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Biomedical subjects

G Lerner

Publications and source records attributed to G Lerner.

At least 19 recordsLinked to original sources
PubMed2001

The use of mycophenolate mofetil suspension in pediatric renal allograft recipients.

Mycophenolate mofetil (MMF) is widely used to prevent acute rejection in adults after renal, cardiac, and liver transplantation. This study investigated the safety, tolerability, and pharmacokinetics of MMF suspension in pediatric renal allograft recipients. One hundred renal allograft recipients were enrolled into three age groups (33 patients, 3 months to <6 years; 34 patients, 6 to <12 years; 33 patients, 12 to 18 years). Patients received MMF 600 mg/m2 b.i.d. concomitantly with cyclosporine and corticosteroids with or without antilymphocyte antibody induction. One year after transplantation, patient and graft survival (including death) were 98% and 93%, respectively. Twenty-five patients (25%) experienced a biopsy-proven (Banff grade borderline or higher) or presumptive acute rejection within the first 6 months post-transplantation. Analysis of pharmacokinetic parameters for mycophenolic acid (MPA) and mycophenolic acid glucuronide showed no clinically significant differences among the age groups. The dosing regimen of MMF 600 mg/m2 b.i.d. achieved the targeted early post-transplantation MPA 12-h area under concentration-time curve (AUC0-12) of 27.2 microg h per ml. Adverse events had similar frequencies among the age groups (with the exception of diarrhea, leukopenia, sepsis, and anemia, which were more frequent in the <6 years age group) and led to withdrawal of MMF in about 10% of patients. Administration of MMF 600 mg/m2 b.i.d. is effective in prevention of acute rejection, provides predictable pharmacokinetics, and is associated with an acceptable safety profile in pediatric renal transplant recipients.

Adolescent↗
PubMed2001

Impact of total body water errors on Kt/V estimates in children on peritoneal dialysis.

Determining Kt/V in peritoneal dialysis (PD) requires estimation of total body water (TBW). The Dialysis Outcomes Quality Initiative (DOQI) guidelines recommend use of the Mellits and Cheek (MC) formulas for the estimation of TBW in children. However, the MC formulas were developed from healthy children and may not apply to children on PD. Re-evaluating the MC data with additional, recent data from healthy infants has led to the development of new formulas. In addition, and as part of a prospective study of children initiating PD, the Pediatric Peritoneal Dialysis Study Consortium (PPDSC) has directly measured TBW using H2[18O]. To assess the impact of various TBW estimates, KPDt/V values prospectively collected in 24 children were calculated using H2[18O]-measured TBW (O18), MC-derived TBW (MCD), and new-formula TBW (NEW). The mean weekly KPDt/V by O18 was 2.2; by MCD, it was 2.0; and by NEW, it was 2.0. The results derived using the O18 method varied from both the MCD and the NEW results (p < 0.001). The mean deviation from the measured KPDt/V using O18 was 9.5% (maximum: 16%) using the MCD estimate and 7.8% (maximum: 18%) using the NEW formulas. Determinations of KPDt/V are significantly affected by the method of estimating TBW. The PPDSC formulas for children on PD based on the use of H2[18O] offer the most accurate means of calculating TBW and should replace formulas derived from healthy children. The use of Kt/V itself as a marker of adequacy in children will be validated only in prospective studies.

Adolescent↗
PubMed1999

Analysis of select folate pathway genes, PAX3, and human T in a Midwestern neural tube defect population.

Neural tube defects (NTDs) are a common birth defect, seen in approximately 1/1,000 births in the United States. NTDs are considered a complex trait where several genes, interacting with environmental factors, create the phenotype. Using a Midwestern NTD population consisting of probands, parents, and siblings from Iowa, Minnesota, and Nebraska, we analyzed a range of candidate genes, including 5,10-methylenetetrahydrofolate reductase (MTHFR), folate receptors-alpha (FOLR1; hereafter abbreviated "FR-alpha") and -beta (FOLR2; hereafter, "FR-beta"), methionine synthase (hereinafter, "MS"), T, the human homolog of the murine Brachyury gene, and the paired-box homeotic gene 3 (PAX3), for association with NTDs. We were unable to demonstrate an association using a previously described Ala-->Val mutation in MTHFR and the majority of our NTD populations. However, we discovered a silent polymorphism in exon 6 of MTHFR which conserved a serine residue and which showed significant association with NTDs in our Iowa population. Analysis of exon 7 of MTHFR then demonstrated an Ala-->Glu mutation which was significantly associated with our Iowa NTD population; however, we could not replicate this result either in a combined Minnesota/ Nebraska or in a California NTD population. Using polymorphic markers for MS, FR-beta, T, and PAX3, we were unable to demonstrate linkage disequilibrium with our NTD populations. A mutation search of FR-alpha revealed one proband with a de novo silent mutation of the stop codon. This work provides a new panel of genetic variants for studies of folate metabolism and supports, in some NTD populations, an association between MTHFR and NTDs.

5,10-Methylenetetrahydrofolate Reductase (FADH2)↗
PubMed1998

Nocturnal polysomnography in obsessive-compulsive disorder.

To determine if sleep abnormalities occur in obsessive-compulsive disorder (OCD), 2 nights of sleep electroencephalographic (EEG) recordings were obtained from 13 medication-free outpatients with OCD and 13 age- and sex-matched normal volunteers. Patients were awake more on night 2 than on night 1, whereas control subjects had less time awake on night 1; no other differences between groups were found on sleep latency, sleep time, minutes of movement, sleep efficiency, rapid eye movement (REM) latency or amount of stage 1, 2, 3, or 4 or REM sleep. Within the patient group, total scores on the Yale-Brown Obsessive-Compulsive Scale were negatively correlated with total sleep time (r = -0.51, P = 0.07), sleep efficiency (r = -0.51, P= 0.07), and duration of stage 1 + 2 sleep (r = - 0.49, P = 0.09) but not with REM time (r = - 0.05, P = 0.87) or latency (r = -0.26, P = 0.39). Previous sleep studies in OCD have had divergent results, especially regarding REM latency; our results suggest that many OCD patients have essentially normal sleep EEG findings.

Adult↗
PubMed1998

Comparison of electron beam computed tomography scanning and conventional risk factor assessment for the prediction of angiographic coronary artery disease.

OBJECTIVE: To determine whether electron beam computed tomography (CT) adds to conventional risk factor assessment in the prediction of angiographic coronary artery disease. BACKGROUND: Electron beam CT scanning can be used to predict the severity of coronary atherosclerosis, but whether it does so independently of conventional risk factors is unclear. METHODS: Electron beam CT scans were performed and conventional risk factors were measured in 290 men and women undergoing coronary arteriography for clinical indications. The association of the electron beam CT-derived coronary artery calcium score and conventional risk factors with the presence and severity of angiographically defined coronary atherosclerosis was analyzed by logistic regression and receiver-operator characteristics analysis. RESULTS: Age, the ratio of total cholesterol to high-density lipoprotein (HDL) cholesterol and the coronary calcium score were significantly and independently associated with the presence of any coronary disease and obstructive coronary disease. In association with any coronary disease, odds ratios for age, the ratio of total cholesterol to HDL cholesterol and calcium score, highest quartile vs. lowest quartile, were 6.01 (95% confidence interval 2.87 to 12.56), 3.14 (1.56 to 6.31) and 94.08 (21.06 to 420.12), respectively. For obstructive coronary disease, highest quartile vs. lowest quartile, the respective odds ratios for age, the ratio of total cholesterol to HDL and calcium score were 3.86 (1.86 to 8.00), 4.11 (1.98 to 8.52) and 34.12 (12.67 to 91.86). Male gender was also significantly associated with any coronary disease (odds ratio 2.19, p=0.04) and obstructive coronary disease (odds ratio 2.07, p=0.04). Cigarette smoking was significantly associated with any coronary disease (odds ratio=2.74, p=0.004), and diabetes was significantly associated with obstructive disease (odds ratio 3.16, p=0.01). After adjustment for the coronary calcium score and other risk factors, it was determined that triglycerides, family history and hypertension were not significantly associated with any disease state. A coronary calcium score >80 (Agatston method) was associated with an increased likelihood of any coronary disease regardless of the number of risk factors, and a coronary calcium score > or = 170 was associated with an increased likelihood of obstructive coronary disease regardless of the number of risk factors (p < 0.001). CONCLUSIONS: Electron beam CT scanning offers improved discrimination over conventional risk factors in the identification of persons with any angiographic coronary disease or angiographic obstructive coronary disease.

Adult↗
PubMed1998

Serum concentration of calcium, 1,25 vitamin D and parathyroid hormone are not correlated with coronary calcifications. An electron beam computed tomography study.

BACKGROUND: The amount of coronary artery calcification, measured using electron beam computed tomography, is correlated with the volume of coronary artery atherosclerotic plaque, the severity of stenosis by angiography, and with the likelihood of future cardiovascular events. The deposition of calcium in atherosclerotic plaques may also be influenced by determinants of calcium metabolism, thus contributing to the variance of the relation between coronary artery calcification and extent of atherosclerosis. Our objective was to determine whether this variance could be explained by differences in the parameters of calcium metabolism. DESIGN AND METHODS: We measured serum concentrations of calcium, 1,25(OH)2 vitamin D and parathyroid hormone (PTH) in 50 subjects undergoing angiography for clinical indications, and evaluated the correlations between these concentrations and calcium deposition in the coronary arteries, and the ratio of calcium deposition to extent of atherosclerosis using coronary angiography. RESULTS AND CONCLUSIONS: Serum concentrations of calcium 1,25(OH)2 vitamin D and PTH were not correlated with coronary calcification or the ratio of coronary calcification to the extent of coronary stenosis. We conclude that, in subjects undergoing coronary angiography, the variance of the relationship between coronary atherosclerosis and coronary calcium is not a result of differences in serum concentrations of calcium, 1,25(OH)2 vitamin D or PTH.

Aged↗
PubMed1997

Relation of coronary calcium score by electron beam computed tomography to arteriographic findings in asymptomatic and symptomatic adults.

Coronary arteriography was performed on 18 asymptomatic, apparently healthy adults with elevated coronary calcium scores. To extend the range of observation to subjects with low calcium scores, arteriograms from 18 patients with exertional dyspnea and/or valvular heart disease and low calcium scores were also analyzed; these 18 patients were considered asymptomatic from the point of view of coronary artery disease (CAD). For the comparison of symptomatic and asymptomatic persons, 3 age and sex-matched symptomatic patients were also selected for each of the original 18 asymptomatic subjects. Arteriograms were analyzed by computer-assisted quantitative coronary arteriography at a remote site without knowledge of the calcium score or any other patient characteristics. In the 18 asymptomatic subjects with elevated calcium scores, the mean calcium score was 573 +/- 504 (Agatston method) and the mean worst stenosis was 45% +/- 16%. For all 36 patients without symptoms of CAD, worst stenosis was closely correlated with the square root of the calcium score (r = 0.85, p <0.0001). Patients with symptomatic coronary disease and calcium scores < 1,000 had stenoses more severe than asymptomatic persons with similar calcium scores. Most asymptomatic adults with elevated calcium scores have nontrivial, nonobstructive CAD or preclinical obstructive CAD, and the relation between coronary calcium score and severity of stenosis is highly significant. These data indicate that electron beam tomography can be used to estimate the severity of CAD in asymptomatic persons.

Adult↗
PubMed1996

Predictive value of electron beam computed tomography of the coronary arteries. 19-month follow-up of 1173 asymptomatic subjects.

BACKGROUND: Coronary electron beam computed tomography (EBCT) detects atherosclerotic coronary artery disease by measuring calcium deposition in the walls of coronary arteries. EBCT-derived coronary artery calcium (CAC) scores correlate with the severity of underlying coronary artery disease. METHODS AND RESULTS: We followed 1173 asymptomatic patients who underwent EBCT between September 1993 and March 1994. During average follow-up of 19 months, 18 subjects had 26 cardiovascular events: 1 death, 7 myocardial infarctions, 8 coronary artery bypass graft procedures, 9 coronary angioplasties, and 1 nonhemorrhagic stroke. For CAC score thresholds of 100, 160, and 680, EBCT had sensitivities of 89%, 89%, and 50% and specificities of 77%, 82%, and 95%, respectively. Odds ratios ranged from 20.0 to 35.4 (P < .0001 for all). CONCLUSIONS: Coronary EBCT predicts future atherosclerotic cardiovascular disease events in asymptomatic subjects.

Angioplasty↗
PubMed1996

Subject selection biases in clinical trials: data from a multicenter schizophrenia treatment study.

To evaluate subject selection biases in clinical trials, demographic characteristics (gender, race, and age) of subjects at different phases of evaluation for a multicenter maintenance trial in schizophrenia were examined. Six thousand twelve diagnostically appropriate subjects were screened for the study; of these, 1,320 met eligibility criteria and 528 (9% of the screened sample) entered the study. Women, blacks, and older subjects were more likely not to meet eligibility criteria; women and older subjects were more likely and blacks were less likely to refuse study participation. Overall, compared with the screened population, the sample of subjects who entered the study contained proportionately fewer women (33 vs. 43%), more blacks (48.5 vs. 41%), and fewer older subjects (mean age of the entered sample was 29.4 +/- 7.4 vs. 34.8 +/- 11.3 years for the screened population). Having identified these selection factors, a second goal was to assess the potential clinical relevance of selection biases of these magnitudes on clinical trials using models of hypothetical studies with different degrees of selection bias. These showed that selection biases would rarely change overall study outcomes to a clinically relevant degree. However, in our models, selection biases did limit the ability to make inferences about results for select small subgroups of the study population. Investigators should consider collecting data on the recruitment process to allow estimation of the effects of selection biases on the generalizability of their findings.

Acute Disease↗
PubMed1995

Reduced caudate nucleus volume in obsessive-compulsive disorder.

BACKGROUND: Current hypotheses about the neuroanatomical structures involved in obsessive-compulsive disorder (OCD) suggest abnormalities in cortical-striatal-thalamic-cortical circuits. This study examined selected brain regions within or adjacent to these circuits. METHODS: Magnetic resonance imaging scans from 26 patients with OCD and 26 healthy controls were analyzed to determine the volumes of the following structures: prefrontal cortex (cortex anterior to the genu of the corpus callosum), caudate nucleus, lateral and third ventricles, and whole brain. RESULTS: Patients with OCD had significantly smaller caudate nucleus volumes than controls (F[1,48] = 9.4, P = .004) but did not differ in prefrontal cortex size or in volumes of the lateral or third ventricles. Structural volumes were not significantly correlated with the duration or severity of OCD symptoms. CONCLUSION: Our findings provide additional evidence for pathological involvement of the caudate in OCD.

Adolescent↗
PubMed1994

Increase in caudate nuclei volumes of first-episode schizophrenic patients taking antipsychotic drugs.

OBJECTIVE: This study examined the pathomorphology of the caudate nuclei in first-episode schizophrenic patients with minimal previous neuroleptic exposure. METHOD: Magnetic resonance imaging (MRI) of the brain was used to examine longitudinally the caudate pathomorphology in 29 first-episode schizophrenic patients and 10 healthy comparison subjects. MRI scans were obtained after the subjects entered the study and at 18-month follow-up. The patients were treated with standardized neuroleptic regimens during the 18-month period. Volumetric assessments of the cerebral cortex, lateral ventricles, and caudate nuclei were performed on T1-weighted coronal brain sections. In addition, the patients were systematically evaluated for psychopathology at baseline and during treatment. RESULTS: Caudate volumes increased 5.7% in the patients during the 18-month treatment interval, whereas they decreased 1.6% in the comparison subjects over the same time period. Greater amounts of antipsychotic medication received by patients before the first scan and younger age at the time of the first scan were associated with larger increases in caudate volume. CONCLUSIONS: Caudate enlargement occurs early in the course of treatment in young first-episode schizophrenic patients. This may be a result of an interaction between neuroleptic treatment and the plasticity of dopaminergic neuronal systems in young patients.

Adult↗
PubMed1993

Hippocampus-amygdala volumes and psychopathology in chronic schizophrenia.

Volumes of the mesiotemporal structures (hippocampus-amygdala complex) were measured in 19 men who were chronic multiepisode schizophrenics and 18 age-matched healthy controls using T1-weighted contiguous coronal magnetic resonance images of 3.1-mm width. Using the level of the mammillary bodies as an anatomical landmark, the whole hippocampus-amygdala complex was divided into an anterior section (mainly containing amygdaloid tissue) and a posterior section (mainly containing the hippocampal formation). Total mesiotemporal tissue volume was reduced significantly in the patient group compared to controls (-11%), with significant reductions in both left (-20%) and right (-15%) hippocampal sections. Reduced limbic tissue volume was associated with increased severity of psychopathology. Severity of positive psychotic symptoms (Brief Psychiatric Rating Scale [BPRS] psychosis factor) was correlated significantly with right and left total mesiotemporal volumes (Spearman rho's = -0.61 p < 0.01). Negative symptom scores (BPRS anergia factor, Scale for Assessment of Negative Symptoms [SANS] global items) were not significantly correlated with any mesiotemporal tissue volumes. The data corroborate and extend previous findings of temporolimbic structure volume reduction in schizophrenia, and suggest that the positive psychotic symptoms of schizophrenia are associated with anatomic anomalies in mesiotemporal structure.

Adult↗
PubMed1986

Acute myocardial infarction among Navajo Indians, 1976-83.

We found that from 1976 through 1983 the incidence of acute myocardial infarction (AMI) diagnosed among Navajo Indians remained low (0.5 per 1,000 persons age 30 years or more), although the incidence in women appears to be climbing. Navajo AMI patients are more likely to be hypertensive and diabetic than age- and sex-matched patients with gallbladder disease. Twenty-four per cent die within one month of AMI.

Adolescent↗