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M L Christensen

Publications and source records attributed to M L Christensen.

At least 19 recordsLinked to original sources
PubMed2001

Pharmacokinetics of naratriptan in adolescent subjects with a history of migraine.

Naratriptan is a novel 5-HT1 agonist developed to treat acute migraine. The study objective was to characterize the pharmacokinetics of oral naratriptan in adolescent migraine patients outside a migraine attack. Subjects received a single 2.5 mg naratriptan tablet. Serial serum samples for naratriptan concentrations were collected over 24 hours. Blood pressure, pulse rate, and 12-lead ECG were recorded at baseline and at regular intervals after dosing. Seven patients--3 males and 4 females, 12 to 16 years of age--received drug and completed the study. The geometric mean and 95% confidence interval maximum concentration (Cmax) was 8.0 ng/mL (5.9-10.7), elimination half-life (t1/2) was 4.9 hours (4.5-5.4), area under the concentration-time curve (AUC) was 74.6 ng.h/mL (56.6-98.2), and apparent total clearance (Cl/F) was 558.8 mL/min (424.3-735.9). The median time to maximal concentration (tmax) was 4 hours, with a range of 1.5 to 4. Blood pressure, pulse rate, and ECG parameters did not change significantly from baseline. No serious adverse events or subject withdrawal after drug administration occurred. Oral naratriptan pharmacokinetic parameters in adolescents were similar to values reported in adults. Naratriptan doses for adolescents older than 12 years of age would be expected to be similar to adult doses.

Adolescent↗
PubMed2000

Increased tacrolimus levels in a pediatric renal transplant patient attributed to chronic diarrhea.

Tacrolimus is an immunosuppressant used to prevent rejection of transplanted organs. It is metabolized in both the gut and the liver by the cytochrome P450 (CYP) 3A4 enzyme system and is a substrate for the P-glycoprotein (P-gp) drug efflux pump. As CYP3A4 enzymes and P-gp are present at differing concentrations throughout the gastrointestinal tract, the bioavailability of tacrolimus may be influenced by changes in gastrointestinal transit time in addition to changes in hepatic metabolism. We report the case of a pediatric renal transplant patient who experienced a three-fold increase in serum tacrolimus concentrations during an episode of gastroenteritis with chronic diarrhea.

Biological Availability↗
PubMed1999

Chromium and zinc concentrations in pediatric patients receiving long-term parenteral nutrition.

Serum, urine, and parenteral nutrition (PN) chromium and zinc concentrations in pediatric patients receiving long-term PN were studied. Serum, urine, and PN chromium and zinc concentrations were measured at baseline and four to six months later in four infants (less than 1 year old) and seven children (1-12 years old) receiving long-term PN. In the children, serum, urine, and PN solution zinc concentrations were measured monthly after the amino acid product was changed from a standard to a pediatric product with monthly dosages of 0, 20, 30, and 40 mg of cysteine hydrochloride per gram of amino acids. The mean +/- S.D. baseline serum chromium concentration was 4.9+/-1.9 microg/L (normal value, <0.3 microg/L); the urine chromium concentration ranged from 3.4 to 32.2 microg/L. The mean +/- S.D. prescribed chromium dosage was 0.18+/-0.05 microg/kg/day, and the dosage delivered in PN solutions was 0.41+/-0.23 microg/ kg/day. At baseline, the mean +/- S.D. serum zinc concentration was 1383+/-472 microg/L (normal range, 430 to 940 microg/L), and the prescribed and delivered zinc dosages were 177+/-10 and 238+/-145 microg/kg/ day, respectively. With 20, 30, and 40 mg of cysteine per gram of amino acids, the mean +/- S.D. serum zinc concentration was 1728+/-782, 1664+/-349, and 1685+/-268 microg/L, respectively, and the actual zinc dosages delivered were 209+/-10, 270+/-148, and 322+/-194 microg/kg/day, respectively. Serum and urine chromium concentrations were abnormally high in infants and children receiving PN solutions supplemented with normal doses of these trace elements; an escalating dosage of cysteine in the children tended to increase serum and urine zinc concentrations.

Body Height↗
PubMed1998

The clinical pharmacology of loop diuretics in the pediatric patient.

The loop diuretics furosemide and bumetanide are frequently employed in the pediatric population for the management of fluid overload in both acute and chronic disease states. They act mainly by inhibiting sodium reabsorption in the nephron at the thick ascending limb of Henle's loop. Important pharmacokinetic differences between adults and infants include a reduced clearance and prolonged half-life, that may cause accumulation of these agents to potentially toxic levels if dosing intervals are not adjusted. Unfortunately, little is known about the time required for maturation of loop diuretic elimination in older infants, children, and adolescents. Similar to adults, limited pharmacodynamic evidence in neonates suggests that a maximally efficient diuretic dose exists. Increasing the diuretic dose beyond this maximum does not offer further benefit, but may increase the risk of toxicity. Common problems encountered in the pediatric patient as well as in adults are loop diuretic tolerance and resistance. Loop diuretic dosing strategies aimed at overcoming these phenomena include administration by continuous infusion, coadministration with albumin, and coadministration with metolazone or thiazides. This article reviews the pharmacology, pharmacokinetics, and pharmacodynamics of furosemide and bumetanide in pediatric patients. A better understanding of the clinical pharmacology of the loop diuretics should aid clinicians in the development of dosing regimens aimed at producing adequate diuresis without promoting excessive diuretic tolerance.

Bumetanide↗
PubMed1997

New-onset juvenile dermatomyositis: comparisons with a healthy cohort and children with juvenile rheumatoid arthritis.

OBJECTIVE: To determine, in a case-control study, if patients with new-onset juvenile dermatomyositis (juvenile DM) have increased symptoms prior to onset, exposure to certain environmental conditions, frequency of familial autoimmune diseases, or antibody titers, compared with 2 control groups. METHODS: A structured interview with the families of 80 children with juvenile DM, 40 children with juvenile rheumatoid arthritis (JRA), or 23 healthy children, from the same geographic area as the children with juvenile DM, was conducted. All children's sera were tested for antibody to Toxoplasma gondii, herpes simplex virus (HSV), or coxsackievirus B (CVB). RESULTS: A high proportion of children with juvenile DM had constitutional symptoms 3 months before the disease-onset date (P = 0.013 versus control children). Children with JRA had more relatives with rheumatoid arthritis (P = 0.0001) and pernicious anemia (P = 0.003) than did children with juvenile DM or healthy children. Among children < or =7 years of age, elevated enteroviral titers were more frequent in those with juvenile DM (81%) and in healthy controls (90%) than in those with JRA (64%), suggesting a common environmental exposure. Titers to T gondii, HSV, or CVB 1-6 were normal. CONCLUSION: Frequencies of familial autoimmune disease, exposure to environmental factors, or elevated antibody titers to T gondii, HSV, or CVB are not increased in juvenile DM. Children with juvenile DM do have symptoms of illness 3 months before the disease-onset date, and young patients have elevated enteroviral titers, as do young geographic controls.

Animals↗
PubMed1996

Transdermal fentanyl administration in children and adolescents with sickle cell pain crisis.

PURPOSE: The purpose of this study was to determine the dose-concentration relationship and clinical effect of transdermal fentanyl (TF) in patients with sickle cell pain crisis (SCPC). PATIENTS AND METHODS: Ten patients aged 9-16 years were studied. Patients initially received a TF dose of 25 (n = 7) or 50 (n = 3) micrograms/h if morphine use was > 2.5 mg/h. Supplemental morphine usage via patient-controlled analgesia (PCA), sedation status, pain status, respiratory rate, pulse rate, oxygen saturation, and blood pressure were monitored. RESULTS: The average TF dose was 0.77 +/- 0.37 micrograms/kg/h on day 1 and 1.17 +/- 0.46 micrograms/kg/h on day 2. Fentanyl concentrations measured at 24 and 48 h were 0.60 +/- 0.31 and 1.18 +/- 0.44 ng/ml, respectively. A significant relationship existed between TF dose and fentanyl concentration (r2 = 0.56, p < 0.01). There was no difference in any of the clinical monitoring parameters between day 1 and day 2. However, 7 of 10 patients reported subjective improvement in pain control over that achieved with PCA alone. No adverse effects were noted. CONCLUSIONS: Improved understanding of the dose-effect relationship for TF in children and adolescents is necessary before adequate pain control can be achieved with this delivery system.

Administration, Cutaneous↗
PubMed1994

Pharmacokinetics of vincristine in children and adolescents with acute lymphocytic leukemia.

We studied the pharmacokinetics of vincristine in children with acute lymphocytic leukemia by means of a specific high-performance liquid chromatographic assay with ultraviolet and electrochemical detection and a limited sampling strategy. Our objectives were to characterize the disposition of vincristine in pediatric patients, to determine clinical, demographic, or biochemical variables related to variability in vincristine pharmacokinetic parameters, and to assess the relationship between pharmacokinetic parameters and vincristine neurotoxicity. Plasma samples were collected at 5 and 30 minutes, and 1, 3, and 24 hours after a rapid intravenous injection during 3 minutes. Vincristine-induced neurotoxicity was retrospectively evaluated by chart review. Pharmacokinetic studies were completed for 64 doses in 54 children between 2 months and 18 years of age (median, 4.3 years), including 2-month-old monozygous twin girls. Vincristine clearance, estimated by Bayesian methods, was highly variable, with a mean (SD) clearance of 19.9 (14.9) ml/min per kilogram or 482 (342) ml/min per square meter. Mean clearance for all subjects was faster than in published studies of adults, which may be related in part to the greater specificity of the assay used in our study, as well as to age-related differences in drug disposition. Vincristine-associated neurotoxicity was frequent but mild and was not predicted by vincristine systemic exposure; however, neurotoxicity may have been underestimated. Clearance in one patient who received concomitant treatment with pentobarbital exceeded the 75th percentile for all patients, and four of five patients receiving concomitant histamine2 antagonists had clearances below the 25th percentile for all subjects, suggesting that drugs that induce or inhibit hepatic cytochrome P-450 enzymes may affect vincristine disposition. Further studies are needed to identify the factors responsible for interpatient variability in vincristine disposition and to develop improved dosing guidelines.

Adolescent↗
PubMed1993

Parenteral nutrition associated with increased infection rate in children with cancer.

BACKGROUND: Recent meta-analyses of published controlled studies concluded that adult patients with cancer randomly assigned to receive parenteral nutrition had higher rates of infectious complications than control subjects. METHODS: The infection risk associated with parenteral nutrition was assessed in 310 pediatric patients with cancer. These patients had central venous access devices (CVAD), Hickman/Broviac (H/B) catheters, or implantable subcutaneous ports in place for the delivery of chemotherapy and supportive care. RESULTS: The median duration of CVAD placement was 363 days; a total of 450 patient years (i.e., the sum of the total years of catheters experienced from all patients studied) were examined. Overall, the infection rate was 0.06 infections/100 days. During the period of parenteral nutrition administration, the rate increased to 0.5 infections/100 days. Among patients who received parenteral nutrition, there were no significant differences in any clinical parameter between the patients who developed an infection and those who did not. When evaluating the entire study population, infection was more likely to occur in patients who had acute nonlymphocytic leukemia (P < 0.01) or H/B catheters (P < 0.01), or who received parenteral nutrition (P < 0.02); there was no relationship between infection and catheter duration, days hospitalized, or days neutropenic (absolute neutrophil count < 0.5 x 10(9)/l). Only CVAD type and parenteral nutrition retained significance in a multivariate Cox proportional hazards model. After adjustment for diagnosis and CVAD type, the risk of infection was 2.4-fold greater in patients given parenteral nutrition (95% confidence interval 1.5 to 3.9; P < 0.001). CONCLUSION: These data confirm that administration of parenteral nutrition is associated with an increased risk of infection in children who have CVAD in place for cancer therapy.

Adolescent↗
PubMed1993

Plasma amino acids in patients with acute nonlymphocytic leukemia receiving parenteral nutrition.

OBJECTIVE: To assess the effect of parenteral amino acid solutions on plasma amino acid concentrations in patients with acute nonlymphocytic leukemia (ANLL) receiving parenteral nutrition (PN). DESIGN: Ten patients were studied at diagnosis, on the morning PN was started, and three times during PN therapy coinciding with the sequential administration of three different amino acid solutions (Aminosyn, FreAmine HBC, and TrophAmine). The order of amino acid solution administration in each patient was by a randomized, block design. RESULTS: The patients were undergoing identical intensive induction therapy. There was no significant difference in the number of days they received PN or the amount of protein or calories received during the three PN study periods. At diagnosis, phenylalanine and glutamic acid concentrations were elevated compared with previously published normal values and remained elevated at all observation times. During PN, asparagine, aspartic acid, and tyrosine concentrations were significantly lower with all three amino acid solutions compared with their concentrations at diagnosis. Glycine and threonine concentrations were also significantly lower with FreAmine HBC and TrophAmine administration and cysteine concentrations were significantly lower with FreAmine HBC administration than at the time of diagnosis. Aminosyn was associated with plasma amino acid concentrations most similar to those measured at diagnosis. CONCLUSIONS: These results indicate that most amino acid concentrations fall within the normal range at diagnosis in the ANLL patients studied. Plasma concentrations for certain amino acids can be influenced by the amino acid solution used in PN. Further understanding of the derangements in amino acid metabolism and the influence of parenterally administered amino acid solutions on plasma amino acid concentrations may lead to improvements in the nutritional support of cancer patients.

Adolescent↗
PubMed1992

Mental health consequences and correlates of reported medical student abuse.

OBJECTIVE: To assess the prevalence, correlates, and mental health consequences of reported medical training-related abuses. DESIGN: A longitudinal cohort study of 137 students surveyed from medical school entrance (time 1) through the winter of the fourth training year (time 4). SETTING: A state college of medicine. OUTCOME MEASURES: Reported training-related abuses (measured at time 4) and mental health status measured at times 1 and 4 (depressive and anxiety symptoms, hostility, problem drinking, escapist drinking, alcohol consumption levels, and gender role orientations). RESULTS: Seventy-two percent of students reported at least one abusive experience during medical training. Females were significantly more likely than males to report gender discrimination, exclusion from informal settings, discomfort from sexual humor, and unwanted sexual advances. Abuse was significantly related to most psychopathological outcomes, controlling for pre-existing psychopathology. Males low in masculinity and females low in femininity were most likely to report abuse. CONCLUSIONS: The data provide further support for the assumption that a high proportion of medical students not only experience the training process as abusive in nature but also suffer measurable psychopathological consequences. Efforts should be made to reform medical education, with a prominent focus on gender role-related issues.

Alcohol Drinking↗
PubMed1992

Increased teniposide clearance with concomitant anticonvulsant therapy.

PURPOSE: A possible pharmacokinetic interaction between teniposide and anticonvulsant medications was evaluated in pediatric patients. PATIENTS AND METHODS: The systemic clearance of teniposide was determined in six pediatric patients with acute lymphocytic leukemia receiving concomitant therapy with anticonvulsants. Clearance was then compared with a control group of patients treated with the same protocol therapy and matched for age at diagnosis, sex, and race but not receiving anticonvulsants or other agents known to induce hepatic metabolism or alter protein binding of drugs. Eight blood samples were obtained during and after 4-hour infusions of teniposide, and plasma concentrations were measured by a specific high-performance liquid chromatography (HPLC) assay. A two-compartment model was fitted to each subject's data. RESULTS: The mean systemic clearance (range) for the six anticonvulsant-treated patients studied during 22 courses of therapy was 32 mL/min/m2 (range, 21 to 54 mL/min/m2), significantly higher (P less than .001) than the mean value of 13 mL/min/m2 (range, 7 to 17 mL/min/m2) for the control patients studied during 26 courses of therapy. Clearance estimates for control patients were similar to previously published values for pediatric patients. CONCLUSION: These data indicate that the systemic clearance of teniposide is consistently increased two- to three-fold by concomitant phenobarbital or phenytoin therapy. The consequent substantial reduction in systemic exposure may reduce teniposide's efficacy.

Adolescent↗
PubMed1992

Use of moderate hypothermia during elective craniotomy.

Use of moderate hypothermia as an adjunct to elective craniotomy is described in 21 patients. Systemic hypothermia to 32 degrees C was induced by cooling blankets at a mean cooling rate of 1.6 degrees C/min. Patients were rewarmed at the same rate prior to closure of wounds. There were no hypothermia-related complications and the method increased brain relaxation. The rationale for use of this therapy in elective craniotomy and severe head injury is reviewed.

Aortic Dissection↗
PubMed1991

Age-related differences in hepatic drug clearance in children: studies with lorazepam and antipyrine.

The disposition of intravenous antipyrine and lorazepam, administered as model substrates for hepatic oxidative metabolism and conjugation, was evaluated in 50 children (mean age, 7.8 years; range, 2.3 to 17.8 years) with acute lymphocytic leukemia in complete remission and compared with a group of ten healthy adults. Antipyrine clearance normalized to body weight was significantly greater in children than in adults (0.91 versus 0.59 ml/min/kg; p = 0.012), but was not different when normalized to body surface area. In contrast, lorazepam total clearance (CL) and unbound clearance (CLu) normalized to body weight were not significantly different between children and adults but were smaller in children when normalized to body surface area (CL = 31.9 versus 40.6 ml/min/m2, p = 0.036; CLu = 352 versus 485 ml/min/m2, p = 0.010). The mean lorazepam fraction unbound in children was 0.087, which was not different from adult volunteers (0.084). This study has identified significant differences between children and adults in the disposition of these two compounds, with higher milliliter per minute per kilogram clearance for antipyrine but not lorazepam.

Adolescent↗
PubMed1991

Toxicities of parenteral nutrition in the critically ill patient.

Critically ill patients have unique nutritional substrate requirements. Although important advances have been made in understanding these requirements in the face of pathophysiologic and biochemical alterations induced by stress or trauma, nutrition-associated toxicities still occur. The importance of these toxicities to the critically ill patients cannot be over-stated. Many of these toxicities can be avoided by conservative use of selected nutrition substrates in specific subsets of the critically ill population. Practitioners must continue to anticipate and recognize parenteral nutrition-associated toxicities, however, as well as delineate any toxicity from the progression or exacerbation of disease.

Catheters, Indwelling↗
PubMed1990

Induction, accumulation, and persistence of sister chromatid exchanges in women with breast cancer receiving cyclophosphamide, adriamycin, and 5-fluorouracil chemotherapy.

The induction, accumulation, and persistence of sister chromatid exchanges (SCEs) and high SCE frequency cells (HFCs) was measured in peripheral blood lymphocytes of women with breast cancer before chemotherapy and on multiple occasions during and after therapy. Chemotherapy consisted of i.v. infusion of cyclophosphamide, Adriamycin, and 5-fluorouracil, administered on day 1 of each of approximately six 21-day cycles. This treatment resulted in a highly significant induction of SCEs (1.8-fold, P less than 0.0001) and HFCs (5-fold, P less than 0.0001) measured in samples obtained 1 week after the first therapy. Accumulation of lesions leading to SCEs was measured by comparing samples surrounding the first and last rounds of therapy and was significant for both SCEs and HFCs in most comparisons. Persistence of lesions leading to SCEs was evaluated at multiple times until 9 months after completion of therapy, and both SCEs and HFCs remained significantly elevated throughout this time. Differences between donors were observed throughout the study, although they were not always consistent with time. Our results also indicate that the SCE frequency declines rapidly within a few weeks after treatment but that residual damage remains up to 9 months after the end of chemotherapy.

Adult↗