14.1 when nifedipine was taken alone, to 115.7 +/- 12.1 (SE) ng/ml (P less than 0.02) when the agent was combined with propranolol. The AUC0----infinity increased as well, from 287.1 +/- 33.5 to 363.0 +/- 54.3 (SE) (micrograms.hr)/l (P less than 0.01), indicating an increase in bioavailability. Propranolol treatment did not significantly affect the nifedipine half-life (alpha or beta phase) or the estimated volume of distribution, whereas systemic clearance tended to decrease in 6 of the subjects. The most likely explanation for increased bioavailability of nifedipine when coadministered with propranolol is by a reduction of the hepatic "first-pass" clearance, as a result of changes in hepatic blood flow.

Administration, Oral↗